Digital Edition

Transcription

Digital Edition

NEW DRUG REVIEW
TRIFLURIDINE/TIPIRACIL > FOR COLORECTAL CANCER pg. 27
®
Drug Topics®
DrugTopics.com
July 2016 | Vol. 160 No. 7
J u l y 2016
VOICE OF THE PHARMACIST SINCE 1856
C E : EXPANDING VACCINATION RATES THROUGH PHARMACIST-INITIATED PATIENT IDENTIFICATION AND ASSESSMENT
OPIOID CRISIS
PHARMACIST
‘Naloxone should
be the fire extinguisher
in the home of everyone
who is at risk.’
PAGE 15
r
O T C: EYES AND EARS
Jeffrey P. Bratberg, PharmD, BCPS
2
CPE
CREDITS
Increasing Vaccination Rates
for Adolescents, Adults pg.58
R EG UL ATORY/LEGAL
DEA to Consider Rescheduling
Marijuana — for the Fourth Time 57
VOICES
Pharmacy’s Catch-22:
Save a Life, or Save Your Livelihood 18
VOL . 16 0 NO. 7
One Drug, Two Prices:
The Medicare/Medicaid Disparity 14
The Secret to a Rewarding
Pharmacy Career 13
RECOMMEND THE
MOST POWERFUL
OTC PPI FROM THE START1,2
TAME THE
ACID
BEAST
STRONGER, LONGER ACID CONTROL
compared with Prilosec OTC (omeprazole 20 mg)1,2*
For samples and coupons visit StartNexium24HR.com
Nexium Level Protection®
*Acid control (pH >4) does not imply symptom relief. The correlation of pH data to clinical outcome has not been directly established.
References: 1. Lind T, Rydberg L, Kylebäck A, et al. Esomeprazole provides improved acid control vs. omeprazole in patients with
symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000;14(7):861-867. 2. Katz P, Kahrilas PJ, Johnson DA, et al.
Daytime intragastric acid control: post hoc analyses of esomeprazole 20 mg and over-the-counter proton-pump inhibitors. Therap Adv
Gastroenterol. 2015;8(6):322-330.
©2016 Pfizer Inc.
NXM031631-01
5/16
StartNexium24HR.com
EDITORIAL ADVISORY BOARD
Philip P. Burgess, RPh, MBA
Mary E. Inguanti, RPh, MPH, FASCP
Marvin R. Moore, PharmD
Chairman
Community Pharmacy Foundation
Illinois Board of Pharmacy
Strategic Customer
Vice President
BD
Pharmacy manager & co-owner
The Medicine Shoppe/Pharmacy
Solutions Inc.
Chicago, Ill.
South Windsor, Conn.
Two Rivers, Wisc.
Perry Cohen, PharmD, FAMCP
Debbie Mack, BS Pharm, RPh
David D. Pope, PharmD, CDE
The Pharmacy Group LLC
Director
Pharmacy Regulatory Affairs
Wal-Mart Health and Wellness
Chief of Innovation, Co-Founder
Creative Pharmacist
Glastonbury, Conn.
Augusta, Ga.
Bentonville, Ark.
David J. Fong, PharmD
Frederick S. Mayer, RPh, MPH
Brian Romig, RPh, MBA
Former community chain store
senior pharmacy executive
President
Pharmacists Planning Service Inc.
Danville, Calif.
San Rafael, Calif.
Vice President
Corporate Pharmacy Director
Supply Chain
Adventist Health System
Altamonte Springs, Fla.
Anna Garrett, PharmD, BCPS
Gene Memoli Jr., RPh, FASCP
Jack Rosenberg, PharmD, PhD
President
Dr. Anna Garrett
Director
Customer Development, Omnicare
Asheville, N.C.
Cheshire, Conn.
Professor Emeritus
Pharmacy Practice and Pharmacology
Long Island University
Brooklyn, N.Y.
Salvatore J. Giorgianni, Jr., PharmD, BSc, CMHE
Ned Milenkovich, PharmD, JD
Stephen W. Schondelmeyer, PharmD, PhD
Consultant Pharmacist
Griffon Consulting Group, Inc.
Chair, Men’s Health Caucus,
American Public Health Association
Advisory Board, Pharmacist Partners, LLC
and The Men’s Health Network
Partner
Health, Drug, and Pharmacy Practice
Much Shelist PC
Director, PRIME Institute
College of Pharmacy
University of Minnesota
Chicago, Ill.
Minneapolis, Minn.
CONTENT
ASSOCIATE PUBLISHER Mark Hildebrand
PERMISSIONS Maureen Cannon
VP, CONTENT & STRATEGY Sara Michael
732-346-3006 | [email protected]
GROUP EDITORIAL DIRECTOR Susan Kweskin
SALES MGR. CLASSIFIED/DISPLAY ADVERTISING Tod McCloskey
440-891-2742 / [email protected]
REPRINTS 877-652-5295, ext. 121 [email protected]
Outside US, UK, direct dial: 281-419-5725, ext. 121
EDITORIAL DIRECTOR Julia Talsma
MANAGING EDITOR Julianne Stein
EDITOR Mark Lowery
ACCOUNT MANAGER,CLASSIFIED/DISPLAY Patrick Carmody
PUBLISHING AND SALES
EVP, MANAGING DIRECTOR Georgiann DeCenzo
VICE PRESIDENT, GROUP PUBLISHER Ken Sylvia
GROUP PUBLISHER William Mulderry
SPECIAL PROJECTS DIRECTOR Meg Benson
ACCOUNT MANAGER, RECRUITMENT Joanna Shippoli
SALES DIRECTOR,DIGITAL MEDIA Don Berman
VP, MARKETING Amy Erdman
DIRECTOR, MARKETING & RESEARCH SERVICES Gail Kaye
LIST ACCOUNT EXECUTIVE Renee Schuster
DESIGN
DIRECTOR, DESIGN & DIGITAL PRODUCTION Nancy Bitteker
ART DIRECTOR Lecia Landis
PRODUCTION
PRODUCTION DIRECTOR Karen Lenzen
AUDIENCE DEVELOPMENT
VP, MARKETING & AUDIENCE DEVELOPMENT Joy Puzzo
DIRECTOR, AUDIENCE DEVELOPMENT Christine Shappell
AUDIENCE DEVELOPMENT MANAGER Kelly Kemper
EDITORIAL MISSION: Drug Topics is the top-ranked pharmacy resource for community and health-system professionals. Since 1857,
readers have turned to Drug Topics for coverage of issues and trends important to the practice of pharmacy, and for a forum in which
they can share viewpoints and practical ideas for better pharmacy management and patient care.
DRUGTOPICS.COM | JULY 2016 | DrugTopics
1
TABLE OF CONTENTS
July 2016 | Vol. 160 | No. 7
COVER STORY
Opioid Crisis
AND
THE Pharmacist
The opioid epidemic has touched thousands of Americans and their families. Pharmacists in the U.S. have
stepped up to this challenge, including training in
naloxone use. Are you prepared to save lives? 15
GENEVIEVE REGAL, PHARMD, HC-MBA
REIN IN MEDICARE DRUG COSTS
Equalize Medicare and Medicaid rates 14
Quit stigmatizing naloxone
Learn to use naloxone now
20 Opioid use for chronic pain
42 Naloxone rules and regulations
7
12
DAVID STANLEY, RPH
WHAT’S BEST FOR THE PATIENT?
PRESCRIBED READING
13
FIND SATISFACTION IN YOUR VOCATION
Have you forgotten? 18
Peter A. Kreckel, RPh, shares secrets to a rewarding pharmacy career
18
PHARMACY’S CATCH-22
Save a life or save your livelihood?
19
KEEPING THE FAITH
How one pharmacy survived the Baltimore riots
JULY 2016:
AND
Expanding vaccination rates
2
CPE
CREDITS
JEFFREY FUDIN, PHARMD, DAAPM, FASHP
OPIOID USE FOR CHRONIC PAIN
The debate continues 20
EARN 2 CPE CREDITS.
Go Online to > www.drugtopics.com/cpe
Drug Topics and The University of Connecticut School of Pharmacy present a new CPE activity
for pharmacists and pharmacy technicians. Earn up to 2 hours of CPE credit with this activity.
> JULY 2016: Expanding vaccination rates through pharmacist-initiated patient
identification and assessment
> JUNE 2016: The rundown: Management of acute and chronic diarrhea
DEWEY HOWELL, MD, PHD
BEST PRACTICES IN MED REC
TABLE OF CONTENTS CONTINUED ON PAGE 6 >
2
DrugTopics | JULY 2016 | DRUGTOPICS.COM
Helping patients through transitions 23
PHOTOS:GETTYIMAGES/SBAYRAM/AMBIENTIDEAS
A NE W CPE AC T IVI T Y
TABLE OF CONTENTS
July 2016 | Vol. 160 | No. 7
2
CPE
CREDITS
C O N T I N U I N G E D U C AT I O N
Expanding vaccination rates
for adolescents, adults
As the number of available
vaccines continues to grow,
pharmacists can serve as a
useful resource by providing
data and administering
vaccines to patients.
JEFFREY P. BRATBERG, PHARMD
SOLUTIONS TO THE OPIOID EPIDEMIC
Education, training is key 15
58
COUNTER POINTS
QUIT STIGMATIZING NALOXONE
Change the terminology and save lives
12
GET TRAINING NOW
Student advocates training in naloxone
use, buprenorphine education
14
UNCONTROLLABLE DRUG COSTS
23
EFFICIENCY IN MED RECONCILIATION
Hospitals strive for a “clean” list of meds
28
TIME TO CREATE YOUR OWN ASP
Lessons from three health systems
CAMDEN E. SVEC, 2016 PHARMD CANDIDATE
CLINICAL
Is Medicare Part D growth unsustainable?
27
ISSUES & TRENDS
Trifluridine/tipiracil for the treatment of
metastatic colorectal cancer
19
NEW CAMPAIGN TARGETS SENIORS
Buying drugs from illegal online pharmacies is risky. Spread the word
19
SURVIVING THE BALTIMORE RIOTS
Pharmacy continued to serve patients
during, after looting
54
A review of trifluridine/tipiracil 27
SPECIALTY PHARMACY UPDATE
Explore pathways to fastest-growing niche
R E G U L AT O R Y & L E G A L
57
RESCHEDULING MARIJUANA?
DEA responds to U.S. Senators
INNOVATIONS
Point-of-care testing in Hawaii
67
34
NEW DRUG REVIEW
OPTION FOR COLORECTAL CANCER
REMEMBER WHEN
Pharmacists accurately predicted the
winner of the 1984 presidential election.
Will you be right again? Take our poll
and let us know where you stand
P R O D U C T U P DAT E S
51
OTC: EYES AND EARS
Revive tired, dry eyes; safely clear ears of
wax buildup
56
MONTGOMERY WILLIAMS, PHARMD, BCPS
PHARMACISTS LEAD THE CHARGE
ASPs vs. microbial resistance 28
NEW PRODUCTS
Brivaracetam for epilepsy now available
Drug Topics (ISSN# 0012-6616) is published monthly and Drug Topics Digital Edition (ISSN# 1937-8157) is issued every week by UBM Medica 131 West First St., Duluth, MN 55806-2065. One-year subscription rates: $61 in the United States & Possessions; $109 in Canada and Mexico; all other
countries, $109. Single copies (prepaid only) $10 in the United States; $10 in Canada and Mexico; all other countries, $15. Include $6 per copy for U.S. postage and handling. Periodicals postage paid at Duluth, MN 55806 and additional mailing offices. POSTMASTER: Please send address
changes to Drug Topics, P.O. Box 6079, Duluth, MN 55806-6079. Canadian G.S.T. number: R-124213133RT001. Publications Mail Agreement Number 40612608. Return undeliverable Canadian addresses to: IMEX Global Solutions PO Box 25542 London, ON N6C 6B2 CANADA. Printed in the U.S.A.
©2016 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical including by photocopy, recording, or information storage and retrieval without permission in writing from the publisher.
Authorization to photocopy items for internal/educational or personal use, or the internal/educational or personal use of specific clients is granted by Advanstar Communications Inc. for libraries and other users registered with the Copyright Clearance Center, 222 Rosewood Dr. Danvers, MA 01923, 978-750-8400 fax 978-646-8700 or visit http://www.copyright.com
online. For uses beyond those listed above, please direct your written request to Permission Dept. fax 440-756-5255 or email: [email protected]. Microfilm or microfiche copies of issues are available through Advanstar Marketing Services, (800) 225-4569, Ext. 839. Unsolicited manuscripts, photographs, art, and other material will not be returned. Publisher
assumes no responsibility for unsolicited manuscripts, photographs, art, and other material. Drug Topics provides certain customer contact data (such as customers’ names, addresses, phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, services, and other opportunities that may be of interest to you. If you do not want UBM
Medica to make your contact information available to third parties for marketing purposes, simply call toll-free 866-529-2922 between the hours of 7:30 a.m. and 5 p.m. CST and a customer service representative will assist you in removing your name from UBM Medica’s lists. Outside the U.S., please phone 218-740-6477. Drug Topics does not verify any claims or
other information appearing in any of the advertisements contained in the publication, and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. Drug Topics welcomes unsolicited articles, manuscripts, photographs and other materials but cannot be held responsible for their safekeeping or return. LIBRARY ACCESS
Libraries offer online access to current and back issues of Drug Topics through the EBSCO host databases.
TO SUBSCRIBE, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477.
6
GETTY IMAGES/SUSAN CHIANG
7
HE ALT H SYST EMS
COUNTER POINTS
DISPENSED AS WRITTEN
Jeffrey Fudin, PharmD, DAAPM, FCCP, FASHP;
Mena Raouf, PharmD
Quit stigmatizing naloxone
If vocabulary is the problem, change terminology and start saving lives
What do naloxone and epinephrine formulations for in-home use have in common? Both are lifesaving
medications that have been around for more than 40 years. Naloxone, however, has at times been treated
as the “redheaded stepchild” of emergency medicines, especially in connection with in-home use.
Few pharmaceuticals can serve as antidotes, and fewer can be used in the home.
Some that come to mind are parasympathomimetics such as neostigmine or
edrophonium for tubocurarine exposure or myasthenia crisis respectively,
antihistamines and epinephrine for
anaphylaxis, flumazenil for benzodiazepines, etc.
While mortality from anaphylaxis has
declined over the years, in large part as a
result of in-home availability of epinephrine1, mortality and morbidity from opioid “overdose” have increased sixfold.2
As the number of cases of chronic pain
and substance-abuse disorder continues to increase across the United States,
opioid-related morbidity and mortality
also continue to pose a costly and dangerous public health threat.
3,300
THE NUMBER OF ACCIDENTAL
OPIOID DEATHS IN CHILDREN
UNDER 5 YEARS OLD IN 2013
macy professionals have succumbed to
such a mindset.
The vocabulary problem
The term “overdose” is part of the problem. It has its own associated stigma.
Merriam-Webster defines overdose
as “an amount of a drug or medicine
that is too much and usually dangerous … also: a lethal or toxic amount (as
of a drug)”.5
comitant use of CNS depressant medications or substances.”6
We need to educate ourselves. We
need to shift away from using the term
“overdose” and begin to employ a different term, such as “opioid-related toxicity.” This defuses part of the stigma and
opens the door for a more comfortable
conversation with patients about the possibility of opioid-related toxicity, including respiratory depression.
“Narcotic” is another derogatory term,
defined by Merriam-Webster Dictionary
Online as “a drug (such as cocaine, heroin, or marijuana) that affects the brain
and that is usually dangerous and illegal.”
Its secondary medical defi nition is
“a drug that is given to people in small
amounts to make them sleep or feel less
pain.” In other words, not only opioids
are narcotics.7
The bee-sting analogy
If someone allergic to bee stings were
forced to become a beekeeper, would
you deny that person an Epi-Pen?
Did you answer no? Then why should
naloxone be denied as the standard of
care for chronic pain patients who can
find no alternative for relief but opioids?
Many federal and state efforts have
sought to increase access to naloxone
and reduce liability risk through the passage of Good Samaritan laws.3,4 However, there remains a stigma associated
with naloxone that poses a barrier to
widespread prescribing.
A common misconception holds that
naloxone is for heroin users or “junkies”
and labels those who carry in-home naloxone as drug addicts. Even some phar-
We need to shift away from using the term
‘overdose’ and begin to employ a different term,
such as ‘opioid-related toxicity.’”
However, there are factors other than
the amount of opioid administered (i.e.,
dose) that contribute to fatal respiratory
depression. According to Dr. Zedler et al,
“Substantial risk for serious opioid-related
toxicity and overdose exists at even relatively low maximum prescribed morphine equivalent daily doses (MEDD),
especially in patients already vulnerable due to underlying demographic
factors, comorbid conditions, and con-
The opioid toxicity talk
It is important to make clear to patients
that a reference to opioid-related toxicity doesn’t mean that patients are “on
too much pain medication” or that they
“are addicted.”
Patients should understand that there
are predisposing risk factors, some modifiable and some nonmodifiable, for opioid toxicity.
CONTINUED ON PAGE 8 >
7
COUNTER POINTS
DISPENSED AS WRITTEN
QU I T ST IG M AT IZ I NG NA LOXON E
< CONTINUED FROM PAGE 7
Patients also should be educated about
the risk associated with drug-drug interactions.
And patients should be advised to communicate with their prescribers before
starting new medications — even shortterm antibiotics from urgent care.
A common scenario that could occur
is when a patient on oxycodone goes to
an urgent-care facility for a fungal infection and is prescribed fluconazole, which
would decrease oxycodone’s metabolism and increase its levels.
Using the RIOSORD score validated
by Zedler can open the door to a nonconfrontational professional dialogue
with patients.
In this type of exchange, quantified hazards can be addressed with the
patient one by one in an effort to lower
the overall percentage risk of opioidinduced respiratory depression, much
as we address a stepwise approach to
lowering HbA1c in diabetes patients or
cholesterol in patients with hyperlipidemia, starting first with diet and exercise.
The naloxone talk
When offering patients naloxone for
in-home use, healthcare providers should
Sixfold
tal ingestion by another family member
or even a pet.8
Underutilized
Naloxone remains an underutilized lifesaving device while the opioid pandemic
continues to grow.
Opioids will continue to claim more
lives if no proactive measures are
employed. A standard of care for opioid prescribing should include screening for overdose or respiratory depression and continuous monitoring
focus on safety and the precaution
throughout therapy.
of having emergency response
OPIOID
Patients should be educated
at the ready, just as airports
CRISIS
on risk factors and those at
keep defibrillators, homes
For More from Dr. Fudin, see
high risk should be offered
have fire extinguishers, and
PAIN MANAGEMENT
naloxone for in-home use.
vulnerable patients make
pg.
sure nitroglycerin is nearby
for attacks of acute angina or
REFERENCES
even a rescue beta adrenergic
1. American Academy of Allergy, Asthma & Immunolinhaler for instances of acute unsta- ogy (AAAAI) 2013 Annual Meeting: Abstract 511. Presented
February 24, 2013.
ble asthma.
2. Rudd RA, Aleshire N, Zibbell JE, et al. Increases in drug and
If further clarification is necessary, as opioid overdose deaths — United States, 2000–2014. Centers for
a pharmacist you might point out that Disease Control and Prevention Morbidity and Mortality Weekly
Report (MMWR). 2016 Jan 1;64(50-51):1378-1382.
in 2013 there were approximately 3,300
3. Davis CS, Carr D. Legal changes to increase access to naloxaccidental opioid deaths in children under one for opioid overdose reversal in the United States. Drug Alcothe age of five, or bring up scenarios in hol Depend. 2015;157:112-120.
which naloxone could be a life-saving 4. Network for Public Health Law. Legal interventions to
overdose mortality: Naloxone access and overdose Good
asset, such as the possibility of acciden- reduce
Samaritan laws. Updated April 2016. http://bit.ly/networkforphl.
THE INCREASE IN MORBIDITY
AND MORTALITY FROM OPIOID
“OVERDOSE,” FROM 2000 TO
2014, WHILE MORTALITY FROM
ANAPHYLAXIS DECLINED
20
Accessed April 29, 2016.
5. Merriam-Webster Dictionary Online. http://www.merriamwebster.com/dictionary/overdose.
6. Zedler B, Xie L, Wang L, et al. Development of a risk index for
serious prescription opioid-induced respiratory depression or
overdose in Veterans’ Health Administration patients. Pain Med.
2015;16(8):1566-1579.
7. Merriam-Webster Dictionary Online. http://www.merriamwebster.com/dictionary/narcotic.
8. Burghardt LC, Ayers JW, Brownstein JS, et al. Adult prescription
drug use and pediatric medication exposures and poisonings.
Pediatrics. 2013; 132(1):18-27.
Jeffrey Fudin is clinical pharmacy specialist, Stratton V.A. Medical Center, Albany N.Y.; CEO, Remitigate LLC, Delmar N.Y.; and adjunct
associate professor, Western New England University College of Pharmacy. He is adjunct assistant professor at the University of Connecticut
School of Pharmacy and owner and managing editor of PainDr.com. Contact him at [email protected]. Disclosures: Astra Zeneca (speakers
bureau, advisory board); DepoMed (advisory board); Endo (speakers bureau, consultant); Kaléo (speakers bureau, advisory board); Kashiv
Pharm (consultant); KemPharm (consultant); Millennium Health LLC (speakers bureau); Remitigate LLC (founder, owner); Scilex Pharmaceuticals (consultant); and Pernix (speaker). Mena Raouf graduated from Albany College of Pharmacy and Health Sciences with a concentration in Nephrology and is pursuing a PGY-1 Pharmacy Practice Residency at the VA Tennessee Valley Healthcare System. This article is the
sole work of the authors; it does not reflect the opinions of employers, employee affiliates, or pharmaceutical companies.
8
CREDIT:GETTYIMAGES/SBAYRAM
Just as airports keep defibrillators, homes have
fire extinguishers, and vulnerable patients make sure
nitroglycerin is nearby for attacks of acute angina or
even a rescue beta adrenergic inhaler for instances
of acute unstable asthma, so patients should have
naloxone available for in-home use.”
Now more than ever before,
patients look to you for vaccinations1,2
When it comes to Medicare Part D
vaccinations like ZOSTAVAX—
Pharmacists play a most critical role1
If you don’t recommend vaccination in your pharmacy, who will?
As an active member of your community, make sure patients
are aware of the CDC recommendation, which suggests they
be offered the shingles vaccine at the first clinical encounter
once they reach age 60.3
Laws and regulations regarding in-store pharmacy vaccinations vary by state. Consult the appropriate resources,
including the relevant state pharmacy boards, for more information.
About ZOSTAVAX
ZOSTAVAX is a live attenuated virus vaccine indicated for prevention of herpes zoster (shingles) in individuals
50 years of age and older. ZOSTAVAX is not indicated for the treatment of zoster or postherpetic neuralgia.
ZOSTAVAX should not be used for prevention of primary varicella infection (Chickenpox).
Select Safety Information
Vaccination with ZOSTAVAX does not result in protection of all vaccine recipients.
ZOSTAVAX is contraindicated in: persons with a history of anaphylactic or anaphylactoid reaction to
gelatin, neomycin, or any other component of the vaccine; persons with a history of primary or acquired
immunodeficiencies; persons on immunosuppressive therapy; pregnant women or women of childbearing age.
A reduced immune response to ZOSTAVAX was observed in individuals who received concurrent administration
of PNEUMOVAX®23 (Pneumococcal Vaccine Polyvalent) and ZOSTAVAX compared with individuals who
received these vaccines 4 weeks apart. Consider administration of the two vaccines separated by at least
4 weeks.
Serious vaccine-related adverse reactions that have occurred following vaccination with ZOSTAVAX include
asthma exacerbation and polymyalgia rheumatica. Other serious adverse events reported following vaccination
with ZOSTAVAX include cardiovascular events (congestive heart failure, pulmonary edema). Common adverse
reactions occurring in ≥1% of vaccinated individuals during clinical trials include injection-site reactions
(erythema, pain/tenderness, swelling, hematoma, pruritus, warmth) and headache.
Transmission of vaccine virus may occur between vaccinees and susceptible contacts.
Deferral should be considered in acute illness (for example, in the presence of fever) or in patients with active
untreated tuberculosis.
Please read the adjacent Brief Summary of the Prescribing Information.
CDC=Centers for Disease Control and Prevention.
References: 1. National Vaccine Advisory Committee. Recommendations from the National Vaccine Advisory Committee: standards for
adult immunization practice. Public Health Rep. 2014;129(2):115–123. 2. Goad JA, Taitel MS, Fensterheim LE, et al. Vaccinations
administered during off-clinic hours at a national community pharmacy: implications for increasing patient access and convenience. Ann
Fam Med. 2013;11(5):429–436. 3. Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of
the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1–30.
Make a difference—
Identify eligible patients and initiate a
discussion about zoster vaccination today
Copyright © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved.
VACC-1141203-0016 04/16
ZOSTAVAX® (Zoster Vaccine Live)
BRIEF SUMMARY OF PRESCRIBING INFORMATION
INDICATIONS AND USAGE
ZOSTAVAX is a live attenuated virus vaccine indicated for prevention of herpes zoster (shingles)
in individuals 50 years of age and older.
Limitations of Use of ZOSTAVAX:
I,#&')+7A<=B7<271/B324=@B63B@3/B;3<B=4H=AB3@=@>=AB63@>3B71<3C@/:57/$"
I,#&')+7A<=B7<271/B324=@>@3D3<B7=<=4>@7;/@GD/@713::/7<431B7=<67193<>=F
CONTRAINDICATIONS
Hypersensitivity: Do not administer ZOSTAVAX to individuals with a history of anaphylactic/
/</>6G:/1B=72@3/1B7=<B=53:/B7<<3=;G17<=@/<G=B63@1=;>=<3<B=4B63D/117<3"3=;G17<
allergy manifested as contact dermatitis is not a contraindication to receiving this vaccine.
Immunosuppression: ZOSTAVAX is a live, attenuated varicella-zoster vaccine and administration
may result in disseminated disease in individuals who are immunosuppressed or immunodeficient.
Do not administer ZOSTAVAX to immunosuppressed or immunodeficient individuals including
B6=A3E7B6/67AB=@G=4>@7;/@G=@/1?C7@327;;C<=23L173<1GAB/B3A:3C93;7/:G;>6=;/=@
other malignant neoplasms affecting the bone marrow or lymphatic system, AIDS or other clinical
manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive
therapy.
Pregnancy:=<=B/2;7<7AB3@,#&')+B=>@35</<BE=;3<B7A<=B9<=E<E63B63@,#&')+
can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
=E3D3@</BC@/::G=11C@@7<5D/@713::/H=AB3@D7@CA),)7<431B7=<7A9<=E<B=A=;3B7;3A1/CA343B/:
harm. Therefore, ZOSTAVAX should not be administered to pregnant women, and pregnancy should
be avoided for 3 months following administration of ZOSTAVAX.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:&3@7=CA/2D3@A3@3/1B7=<A7<1:C27<5/</>6G:/F7A6/D3=11C@@32E7B6
ZOSTAVAX. Adequate treatment provisions, including epinephrine injection (1:1,000), should be
available for immediate use should an anaphylactic/anaphylactoid reaction occur.
Transmission of Vaccine Virus: Transmission of vaccine virus may occur between vaccinees and
susceptible contacts.
Concurrent Illness:343@@/:A6=C:2031=<A723@327</1CB37::<3AA4=@3F/;>:37<B63>@3A3<13=4
fever) or in patients with active untreated tuberculosis.
Limitations of Vaccine Effectiveness: Vaccination with ZOSTAVAX does not result in protection
of all vaccine recipients.
'632C@/B7=<=4>@=B31B7=<03G=<2G3/@A/4B3@D/117</B7=<E7B6,#&')+7AC<9<=E<'63<332
for revaccination has not been defined.
ADVERSE REACTIONS
The most frequent adverse reactions, reported in ≥1% of subjects vaccinated with ZOSTAVAX, were
headache and injection-site reactions.
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions,
rates of adverse reactions observed in the clinical trials of a vaccine cannot be directly compared to
rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
ZOSTAVAX Efficacy and Safety Trial (ZEST) in Subjects 50 to 59 Years of Age: In the ZEST study,
AC0831BA@3137D32/A7<5:32=A3=437B63@,#&')+"=@>:/130="'63@/17/:
27AB@70CB7=</1@=AA0=B6D/117</B7=<5@=C>AE/AA7;7:/@*67B3:/197A>/<71
/<2#B63@7<0=B6D/117</B7=<5@=C>A'6353<23@27AB@70CB7=<E/A;/:3/<2
43;/:37<0=B6D/117</B7=<5@=C>A'63/5327AB@70CB7=<=4AC0831BA3<@=::32
B=G3/@A
E/AA7;7:/@7<0=B6D/117</B7=<5@=C>A::AC0831BA@3137D32/D/117</B7=<@3>=@B1/@2)%B=
@31=@2/2D3@A33D3<BA=11C@@7<54@=;/GAB=>=ABD/117</B7=<
In the ZEST study, serious adverse events occurred at a similar rate in subjects vaccinated with
,#&')+
=@>:/130=
4@=;/GAB=>=ABD/117</B7=<
In the ZEST study, all subjects were monitored for adverse reactions. An anaphylactic reaction was
reported for one subject vaccinated with ZOSTAVAX.
Most Common Adverse Reactions and Experiences in the ZEST Study: The overall incidence of
vaccine-related injection-site adverse reactions within 5 days post-vaccination was greater for
subjects vaccinated with ZOSTAVAX as compared to subjects who received placebo (63.6% for
ZOSTAVAX and 14.0% for placebo). Injection-site adverse reactions occurring at an incidence
≥1% within 5 days post-vaccination are shown in Table 1.
Table 1
Injection-Site Adverse Reactions Reported in ≥1% of Adults Who Received ZOSTAVAX
or Placebo Within 5 Days Post-Vaccination in the ZOSTAVAX Efficacy and Safety Trial
Injection-Site Adverse Reaction
ZOSTAVAX
"
Placebo
"
Solicited*
$/7<
Erythema
Swelling
53.9
40.4
9.0
4.3
Unsolicited
$@C@7B7A
Warmth
3;/B=;/
Induration
11.3
3.7
1.6
1.1
0.7
1.6
0.0
&=:717B32=<B63)/117</B7=<%3>=@B/@2
&GAB3;71/2D3@A3@3/1B7=<A/<23F>3@73<13A@3>=@B322C@7<5/GA/B/< incidence of ≥1% in
37B63@D/117</B7=<5@=C>E3@363/2/163,#&')+>:/130=/<2>/7<7<B633FB@3;7BG
,#&')+>:/130=
@3A>31B7D3:G
'63=D3@/::7<1723<13=4AGAB3;71/2D3@A33F>3@73<13A@3>=@B322C@7<5/GAE/A67563@4=@
ZOSTAVAX (35.4%) than for placebo (33.5%).
Shingles Prevention Study (SPS) in Subjects 60 Years of Age and Older: <B63&$&B63:/@53AB
1:7<71/:B@7/:=4,#&')+AC0831BA@3137D32/A7<5:32=A3=437B63@,#&')+<
=@
>:/130=<'63@/17/:27AB@70CB7=</1@=AA0=B6D/117</B7=<5@=C>AE/AA7;7:/@*67B3
:/19
7A>/<71
/<2#B63@
7<0=B6D/117</B7=<5@=C>A'6353<23@
distribution was 59% male and 41% female in both vaccination groups. The age distribution of
subjects enrolled, 59-99 years, was similar in both vaccination groups.
'632D3@A3D3<B!=<7B=@7<5&C0ABC2G=4B63&$&23A75<32B=>@=D72323B/7:322/B/=<B63A/43BG
>@=L:3=4B63H=AB3@D/117<3<@3137D32,#&')+/<2<@3137D32>:/130=CA32
D/117</B7=<@3>=@B1/@2A)%B=@31=@2/2D3@A33D3<BA=11C@@7<54@=;/GA
B=>=ABD/117</B7=<
=4AC0831BA1=;>:3B32)%7<0=B6D/117</B7=<5@=C>A</227B7=<;=<B6:GAC@D37::/<134=@
6=A>7B/:7H/B7=<E/A1=<2C1B32B6@=C56B633<2=4B63ABC2GB=G3/@A>=ABD/117</B7=<
'63@3;/7<23@=4AC0831BA7<B63&$&<@3137D32,#&')+/<2<
@3137D32
>:/130=E3@3/1B7D3:G4=::=E324=@A/43BG=CB1=;3AB6@=C56/G>=ABvaccination and passively
4=::=E324=@A/43BG/4B3@/G
Serious Adverse Events Occurring 0-42 Days Postvaccination:<B63=D3@/::&$&ABC2G>=>C:/B7=<A3@7=CA
adverse events occurred at a similar rate (1.4%) in subjects vaccinated with ZOSTAVAX or placebo.
In the AE Monitoring Substudy, the rate of SAEs was increased in the group of subjects who
@3137D32,#&')+/A1=;>/@32B=B635@=C>=4AC0831BAE6=@3137D32>:/130='/0:3
Table 2
Number of Subjects with ≥1 Serious Adverse Events (0-42 Days Postvaccination)
in the Shingles Prevention Study
Cohort
ZOSTAVAX
<"
Placebo
<"
Relative Risk
(95% CI)
#D3@/::&BC2G=6=@B
(60 years of age and older)
1.4%
1.4%
1.01
60-69 years old
113/10100
1.1%
115/7351
1.6%
101/10095
1.0%
1.6%
1.36
!=<7B=@7<5&C0ABC2G=6=@B (60 years of age and older)
1.9%
1.3%
1.53
60-69 years old
1.1%
19/1367
1.4%
4/173
1.61
(0.75, 6.45)
70-79 years old
J
G3/@A=:2
70-79 years old
J
G3/@A=:2
1.3%
5.1%
"<C;03@=4AC0831BA7<1=6=@BE7B6A/43BG4=::=EC>
<<C;03@=4AC0831BA@3>=@B7<5/<&
/GA>=ABD/117</B7=<
;=<5@3>=@B32A3@7=CA/2D3@A33D3<BA7<B63&$&/GA
B=>=ABD/117</B7=<A3@7=CA
cardiovascular events occurred more frequently in subjects who received ZOSTAVAX
-
.B6/<7<AC0831BAE6=@3137D32>:/130=-
.7<B63!=<7B=@7<5&C0ABC2G'63
frequencies of serious cardiovascular events were similar in subjects who received
,#&')+-
./<27<AC0831BAE6=@3137D32>:/130=-
.7<B633<B7@3ABC2G1=6=@B
/GA
B=>=ABD/117</B7=<
Serious Adverse Events Occurring Over the Entire Course of the Study: Rates of hospitalization
were similar among subjects who received ZOSTAVAX and subjects who received placebo in the AE
Monitoring Substudy, throughout the entire study.
74BG=<37<27D72C/:A@3137D7<5,#&')+E3@3@3>=@B32B=6/D31=<53AB7D363/@B4/7:C@3
=@>C:;=</@G323;/1=;>/@32B=7<27D72C/:A@3137D7<5>:/130=7<B63!=<7B=@7<5
&C0ABC2G7<27D72C/:A
@3137D7<5,#&')+E3@3@3>=@B32B=6/D31=<53AB7D363/@B4/7:C@3
=@>C:;=</@G323;/1=;>/@32B=
7<27D72C/:A@3137D7<5>:/130=7<B63=D3@/::ABC2G
<B63&$&/::AC0831BAE3@3;=<7B=@324=@D/117<3@3:/B32&A<D3AB75/B=@23B3@;7<32
D/117<3@3:/B32A3@7=CA/2D3@A33F>3@73<13AE3@3@3>=@B324=@AC0831BAD/117</B32E7B6
,#&')+/AB6;/3F/13@0/B7=</<2>=:G;G/:57/@63C;/B71//<2AC0831BAE6=@3137D32
placebo (Goodpasture’s syndrome, anaphylactic reaction, and polymyalgia rheumatica).
Deaths: The incidence of death was similar in the groups receiving ZOSTAVAX or placebo during
B63/GA
>=ABD/117</B7=<>3@7=223/B6A=11C@@327<B635@=C>=4AC0831BAE6=@3137D32
ZOSTAVAX and 16 deaths occurred in the group of subjects who received placebo. The most
common reported cause of death was cardiovascular disease (10 in the group of subjects who
@3137D32,#&')+7<B635@=C>=4AC0831BAE6=@3137D32>:/130='63=D3@/::7<1723<13
of death occurring at any time during the study was similar between vaccination groups: 793
ZOSTAVAX® (Zoster Vaccine Live)
BRIEF SUMMARY OF PRESCRIBING INFORMATION (continued)
deaths (4.1%) occurred in subjects who received ZOSTAVAX and 795 deaths (4.1%) in subjects
who received placebo.
Most Common Adverse Reactions and Experiences in the AE Monitoring Substudy of the SPS:
Injection-site adverse reactions reported at an incidence ≥1% are shown in Table 3. Most of these
adverse reactions were reported as mild in intensity. The overall incidence of vaccine-related
injection-site adverse reactions was significantly greater for subjects vaccinated with ZOSTAVAX
versus subjects who received placebo (48% for ZOSTAVAX and 17% for placebo).
Table 3
Injection-Site Adverse Reactions* in ≥1% of Adults Who Received ZOSTAVAX
or Placebo Within 5 Days Postvaccination from the AE Monitoring Substudy
of the Shingles Prevention Study
Adverse Reaction
ZOSTAVAX
(N = 3345)
%
Placebo
(N = 3271)
%
Solicited †
Erythema
Pain/Tenderness
Swelling
35.6
34.3
26.1
6.9
8.3
4.5
Unsolicited
Hematoma
Pruritis
Warmth
1.6
6.9
1.6
1.4
1.0
0.3
* Patients instructed to report adverse experiences on a Vaccination Report Card
†
Solicited on the Vaccination Report Card
Headache was the only systemic adverse reaction reported on the vaccine report card between
Days 0-42 by ≥1% of subjects in the AE Monitoring Substudy in either vaccination group
(ZOSTAVAX 1.4%, placebo 0.8%).
The numbers of subjects with elevated temperature (≥38.3ºC [≥101.0ºF]) within 42 days
postvaccination were similar in the ZOSTAVAX and the placebo vaccination groups [27 (0.8%)
vs. 27 (0.9%), respectively].
The following adverse experiences in the AE Monitoring Substudy of the SPS (Days 0 to 42
postvaccination) were reported at an incidence ≥1% and greater in subjects who received
ZOSTAVAX than in subjects who received placebo, respectively: respiratory infection (65 [1.9%]
vs. 55 [1.7%]), fever (59 [1.8%] vs. 53 [1.6%]), flu syndrome (57 [1.7%] vs. 52 [1.6%]), diarrhea
(51 [1.5%] vs. 41 [1.3%]), rhinitis (46 [1.4%] vs. 36 [1.1%]), skin disorder (35 [1.1%] vs. 31
[1.0%]), respiratory disorder (35 [1.1%] vs. 27 [0.8%]), asthenia (32 [1.0%] vs. 14 [0.4%]).
VZV Rashes Following Vaccination: Within the 42-day postvaccination reporting period in the
ZEST, noninjection-site zoster-like rashes were reported by 34 subjects (19 for ZOSTAVAX and 15
for placebo). Of 24 specimens that were adequate for Polymerase Chain Reaction (PCR) testing,
wild-type VZV was detected in 10 (3 for ZOSTAVAX, 7 for placebo) of these specimens. The Oka/
Merck strain of VZV was not detected from any of these specimens. Of reported varicella-like
rashes (n=124, 69 for ZOSTAVAX and 55 for placebo), 23 had specimens that were available
and adequate for PCR testing. VZV was detected in one of these specimens in the ZOSTAVAX
group; however, the virus strain (wild-type or Oka/Merck strain) could not be determined.
Within the 42-day postvaccination reporting period in the SPS, noninjection-site zoster-like rashes
were reported by 53 subjects (17 for ZOSTAVAX and 36 for placebo). Of 41 specimens that were
adequate for Polymerase Chain Reaction (PCR) testing, wild-type VZV was detected in 25 (5 for
ZOSTAVAX, 20 for placebo) of these specimens. The Oka/Merck strain of VZV was not detected from
any of these specimens.
Of reported varicella-like rashes (n=59), 10 had specimens that were available and adequate for
PCR testing. VZV was not detected in any of these specimens.
In clinical trials in support of the initial licensure of the frozen formulation of ZOSTAVAX, the reported
rates of noninjection-site zoster-like and varicella-like rashes within 42 days postvaccination were
also low in both zoster vaccine and placebo recipients. Of 17 reported varicella-like rashes and noninjection site zoster-like rashes, 10 specimens were available and adequate for PCR testing, and 2
subjects had varicella (onset Day 8 and 17) confirmed to be Oka/Merck strain.
Postmarketing Experience
The following additional adverse reactions have been identified during postmarketing use of
ZOSTAVAX. Because these reactions are reported voluntarily from a population of uncertain size, it is
generally not possible to reliably estimate their frequency or establish a causal relationship to the vaccine.
Gastrointestinal disorders: nausea
Infections and infestations: herpes zoster (vaccine strain)
Skin and subcutaneous tissue disorders: rash
Musculoskeletal and connective tissue disorders: arthralgia; myalgia
General disorders and administration site conditions: injection-site rash; pyrexia; injection-site
urticaria; transient injection-site lymphadenopathy
Immune system disorders: hypersensitivity reactions including anaphylactic reactions
Eye Disorders: necrotizing retinitis (patients on immunosuppressive therapy)
Reporting Adverse Events: The U.S. Department of Health and Human Services has established a
Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events
after the administration of any vaccine. For information or a copy of the vaccine reporting form, call
the VAERS toll-free number at 1-800-822-7967 or report online to www.vaers.hhs.gov.
DRUG INTERACTIONS
Concomitant Administration with Other Vaccines: In a randomized clinical study, a reduced immune
response to ZOSTAVAX as measured by gpELISA was observed in individuals who received concurrent
administration of PNEUMOVAX® 23 and ZOSTAVAX compared with individuals who received these
vaccines 4 weeks apart. Consider administration of the two vaccines separated by at least 4 weeks
[see Clinical Studies].
For concomitant administration of ZOSTAVAX with trivalent inactivated influenza vaccine,
[see Clinical Studies].
Antiviral Medications: Concurrent administration of ZOSTAVAX and antiviral medications known
to be effective against VZV has not been evaluated.
USE IN SPECIFIC POPULATIONS
Pregnancy: Pregnancy Category: Contraindication [see Contraindications].
ZOSTAVAX should not be administered to pregnant females since wild-type varicella can sometimes
cause congenital varicella infection. Pregnancy should be avoided for three months following
vaccination with ZOSTAVAX [see Contraindications and Patient Counseling Information].
Pregnancy Registry
From 1995 to 2013, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., maintained
a Pregnancy Registry to monitor fetal outcomes following inadvertent administration of VARIVAX®
during pregnancy or within three months prior to conception. In 2006, reports of exposure to two
other varicella (Oka/Merck)-containing vaccines, ProQuad® (Measles, Mumps, Rubella and Varicella
Virus Vaccine Live) and ZOSTAVAX, were added to the Registry. The Pregnancy Registry has been
discontinued. As of March 2011, 811 women with pregnancy outcome information available for
analysis were prospectively enrolled following vaccination with VARIVAX, within three months prior
to conception or any time during pregnancy. Of these women, 170 were seronegative at the time
of exposure and 627 women had an unknown serostatus. The remaining women were seropositive.
Nine exposures to either ProQuad or ZOSTAVAX have been reported that met criteria for inclusion
into the Registry.
None of the 820 women who received a varicella-containing vaccine delivered infants with
abnormalities consistent with congenital varicella syndrome.
All exposures to VARIVAX, ProQuad, or ZOSTAVAX during pregnancy or within three months prior
to conception should be reported as suspected adverse reactions by contacting Merck Sharp &
Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or VAERS at 1-800-822-7967
or www.vaers.hhs.gov.
Nursing Mothers: ZOSTAVAX is not indicated in women who are nursing. It is not known whether
VZV is secreted in human milk. Therefore, because some viruses are secreted in human milk,
caution should be exercised if ZOSTAVAX is administered to a nursing woman.
Pediatric Use: ZOSTAVAX is not indicated for prevention of primary varicella infection (Chickenpox)
and should not be used in children and adolescents.
Geriatric Use: The median age of subjects enrolled in the largest (N=38,546) clinical study of ZOSTAVAX
was 69 years (range 59-99 years). Of the 19,270 subjects who received ZOSTAVAX, 10,378 were
60-69 years of age, 7,629 were 70-79 years of age, and 1,263 were 80 years of age or older.
CLINICAL STUDIES
Concomitant Use Studies: In a double-blind, controlled substudy, 374 adults in the US, 60 years
of age and older (median age = 66 years), were randomized to receive trivalent inactivated influenza
vaccine (TIV) and ZOSTAVAX concurrently (N=188), or TIV alone followed 4 weeks later by ZOSTAVAX
alone (N=186). The antibody responses to both vaccines at 4 weeks postvaccination were similar in
both groups.
In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized
to receive ZOSTAVAX and PNEUMOVAX 23 concomitantly (N=237), or PNEUMOVAX 23 alone
followed 4 weeks later by ZOSTAVAX alone (N=236). At four weeks postvaccination, the VZV
antibody levels following concomitant use were significantly lower than the VZV antibody levels
following nonconcomitant administration (GMTs of 338 vs. 484 gpELISA units/mL, respectively;
GMT ratio = 0.70 (95% CI: [0.61, 0.80]).
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
L&E5CD9?>D85@1D95>D12?EDB513D9?>CD?@B5F9?ECF1339>5C
L%B?F94513?@I?6D85@1D95>D9>6?B=1D9?>%% 1>449C3ECC1>IAE5CD9?>C?B3?>35B>C
L >6?B=@1D95>D?6D8525>5QDC1>4B9C;C?6.$()+-9>3<E49>7D85@?D5>D91<B9C;?6DB1>C=9DD9>7
the vaccine virus to susceptible individuals, such as immunosuppressed or immunodeficient
individuals or pregnant women who have not had chickenpox.
L >CDBE3D@1D95>DD?B5@?BD1>I14F5BC5B513D9?>C?B1>ICI=@D?=C?63?>35B>D?D859B851<D831B5
professional.
For more detailed information, please read the Prescribing Information.
uspi-v211-i-fro-1602r019
Revised 02/2016
Copyright © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved. VACC-1141203-0016 04/16
COUNTER POINTS
STUDENT CORNER
Michael Lee Phorth, MPH/PharmD Candidate 2016
Pharmacists should get
training in naloxone use now
The epidemic of abuse of prescription drugs and heroin made national news when President Obama brought it
up in January’s State of the Union address, not long after signing a Presidential Memorandum addressing this
issue in October 2015. Through my involvement with the Marin County Pharmacists Association and Pharmacists Planning Services Inc., I learned why pharmacists should be trained in naloxone use and educated about buprenorphine.
Key numbers
Naloxone formulations
According to the CDC, in 2014 alone
more than 14,000 deaths occurred from
prescription opioids, and from 1999 to
2014, the total was 165,000.1
Prescription opioids are so commonly
prescribed that friends or family were
cited as sources of 54.4% of opioids; by
comparison, 19.7% were acquired from
a physician’s prescription.2,3
In response to these alarming statistics, the Presidential Memorandum
mandated a change in policy, calling
for federal prescribers to be trained on
appropriate prescribing of opioids and
naloxone, as well as for improved access
to treatments.4
There are three different naloxone formulations: Naloxone HCl, Evzio Autoinjector, and Narcan Nasal Spray.
Generic naloxone HCl can be given
intravenously (IV), intramuscularly
(IM), or intranasally. The duration of
Naloxone and the law
Laws addressing naloxone dissemination are being implemented throughout the country. For example, California passed a law that allows pharmacists to furnish naloxone under the protocol of the Board of Pharmacy, upon
completion of a one-hour continuing
education training program.
Before naloxone can be dispensed, the
patient must be trained in the use of the
naloxone product and must understand
symptoms of both opioid overdose and
withdrawal from use of the antagonist.
This mandate enables pharmacists to
initiate a conversation about accidental
overdose, safe use of the medication,
and safe storage.
12
injector, the other formulations are more
commonly dispensed.
In California, Ralph’s pharmacies and
limited CVS and Walgreens locations
now dispense naloxone without a prescription.6
Buprenorphine
165,000
DEATHS FROM RX OPIOIDS,
1999-2014
2-5Minutes
DURATION OF ONSET
FOR IV OR IM NALOXONE
onset takes two to five minutes for IV
and IM, while intranasal onset takes
eight to 13 minutes due to lower intranasal bioavailability.5 Consequently, the
intranasal dose (2 mg) is much higher
than the injection dose (0.4 mg –2 mg).5
The Evzio Auto-injector combines a
vocal device that gives instructions with
an injection of 0.4 mg IM.
Narcan is a nasal spray that contains
a 4-mg intranasal dose.5
Because of the expense of the auto-
Buprenorphine is an opioid partial agonist that is prescribed in cases of opioid
and heroin abuse.
Compared to methadone, the drug has
a lower risk of abuse and addiction, as
well as a better side-effect profile.
The most commonly prescribed formulation is Suboxone, a sublingual film
that contains a 4:1 ratio of buprenorphine and naloxone.7 Taken sublingually, naloxone has low bioavailability; it is added to the formulation in case
a patient decides to inject the Suboxone, in which case the naloxone will
produce the full effect of opioid withdrawal on the patient.
Public health interventions
Another approach to curbing this epidemic is being conducted by Partnership HealthPlan of California (PHC), a
nonprofit managed care organization
serving Medi-Cal recipients.
PHC’s Managing Pain Safely program
implements 20 different public health
intervention initiatives designed to help
reduce the high opioid use in the state. 8
C O N T I N U E D O N P A G E 29 >
COUNTER POINTS
IN MY VIEW
Peter A. Kreckel, RPh
Find satisfaction and reward
in your pharmacy career
My first college class was in pre-pharmacy at the University of Pittsburgh in 1976. The class was English
Comp-I, taught by the delightful and energetic Mrs. Joan Smith. When she asked us to write an essay about
anything, I wrote about my grandfather Joe, a consummate storyteller. At his knee I learned the values of working
hard, being faithful, and most of all, being thankful for one’s blessings.
Mrs. Smith loved my essay — and the
ones that followed. She always commented that my essays were so personal, she felt as though she were sitting right beside me.
I got an A in her class.
Next semester, all confident from my
success, I enrolled in English Comp-II.
This time I had Mr. Paul Mormack, who
read a couple of my essays and wrote,
“Peter, this is all bull — you’re not a
writer, you’re a storyteller.”
He went on to say that “you can’t
compose, you just write down stuff
ple, a dozen pharmacy careers,” May
2016]. Basically, I’m a very regular guy
who works on the bench.
I’ve been blessed with many opportunities throughout my career. The truth
is, every opportunity has called for a
large dose of self-sacrifice, which has
paid off very handsomely for me, if not
necessarily always in a financial way.
Can you imagine going to work every
morning with a smile on your face, facing
a very busy day but getting satisfaction
from the fact that you have the opportunity to do your very best?
I firmly believe that the sacrifices I have made have
always led to personal satisfaction. I’ve found out that
every time I give away a dime, I get a dollar back.”
as if you were saying it.”
Looked at either way, it was pretty
clear where I was headed.
Just saying
I didn’t inherit my Grandpa Joe’s blue
eyes, thin frame, or the callouses on his
hands, but I did inherit his ability to tell
stories. I’ve written down many stories
for future generations of our family; I
describe them as somewhere between
the whole truth and Aesop’s fables, stories meant to teach a lesson or to share
the passion of the teller.
You can read the outline of my professional life in the May issue [“Four peo-
A dime for every dollar
With this column, I hope to share stories from my 35-year career.
I started out as a very dissatisfied
chain pharmacist. Today I have an
amazing employer who makes it possible for me to work in a physician’s
office; to write a weekly clinical column for our warehouse, Value Drug;
to teach in a physician assistant program; and to act as preceptor to students at Pitt and Duquesne.
Oh, and I work for FreeCE.com, an
opportunity that grew out of my lecturing at St. Francis University.
I’m blessed.
The purpose of this column is not to
pontificate or even worse brag, but to
share some things I’ve learned about
how we can achieve satisfaction in the
profession of pharmacy.
There are so many opportunities out
there. Technology can help us uncover
them, and we can follow them to a fulfilling career.
I firmly believe that the sacrifices I
have made — whether packing lunch for
my student pharmacist-boarder in the
morning or writing a column like this
one — have always led to personal satisfaction. I have found out that every time
I give away a dime, I get a dollar back.
Stick around
There’s a lot I look forward to sharing.
I remember all the changes and challenges this profession has seen since I
turned on my IBM Selectric typewriter
in 1981. I look forward to sharing them,
good and bad alike.
One thing has not changed — our
desire to take care of patients and to contribute to this amazing profession.
So with a nod to Mr. Mormack, the
teacher who told me I’m just a storyteller, and to Mrs. Smith, who loved my
stories, I look forward to beginning this
round of storytelling. I hope you’ll come
along for the ride.
Pete Kreckel practices independent community pharmacy in Altoona,Penn. He
welcomes e-mail at [email protected].
13
COUNTER POINTS
IN MY VIEW
Genevieve Regal, PharmD, HC-MBA
Gail Bloom, OTD, MA, OTR/L
Medicare drug costs should
parallel those of Medicaid
In the United States, the uncontrolled escalation of Medicare Part D prescription drug costs is a
national problem. Experts predict that this price growth will continue. This presents a challenge for
Medicare beneficiaries on fixed incomes.
Medicare Part D costs approximately
In 2029, the total number of Americans
eligible for Medicare will rise to 71 mil- $80 billion per year. This figure will
lion, a surge that will push Medicare double by 2022, as more people age
costs 4.1% higher than they were in into Medicare eligibility. Over the next
previous decades. Because an increasing 10 years, data project a 6.5% annual
number of Medicare beneficiaries can- overall increase in per capita costs in
not afford medication therapy, the need Part D Rx drug spending contingent
to control the cost of Medicare Part D upon the specialty drug market.
The 2014 Med ica re
prescription drugs has beBy the Numbers
drug spend was $143 bilcome a national concern.
lion, with $317 billion on
The Medicare Part D prototal sales for the pharmagram launched in Januceutical industry.
ary 2006, and as a consequence millions of MedBILLION
icaid patients moved from
Noninterference
Total Pharmaceutical
state/federal Medicaid proIndustry Sales in 2014 The “noninterference”
grams to Medicare Part D
clause of the Medicare
programs. Drug costs quickly
Modernization Act specincreased, as low-income
ifies that the government
Medicaid beneficaries were
“may not interfere with
transferred to Medicare.
the negotiations between
BILLION
For the same medication,
drug manufacturers and
Medicare Drug
patients see far higher drug
pharmacies and PDP sponSpend in 2014
prices from Medicare than
sors, and may not require
they do from Medicaid. In
a particular formulary or
the case of Medicaid, reguinstitute a price structure
latory law requires mandafor the reimbursement of
tory drug-price rebates and
covered part D drugs.”
BILLION
matching of drug prices to
North Carolina Rep. WalThe Current Cost
those paid by the Departter Jones has stated that
of Medicare Part D
ment of Veterans Affairs.
“the pharmaceutical lobPer Year
No such regulations cover
byists wrote the bill. The
Medicare.
bill was over 1,000 pages.
In 2007 alone, according
And it got to the members
to Congressional estimates,
of the House that mornMedicare Part D overspent
ing, and we voted for it at
BILLION
by $15 billion on drug selecabout three in the mornThe cost of Medicare
Part D in 2022
tion and delivery systems.
ing.”
$
317
$
143
$
80
$
160
14
Although Congress voted against
granting Medicare the authority to negotiate rebates and drug prices directly
with pharmaceutical manufacturers,
83% of the public supports it. However, Congress mandated that unlike
Medicaid drug prices, Medicare drug
prices be managed by private insurance companies that do not have the
purchasing power of Medicare.
Parity pays
Medicare should have the same authority that Medicaid has to negotiate
drug prices directly with manufacturers.
If Medicare had the same authority and received mandatory drug-price
rebates, the federal government could
save $15.2 billion to $16 billion annually.
The Congressional Budget Office has
concluded that drug company rebates,
provided to both state and federal governments, would save $103 billion for
the 9 million beneficiaries over the next
10 years.
If Medicare received the same 40%
rebate and pricing as the Department
of Veterans Affairs Health Program,
$30 billion would be saved annually.
Alternative solution
One alternative proposal would allow
the Secretary of Health and Human
Services (SHHS) to negotiate drug costs
for biologics and expensive medications.
The proposed plan would allow SHHS
to negotiate prices for a limited numC O N T I N U E D O N P A G E 69 >
COVER STORY
Solutions to the ongoing
opioid epidemic take shape
Julia Talsma, Editorial Director
This year, APhA’s Generation Rx Award of Excellence has gone to
Jeffrey P. Bratberg, PharmD, BCPS, in recognition of his commitment to
educate pharmacists and future pharmacists about prevention of
prescription medication abuse and misuse.
In 2012, Bratberg, a clinical professor of pharmacy practice, University of Rhode Island College of Pharmacy, Kingston, R.I., and his student pharmacist Tara Thomas, a 2013 PharmD
candidate, developed a continuing education
program to train pharmacists under the first
statewide collaborative pharmacy practice
agreement (CPA) for naloxone.
The pilot program started in a few Walgreens
drugstores in Rhode Island. As the epidemic continued to rage, the program expanded throughout the state and has since been used by other
chains nationwide.
THE PROGRAM
DT: Can you describe the overdose education and
training program that you co-developed in 2012?
need to fight this, and this seems to be the best
way to do this.”
Asking pharmacists to find five credits of overdose education in 2012 would be difficult. It is
a lot easier now.
STAKEHOLDERS
DT: Who were the major stakeholders
who had to be persuaded?
BRATBERG: That is what is great about the Rhode
Island model. Everybody was on board from
the start.
We have one department of health, one Board
of Pharmacy, and everybody knows each other.
The Board had already been working on solutions for naloxone from pharmacies for over
a year when we came to them with this plan.
PHOTOS:GETTYIMAGES/SBAYRAM/AMBIENTIDEAS
BRATBERG: It is a little complex in how it started.
The regulations governing CPAs in Rhode
Island actually don’t allow initiation of therapy
by pharmacists. CPAs also require that pharmacists have two years of experience or a residency.
In addition, when you are entering into these
agreements to manage certain conditions like
diabetes or hypertension, five credits in that
specialty are needed.
We asked the state Board of Pharmacy to
acknowledge that only one credit is needed
due to a CPA to initiate naloxone.
Each company or group that went before the
board received a waiver that stated pharmacists in training don’t need five credits, just one
credit per year to be able to prescribe, counsel,
and dispense naloxone.
Basically, we worked out an agreement with
the board to say, “Look, here is an epidemic. We
THE EPIDEMIC
DT: How has Rhode Island been affected by the
prescription opioid epidemic?
BRATBERG: When the deputy director of the
Office of National Drug Control Policy came to
Rhode Island because we had a spike in deaths
[38] in the first six weeks of 2014, it sort of said
that we had an epidemic that was evolving. Of
these deaths, 25 were caused by acetyl fentanyl.
In 2016 so far, 50% to 60% of all overdose
deaths in Rhode Island were actually due entirely
to fentanyl, according to data from the governor’s office. The deaths from nonprescription fentanyl between 2012 and 2016 increased 1,500%.
My clinical practice site is at a hospital with an
addiction unit. A person came to our hospital following an overdose at his group home and had
38
DEATHS
in R.I. during the first six
weeks of 2014
%
%
50-60
of all overdose deaths
in R.I. in 2016 were due
to nonprescription fentanyl
%
1,500
INCREASE
in deaths in R.I. from
nonprescription fentanyl
between 2012 and 2016
15
Up front
COVER STORY
SOLU T IONS TA K E SH A P E
Industry News & Analysis
DOOR-TO-DOOR SERVICE
< C O N T I N U E D F R O M P A G E 15
Digital pharmacy delivers in NYC
been revived with naloxone. He admitted that he did heroin,
but none was detected in his urine. While our hospital routinely screens for heroin, it doesn’t routinely test urine for fentanyl or its metabolites. So he probably overdosed on fentanyl.
This epidemic is changing so quickly. That is why pharmacists have to be there.
I conducted a training program at the Utah Experience
with the APhA Institute on Alcoholism and Drug Dependencies. It is probably one of the best conferences that I’ve
been to. Students would be saying, “Why would fentanyl be
killing the patients? Why is it out there?” We don’t know.
Research has shown that only about half of users don’t
know the difference between heroin’s and fentanyl’s power
for injection. Most users surveyed report preferring fentanylfree heroin. Fentanyl is 50 times more powerful than heroin.
So we are trying to figure out ways to get naloxone
into the hands of those at the highest risk. One potential
intervention to get naloxone into the hands of high-risk
opioid users is to dispense naloxone with nonprescription syringe purchases, which are typically used by people who inject opioids.
Business is picking up for a New York City-based digital pharmacy that delivers scripts right to patients’ doors.
Opened for business in mid-May and billing itself as “the
only pharmacy you’ll never have to visit but might want
to,” Capsule was formed by Sonia Patel, PharmD, a former troubleshooter for underperforming Walmart pharmacies, and Eric Kinariwala, founder and CEO.
Patel and Kinariwala said they realized the need for an
online-only pharmacy after discovering that the average
wait time to pick up a prescription is one hour, and that
four in 10 customers have to return to their pharmacies
for out-of-stock prescriptions.
Same day, no charge
Here’s how it works: The patient’s doctor sends a script to
Capsule, or the patient notifies the pharmacy online that
they need a refill. Then the pharmacy delivers the script
to the patient’s home or office the same day. There is no
extra charge to the patient. The delivery is free and is limited to the city. When patients have questions on how to
take medications or other issues, Capsule welcomes oldfashioned phone calls.
After operating for only a month, the service was already
proving popular with New York City residents.
“We’ve had a tremendous response so far and have gotten fantastic feedback from people who have tried Capsule and from their doctors about the level of service and
care we provide,” Kinariwala told Drug Topics. “We’re not
sharing any exact figures yet, but each day in the pharmacy is busier than the day before.”
Patel, chief pharmacist, leads Capsule’s pharmacy team
of around 10 people. “We’re actively growing this team
as volume scales,” Kinariwala said. “We built our centralized pharmacy with scale in volume, so we will be able to
accommodate the volume of several traditional pharmacies from this location.”
Kinariwala said that launching Capsule in New York
has given the company founders “the opportunity to test
our model in one of the largest, busiest, and most innovative cities in the world.”
Plans to expand
TRAINING NUMBERS
DT: Since the overdose education program has been in
place, approximately how many pharmacists have been
trained?
BRATBERG: We just added up the number of physi-
cians and pharmacists who completed evaluations for
prescribetoprevent.org, which has been out for about one
and a half years. The total was almost 15,000.
It was sponsored by SAMHSA [Substance Abuse and
Mental Health Services Administration], so it is available
to physicians, nurses, and pharmacists.
Connecticut’s Governor Dannel Malloy has asked academic experts and others within his state to assemble a
strategic plan modeled on ours in Rhode Island.
With supply-driven models like this one, we just can’t
cut off prescription medication supply. We also have to
have demand-driven models to address people using heroin and people misusing prescription drugs. Treatment
on demand is necessary.
THE TASK FORCE
DT: What is your main role on the Rhode Island Governor’s
Overdose Prevention and Intervention Task Force?
The company founders will not be satisfied with just revolutionizing the traditional pharmacy model in New York.
“It is a model that can work in areas across the country
— in both larger cities and more rural areas, Kinariwala
said, adding, “We’re working on bringing Capsule to a few
more cities in the not-so-distant future.”
macy association (I am a former president). I am a connector. If people want to duplicate my role — and I think
they should — it is literally having a seat at the table where
there are individuals from industry and policymakers and
— CHRISTINE BLANK, CONTRIBUTING EDITOR
BRATBERG: I represent both the university and our phar-
COUNTER POINTS
VIEW FROM THE ZOO
David Stanley, RPh
Pharmacy’s Catch-22: Save a
life — or save your livelihood?
I remember staring out the window of my pharmacy school on a sunny day longer ago than I care to admit,
suffering from a full-scale attack of senioritits. Graduation was just around the corner, and the professor
was doing her best to keep the roomful of restless future pharmacists engaged in something productive. I was tuning in and out of the conversation until I heard the professor say something like the following.
“Say a person was walking past your
pharmacy counter and suddenly started
having serious chest pain. They’d never
been in your store before, so they’d have
no prescriptions on file with you. Would
you give them a nitroglycerin tablet?”
I ignored what I thought a silly question (of course you would!) and went
back to my daydreaming, until I realized to my amazement that a lively discussion was going on, with many soonto-be professional pharmacists asserting
that it would be the best decision not to
offer relief to a person in serious distress.
Katherine O’Connor was having an asthma
attack while walking home in New Jersey
with her boyfriend. Luckily, there was a drug
store right there. But she only had $20, and
the inhaler cost $21. And the pharmacist
wouldn’t give it to her.
“I said, ‘Can you just give her the pump?
She’s on the floor wheezing ... I didn’t know
if an ambulance would get there on time. He
said there was nothing he could do for me.”
The above came from a story reported
by New York’s Fox5 TV that made its
way around the internet a few years ago.
By the time I saw it, I wasn’t nearly so
So when a snap decision is called for, ‘What is
our corporate loss-prevention policy?’ can compete
in an employee’s brain with ‘What is the best thing
for the patient?’”
When I took my first pharmacist job
I asked my boss, who was then serving
on the Ohio Board of Pharmacy, about
this, and he chuckled.
“No matter what you do,” he assured
me, “if you can frame it as ‘It was what was
best for the patient,’ then you’ll be fine.”
Sound, commonsense advice for professionals who uses their judgment and
expertise to make decisions, I thought.
Best, yes — but for whom?
Fast forward a couple decades, and as it
turnsout,thatclassroomdiscussionwasn’t
so hypothetical after all. Consider this:
18
surprised as I was in the classroom that
day long ago. It was an extreme case, but
after 20 years spent working for chain
drugstores, I can understand how the
corporate environment could intimidate
someone into making the wrong decision.
Zero tolerance
Don’t get me wrong. I’m sure that if you
were to ask any of the corporate bigwigs
directly, they would tell you not to leave
an asthmatic wheezing on the floor of
their store. But those same bigwigs are
also constantly sending out memos that
say you must do this and we have zero
tolerance for that, while the company’s
liability lawyers have done everything
they can to come up with a policy for
every situation, which employees violate at their peril.
So when a snap decision is called for,
“What is our corporate loss-prevention
policy?” can compete in an employee’s
brain with “What is the best thing for
the patient?”
This means we have too many pharmacists who want all the credit for being professional without ever taking the responsibility for making a decision, such as ones
who won’t dispense syringes to a patient
with insulin in their medication profile,
or who tell a tourist with no refills on a
blood pressure medication that they’re
just out of luck over the weekend.
We’ve all worked with one of “those”
pharmacists, and from what I’ve seen,
correcting “those” pharmacists doesn’t
seem to be a priority among the big chains.
Am I wrong?
I might be wrong. Maybe there are now
state board regulators who would discipline a pharmacist for giving nitroglycerin to a heart attack victim. If so, I’m
dying to hear from one.
But not so literally as the patient who
might be affected.
David Stanley is a pharmacy owner, blogger, and professional writer in northern
California. To contact him, drugmonkey
[email protected]
ISSUES & TRENDS
Up front
Campaign targets illegal online pharmacies
Last month, the Alliance for Safe Online Pharmacies
(ASOP Global), the Center for Safe Internet Pharmacies (CSIP), and the National Consumers League (NCL)
launched a campaign to educate seniors and their caregivers about the risks of buying drugs from illegal online pharmacies. They also unveiled a new website, www.xtherisk.
com, to provide information to consumers, pharmacists,
physicians, and others about the risks.
“We are trying to raise awareness about this new tool, so
it becomes common for consumers to look to the right of
the dot for the word ‘pharmacy’” to help identify legitimate
online pharmacy sites, said Libby Baney, executive director for ASOP Global.
The high cost of drugs prescribed for chronic conditions
such as cancer, rheumatoid arthritis, multiple sclerosis,
and hepatitis C has driven many older Americans to look
for cheaper alternatives on the internet.
The problem is that the majority of online pharmacies
(approximately 35,000 to 45,000) are illegal — they don’t
comply with U.S. laws, and half the medicines sold online
are counterfeit, she noted.
“It is a risky proposition, especially for seniors who are
spending large portions of their income on out-of-pocket
costs,” Baney said. Medicare beneficiaries with Part D coverage have spent $4,000 to $12,000 on out-of-pocket costs
associated with the four chronic conditions listed above.
To verify an online pharmacy, consumers can go to the
www.xtherisk.com website and enter the url of the online
pharmacy they want to purchase from, to see whether it
has undergone the National Association of Boards of Pharmacy’s screening process, said Marjorie Clifton, executive
director of CSIP, whose organization took down more than
1 million illegal websites last year.
In the fall, ASOP Global, CSIP, and NCL will be reaching out to healthcare providers, including pharmacists, to
deliver the message about health and safety through the
use of legitimate online pharmacies.
KEEPING THE FAITH
IMAGE COURTESY OF THE MARYLAND GOVERNOR’S OFFICE
How one pharmacy survived
the Baltimore riots
Pharmacist Maisha McCoy will never
forget those tense days in late April 2015
following the death of Freddie Gray,
when accusations of police brutality
led to rioting and widespread looting
throughout Baltimore.
Her independent pharmacy Breathe 4
Sure (doing business as Pharmacy Solu- Gov. Larry Hogan, pharmacist Maisha McCoy, outside
the Breathe 4 Sure pharmacy
tions, LLC) continued operating throughout the chaos, despite the fact that it was stopped [operating],” McCoy recalled.
Even if they were not previous Pharone of many pharmacies targeted for looting and lost about $100,000 in inventory. macy Solutions’ customers, “when the
McCoy, the pharmacy’s owner, quietly word got out I still had maintenance drugs,
continued filling scripts for loyal patients, I helped some of the people in the comaround 100, through a bar above the munity who couldn’t get out to get their
building’s broken window. She didn’t medications,” McCoy said.
want to draw attention to the customers
who were visiting the store because she Beginning to see the light
was afraid they would face violence. So, Now, with the riot in the past, McCoy is
patients picked up their scripts one by one. beginning to see the light – literally. The
“We retained around three-quarters pharmacy recently reopened after installof our customers because we never really ing new windows and doors.
—JULIA TALSMA, EDITORIAL DIRECTOR
“We are in a much better position now
than before the riot,” she said. “With the
renovation, it is nice and bright inside.”
The City of Baltimore gave the pharmacy a grant for new roll-down windows and doors, and the pharmacy also
received a loan through the state. In addition, the office of Maryland Governor
Larry Hogan recently gave the pharmacy
a grant for improvements to the exterior of the store. McCoy plans to use that
money for lights and awnings.
Apprenticeship program
McCoy wants to work with local high
schools to create an apprenticeship program designed to help students learn about
the pharmacy business and entrepreneurship. She also plans to add screening services through the Maryland Department
of Health and Mental Hygiene.
“Coming back, we really need to implement screenings for some of the epidemics in the community, such as hepatitis,
HIV, and syphilis, along with blood-sugar
19
ISSUES & TRENDS
PAIN MANAGEMENT
Valerie DeBenedette
Opioid use for chronic pain:
The debate goes on
The use, overuse, misuse, and abuse of opioids for pain management are subjects that pharmacists need
to know more about. However, differences of opinion rage when it comes to determining what should be
done to help both patients in pain and society as a whole.
Many areas of the country report serious problems with opioid and heroin
addiction. States are attempting to relieve
these problems by limiting the amounts
or types of opioids that can be prescribed
or by dictating who is allowed to prescribe them.
These and other issues involving the
use of opioid therapy for chronic pain
management were discussed in a debate
at the American Pharmacists Association annual meeting this year.
“As pharmacists, I think we are interested in getting the right drug to the right
patient in the right dose at the right time,”
said Anthony Tommasello, RPh, PhD,
medical affairs manager with Indivior
in Richmond, Va., who moderated the
debate. “I think we all agree that pharmacotherapy decisions must weigh the
risk and benefit not only to the individual, but also to society.”
Guidelines and risk assessment
Jeffrey Fudin, PharmD, DAAPM, FASHP,
a clinical pharmacy specialist and PGY2
pain residency director at Stratton VA
Medical Center in Albany, N.Y., spoke in
favor of opioid use by noncancer patients
with chronic pain. “I am not going to
take the pro side, I am going to take the
practical side,” he said. “I really am antimyth and anti-hysteria.”
Fudin noted that several medical organizations have created opioid prescription guidelines or risk-assessment tools,
both of which usually discuss how to
screen individual patients for pain and
for risk of misuse.
“Before we go down the road of putting patients on opioids, we need to try to
stratify risk,” he said. “We need to decide
whether or not this patient is going to
be a problem patient. There are various
validated tools to do that.”
Some experts believe that extendedrelease opioids are more dangerous than
immediate-release opioids. Fudin called
this a myth. “Are 30 mg of extendedrelease morphine somehow more potent
than 30 mg of immediate-release morphine?” he asked.
Studies that have shown increased
risk of adverse effects with extendedrelease opioids did not define chronic
pain appropriately and/or do not differentiate between post-surgical and
acute pain, he said.
Conversion calculators
Opioid conversion calculators used to
determine equivalencies between different opioids have problems, said Fudin,
noting that there is no validated mathematical model of what constitutes an
equivalent dose upon which all medical professionals agree.
Even with an agreed-upon daily dosage, the treatment would still need to be
individualized, which does not always
happen, said Fudin. “Probably one of
the most important points is this business of treating all patients the same
way vs. as individuals.”
Conversion tools do not take into
account a patient’s pharmacogenetics,
which make individuals react differently to the same amount of drug. Diet
and interactions with other medications, which also affect opioid metabolism in an individual, are also left out
of these equations, he said.
Fudin noted that 16,000 deaths were
associated with opioid therapy in 2014.
That same year, 17,000 deaths were associated with nonsteroidal anti-inflammatory drugs. “Any death is bad, but
Before we go down the road of putting patients on
opioids, we need to try to stratify risk. We need to decide
whether or not this patient is going to be a problem patient.
There are various validated tools to do that.”
JEFFREY FUDIN
PHARMD, DAAPM, FASHP
20
Another Miracle?
No, it’s MiraFIBER
™
a new fiber supplement
less likely to cause gas.
Introducing MiraFIBER—from the trusted makers of MiraLAX®
A nonfermentable fiber less likely to cause uncomfortable gas
Adds bulk to stool to help support regularity*
100% soluble fiber for nongritty taste
Also available in convenient caplets
Recommend MiraFIBER. Help keep your patients going.
*This statement has not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
© 2016 Bayer
June 2016
62871-PP-MLX-FIB-US-0086
ISSUES & TRENDS
PAIN MANAGEMENT
OP IOI D USE FOR CH RON IC PA I N: T H E DE B AT E GOE S ON
30 days have been found
to have worse pain tolerance than people who
have not been exposed.
“We might be treating
the problem that we are
causing.”
CHRISTOPHER HERNDON
Then there is the issue
PHARMD, BCPS, CPE
of opioid drug abuse,
that they help with long-term or per- Herndon said. In the past few years,
sistent noncancer pain. Long-term pre- there has been a slight downward trend
scribing and dose escalation for opioids in nonmedical use of opioids, which is
are based on anecdotal evidence. There promising, he noted. But the use of heris no evidence to suggest that opioids are oin has been going up. Almost 40% of
effective in the long term for persistent heroin users said that they had used or
noncancer pain, he said.
misused opioids before their first use of
Herndon noted a study of a population heroin, he said.
of patients with chronic pain made by
Herndon also noted other problems
Naliboff et al that found no difference in that can accompany the use or misuse of
three primary outcome measures when opioids. These include risk of falls, sleepa low dose was compared to an escalat- disordered breathing problems, increased
ing dose of opioids.2 A study by Bostick endocrine problems, depression, drug tolet al found lower results on the Pain Dis- erance, overdose, and death. “These are
ability Index and Physical Component all issues that I think are very important.”
Summary Score for patients receiving
no or lower doses of opioids,he said.3
CDC recommendations
Both Fudin and Herndon mentioned
the draft guidelines on the use of opioids
Access problems
When patients are prescribed opioids created by the CDC. Most of the CDC
for a long time, they can run into prob- recommendations are common sense,
lems if they then cannot get their med- said Herndon. The recommendations
include prescribing the lowest possible
ication, Herndon added.
He works on a chronic pain service in effective dose and periodically evaluata large family medicine program, where ing the patient for opioid-related harm.
Fudin encouraged the use of
he sees patients who have been put
tools for risk stratification such
on opioids and then lose their
OPIOID
as those available at www.
prescription coverage when
CRISIS
painedu.org, which offers
they lose their jobs, or who
For More from Dr. Fuin, see
access to opioid risk manlose their prescription renewDISPENSED AS WRITTEN
agement tools. He also called
als when the doctor who prepg.
for more education for both
scribed for them retires. “And
prescribers and pharmacists,
then they have nowhere else
including more education on
to go,” he said.
drug interactions.
What is the number needed to treat for
opioids? Is it no pain? Thirty percent pain
relief? Is it ‘I just feel better and I can sleep?’
How do we assess a response to an opioid?”
let’s not focus all our attention on opioids,” he said.
He also referred to a finding by Dasgupta et al that 80% of opioid analgesic deaths in an observational cohort in
North Carolina involved patients who
also received benzodiazepines, a rate
that was 10 times higher than for those
using opioids alone.1
Too many Rxs, not enough evidence
Speaking on the opposite side of the issue
was Christopher Herndon, PharmD,
BCPS, CPE, associate professor in the
department of Pharmacy Practice at
Southern Illinois University, Edwardsville, School of Pharmacy and clinical
assistant professor, Department of Community and Family Medicine at St. Louis
University. He argued that too many
patients with chronic pain are being
prescribed opioids when they should not
be. “I think there is some relevance to
the idea that we might have gone overboard,” he said.
“First, we need to look at whether there
is a benefit vs. risk assessment of these
drugs,” Herndon said, citing as an example the use of metformin to treat diabetes. “We know that if you take metformin and your A1c goes from 8 to 7, that
is a response, and we are all good,” he
said. “But what is the number needed
to treat for opioids? Is it no pain? Thirty
percent pain relief? Is it ‘I just feel better and I can sleep?’ How do we assess
a response to an opioid?”
Opioids are undeniably effective for
short-term severe pain, Herndon said.
But studies have found little evidence
22
7
Making things worse?
Another issue is hyperalgesia, said Herndon. “When I give someone an opioid for
their pain, am I actually making their
pain worse by giving it to them?” Patients
who have been exposed to morphine for
Referencesavailableatwww.drugtopics.com.
Valerie DeBenedette is a medical news
writer in Putnam County, N.Y.
SPECIAL REPORT
MEDICATION RECONCILIATION
Anthony Vecchione
Pharmacists take aim at med
errors during care transitions
Government mandates and increasingly complex patient medication regimens are fueling a need in hospitals
for medication reconciliation systems that will provide close and thorough review of patients’ drug lists upon
admission, transfer, and discharge, in order to prevent inconsistencies or errors across transitions of care.
Error prevention
State of the art
The subject is not new to healthcare institutions. Medication errors, including
those resulting from unsuccessful medication reconciliation, have come under
increasing scrutiny for more than a decade
and continue to be a persistent problem.
“Preventing Medication Errors,” a report
published in 2006 by
the Institute of Medicine (now the National
Academy of Medicine),
said the average hospitalized patient is subject
to at least one medication
mistake per day, putting
drug errors at the head of the list for
patient safety errors.
A study published in The Joint Commission Journal on Quality and Patient Safety
in 2004 found that more than 40%
of medication errors were believed to
result from inadequate reconciliation
in handoffs during admission, transfer, and discharge of patients. Of these
errors, approximately 20% were believed
to result in harm.
The Joint Commission made medication reconciliation a National Patient
Safety Goal in 2005, and meaningful
use requirements include a medication
reconciliation mandate.
Industry insiders suggest that one
way to prevent medication errors is for
healthcare organizations to make it a
priority to develop, implement, and sustain effective medication reconciliation practices.
Hospitals and health systems are turning
to state-of-the art reconciliation systems.
Munroe Regional Medical Center in
Ocala, Fla, has adopted the MedsTracker
MedRec system from First Databank. So
far, the program has been well received
“The system itself draws people along
to better practice and behavior in doing
the right thing, because it’s easier to do
the right thing,” Willis said.
Flexible interface
Dewey Howell, MD, PhD, vice president of
Patients are on complicated med regimens and have several diagnoses. The complexity of healthcare has gone up tremendously — particularly hospital medicine.”
DEWEY HOWELL
MD, PHD
by the medical, nursing, and pharmacy
staffs.
David Willis, MD, chief medical information officer, said users have found the
system very intuitive. “On admission,
we have benefited from a couple of the
key features from the MedsTracker app.
We’ve been able to pull information from
the community when a patient may not
remember all of his meds — we can find
some lists within the community so we
can at least have a conversation [with
the patient],” said Willis.
Another beneficial feature, he said,
is system groups. Providers can easily
compare the patient’s home medication list to the list of hospital medications, as the lists are presented side-byside and delineated by color.
Willis noted that his facility met Stage
2 Meaningful Use on all measures after
using the system for only 11 days.
clinical applications, First Databank, said
that customers want a med rec system
that integrates with many data sources.
Among the challenges in medication reconciliation, according to Howell, is getting
a good, “clean” list of medications. When
patients don’t know what 20 medicines
they are taking, it is difficult to gather and
document data. “To make that work, you
not only have to integrate it into the doctors’ workflow, you have to bring as much
data together as you can and present it in
a usable way. We have a commitment to
integrate data sources and pull disparate
data sources together,” he said.
He pointed out that over the last decade
in particular, the growing complexity of
healthcare and hospital medications has
been driving the need for more efficient
ways to reconcile medications.
For example, in the past a hospitalized
23
SPECIAL REPORT
P H A R M ACISTS TA K E A I M AT M E D E R RORS DU R I NG CA R E T R A NSI T IONS
patient with pneumonia would stay in
the hospital for three days with antibiotic
treatment. That doesn’t happen anymore,
because the condition is now treated at
home. Instead, patients who come into
the hospital have multiple issues.
“Patients are on complicated med regimens and have several diagnoses. The
complexity of healthcare has gone up
tremendously — particularly hospital
medicine,” said Howell.
Another challenge is related to complex care teams. For instance, in the past
the physician who saw the patient in the
clinic would go to the hospital and take
I went with this product is because it can
give me 92% of the data for a full medication review,” she added.
“The MedMined team also gave us the
opportunity to request builds to improve
the tool. When I can partner with a vendor that is willing to listen and improve
their product, we end up with better tools
and a better partner for future projects.”
Ochsner plans to use the med rec system in-house to ensure that hospital
medications that the patient did not take
before admission are included before
discharge.
The skill set [for medication
reconciliation] is there, and ... a lot
more pharmacists and pharmacy
techs are getting involved.”
VIKAS GUPTA
PHARMD
care of that patient. The physician knew
everything about the patient, and there
was no gap or miscommunication.
Medicine doesn’t work that way today,
said Howell. The physician caring for the
patient in the hospital often is not the one
fromtheclinic.Today,acomplexcareteam
composed of physicians, nurses, pharmacists, and care managers is the norm.
Piloting a new system
Louisiana-based Ochsner Health System is using the MedMined Surveillance
Advisor from BD (Becton, Dickinson and
Company) in a pilot program expected
to go live this month at 12 hospitals.
“We plan to use technicians on admission to review the meds with the patient.
The technician will look at a 365-day
review of where the patient has filled
meds and interview the patient. The
pharmacist will oversee and check off
the final med list,” said Debbie Simonson, PharmD, vice president of pharmacy services. “One of the reasons why
24
Admission and discharge
Simonson noted that the Ochsner pharmacy team has a defi ned medication
review process for patients on admission to the hospital.
“This review now falls to the physician and nurse. Our goal is to complete
that review with our team. We will use
a technician to complete the history
and a pharmacist for final approval. A
comprehensive medication history can
take 15 to 30 minutes. Our plan is to
use the MedMined tool in this process
to help streamline the workflow process,” she said.
The Ochsner pharmacy team also will
handle the medication review process at
discharge. According to Simonson, this
comprehensive review will take into
account the active medication refills the
patient had upon admission, so that if
medications are discontinued, the pharmacist can ensure their termination. If
a prescription has been changed, the
pharmacist will ensure, as an agent of
the provider, that the discontinued prescription has been discontinued with
the retail pharmacy, so that the patient
does not continue to get that discontinued medication.
Upon discharge, if a patient has been
prescribed any new medications in the
hospital, the pharmacist will review
the order to make sure the medications
are covered on the patient’s insurance
and are affordable. “If they are not, the
pharmacist will work with the provider
to change the prescriptions before they
leave,” said Simonson. “The pharmacy
team will also offer to fill those new
medications before they leave the hospital. Patients who need assistance are
referred to outpatient assistance programs,” said Simonson.
The team will use the MedMined tool
to help streamline this workflow.
The staffing models in the 12 hospitals that compose the Ochsner system vary by hospital. Each hospital will
pilot defined processes, and each site
will target defined populations or areas,
depending on its staffing and support.
The goal will be to expand this process
to all patients, said Simonson.
“The pilot will help determine what
resources are needed. My hope is, we
can support hospitals from a centralized point to cover verification of orders,
to ensure that the local team has manpower to do these tasks at the hospital.”
Pharmacists’ role
Simonson said that some of the system’s
hospitals have an extensive number
of clinical pharmacists already rounding with the teams who will be able to
cover 80% of patients. However, some of
the smaller hospitals have limited staff.
According to Simonson, those hospitals
will have to decide which patients to target first. “My goal will be to figure out
how to support those sites so they can
complete this task. “
The plan, she said, is to maximize the
Tresiba® U-200 FlexTouch®—2 to 160 units in a
single injection (in 2-unit increments)
®
®
U-100 Also available in Tresiba U-100 FlexTouch —Maximum dose of 80 units
per injection (in 1-unit increments)
For both the Tresiba® U-100 and U-200 FlexTouch® pens, the dose window
shows the number of units to be delivered
76
MORE T
NO
the Tresiba® Instant Savings Card, eligible patients can pay no more
15 With
than $15 per Tresiba® prescriptiona
PE
R
P RE
ON
$
N
HA
PAY
Tresiba® FlexTouch® has no push-button extension, regardless of dose
S C RIP
TI
– Patients can apply either by going online to Tresiba.com or by calling 1-855-834-3466.
Patients should activate the card before filling their prescription
a
Eligibility and other restrictions apply. Offer valid for select Novo Nordisk products. Offer not valid for patients enrolled in any government, state, or federally
funded medical or prescription benefit program, including Medicare, Medicaid, VA, DoD, and TRICARE®. The federal employee health benefits program is not a
federal or state government health care program for purposes of this savings program. Offer is valid for a maximum benefit of $500/month. Card is valid for up to
24 prescriptions. Complete details are provided with the card.
Explore additional Tresiba® support resources at TresibaPro.com
Needles are sold separately and may require a prescription in some states.
Needles and FlexTouch® are for single patient use only.
FlexTouch® and Tresiba® are registered trademarks of Novo Nordisk A/S.
Novo Nordisk is a registered trademark of Novo Nordisk A/S.
TRICARE® is a registered trademark of the Department of Defense (DoD), DHA.
© 2016 Novo Nordisk All rights reserved. USA16TSM00594 April 2016
CLINICAL
NEW DRUG REVIEW
Camden E. Svec, 2016 PharmD Graduate;
Lisa M. Holle, PharmD, BCOP, FHOPA
FDA approves trifluridine/
tipiracil for colorectal cancer
On September 22, 2015, FDA approved trifluridine/tipiracil (Lonsurf; Taiho Oncology), a new, orally administered cytotoxic drug for the treatment of patients with metastatic colorectal cancer (CRC). CRC is the third
most commonly diagnosed cancer in men and second most common cancer in women worldwide. Unless it is caught
early with preliminary screening, this cancer usually is diagnosed at an advanced stage.
In patients with stage IV CRC, the cancer has spread to outside organs; therefore, surgical resection is not so useful
and combination chemotherapy is the
main treatment option.
Treatment regimens typically include
active drugs, either in combination or
as single agents, such as fluoropyrimidines (capecitabine, fluorouracil/leucovorin); oxaliplatin, irinotecan, antivascular endothelial growth (VEGF)
biologic therapy (bevacizumab, ramucirumab, ziv-aflibercept); multikinase
inhibitors (regorafenib) and/or an antiEGFR monoclonal antibody, if the tumor
is KRAS wild-type (cetuximab, panitumumab).
Patients often will receive an initial
chemotherapy regimen until their disease
progresses, at which time they’ll go on to
receive a second regimen that contains
one or more of the other active drugs.
This process usually continues until the
patient has received all the active drugs.
Trifluridine/tipiracil is now an option
for patients who were previously treated
with the available agents fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, and anti-VEGF biologic product; and an anti-EGFR monoclonal antibody, if KRAS wild-type.
Efficacy
Trifluridine/tipiracil’s efficacy was demonstrated in a multicenter, double-blind,
placebo-controlled, intention-to-treat
study known as the RECOURSE trial,
which included 800 patients previously
treated for metastatic CRC. Patients were
randomized (2:1) to receive trifluridine/
tipiracil (N=534) or matching placebo
(N=266). At baseline all patients in both
study arms had received previous chemotherapy regimens containing fluoropyrimidine, oxaliplatin, and irinotecan. All patients except one in the placebo group had received bevacizumab.
All but two patients (one in each study
group) with KRAS wild-type tumors had
received cetuximab or panitumumab.
Regorafenib, an oral multikinase inhibitor, was used in 17% of the trifluridine/
tipiracil group and 20% of the placebo
group. Patients received 35 mg/m2 trifluridine/tipiracil or placebo twice daily
after morning and evening meals on
days 1–5 and 8–12 followed by a 14-day
rest period. The regimen was repeated
until disease progression or unacceptable toxicity occurred.
Treatment resulted in an improvement in overall survival, progressionfree survival (PFS), and performance
status scores. The median overall survival was 7.1 and 5.3 months in the trifluridine/tipiracil and placebo groups
respectively (HR 0.68 [95% CI: 0.58,
0.81], P<0.001). Increased PFS was also
improved in patients receiving trifluridine/tipiracil (2 months) vs. placebo
(1.7 months; [HR 0.47 (95% CI: 0.40,
0.55), P<0.001]). The Eastern Cooperative Oncology Group (ECOG) performance score, a commonly used perfor-
mance status measure in cancer patients,
was also significantly improved in the
trifluridine/tipiracil group vs. placebo
group [HR 0.66 (95% CI: 0.56, 0.78),
P<0.001]. The median time to an ECOG
performance status of 2 or higher was
5.7 months and 4.0 months in the trifluridine/tipiracil and placebo groups,
respectively.
Safety
Adverse effects and abnormal laboratory
values were more common with trifluridine/tipiracil than with placebo, and
included anemia (77%), neutropenia
(67%), nausea (48%), decreased appetite (39%), diarrhea (32%), vomiting
(28%), abdominal pain (21%), fatigue
(52%), and pyrexia (19%).
This regimen is considered to have a
moderate-to-high emesis risk and should
be pretreated with an oral daily dose of
a serotonin (5-HT3) antagonist such as
ondansetron, granisetron, or dolasetron
to reduce nausea and vomiting. If breakthrough emesis occurs, one agent from
a different drug class can be added to the
current regimen as needed (olanzapine,
lorazepam, dronabinol, prochlorperazine, metoclopramide, etc).
The most common adverse reactions
leading to dose reduction were neutropenia, anemia, febrile neutropenia, fatigue,
asthenia, and diarrhea. However, no
clinically meaningful differences were
observed with respect to hepatic or renal
27
BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR
GRANIX® (tbo-filgrastim) injection, for subcutaneous use
SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
1
GRANIX is indicated to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a
clinically significant incidence of febrile neutropenia.
4
CONTRAINDICATIONS
None.
5
5.1
Splenic Rupture
Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder
pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or
splenic rupture.
5.2
Acute Respiratory Distress Syndrome (ARDS)
Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates
or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients
with ARDS.
5.3
Allergic Reactions
Serious allergic reactions including anaphylaxis can occur in patients receiving human
granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The
administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may
reduce the severity of the reactions. Permanently discontinue GRANIX in patients with
serious allergic reactions. Do not administer GRANIX to patients with a history of serious
allergic reactions to filgrastim or pegfilgrastim.
5.4
Use in Patients with Sickle Cell Disease
Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease
receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients
with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.
5.5
Capillary Leak Syndrome
Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and
hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if
treatment is delayed. Patients who develop symptoms of capillary leak syndrome should
be closely monitored and receive standard symptomatic treatment, which may include a
need for intensive care.
5.6
Potential for Tumor Growth Stimulatory Effects on Malignant Cells
The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts
has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for
any tumor type, including myeloid malignancies and myelodysplasia, diseases for which
GRANIX is not approved, cannot be excluded.
6
ADVERSE REACTIONS
The following potential serious adverse reactions are discussed in greater detail in other
sections of the labeling:
UÊ -«iVÊ,Õ«ÌÕÀiÊQsee Warnings and Precautions (5.1)]
UÊ VÕÌiÊ,iÃ«À>ÌÀÞÊÃÌÀiÃÃÊ-Þ`ÀiÊQsee Warnings and Precautions (5.2)]
UÊ -iÀÕÃÊiÀ}VÊ,i>VÌÃÊQsee Warnings and Precautions (5.3)]
UÊ 1ÃiÊÊ*>ÌiÌÃÊÜÌÊ-V
iÊ
iÊÃi>ÃiÊQsee Warnings and Precautions (5.4)]
UÊ >«>ÀÞÊi>
Ê-Þ`ÀiÊ[see Warnings and Precautions (5.5)]
UÊ *ÌiÌ>ÊvÀÊ/ÕÀÊÀÜÌÊ-ÌÕ>ÌÀÞÊvviVÌÃÊÊ>}>ÌÊ
iÃÊQsee Warnings and
Precautions (5.6)]
The most common treatment-emergent adverse reaction that occurred at an incidence of
at least 1% or greater in patients treated with GRANIX at the recommended dose and was
numerically two times more frequent than in the placebo group was bone pain.
6.1
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in clinical practice.
GRANIX clinical trials safety data are based upon the results of three randomized clinical
trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung
cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of
patients were female, the median age was 50 years, and 86% of patients were Caucasian.
In the lung cancer study, 80% of patients were male, the median age was 58 years, and
95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients
were male, the median age was 55 years, and 88% of patients were Caucasian. In all three
studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim
product were administered at 5 mcg/kg subcutaneously once daily beginning one day
after chemotherapy for at least five days and continued to a maximum of 14 days or until
an ANC of *10,000 x 106/L after nadir was reached.
Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at
least 1% or greater in patients treated with GRANIX at the recommended dose and was
numerically two times more frequent than in the placebo group. The overall incidence of
bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-USapproved filgrastim product).
Leukocytosis
In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than
1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies.
Additional Adverse Reactions
Other adverse reactions known to occur following administration of human granulocyte
colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute
febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia.
6.2
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of
antibody development in patients receiving GRANIX has not been adequately determined.
7
DRUG INTERACTIONS
No formal drug interaction studies between GRANIX and other drugs have been performed.
Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used
with caution.
Increased hematopoietic activity of the bone marrow in response to growth factor therapy
has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.
8
8.1
Pregnancy
Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies of GRANIX in pregnant women. In
animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in
increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Animal Data
In an embryofetal developmental study, pregnant rabbits were administered subcutaneous
doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day.
Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day.
This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean
live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and
cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC) of
approximately 50-90 times the exposures observed in patients treated with the clinical
tbo-filgrastim dose of 5 mcg/kg/day.
8.3
Nursing Mothers
It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when GRANIX is administered to
a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk
and G-CSF is not orally absorbed by neonates.
8.4
Pediatric Use
The safety and effectiveness of GRANIX in pediatric patients have not been established.
8.5
Geriatric Use
Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients
were 65 years of age and older. No overall differences in safety or effectiveness were
observed between patients age 65 and older and younger patients.
8.6
Renal Impairment
The safety and efficacy of GRANIX have not been studied in patients with moderate or
severe renal impairment. No dose adjustment is recommended for patients with mild
renal impairment.
8.7
Hepatic Impairment
The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment.
10
OVERDOSAGE
No case of overdose has been reported.
©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd.
All rights reserved.
GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd.
Manufactured by:
Distributed by:
Sicor Biotech UAB
Teva Pharmaceuticals USA, Inc.
Vilnius, Lithuania
North Wales, PA 19454
U.S. License No. 1803
Product of Israel
GRX-40580 January 2015
This brief summary is based on TBO-004 GRANIX full Prescribing Information.
HEALTH SYSTEMS
ANTIMICROBIAL RESISTANCE
Valerie DeBenedette
ASPs vs. microbial resistance:
Pharmacists lead the charge
In the best of all possible worlds, an antibiotic would be prescribed only when it is known to be effective against
the bacterial infection being treated. We don’t live in that world yet, but as more antibiotic stewardship programs (ASPs) are being created, at least we are heading that way.
The goal of ASPs is to slow the spread
of microbial resistance through drug
management as well as to minimize
any harm to patients from inappropriate or unneeded antibiotic use. Federal
health policy pushes for the creation of
ASPs, but so far, they are in fewer than
40% of American hospitals. California
is ahead on this issue; it now requires
them in acute care hospitals.
The Pew Report
The Antibiotic Resistance Project of the
Pew Charitable Trusts has evaluated ASPs
to help determine how to improve antibiotic use in acute and long-term-care facilities. The nonprofit organization’s report,
in healthcare settings.1
Guidelines on ASPs from the CDC call
for inclusion of seven elements: leadership commitment, accountability, drug
expertise (with a pharmacist leading the
effort to improve antibiotic use), action,
education, tracking,
FEWER THAN
and reporting.2 The
Infectious Diseases
Society of America
(IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have issued joint recommendations, as well.
Three of the hospitals described in the
report are Williamson Medical Center
in Nashville, Tenn., St. Tammany Parish
place since 2009; before which there had
been an open and unrestricted antibiotic formulary. The ID physician and the
pharmacist developed a list of restricted
or nonformulary antibiotics, with suggested substitutions. Since 2012, the ASP
has been formalized as
of American a subcommittee of the
pharmacyandtherapeuhospitals
have ASPs
tics committee.
The program uses
IDSA/SHEA guidelines on antibiotic
stewardship, tools from the Society of
Infectious Diseases Pharmacists Certificate Program in Antimicrobial Stewardship, and the CDC Checklist of Core Elements. A clinical decision support system
(CDSS) triggers alerts when an
antibiotic has been ordered for
more than three days, when a
patient tests positive for C. difficile, or when a patient is shifted
from intravenous to oral antibiotics.
“Our ASP has evolved to
MONTGOMERY WILLIAMS include more members of the
PHARMD, BCPS
pharmacy on the ASP commitHospital in Covington, La., and Strong tee: A critical care pharmacist, a pediatric pharmacist, and a clinical pharmacy
Memorial Hospital in Rochester, N.Y.
manager,” said Montgomery Williams,
PharmD, BCPS, the internal medicine
Williamson Medical Center
Williamson Medical Center is a 185-bed and antibiotic stewardship pharmacist
hospital with an emergency room and with Williamson and Belmont Univera pharmacy staffed by 16 clinical staff sity College of Pharmacy in Nashville.
“I would encourage other programs
pharmacists and a half-time internal
medicine clinical pharmacist. Four phy- that are beginning an ASP to start small.
sicians manage an infectious disease (ID) Identify a physician champion and select
consultation service. Its ASP has been in
40%
Our ASP has evolved to include more members of the pharmacy on the ASP committee:
A critical care pharmacist, a pediatric pharmacist, and a clinical pharmacy manager.”
“A path to better antibiotic stewardship
in inpatient settings,” looks at 10 case
studies in hospitals across the country.1
The report notes that up to 50% of all
antibiotics prescribed in the United States,
including many used in hospitals, were
unneeded or used inappropriately. This
inappropriate use gives rise to antibioticresistant organisms that cause more than
23,000 deaths each year and increase
the risk of Clostridium difficile infections
28
COUNTER POINTS
STUDENT CORNER
P H A R M ACISTS SHOU L D G ET T R A I N I NG I N NA LOXON E USE NOW
OPIOID
PHC has mandated that prescriptions
written for opioid doses greater than
120 mg MED (morphine equivalence
per daily dose) are not safe. It requires a
treatment authorization request, a medical justification, and a plan for tapering
treatment when the prescribed dose is
higher than recommended.
In addition, through its data collection
and analysis, PHC is able to provide statistics on physicians’ patterns of opioid
prescription in each county. Through the
introduction of such measures, PHC has
been able to decrease opioid prescribing
rates between 9% and 66%, depending
on the county.
When it comes to curbing this country’s epidemic of prescription drug abuse,
in many communities pharmacists are
Inform.
5. Naloxone. Lexi-Drugs Online. Hudson, OH:
CRISIS
the most accessible healthLexi-Comp, Inc. http://0-online.lexi.com.liFor Another Perspective, see
care resource. Once trained
brary.touro.edu/lco/action/doc/retrieve/
DISPENSED
AS
WRITTEN
docid/patch_f/7338.
in naloxone use, we can train
6. Drug Policy Alliance. Press release. Drug Polpg.
our patients in all aspects of
icy Alliance applauds Ralphs for being first chain
opioid use. This will make a
supermarket in California to make overdose antidote naloxone available without a prescription. Dec.
difference.
7
12, 2015. http://www.drugpolicy.org/news/2015/12/drugpolicy-alliance-applauds-ralphs-being-first-chain-supermarketcalifornia-make-over.
REFERENCES
1. National Institute on Drug Abuse. Overdose death rates.
https://www.drugabuse.gov/related-topics/trends-statistics/
overdose-death-rates.
2. Jones CM, Paulozzi LJ, Mack K A. Sources of prescription
opioid pain relievers by frequency of past-year nonmedical
use: United States, 2008-2011. JAMA Intern Med. 2014 May;
174(5):802-803.
3. Centers for Disease Control and Prevention. Injury prevention
and control: Opioid overdose prescribing data. http://www.cdc.
gov/drugoverdose/data/prescribing.html.
4. Obama BH. Presidential memorandum: Addressing prescription drug abuse and heroin use. Oct. 21, 2015. https://www.
whitehouse.gov/the-press-office/2015/10/21/presidentialmemorandum-addressing-prescription-drug-abuse-and-heroin.
7. Suboxone [package insert]. 2015. Warren, NJ: MonoSol Rx, LLC.
8. Partnership HealthPlan of California. Forum: Managing pain
safely. Jan. 15, 2015. www.partnershiphp.org/Providers/HealthServices/Documents/Managing%20Pain%20Safely/MPSFourmII/MPSForumIISlides_SR.pdf.
Michael Phorth is a 2016 MPH/PharmD
candidate at Touro University, Vallejo, Calif.
He acknowledges assistance provided by Aglaia
Panos, PharmD, in the preparation of this article. To contact him, [email protected].
Market.
Sell.
Pharmacies have long embraced new technologies to strengthen their businesses.
So why use your in-store TV screens for pointless customer entertainment or generic content that has no impact
on your bottom line? Introducing ePillboard™—a breakthrough in pharmacy marketing. Through a series of digital
screens, ePillboard™ provides custom content to pharmacies on in-store electronic billboards that enhances
marketing, improves customer communication and drives business to your products and services.
Call marketing director Ken Penland at 800.392.9824 to learn how you can
communicate, educate and profit with ePillboard™ today.
Pharmacy marketing for the digital age.
HEALTH SYSTEMS
ANTIMICROBIAL RESISTANCE
A S PS VS. M ICROBI A L R E SISTA NCE: P H A R M ACISTS L E A D T H E CH A RG E
an initiative or project that can be implemented with minimal resources, such
as a formulary review or MUE [medically unlikely edit],” she said.
Williamson’s ASP involves fourth-year
pharmacy students. “This has been a
great learning experience for the students
in an interdisciplinary setting. Beyond
patient care, they are also able to experience the administrative aspect of the
program and help with data collection
and projects as available,” Williams said.
At Williamson, the ASP has reduced
the number of C. difficile cases from 26.3
per 10,000 patient days in 2012 and 2013
to 21.1 in 2014, and increased the susceptibility rates to levofloxacin of Pseudomonas aeruginosa from 58% in 2009
to 79% in 2014.
St. Tammany Parish Hospital
St. Tammany Parish Hospital (STPH) has
244 beds and includes a neonatal intensive
“The most effective part of our program is real-time interventions,” said Jo
W. Watkins, RPh, clinical coordinator
at STPH. If you are running reports on a
weekly basis, “you don’t get the bang for
your buck,” she said. “Real-time, face-toface discussion is where we got a major
impact from the program.”
Having a physician who will go to bat
through the University of Rochester’s ID
division. One ID physician, one ID pharmacist, and one resident pharmacist provide service for the hospital’s ASP.
Strong’s ASP is nearly 20 years old. It
started as an antibiotic management program focused on cost savings through
drug restrictions. It later expanded into
monitoring outpatient use of parenteral
antibiotics and an emergencyUP TO
of all antibiotics prescribed department-based stewardship
program.
in the U.S. were used
“There are a lot of different
inappropriately
interventions that would qualfor the program is important, and at STPH ify as antibiotic stewardship,” said Christhat was Dr. Michael Hill, Watkins added. topher Evans, PharmD, infectious dis“I cannot say enough on how important ease pharmacist with the University of
our physician champion was to the suc- Rochester-Strong Memorial Hospital.
cess of this program.” However, she also “Choosing what works for your hospinoted that STPH has a strong hospitalist tal may not be what everyone else has
group whose cooperation was another done. You have to figure what is needed
key to the program’s success.
and what you can do and what you can
STPH saw a decrease in the number of see results from. You are going to find
one or two interventions that you can
work on and then build up from there.”
Because of Strong’s ASP, antibiotic use
in days of therapy per 1,000 patient-days
and antibiotic cost per patient-day has
remained low since the program was
implemented. The ASP teams found that
the electronic health record system and
JO W. WATKINS
computerized physician order entry sysRPH
tem can help guide therapy choices withC. difficile cases from 9.6 cases per 10,000 out the use of a CDSS.
In addition to its own ASP, Strong also
patient days in the third quarter of 2013
to 6.4 cases per 10,000 patient days by the participates in a collaborative ASP with
end of 2014. Total antimicrobial cost per other hospitals in the Rochester area.
adjusted patient-day was reduced from This regional ASP targets the high-risk
$25.93 in October 2012 to an average cost antibiotics that increase the risk of C. difof $8.32 per patient-day after the pro- ficile infections, Evans said.
gram was implemented. Between July References
2013 and December 2014, ASP review 1. Pew Charitable Trusts. A path to better antibiotic stewardship
of antimicrobials has resulted in a total in inpatient settings. April 2016. Available at www.pewtrusts.org/
en/research-and-analysis/reports/2016/04/a-path-to-better-ansavings of $1.3 million.
tibiotic-stewardship-in-inpatient-settings. Accessed May 2016.
50%
The most effective part of our program
is real-time interventions. Real-time,
face-to-face discussion is where we
got a major impact from the program.”
care unit. There are three ID physicians
on staff, and the pharmacy has a department head, an operations and information technology manager, two clinical
pharmacists, and 11 staff pharmacists.
The hospital’s ASP originated with an
ID physician who started a “Bug Club”
after noticing a pattern of infections in
coronary artery surgeries in the New
Orleans area. The first members were
ID physicians, infection preventionists,
and clinical pharmacists from several
area hospitals. When another hospital
started an ASP and showed decreased
antibiotic use, staffers at STPH were able
to make the case for a similar program
and obtain funding for a CDSS.
30
Strong Memorial Hospital
Strong Memorial Hospital is an academic
medical center associated with the University Rochester; it has more than 700
beds. Infectious disease care is provided
2. Centers for Disease Control and Prevention. Core elements of
hospital antibiotic stewardship programs. Available at www.cdc.
gov/getsmart/healthcare/implementation/core-elements.html.
Valerie DeBenedette is a medical news
writer in Putnam County, N.Y.
“At Amneal, we never
forget that every dose of
medication we produce is
prescribed to somebody’s
loved one. Today it might be
your daughter. Tomorrow, it
could just as easily be mine.
This is why we all work so
hard, and why we feel so
grateful to be a part of the
Amneal team”
Amneal Senior Corporate
Quality Management
At Amneal, we view the
world as our family.
We treat every patient and customer as a member of our
extended family. That’s why great care goes into creating
and preserving the confidence you’ve placed in us. Our
goal, every day, is to produce the best-quality, affordable
medicines; because what matters most to us is our patients’
health—as if they were family.
The World Is Our Family ™
a m n e a l. co m
Copyright © 2016 Amneal Pharmaceuticals, All Rights Reserved - AMN-DT 7/16
ISSUES & TRENDS
Up front
HOW ONE PHARMACY SURVIVED
THE BALTIMORE RIOTS
and blood-pressure screenings,” she said.
She hopes her pharmacy can spur other
improvements throughout the community. “There is so much land around here.
I am looking at some vacant land to adopt
that can be used for a community garden.”
PRISON
Pharmacists in tainted drugs
case sentenced
Two pharmacists from Alabama have
received federal prison sentences for distributing tainted drugs that contributed
to the deaths of nine patients at Birmingham-area hospitals in 2011.
David Allen, 60, and William Timothy
Rogers,48,bothworkedatthenow-defunct
compounding pharmacy Advanced Specialty Pharmacy in Birmingham, which
did business as Meds IV. Earlier this year,
both pharmacists pleaded guilty to misdemeanor violations of the Federal Food,
Drug and Cosmetic Act.
On June 21, 2016, U.S. District Judge
Virginia Hopkins sentenced Allen to 12
months in prison and fined him $5,000.
Allen is the former pharmacist-in-charge
at Meds IV. Hopkins sentenced Rogers,
former president of the pharmacy, to 10
months and fined him $5,000.
Joyce White Vance, U.S. Attorney for
the Northern District of Alabama, said
that Meds IV compounded intravenous
nutrition without taking legally required
precautions. “As a result, a number of
patients developed serious infections,”
Vance said. “We are committed to prosecuting this type of practice to the fullest extent the law provides for.”
According to prosecutors, Meds IV compounded total parenteral nutrition (TPN).
Starting in February 2011, the company
compounded its own amino acid solution that was mixed with other ingredients to form TPN. Prosecutors alleged
that amino acid used to compound the
TPN was contaminated with bacteria
32
that can cause bloodstream infections.
CDC investigators traced the bacteria
to a tap-water faucet, an open container
of amino acid powder, and the surface of
mixing equipment at Meds IV. CDC said
Meds IV prepared the amino acid outside a laminar airflow workbench, and
stored it unrefrigerated in a room that
was not sterile, sometimes overnight.
In March 2011, nine patients at Birmingham-areahospitalsdevelopedbloodstream infections and died after receiving TPN compounded by Meds IV. Several others developed bloodstream infections but survived.
“Producing unsafe and contaminated
drugs poses a serious threat to the U.S.
public health and cannot be tolerated,”
said Director George Karavetsos of the
FDA’s Office of Criminal Investigations.
“The FDA remains fully committed to
aggressively pursuing those who place
unsuspecting American consumers at
risk by distributing adulterated drugs.”
— MARK LOWERY, CONTENT EDITOR
PHARMACY CAREERS
Can a student with cerebral
palsy thrive in pharmacy school?
Last month, Kelli Sem was granted conditional acceptance into the pharmacy
school at North Dakota State University
(NDSU). Her acceptance has gained widespread attention because Sem, 23, has
cerebral palsy, uses a motorized wheelchair, and is likely to need an assistant
to act as her hands to meet certain laboratory requirements.
Before she even applied to pharmacy
school, the North Dakota Board of Pharmacy unanimously agreed that Sem, with
reasonable accommodations, would be
able to complete an academic pharmacy
program and gain a license. The pharmacy board noted: “There are many roles
in pharmacy encompassing mostly cognitive tasks, which would pose no barrier to Ms. Sem. Reasonable accommodations might also allow her to perform
most pharmacy duties, with the help of
registered pharmacy technicians.”
NDSU cannot comment on the case,
owing to concern for both privacy and
possible legal action. And it is unclear
what accommodation NDSU will provide.
Sem spoke exclusively toDrug Topics.
DT: When did you become interested in becoming a pharmacist and why?
Sem:As a junior in high school, we had
to write a report on a career that interested us. When I came across pharmacy,
it seemed like a perfect fit, because technicians worked alongside pharmacists to
assist them with many tasks that would
be physically difficult for me.
DT: Have you spoken with pharmacists about
your ability to perform the tasks of a pharmacist?
Sem: I’ve visited with many pharmacists in a variety of settings and locations.
I have job-shadowed in retail, consultative, and hospital positions. In addition,
I met with the North Dakota Pharmacy
Board in 2012 ,where its members collectively agreed that technologic advances
have opened up opportunities for me.
DT:Do you believe some pharmacist settings are
more conducive than others for you?
Sem: Hospital settings would be challenging because of on-site compounding and sterilization requirements. But
there are plenty of pharmaceutical jobs
that require little or no compounding. I
approach life the way my parents raised
me. Even if I can’t do tasks completely
independently, I should contribute my
talents wherever they can be used.
DT: Since your story became public, what type
of feedback have you received?
Sem: I’vereceivedfarmoresupportthan
criticism from family, friends, and even
strangers.Afewpeoplehavebeenopposed.
I want them to know if I thought I would
bring any sort of incompetency to this profession, I wouldn’t be pursuing a degree in
pharmacy. I believe my communication
skills and advocacy skills will help others.
I would like to thank those individuals
who’ve given me support and encouragement. For them, I am full of appreciation.
— MARK LOWERY, CONTENT EDITOR
ISSUES & TRENDS
Up front
MED SYNC
Synchronized meds
boost patient adherence,
pharmacy efficiency
Results from an Arkansas study show that
medication synchronization, the alignment for simultaneous monthly pickup
of all a patient’s prescriptions, increases
the likelihood of medication compliance
among patients while streamlining pharmacy workflow.
Medication adherence
Between May, 2014 and May, 2015,
the National Community Pharmacists
Association (NCPA), the Arkansas Pharmacists Association, and the medication software provider PrescribeWellness studied patients of 82 independent
Arkansas pharmacies for health bene-
fits gained from an appointment-based
model supported by the StarWellness
med sync software. Their study of nearly
4,300 StarWellness users (and more than
17,000 control patients) found significantly improved medication adherence.
More efficient workflow
Pharmacies participating in the NCPA
study realized increased efficiencies by
switching pharmacy workflow from a
manual to an automated method and
by proactively filling scripts. According
to NCPA, med sync can reduce pharmacy hours by around 10 per week
and increase prescription volume by
about 30%.
“Because these pharmacies are taking a
proactiveapproach,theyareabletoidentify
patient needs ahead of time and are able to
order more according to their needs,” said
Grace Gavin, product marketing manager for StarWellness. “It also frees up time,
allowing pharmacies to
focusonotheradditional
clinical services.”
As well as synchronizing meds so that
patients pick up all
their prescriptions on
GRACE GAVIN
the same day each
month, StarWellness allows pharmacists
to schedule appointments with patients.
“They can identify any therapy lapses
or conduct comprehensive medication
reviews,” Gavin said.
“The reason med sync is so important
is that the industry is changing from a
pill-centered model to a patient-centered
model,”Gavinsaid.“Outcomes-basedcare
is going to be the future of pharmacy.”
ITCH LESS.
OUTDOOR MORE.
The Tecnu® family of products have been trusted by outdoor enthusists since 1962. From cleansers to
remove the rash-causing oil from poison ivy to long-lasting, cooling itch relief, Tecnu can help!
Sign up for FREE seasonal samples:
teclabs.com/sample-request
teclabs.com
1-800-ITCHINGTM
CLINICAL
SPECIALTY PHARMACY
Jill Sederstrom
Explore three pathways
to fast-growing niche
Specialty pharmacy, the niche that focuses on high-cost medications and high-touch care, is now practiced in
all types of healthcare settings — clinics for specific disease states, health systems, community pharmacies,
and ambulatory care sites, as well as dedicated specialty pharmacy providers.
As more specialty medications enter the
market, the reach of this type of pharmacy
practice is expected to expand.
“It’s one of the fastest-growing areas
of our profession today,” said Elizabeth
Cardello, BPharm, RPh, senior director of corporate alliances for the American Pharmacists Association (APhA).
More pharmacies are beginning to
explore specialty pharmacy and the
macies, the lack of existing technology
programs to support specialty pharmacy
efforts, and maintenance of quality in
an ever-changing market.
Affeldt and two other pharmacists
from specialty pharmacies across the
country led a roundtable discussion of
those challenges at APhA’s annual meeting this spring.
During the session, which was moder-
Many or even all health systems
right now are either getting involved in
specialty pharmacy or they are already
involved in specialty pharmacy.”
TIM AFFELDT
PHARMD
opportunity it has created in the industry. As more specialty pharmaceuticals
hit the market, the need for knowledgeable pharmacists grows.
“Many or even all health systems right
now are either getting involved in specialty pharmacy or they are already
involved in specialty pharmacy,” said
Tim Affeldt, PharmD, director of specialty/infusion operations for Fairview
Specialty Pharmacy, LLC.
But while the opportunity is large, specialty pharmacy is an area that requires
the management of complex medications
and disease states, and it brings with it a
series of challenges and obstacles. These
include competition with pharmacy
benefit managers (PBMs) that restrict
patient access to outside specialty phar-
34
ated by Cardello, the panelists recounted
their companies’ progression into specialty pharmacy, described how their
specialty pharmacies operate, and outlined potential roadblocks.
Each path to specialty pharmacy is
unique, and the examples of the three
pharmacies highlighted during the session made that clear.
Health system
For Fairview Specialty Pharmacy, a business unit of Fairview Health System and
a partner of the University of Minnesota
Medical Center, the interest in specialty
pharmacy began about two decades ago.
It originated in a need to provide better
service to the 300 to 400 patients each
year who received solid organ trans-
plants at the University of Minnesota
Medical Center.
“There was a need from that group that
they felt they weren’t getting from their
pharmacies at the time,” Affeldt said.
Today, Fairview Specialty Pharmacy
serves approximately 12,000 specialty
pharmacy patients a year and has 55
specialty clinics within its health system. In addition, the specialty pharmacy serves other specialty clinics outside the health system.
“We have access to more than 90 limited-distribution drugs, which can be very
important for your specialty pharmacy,”
Affeldt said. “We have a little more than
200 different payer contracts.”
Specialty-pharmacy group
Brian Komoto, PharmD, president and
chief executive officer of Komoto Healthcare, began his journey in 1981 when
he purchased a small community pharmacy in Delano, Calif.
Komoto Healthcare — which has
expanded to include a custom-care
pharmacy with a compounding facility, a synergy pharmacy solutions company, and a family foundation created
to help patients obtain access to medications — entered the specialty market in 2000 after teaming with a local
managed care plan to find a better way
to meet the needs of hepatitis C patients.
“We came up with the novel idea of
having our own nurses track and work
with the patients on a monthly basis
to help them through the patient-service issues,” Komoto said. “We felt that
CLINICAL
EXPLORE THREE PATHWAYS TO FAST-GROWING NICHE
nursing was a good complement to the
pharmacist.”
The company now has several areas
of specialty pharmacy, Komoto said,
including respiratory syncytial virus
(RSV), rheumatology, oncology, hepatitis C, and intravenous immunoglobulin (IVIG). It serves between 200 to 400
patients each month.
Independent specialty pharmacy
Health, a company division that offers
patients individualized services such as
clinical care management, reimbursement support, or patient-access management.
“Diplomat is unique because of our singular focus on specialty,” Lee said. “We
also have a high-touch model, which
makes us unique from some of our partners that dispense on a scale similar to
what we do.”
With 19 locations across the United States,
was related to technology and the need
not only to collect but also to report necessary data to payers or pharmaceutical companies. He said a successful program requires an IT infrastructure with
a data warehouse or central repository
of data from multiple sources, which
stores dispensing data but also has the
functionality for the pharmacist to pull
reporting information.
“That’s something that certainly was
a challenge when we started, and it con-
Our medical assistants and pharmacy technicians ... usually
have their list of patients, or family members of that patient, that
they are communicating with on a personal basis, so we know if
they are on target or if they are actually taking medications.”
BRIAN KOMOTO
PHARMD
Diplomat Pharmacy is the nation’s largest independent specialty pharmacy. In
2015, Diplomat dispensed 911,000 prescriptions throughout all 50 states and
Puerto Rico, but there was a time when
the company’s reach wasn’t nearly so
expansive.
The company began about 40 years
ago as a small retail pharmacy in Flint,
Mich., said Claire Lee, PharmD, CSP,
CPHQ, clinical quality improvement
supervisor at Diplomat. Between 2005
and 2012, the pharmacy expanded, adding locations in Michigan, Ohio, Illinois, California, and Florida. In 2013,
the company expanded again through
a series of acquisitions.
Diplomat now has a hospital specialty
Rx program that encompasses a partnership with hospital outpatient pharmacies to provide 340B limited distribution and accountable care support; a
retail specialty network, created to bridge
the gap between community pharmacies and the specialty pharmacy market, which provides back-end services
to its community pharmacy partners;
specialty infusion services; and Envoy-
Growing pains
While all three specialty pharmacies have
been established for at least a decade,
the speakers acknowledged that getting established posed some unique
challenges.
Networks. As a regional player in the
specialty pharmacy space, Komoto said,
his company faced the serious challenge of being locked out of networks.
He said that in some cases, patients who
had been referred to his company were
forced to go through the mail-order system. While his company was working
to establish itself, Komoto said, it relinquished these patients to the mail-order
system, although it still worked with
patients’ physicians’ offices to help manage their care.
“The physician’s office still wanted
us involved in following the patient,
because we would help order labs; we
would also provide the end result, the
outcome, back to the office after treatment, and so we were still involved,”
he said.
Technology. One of the biggest challenges that Fairview faced, Affeldt said,
tinues to be a challenge. How do you
[the specialty pharmacy] put all the data
points together that they want?” he said.
Lee added that another challenge
related to technology is the lack of existing programs to support everyday functions in specialty pharmacy.
“As we move beyond a pure dispensing role, we are looking for ways to track
the care management of our patient populations,” she said.
To address the problem, Diplomat has
had to develop its own proprietary software that allows the company to track
data about patient interventions and
outcomes.
The need for compliance data
At Fairview, gathering the necessary
compliance data from patients is usually done with assistance from outside
software solutions. For instance, Fairview uses McKesson’s EnterpriseRx to
track dispensing data necessary to calculate various adherence metrics. Pharmacist nurses, care coordinators, and
account managers also interact reguC O N T I N U E D O N P A G E 36 >
35
CLINICAL
larly with patients to gather and collect
patient information.
Pharmacy staff also play a key role in
gathering compliance data at Komoto
Healthcare.
“We’re high touch, so that’s where
our medical assistants and pharmacy
technicians get involved,” Komoto said.
“They usually have their list of patients,
or family members of that patient, that
they are communicating with on a personal basis, so we know if they are on
target or if they are actually taking medications.”
In addition to company software that
helps collect data, said Lee, Diplomat
collects its compliance data through
patient interviews it conducts before
each billing cycle.
“Prior to every dispense, we ask the
patient not only about the quantity on
hand, but also the number of missed doses
that have occurred, so we have two data
points to evaluate whether or not the
fill date is in alignment with the number of pills or the number of injections
the patient still has on hand,” she said.
If the patient-care coordinator identifies a discrepancy in the data, the patient
is routed to a pharmacist for an evaluation to determine whether an intervention may be needed.
Every quarter, Diplomat conducts a
retrospective analysis of its data on all
its clinical management programs and
evaluates the average medication-possession ratio and the proportion of days
covered. This enables the company to
determine whether it is meeting its own
established benchmarks.
It takes a village
All three specialty pharmacies stressed
the importance of collaboration, between
pharmacy team members and with outside physicians and care managers, to
better meet the needs of each patient.
At Diplomat, every time the company
36
Paying for specialty drugs
through the medical benefit
CASEY STOCKMAN
PHARMD
A new report by MagellanRx Management highlights medical benefit drug costs, trends, and siteof-service changes in 2015.
“This is the only report out there that even has medical benefit data for benchmarking available for payers, so that is a key differentiator of the report,” said
Casey Stockman, PharmD, vice president of medical pharmacy strategy at Magellan.
SOME OF THE REPORT’S KEY FINDING OF THE REPORT INCLUDE:
> Oncology and oncology support medications continue to represent the
largest portion of medical pharmacy costs. In 2014, they represented
52.8% of medical pharmacy costs in the commercial arena and 63.1%
of medical pharmacy costs in Medicare.
> Commercial-per-member-per-month costs in 2014 increased 11% to
$23.60. Medicare saw an increase of 5% to $44.84.
> The average annual cost for the top 25 drugs for a commercial
patient in 2014 was more than double the cost for a Medicare patient
($22,423 vs. $10,551).
> Over the last five years, there has been a 21% increase in the representative cost of the top 25 drugs on the commercial medical benefit.
> Ninety-two percent of payers say they have product-preferencing in
place.
> In the physician’s office, in 2015, 70% of the medical benefit drug volume was supplied by physician buy-and-bill methodology, while 26%
came from a specialty pharmacy provider. In the hospital setting, 87%
of the medical benefit drug volume was supplied by the buy-and-bill
methodology, while 9% came from a specialty pharmacy and 3% was
attributed to infusion sites and internal distribution centers.
> More than half, or 51%, of payers in 2015 said they had seen officebased practices in their area purchased by hospital systems. Over the
last 10 years, payers said, this acquisition was most commonly for
oncology practices, which represented 21% to 30% of the acquisitions,
followed by rheumatology practices, which accounted for 11% to 20%
of the acquisitions.
> The top reasons cited for health systems to purchase independent
practices had to do with incentives for expansion of infusion centers:
either access to 340B acquisition costs (57%) or reimbursements
based on the percentage of charges (47%).
— Jill Sederstrom
A shifting healthcare market has placed added pressure
on community pharmacists to strengthen business. PRxO
Generics SM offers competitive economics and reliable supply.
Additionally, Elevate Provider Network SM delivers profitable
patient access and integ rated business tools. Ensu ring
business success takes access to the right programs and
networks. It takes AmerisourceBergen.
ItTakesAmerisourceBergen.com
MAXIMIZE DISTRIBUTOR VALUE \ OPTIMIZE PATIENT ACCESS \ IMPROVE PROFITABILITY \ BUILD HEALTHIER COMMUNITIES
CLINICAL
receives a prescription order from a pharmacy, a member of Diplomat’s patientaccess team contacts the patient to outline what the patient can expect from
the specialty pharmacy.
The prescription will then go through
the member benefit management team,
which assesses whether the patient has
coverage for the medication and whether
a prior authorization is needed.
“If the patient is not covered, or if
the prior authorization still leaves the
patient with a very high copay that the
patient may not be able to afford, then
the patient will go to our funding assistance team,” Lee said.
Challenges remain
Specialty pharmacy is an area rich in
opportunity; however, those in the field
say challenges and obstacles are also a
prevalent part of the industry.
When asked to identify the biggest
challenge facing the industry today, the
panel speakers brought up issues already
discussed, such as access and technology, but they also cited the importance
of having the necessary cash flow on
hand, maintenance and establishment
of quality check points in a rapidly growing market, and the role significant costs
can play in dictating which therapies are
approved for treatment.
“I think that is one of the biggest challenges and concerns, but it’s also certainly understandable when you are
looking at costs and how can you reduce
costs,” he said.
The takeaway
The speakers concluded their presentation with advice for pharmacists interested in pursuing specialty pharmacy.
Lee recommended that pharmacists take advantage of resources that
would give them a better understanding about the nature of specialty pharmacy, whether that is done by reaching out to a specialty pharmacy, going
Prior to every dispense, we ask the patient not only about the
quantity on hand, but also the number of missed doses that have
occurred, so we have two data points to evaluate whether or not
the fill date is in alignment with the number of pills or the number
of injections the patient still has on hand.”
Once payment challenges have been
addressed, the patient receives a call to
set up delivery of the prescription, and
patient background information is gathered and assessed by a pharmacist before
any medication is sent to a patient.
The process at Fairview usually starts
in the clinic, where the specialty pharmacy works with the provider, care
coordinator, or nurse manager working with the patient to set up and chose
the appropriate therapy. The prescription order then follows a process similar to Diplomat’s, with identification of
the treatment, prior authorization, and
identification of any obstacles to care,
Affeldt said.
An electronic medical record seen by
all involved in a patient’s care helps the
pharmacists communicate with other
members of the healthcare team in real
time to speed up the approval process
and address any obstacles to patient care.
38
Access has been a growing problem for
his pharmacy, said Komoto, as increasing numbers of PBMs own their own
mail-order companies and often require
patients to use them for specialty services. Whereas four years ago, 10% of
business in his service area went to mandatory mail-order, he said, more than
70% does so today.
Komoto said he has tried to address the
problem by going to state and national
pharmacy associations, but he believes
that ultimately legislation will be needed
in order to bring about real changes.
According to Affeldt, the industry is
starting to see more instances of a large
payer or payer organization working with
a pharmaceutical company to negotiate
the cost of a specific product. This can
have implications for patient therapy,
he said, if pharmacists and physicians
need to look at a specific product rather
than all available therapies.
CLAIRE LEE
PHARMD, CSP, CPHQ
through a certification program, visiting
the Specialty Pharma Education Center
online, or reading specialty pharmacy
publications.
Affeldt made the point that pharmacies don’t have to try to be everything
right away, but instead should focus on
what they can be good at initially.
“How can you fill a gap that’s possibly being seen in your marketplace or
how can you possibly partner with a
provider in your marketplace?” he said.
Regardless of the challenges that
exist, said Komoto, pharmacists need
to keep the focus where it belongs – on
the patient.
“When you get involved in these areas
of specialty, you can really make a huge
difference in the lives of that patient,”
he said.
Jill Sederstrom is a freelance writer
based in Kansas City.
COVER STORY
SOLU T IONS TA K E SH A P E
It is important to think of substance-use disorder as a disease.
Starting with that foundation, it is necessary to have insurance coverage
for managing this chronic disease, including naloxone. We should make
it standard of care with dangerous opioid combinations.”
JEFFREY BRATBERG
PHARMD, BCPS
the department of health and the state
Board of Pharmacy. We are essential to
developing solutions for the epidemic,
so pharmacy has to be there.
It is not just this public health issue,
but it is fighting epidemics such as Zika
virus, pandemic influenza, bioterrorism,
and emergency preparedness. Those are
all things that I have been involved with
in our department of health.
There are other states that don’t think
of pharmacy as essential to sit at the table,
but because of our almost 15 years’ work
with the health department, it is natural
that they call us to say, “Let’s see what
pharmacy can do.”
Once you get a seat at the table, as I
did 15 years ago, doing emergency preparedness, it is sort of natural to have
pharmacy as part of this task force.
I had two roles: I represented “pharmacy,” but I was also one of the four members of the naloxone work group, which
is implementing the overdose rescue portion of the strategic plan. I have helped
to figure out how we encourage pharmacists to proactively dispense naloxone, and I am involved in lots of efforts
to track naloxone through all the outlets that we have.
PHARMACIST RESPONSE
DT: Are most pharmacists enthusiastic
about counseling patients about naloxone and dispensing the drug?
BRATBERG: Community pharmacists
have had this very difficult role when
Jef the Professor says, “Here is how we
do patient-centered care.”
Then, in the pharmacy, there are the
realities of managing time, personnel,
and logistics of just getting the prescrip- Maybe we have shifted the curve.
tions dispensed.
Massachusetts saw a 18% rise in its
Then I throw a wrench in and say, “Here overdose deaths reported from 2013is something that you really haven’t done 2014. New Hampshire saw a 73% rise
before. Now you have this CPA or a stand- in its overdose deaths, also during that
ing order that says anybody can walk up time period.
to the counter and ask for naloxone, and
But there is positive news, and nalyou now are the prescriber of one of four oxone is part of the positive news. New
naloxone products that we have taught Mexico just showed a 9% decline in
in our training.”
overdose deaths from 2014-2015, and
That is just not part of our culture, nor it was among the top states per capita
is it part of what we teach, such as “Is this for overdose deaths for over 10 years.
the right drug for the right patient in the
right disease?”
BOTTOM LINE
The other side of the issue is danger- DT: Any last thoughts to share?
ous combination drugs, like a prescrip- BRATBERG: It is important to think
tion for a benzodiazepine and an opioid. of substance-use disorder as a dis“How do I counsel individuals who are ease. Starting with that foundation,
prescribed a dangerous combination to it is necessary to have insurance covget naloxone?”
erage for managing this chronic disIf you are in a state or a pharmacy that ease, including naloxone. We should
lacks a model that permits pharmacists make it standard of care with dangerto prescribe naloxone, you need to call ous opioid combinations and opioid
the patient’s doctor and ask the docdisease combinations.
tor to prescribe naloxone.
In addition, we need to be
Are you ready to have that
the
educators of our prescribOPIOID
conversation? Does the docers,
so that co-prescribing
CRISIS
tor even know that naloxbecomes standard of care.
For More on Naloxone Training, see
STUDENT CORNER
one exists? Does the physiThat is recommended by sevcian know about dangerous
eral
national bodies.
pg.
opioid-drug combinations?
Three years from now,
the goal of [our] task force is
to reduce overdose deaths by oneIS IT WORKING?
third. I want people to wonder why they
DT: So is naloxone dispensing saving
didn’t get naloxone with their opioid,
lives?
because they know that there is a small
BRATBERG: We have seen a 1,100% rise
in naloxone dispensing, according to chance of a very bad outcome with overone report. But our overdose deaths in dose or death.
Naloxone should be the fire extinRhode Island have continued, despite
being one of the states with the great- guisher in the home of everyone who
est access and marketing of naloxone. is at risk.
12
39
Important Safety Information
Myelosuppression: Bendamustine hydrochloride caused severe
myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies.
Three patients (2%) died from myelosuppression-related adverse
reactions. Monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils
frequently. Myelosuppression may require dose delays and/or subsequent
dose reductions if recovery to the recommended values has not occurred
by the first day of the next scheduled cycle.
Infections: Infection, including pneumonia, sepsis, septic shock, hepatitis
and death has occurred. Patients with myelosuppression following
treatment with BENDEKA are more susceptible to infections. Patients
treated with bendamustine hydrochloride are at risk for reactivation of
infections including (but not limited to) hepatitis B, cytomegalovirus,
Mycobacterium tuberculosis, and herpes zoster. Patients should undergo
appropriate monitoring, prophylaxis, and treatment measures prior to
administration.
Anaphylaxis and Infusion Reactions: Infusion reactions to bendamustine
hydrochloride have occurred commonly in clinical trials. Symptoms include
fever, chills, pruritus, and rash. In rare instances severe anaphylactic and
anaphylactoid reactions have occurred, particularly in the second and
subsequent cycles of therapy. Monitor clinically and discontinue drug for
severe (Grade 3-4) reactions. Ask patients about symptoms suggestive
of infusion reactions after their first cycle of therapy. Consider measures
to prevent severe reactions, including antihistamines, antipyretics, and
corticosteroids in subsequent cycles in patients who have experienced
Grade 1 or 2 infusion reactions.
Tumor Lysis Syndrome: Tumor lysis syndrome associated with
bendamustine hydrochloride has occurred. The onset tends to be within
the first treatment cycle with bendamustine hydrochloride and, without
intervention, may lead to acute renal failure and death. Preventive
measures include vigorous hydration and close monitoring of blood
chemistry, particularly potassium and uric acid levels. There may be an
increased risk of severe skin toxicity when bendamustine hydrochloride and
allopurinol are administered concomitantly.
Skin Reactions: Skin reactions have been reported with bendamustine
hydrochloride treatment including rash, toxic skin reactions, and bullous
exanthema. In a study of bendamustine hydrochloride (90 mg/m2) in
combination with rituximab, one case of toxic epidermal necrolysis (TEN)
occurred. TEN has been reported for rituximab. Cases of Stevens-Johnson
syndrome (SJS) and TEN, some fatal, have been reported when
Please see additional Important Safety Information
on the right and Brief Summary of Full Prescribing
Information for BENDEKA following this ad.
FIRST-LINE THERAPY FOR CLL
Go with the only bendamustine HCl
that has a 10-minute infusion1
Time matters
BENDEKA®is indicated for the treatment of patients with
• Chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established.
Contraindication: BENDEKA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine,
polyethylene glycol 400, propylene glycol, or monothioglycerol.
Recommended dosage for CLL1
• 100 mg/m2 administered intravenously over 10 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles
– Hematologic toxicity ≥Grade 3: reduce dose to 50 mg/m2 on Days 1 and 2 of each cycle; if ≥Grade 3 toxicity recurs, reduce dose to 25 mg/m2
on Days 1 and 2 of each cycle
– Non-hematologic toxicity clinically significant ≥Grade 3: reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle
– Dose re-escalation may be considered
Additional dosing considerations1
• Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity
• Dilute BENDEKA prior to infusion
• Concomitant CYP1A2 inducers or inhibitors have the potential to affect the exposure of bendamustine
• Renal impairment: Do not use if CrCL is <40 mL/min. Use with caution in lesser degrees of renal impairment
• Hepatic impairment: Do not use in moderate or severe hepatic impairment. Use with caution in mild hepatic impairment
Important Safety Information (cont)
bendamustine hydrochloride was administered concomitantly with
allopurinol and other medications known to cause these syndromes. Where
skin reactions occur, they may be progressive and increase in severity
with further treatment. Monitor patients with skin reactions closely. If skin
reactions are severe or progressive, withhold or discontinue BENDEKA.
Other Malignancies: There are reports of pre-malignant and malignant
diseases that have developed in patients who have been treated with
bendamustine hydrochloride, including myelodysplastic syndrome,
myeloproliferative disorders, acute myeloid leukemia, and bronchial
carcinoma. The association with BENDEKA therapy has not been determined.
Extravasation Injury: Extravasations resulting in hospitalizations
from erythema, marked swelling, and pain have been reported with
bendamustine hydrochloride. Assure good venous access prior to starting
drug infusion and monitor the intravenous infusion site for redness, swelling,
pain, infection, and necrosis during and after administration of BENDEKA.
Embryo-fetal Toxicity: Bendamustine hydrochloride can cause fetal harm
when administered to a pregnant woman. Women should be advised to
avoid becoming pregnant while using BENDEKA.
Most Common Adverse Reactions:
• Adverse reactions (frequency >5%) during infusion and within 24 hours
post-infusion are nausea and fatigue.
• Most common non-hematologic adverse reactions for CLL (frequency
≥15%) are pyrexia, nausea, and vomiting.
• Most common hematologic abnormalities (frequency ≥15%) are
lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.
For more information, call 1-800-896-5855 or visit
www.BENDEKAHCP.com
Reference: 1. BENDEKA™ (bendamustine hydrochloride) Injection [Prescribing Information].
North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015.
Please see Brief Summary of Full Prescribing Information
for BENDEKA on following pages.
BENDEKA® is a registered trademark of Cephalon, Inc.
©2016 Cephalon, Inc., a wholly-owned subsidiary
of Teva Pharmaceutical Industries Ltd.
All rights reserved. BEN-40300 May 2016.
BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR
BENDEKA (bendamustine hydrochloride) injection, for intravenous use
SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
1
1.1
Chronic Lymphocytic Leukemia (CLL)
BENDEKA (bendamustine hydrochloride) Injection is indicated for the treatment of patients with chronic lymphocytic leukemia. Efficacy relative to first
line therapies other than chlorambucil has not been established.
2
DOSAGE AND ADMINISTRATION
2.1
Dosing Instructions for CLL
Recommended Dosage:
The recommended dose is 100 mg/m2 administered intravenously over 10
minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles.
Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL:
BENDEKA (bendamustine hydrochloride) Injection administration should
be delayed in the event of Grade 4 hematologic toxicity or clinically significant greater than or equal to Grade 2 non-hematologic toxicity. Once nonhematologic toxicity has recovered to less than or equal to Grade 1 and/or the
blood counts have improved [Absolute Neutrophil Count (ANC) greater than
or equal to 1 x 109/L, platelets greater than or equal to 75 x 109/L], BENDEKA
(bendamustine hydrochloride) Injection can be reinitiated at the discretion
of the treating physician. In addition, dose reduction may be warranted. [see
Warnings and Precautions (5.1)]
Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity,
reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater
toxicity recurs, reduce the dose to 25 mg/m2 on Days 1 and 2 of each cycle.
Dose modifications for non-hematologic toxicity: for clinically significant
Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of
each cycle.
Dose re-escalation in subsequent cycles may be considered at the discretion
of the treating physician.
2.3
Preparation for Intravenous Administration
BENDEKA (bendamustine hydrochloride) Injection is a cytotoxic drug. Follow
applicable special handling and disposal procedures.1
BENDEKA is in a multiple-dose vial. BENDEKA is a clear, and colorless to
yellow ready-to-dilute solution. Allow vial to reach room temperature. If particulate matter is observed, the product should not be used.
Intravenous Infusion
• Aseptically withdraw the volume needed for the required dose from the
25 mg/mL solution as per Table A below and immediately transfer the solution to a 50 mL infusion bag of one of the following diluents:
− 0.9% Sodium Chloride Injection, USP; or
− 2.5% Dextrose/0.45% Sodium Chloride Injection, USP; or
− 5% Dextrose Injection, USP.
The resulting final concentration of bendamustine hydrochloride in the infusion bag should be within 1.85 mg/mL – 5.6 mg/mL. After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a clear,
and colorless to yellow solution.
No other diluents have been shown to be compatible. The 5% Dextrose Injection, USP, offers a sodium-free method of administration for patients with
certain medical conditions requiring restricted sodium intake.
Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration whenever solution and container permit.
Any unused solution should be discarded according to institutional procedures
for antineoplastics.
2.4
Admixture Stability
BENDEKA (bendamustine hydrochloride) Injection contains no antimicrobial
preservative. The admixture should be prepared as close as possible to the
time of patient administration.
If diluted with 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45%
Sodium Chloride Injection, USP, the final admixture is stable for 24 hours
when stored refrigerated (2-8°C or 36-46°F) or for 6 hours when stored at
room temperature (15-30°C or 59-86°F) and room light. Administration of
diluted BENDEKA (bendamustine hydrochloride) Injection must be completed
within this period of time.
In the event that 5% Dextrose Injection, USP is utilized, the final admixture is
stable for 24 hours when stored refrigerated (2-8°C or 36-46°F) or for only
3 hours when stored at room temperature (15-30°C or 59-86°F) and room
light. Administration of diluted BENDEKA must be completed within this
period of time.
Retain the partially used vial in original package to protect from light and
store refrigerated (2-8°C or 36-46°F) if additional dose withdraw from the
same vial is intended.
2.5
Stability of Partially Used Vials (Needle Punched Vials)
BENDEKA is supplied in a multiple-dose vial. Although it does not contain any
antimicrobial preservative, BENDEKA is bacteriostatic. The partially used vials
are stable for up to 28 days when stored in its original carton under refrigeration (2-8°C or 36-46°F). Each vial is not recommended for more than a total
of six (6) dose withdrawals.
After first use, the partially used vial should be stored in the refrigerator in
the original carton at 2°C to 8°C or 36-46°F and then discarded after 28 days.
BENDEKATM (bendamustine hydrochloride) Injection
3
DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/4 mL (25 mg/mL) as a clear and colorless to yellow readyto-dilute solution in a multiple-dose vial.
4
CONTRAINDICATIONS
BENDEKA (bendamustine hydrochloride) Injection is contraindicated in
patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid
reactions) to bendamustine, polyethylene glycol 400, propylene glycol, or
monothioglycerol. [see Warnings and Precautions (5.3)]
5
5.1
Myelosuppression
Bendamustine hydrochloride caused severe myelosuppression (Grade 3-4)
in 98% of patients in the two NHL studies (see Table 4). Three patients (2%)
died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia,
and pneumonia from an opportunistic infection (CMV).
BENDEKA (bendamustine hydrochloride) Injection causes myelosuppression.
Monitor complete blood counts, including leukocytes, platelets, hemoglobin
(Hgb), and neutrophils frequently. In the clinical trials, blood counts were
monitored every week initially. Hematologic nadirs occurred predominantly in
the third week of therapy. Myelosuppression may require dose delays and/or
subsequent dose reductions if recovery to the recommended values has not
occurred by the first day of the next scheduled cycle. Prior to the initiation of
the next cycle of therapy, the ANC should be ≥ 1 x 109/L and the platelet count
should be ≥ 75 x 109/L. [see Dosage and Administration (2.1)]
5.2
Infections
Infection, including pneumonia, sepsis, septic shock, and death have occurred
in adult and pediatric patients in clinical trials and in postmarketing reports for
bendamustine hydrochloride. Patients with myelosuppression following treatment with bendamustine hydrochloride are more susceptible to infections.
Advise patients with myelosuppression following BENDEKA (bendamustine
hydrochloride) Injection treatment to contact a physician immediately if they
have symptoms or signs of infection.
5.3
Anaphylaxis and Infusion Reactions
Infusion reactions to bendamustine hydrochloride have occurred commonly
in clinical trials. Symptoms include fever, chills, pruritus and rash. In rare
instances severe anaphylactic and anaphylactoid reactions have occurred,
particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients
who experienced Grade 3 or worse allergic-type reactions were not typically
rechallenged. Consider measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids in subsequent cycles in patients
who have experienced Grade 1 or 2 infusion reactions. Discontinue BENDEKA
(bendamustine hydrochloride) Injection for patients with Grade 4 infusion
reactions. Consider discontinuation for Grade 3 infusion reactions as clinically appropriate considering individual benefits, risks, and supportive care.
5.4
Tumor Lysis Syndrome
Tumor lysis syndrome associated with bendamustine hydrochloride has
occurred in patients in clinical trials and in post-marketing reports. The onset
tends to be within the first treatment cycle of bendamustine hydrochloride and
may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium
and uric acid levels. Allopurinol has also been used during the beginning of
bendamustine hydrochloride therapy. However, there may be an increased risk
of severe skin toxicity when bendamustine hydrochloride and allopurinol are
administered concomitantly [see Warnings and Precautions (5.5)].
5.5
Skin Reactions
Skin reactions have been reported with bendamustine hydrochloride treatment in clinical trials and postmarketing safety reports, including rash, toxic
skin reactions and bullous exanthema.
Some events occurred when bendamustine hydrochloride was given in combination with other anticancer agents.
In a study of bendamustine hydrochloride (90 mg/m2) in combination with
rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN
has been reported for rituximab (see rituximab package insert). Cases of
Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported
when bendamustine hydrochloride was administered concomitantly with
allopurinol and other medications known to cause these syndromes. The relationship to bendamustine hydrochloride cannot be determined.
Where skin reactions occur, they may be progressive and increase in severity
with further treatment. Monitor patients with skin reactions closely. If skin
reactions are severe or progressive, withhold or discontinue BENDEKA (bendamustine hydrochloride) Injection.
5.6
Other Malignancies
There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with bendamustine hydrochloride,
including myelodysplastic syndrome, myeloproliferative disorders, acute
myeloid leukemia and bronchial carcinoma. The association with BENDEKA
(bendamustine hydrochloride) Injection therapy has not been determined.
5.7
Extravasation
Bendamustine hydrochloride extravasations have been reported in post
marketing resulting in hospitalizations from erythema, marked swelling, and
pain. Assure good venous access prior to starting drug infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and
necrosis during and after administration of BENDEKA (bendamustine hydrochloride) Injection.
5.8
Embryo-fetal Toxicity
Bendamustine hydrochloride can cause fetal harm when administered to a
pregnant woman. Single intraperitoneal doses of bendamustine in mice and
rats administered during organogenesis caused an increase in resorptions,
skeletal and visceral malformations, and decreased fetal body weights.
6.1
Adverse Events in Clinical Trials
The safety of BENDEKA (bendamustine hydrochloride) Injection administered
IV as a 50 mL admixture over a 10-minute infusion is supported by clinical trials using bendamustine hydrochloride administered IV as a 500 mL admixture
over 30-60 minutes infusion time, as well as an open-label, crossover study
in 81 ‘end-of-life’ cancer patients treated with BENDEKA. In total, safety data
from clinical studies are available from over 400 cancer patients exposed to
bendamustine hydrochloride at doses in the range used in the treatment of
CLL and NHL.
No clinically significant differences in the adverse event profile were noted
among bendamustine hydrochloride administered as a 500 mL admixture
over standard infusion time (30-60 minutes) and BENDEKA administered as a
50 mL admixture in a ‘short-time’ infusion over 10 minutes.
The safety and tolerability of BENDEKA was evaluated in an 8-week clinical study
of BENDEKA in 81 ‘end-of-life’ cancer patients, diagnosed with solid tumors and
hematologic malignancies (excluding CLL). The population was 40-82 years of
age, 58% females, 84% white, 12.3% Black, 1.2% Asian and 2.5% were classified as ‘other’. BENDEKA was administered IV at a 120 mg/m2 dose as a 50 mL
admixture over 10 minutes. Patients in the study received BENDEKA (50 mL IV,
over 10 minutes) or bendamustine hydrochloride (500 mL IV, over 60 minutes)
on Days 1 and 2 every 28 days for two consecutive 2-day cycles.
Adverse reactions (any grade) that occurred with a frequency greater than
5% during BENDEKA infusion and within one hour post-infusion were nausea
(8.2%) and fatigue (5.5%).
Adverse reactions (any grade) that occurred with a frequency greater than
5% within 24 hours of BENDEKA were nausea (10.9%) and fatigue (8.2%).
The adverse reactions leading to study withdrawal in 4 patients receiving
BENDEKA were pyrexia (1.2%), nausea (1.2%), vomiting (1.2%), pneumonia
(1.2%) and fatigue (1.2%).
6.2
Clinical Trials Experience in CLL
The data described below reflect exposure to bendamustine hydrochloride in
153 patients. Bendamustine hydrochloride was studied in an active-controlled
trial. The population was 45-77 years of age, 63% male, 100% white, and had
treatment naïve CLL. All patients started the study at a dose of 100 mg/m2
intravenously over 30 minutes on Days 1 and 2 every 28 days.
Adverse reactions were reported according to NCI CTC v.2.0. In the randomized CLL clinical study, non-hematologic adverse reactions (any grade) in the
bendamustine hydrochloride group that occurred with a frequency greater
than 15% were pyrexia (24%), nausea (20%), and vomiting (16%).
Other adverse reactions seen frequently in one or more studies included
asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough;
constipation; headache; mucosal inflammation and stomatitis.
Worsening hypertension was reported in 4 patients treated with bendamustine hydrochloride in the randomized CLL clinical study and none treated with
chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved.
The most frequent adverse reactions leading to study withdrawal for patients
receiving bendamustine hydrochloride were hypersensitivity (2%) and
pyrexia (1%).
Table 1 contains the treatment emergent adverse reactions, regardless of
attribution, that were reported in ≥ 5% of patients in either treatment group in
the randomized CLL clinical study.
Table 1: Non-Hematologic Adverse Reactions Occurring in Randomized
CLL Clinical Study in at Least 5% of Patients
Number (%) of patients
Bendamustine
Hydrochloride
Chlorambucil
(N=153)
(N=143)
System organ class
Preferred term
Total number of patients
with at least 1 adverse
reaction
Gastrointestinal
disorders
Nausea
Vomiting
Diarrhea
All Grades Grade 3/4 All Grades Grade 3/4
25 (17)
96 (67)
52 (34)
21 (79)
31 (20)
24 (16)
14 (9)
1 (<1)
1 (<1)
2 (1)
21 (15)
9 (6)
5 (3)
1 (<1)
0
0
Number (%) of patients
Bendamustine
Hydrochloride
Chlorambucil
(N=153)
(N=143)
System organ class
Preferred term
General disorders and
administration site
conditions
Pyrexia
2 (1)
8 (6)
6 (4)
36 (24)
Fatigue
0
8 (6)
2 (1)
14 (9)
Asthenia
0
6 (4)
0
13 (8)
Chills
0
1 (<1)
0
9 (6)
Immune system
disorders
Hypersensitivity
0
3 (2)
2 (1)
7 (5)
Infections and
infestations
Nasopharyngitis
0
12 (8)
0
10 (7)
Infection
1 (<1)
1 (<1)
3 (2)
9 (6)
Herpes simplex
0
7 (5)
0
5 (3)
Investigations
Weight decreased
0
5 (3)
0
11 (7)
Metabolism and
nutrition disorders
Hyperuricemia
0
2 (1)
3 (2)
11 (7)
Respiratory, thoracic
and mediastinal
disorders
Cough
1 (<1)
7 (5)
1 (<1)
6 (4)
Skin and subcutaneous
tissue disorders
Rash
3 (2)
7 (5)
4 (3)
12 (8)
Pruritus
0
2 (1)
0
8 (5)
The Grade 3 and 4 hematology laboratory test values by treatment group in
the randomized CLL clinical study are described in Table 2. These findings
confirm the myelosuppressive effects seen in patients treated with bendamustine hydrochloride. Red blood cell transfusions were administered to
20% of patients receiving bendamustine hydrochloride compared with 6% of
patients receiving chlorambucil.
Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who
Received bendamustine hydrochloride or Chlorambucil in the Randomized
CLL Clinical Study
Bendamustine
Hydrochloride
Chlorambucil
N=150
N=141
Laboratory Abnormality
n (%)
n (%)
n (%)
n (%)
12 (9)
115 (82)
20 (13)
134 (89)
Hemoglobin Decreased
14 (10)
110 (78)
16 (11)
116 (77)
Platelets Decreased
4 (3)
26 (18)
42 (28)
92 (61)
Leukocytes Decreased
6 (4)
27 (19)
70 (47)
Lymphocytes Decreased 102 (68)
30 (21)
86 (61)
65 (43)
113 (75)
Neutrophils Decreased
In the randomized CLL trial, 34% of patients had bilirubin elevations, some
without associated significant elevations in AST and ALT. Grade 3 or 4
increased bilirubin occurred in 3% of patients. Increases in AST and ALT of
Grade 3 or 4 were limited to 1% and 3% of patients, respectively. Patients
treated with bendamustine hydrochloride may also have changes in their
creatinine levels. If abnormalities are detected, monitoring of these parameters
should be continued to ensure that significant deterioration does not occur.
6.4
Post-Marketing Experience
The following adverse reactions have been identified during post-approval
use of bendamustine hydrochloride. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to drug
exposure: anaphylaxis; and injection or infusion site reactions including phlebitis, pruritus, irritation, pain, and swelling; pneumocystis jiroveci pneumonia
and pneumonitis.
Skin reactions including SJS and TEN have occurred when bendamustine
hydrochloride was administered concomitantly with allopurinol and other
medications known to cause these syndromes. [see Warnings and Precautions (5.5)].
7
DRUG INTERACTIONS
No formal clinical assessments of pharmacokinetic drug-drug interactions
between bendamustine hydrochloride and other drugs have been conducted.
Bendamustine’s active metabolites, gamma-hydroxy bendamustine (M3) and
N-desmethyl-bendamustine (M4), are formed via cytochrome P450 CYP1A2.
Inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) have potential to
increase plasma concentrations of bendamustine and decrease plasma concentrations of active metabolites. Inducers of CYP1A2 (e.g., omeprazole,
smoking) have potential to decrease plasma concentrations of bendamustine
and increase plasma concentrations of its active metabolites. Caution should
be used, or alternative treatments considered if concomitant treatment with
CYP1A2 inhibitors or inducers is needed.
The role of active transport systems in bendamustine distribution has not
been fully evaluated. In vitro data suggest that P-glycoprotein, breast cancer
resistance protein (BCRP), and/or other efflux transporters may have a role in
bendamustine transport.
Based on in vitro data, bendamustine is not likely to inhibit metabolism via
human CYP isoenzymes CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5, or to induce
metabolism of substrates of cytochrome P450 enzymes.
8.6
Renal Impairment
No formal studies assessing the impact of renal impairment on the pharmacokinetics of bendamustine have been conducted. BENDEKA (bendamustine
hydrochloride) Injection should be used with caution in patients with mild or
moderate renal impairment. BENDEKA (bendamustine hydrochloride) Injection
should not be used in patients with CrCL < 40 mL/min.
8.7
Hepatic Impairment
No formal studies assessing the impact of hepatic impairment on the pharmacokinetics of bendamustine have been conducted. BENDEKA (bendamustine
hydrochloride) Injection should be used with caution in patients with mild
hepatic impairment. BENDEKA (bendamustine hydrochloride) Injection should
not be used in patients with moderate (AST or ALT 2.5-10 X ULN and total
bilirubin 1.5-3 X ULN) or severe (total bilirubin > 3 X ULN) hepatic impairment.
16
HOW SUPPLIED/STORAGE AND HANDLING
16.1 Safe Handling and Disposal
BENDEKA (bendamustine hydrochloride) Injection is a cytotoxic drug. Follow
applicable special handling and disposal procedures. Care should be exercised in the handling and preparation of solutions prepared from BENDEKA
(bendamustine hydrochloride) Injection. The use of gloves and safety glasses
is recommended to avoid exposure in case of breakage of the vial or other
accidental spillage. If a solution of BENDEKA (bendamustine hydrochloride)
Injection contacts the skin, wash the skin immediately and thoroughly with
soap and water. If BENDEKA (bendamustine hydrochloride) Injection contacts
the mucous membranes, flush thoroughly with water.
16.3 Storage
BENDEKA (bendamustine hydrochloride) Injection should be stored in refrigerator, 2° to 8°C (36° to 46°F). Retain in original carton until time of use to
protect from light.
Distributed by: Teva Pharmaceuticals USA, Inc., North Wales, PA 19454
Brief Summary of BENDEKA Prescribing Information BEN-002
Rev. 12/2015 All rights reserved.
BEN-40269
PATIENT COMMUNICATIONS
H E A LT H SYST E MS L E V E R AG E SOCI A L
M E DI A FOR PAT I E N T E NG AG E M E N T
< C O N T I N U E D F R O M P A G E 37B
getting more involved with having them electronically
monitoring their care online or via smart phone from
their homes, Weber said.
Collaboration counts
Allie Woods, director, section of pharmacy informatics
and technology, at the American Society of Health System
Pharmacists (ASHP), noted that while the increased use of
apps that allow patients to track their heart rate and blood
pressure is a positive turn of events, questions of accuracy
and efficacy persist.
“They’re engaging patients, but does it address the overall healthcare and the patient’s condition?” said Woods.
“Does whoever created it understand the healthcare and
the patient’s condition? Are they building an app appropriately or working with the programmers who build the
program appropriately to make sure it is accurate and useful, and not steering patients in the wrong direction?”
The growth of mobile health
Matthew Weinstock, director of communications and public
relations for the College of Healthcare Information Management Executives (CHIME), said that patient engagement is
growing because ofpatients’ ability to shop around for their
care; as a result, it’s incumbent on hospitals to engage with
patients in new ways, one of which is technology.
“Patient portals are one avenue that you’re seeing hospitals use. Patients can go in and do everything from set
up appointments to pay bills, to more advanced actions,
like getting more clinical information such as lab results,”
Weinstock said.
Another new and growing area, said Weinstock, is the
mobile health platform. “I think that is an area that will
probably continue to grow. Some hospitals have developed
their own version of the Apple Genius Bar, so that they
can work with patients to help figure out what apps may
be best for their condition, and then actually help them to
load those on to a device and figure out how to use them.”
CHIME’s Weinstock said that going forward there will
be increased portal and app development as health systems integrate patient-generated data and try to get patients
more engaged.
“Part of the challenge is not too dissimilar to what we
see with interoperability: Creating a set of standards by
which the data can flow from one system to another. Even
on the consumer-facing piece – how do you get data from
an individual’s health kit or iPAD into your record?” asked
Weinstock.
Anthony Vecchione is a healthcare journalist based in New Jersey.
CLINICAL
NALOXONE UPDATE
Valerie DeBenedette
Be aware of liability, regulatory
considerations with naloxone
As the epidemic of opioid abuse and heroin use in the United States continues, when it comes to dispensing
naloxone to treat overdose, in many states pharmacists are on the front lines. So you need to be aware of the
liability and regulatory considerations connected with naloxone.
Those concerns were the focus of a discussion at the meeting of the American
Pharmacists Association held in Baltimore this year, moderated by Christopher Herndon, PharmD, BCPS, associ-
oxone only as a rescue drug to be used
for a heroin overdose. “This is not just
about heroin users … it is about the widespread use of opiates throughout the
population,” Tommasello said. “[The]
Stratton VA Medical Center in Albany,
N.Y., addressed other key issues, including whether naloxone administration
routes are interchangeable.
Edwards et al. found that naloxone is used correctly
more often with certain routes of adminstration.2 Specifically,
90% of patients were
able to use an autoinjector correctly a week
after being trained,
CHRISTOPHER HERNDON compared to approxiPHARMD, BCPS, CPE
mately 57% who used
individuals at risk of overdose include the intranasal route.
people who are recipients of chronic
Intranasal administration may be
high-dose opioid pain management in adversely affected by a deviated septum
various forms.”
or an infection. Intramuscular injection
Community education can help reduce has about the same response rate as intradeaths from unintentional opioid over- venous injection, while intranasal can take
dose, Tommasello added. Citing a
a minute or two longer, he added.
study by Walley et al, he said,
On the other hand, intranaOPIOID
“As the community became
sal administration eliminates
CRISIS
more educated about the
the need for needles and the
For More from Dr. Fudin, see
availability and use of intrariskofexposuretobloodborne
PAIN MANAGEMENT
venous naloxone, there was a
pathogens,andthenoseisusupg.
significant reduction in death
ally easy to access in an unconrates from opioids.”1
scious patient.
Opioid-related hospital admissions and deaths have trended upwards in References
Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates
recent years as retail sales of these drugs 1.
and implementation of overdose education and nasal naloxone
increased, Tommasello noted. Also, imple- distribution in Massachusetts: Interrupted time series analysis.
mentation of PDMPs for opioids has been BMJ. Jan. 31, 2013; 346:f174.
accompanied by an increase in heroin 2. Edwards, ET, Edwards ES, Davis E, et al. Comparative usability study of a novel auto-injector and an intranasal system for
use, he added.
naloxone delivery. Pain Ther. 2015 Jun;4(1):89-105.
Jeffrey Fudin, PharmD, DAAPM,
FASHP, a clinical pharmacy special- Valerie DeBenedette is a medical news
ist and PGY2 pain residency director at writer in Putnam County, N.Y.
Some states provide immunity to prescribers
and dispensers of naloxone. Others allow a physician
to issue standing orders for naloxone prescriptions.
Yet other states allow prescribing to a third party.”
ate professor in the Department of Pharmacy Practice at Southern Illinois University, Edwardsville, School of Pharmacy.
Some states provide immunity to prescribers and dispensers of naloxone, Herndon said. Others allow a physician to issue
standing orders for naloxone prescriptions, enabling pharmacists to dispense
as needed to patients at risk of respiratory depression. Yet other states allow
prescribing to a third party (e.g., a family member of a drug abuser).
Naloxone can be administered by intravenous, intramuscular, and subcutaneous injection; intranasal spray; and intramuscular autoinjection. Adverse reactions
are minimal, although severe withdrawal
symptoms may result from the overdose.
If a long-acting opioid was taken, more
than one dose of naloxone may be needed.
During the discussion, Anthony Tommasello, RPh, PhD, medical affairs manager with Indivior in Richmond, Va.,
advised pharmacists not think of nal-
42
20
Your lifeline for quality,
integrity and value in generics
From discovery to delivery, Camber is
dedicated to providing the highest quality
generics, at the most affordable prices.
®
Camber Pharmaceuticals, Inc. | Phone 732.529.0430 | camberpharma.com
CLINICAL
NEW DRUG REVIEW
F DA A P P ROV E S T R I F LU R I DI N E/ T I P I R ACI L FOR COLOR ECTA L CA NCE R
dysfunction, anorexia, stomatitis, handfoot syndrome, or cardiac events.
Management of adverse effects is necessary to minimize morbidity. Monitoring includes collecting a complete blood
count (CBC), differential and absolute
neutrophil count (ANC) prior to therapy
initiation, prior to day 15 of each cycle,
on day 15 of each cycle, and more frequently if needed. If severe myelosuppression occurs, dose should be reduced
or held as clinically indicated.
Animal studies indicate trifluridine/
tipiracil can cause fetal harm and should
not be given to pregnant women. Women
should not breastfeed while using this
medication or for one day following the
final dose. Grades 3 or 4 neutropenia and
thrombocytopenia and grade 3 anemia
occurred more commonly in patients 65
years or older. Patients who have moderate renal impairment may require
dose modifications for increased toxicity.
Dosing
The recommended dose of trifluridine/
tipiracil is 35mg/m2/dose (based on trifluridine component) orally twice daily
on days 1 through 5 and days 8 through
12 of each 28-day cycle. Each dose should
be rounded to the nearest 5-mg increment. Trifluridine/tipiracil comes in
an oral combination tablet in 15-mg/
6.14-mg and 20-mg/8.19-mg strengths.
Patients should be advised to take this
medication within one hour after morning and evening meals. Patients should
not take additional doses to make up for
missed or held doses and should not split
this tablet. No pharmacokinetic drugdrug interaction studies have been conducted with trifluridine/tipiracil.
Do not initiate the cycle of trifluridine/tipiracil until the absolute neu-
trophil count (ANC) is ≥1,500/mm3 or
febrile neutropenia is resolved, platelets are ≥75,000/mm3, or grades 3 or 4
nonhematological adverse reactions are
resolved to grades 0 or 1.
Patients should withhold trifluridine/
tipiracil if during a treatment cycle the
ANC is less than 500/mm3, febrile neutropenia develops, platelets are less than
50,000/mm3, or if grade 3/4 nonhematological adverse reactions occur. After
recovery of febrile neutropenia, thrombocytopenia, or nonhematologic grades
3 or 4 adverse reactions, dosing should
be reduced by 5 mg/m2/dose from the
previous dose level before restarting.
Camden E. Svec is a 2016 PharmD graduate from University of Connecticut School of
Pharmacy, Storrs, Conn. Lisa M. Holle is
an assistant clinical professor at University of
Connecticut School of Pharmacy, Storrs, Conn.
P H A R M ACISTS TA K E A I M AT M E D E R RORS DU R I NG CA R E T R A NSI T IONS
organization as a system, while doing
what is needed to support the different
sites.
“We feel that this task is one that needs
to be local. So what can I do for them
centrally that can support them locally?
We are doing things with medication
management review that we may do
from a centralized location for all areas,
like priority clinic support. We will use
MedMined for that too.”
Ochsner’s goal is to provide the best
quality care in an affordable manner,
Simonson said.
“As a system we will take advantage
of any centralized function to support
the hospitals for tasks or work that must
be done at the site. So if a pharmacist
needs to do discharge counseling and
med review from 1 p.m. to 3 p.m. at a
site, we can help support that hospital
with centralized verification during that
time,” Simonson said.
The Ochsner pharmacy team is planning other ways to support providers,
whether from centralized locations or
by means of telepharmacy.
“Our strategies for the coming years
include telepharmacy activities. We want
the correct pharmacy expertise available to all sites for the specific function
needed. So if a critical access hospital
needs to speak to an infectious-diseasetrained pharmacist, they will have that
access,” Simonson said.
The MedMined tool, Simonson said,
will show where a prescription was filled.
“If we need to contact that site for the
patient, we will have that ability.”
onciliation strategies.
“The skill set is there, and what we’re
seeing is a lot more pharmacists and pharmacy techs getting involved,” said Vikas
Gupta, PharmD, director of clinic strategy at BD MedMined services.
Historically, medication reconciliation
strategies have focused on addressing the
inpatient setting, medication stewardship, antibiotic stewardship, and anticoagulation.
“What we wanted to do is link both
the inpatient and outpatient settings.
Healthcare has changed. Readmissson
penalties have put a greater focus on the
ambulatory setting. Instead of the term
med rec, we use more clear transitions,”
said Gupta.
Readmission issues
Readmission penalties are another factor forcing hospitals to incorporate pharmacists into aggressive medication rec-
Anthony Vecchione is a healthcare journalist based in New Jersey.
43
CLINICAL
ANTICOAGULATION THERAPIES
Anna D. Garrett, PharmD, BCPS
Warfarin for CKD, aspirin for
TIA,and what to do about ICH
Risks of warfarin use may outweigh
benefits in AF, CKD
Chronic kidney disease (CKD) is associated with increased atrial fibrillation (AF)
and greater risk of thromboembolic events,
bleeding, and mortality. The use of warfarin in patients with AF and CKD can be
a problem because of that added bleeding
risk. A literature review suggests that the
risks of warfarin therapy in patients with
AF and CKD may outweigh the benefits.
11,600
PATIENTS
with CKD
and AF
included
in the study
The study included >11,600 patients
with CKD and AF who were treated with
warfarin. In patients with AF and nonend-stage CKD, warfarin use resulted in
a lower risk of ischemic stroke/thromboembolism and mortality, but had no
effect on major bleeding. In patients with
AF and end-stage renal disease, warfarin had no effect on the risks of stroke
and mortality, but increased the risks of
major bleeding.
At present, anticoagulation is recommended for patients with AF and mildmoderate CKD. In those with severe
CKD, warfarin still may be beneficial,
provided that it is well-managed and a
TTR>70% is maintained.
SOURCE: Dahal K, Kunwar S, Rijal J, et al. Stroke,
major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: A meta-analysis of observational
studies. Chest. 2016;149(4):951-959.
Benefits of early aspirin therapy
underestimated in stroke, TIA
Aspirin is recommended for secondary
prevention after transient ischemic attack
44
(TIA) or ischemic stroke, based on trials
showing a 13% reduction in long-term
risk of recurrent stroke.
To assess the benefits of early aspirin
therapy, investigators used pooled data
from all trials of aspirin vs. control for secondary prevention. Patients were stratified according to the length of time from
their initial event (<6 weeks, 6-12 weeks,
>12 weeks). The study included 15,778
participants from 12 studies.
Aspirin reduced the 6-week risk of
recurrent ischemic stroke by about 60%
and of disabling or fatal ischemic stroke
by about 70%, with greatest benefit noted
in patients presenting with TIA or minor
stroke. Some further reduction in risk
of ischemic stroke accrued for aspirin
vs. control from 6 to 12 weeks; after 12
weeks there was no benefit.
40,531
PATIENTS
were assessed
for aspirin
efficacy in major
acute stroke
The authors also pooled data for 40,531
participants from three trials of aspirin
vs. control in major acute stroke. The
reduction in risk of recurrent ischemic
stroke at 14 days was most evident in
patients with less severe baseline deficits,
and was substantial (60% reduction) by
the second day after starting treatment.
The authors concluded that the considerable early benefit from aspirin warrants public education about self-administration after possible TIA.
SOURCE: Rothwell PM, Algra A, Chen Z, et al. Effects
of aspirin on risk and severity of early recurrent
stroke after transient ischaemic attack and ischaemic stroke: Time-course analysis of randomised
trials. Lancet. 2016. Published online May 18,
2016. http://bit.ly/timecourseaspirin.
Is oral anticoagulation use safe
in patients with history of ICH?
A Taiwanese study examined risks and
benefits of antithrombotic therapy in
AF patients with previous intracerebral
hemorrhage (ICH ) treated with warfarin or antiplatelet drugs vs. no antithrombotic therapies.
This study used the National Health
Insurance Research Database in Taiwan.
Among 307,640 patients who have AF
12,917
were divided
into three
groups
ICH PATIENTS
with a CHA2DS2-VASc score ≥2, 12,917
patients with a history of ICH were identified and assigned to one of three groups:
no treatment, antiplatelet therapy, and
warfarin.
Among patients with previous ICH,
rates of ICH and ischemic stroke in
untreated patients were 4.2 and 5.8 per
100 person-years, respectively. Among
warfarin users, annual ICH and ischemic stroke rates were 5.9% and 3.4%,
respectively. Among users of antiplatelet
agents, the rates were 5.3% per year and
5.2% per year, respectively. The greatest benefit was seen in patients with a
CHA2DS2-VASc score ≥6.
SOURCE: Chao T, Liu C, Liao J, et al. Use of oral anticoagulants for stroke prevention in patients with
atrial fibrillation who have a history of intracranial
hemorrhage. Circulation. 2016;133:1540-1547.
Anna D. Garrett is a clinical pharmacist
and president of Dr. Anna Garrett (www.
drannagarrett.com). Her mission is to help
women in midlife maximize their mojo!
Contact her [email protected].
The name
BRINTELLIX (vortioxetine)
has changed to
Now
Available to
Order
ONLY the name and NDC numbers have changed
Tablets
5 mg
10 mg
20 mg
64764-550-30
64764-560-30
64764-580-30
BRINTELLIX NDC Numbers
Bottles of 30
New TRINTELLIX NDC Numbers Please link the NDC numbers in your system
New name. Same medication.
Bottles of 30
64764-720-30
64764-730-30
64764-750-30
Tablets are not actual size.
Indication
TRINTELLIX is indicated for the treatment of major depressive disorder (MDD) in adults.
Important Safety Information
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did
not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a trend toward reduced risk
with antidepressant use in patients aged 65 and older.
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors.
Advise families and caregivers of the need for close observation and communication with the prescriber.
TRINTELLIX has not been evaluated for use in pediatric patients.
CONTRAINDICATIONS
Patients with hypersensitivity to vortioxetine or to any components of the TRINTELLIX formulation should not take TRINTELLIX. Angioedema has been reported in patients
treated with TRINTELLIX.
Do not use an MAOI with TRINTELLIX or within 21 days of stopping TRINTELLIX. Do not use TRINTELLIX within 14 days of stopping an MAOI. Do not start TRINTELLIX in a
patient being treated with linezolid or intravenous methylene blue.
Clinical Worsening and Suicide Risk: All patients being treated with antidepressants for any indication should be monitored appropriately and observed
closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times
of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, or discontinuing the medication. Families and
caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the
need to monitor patients daily.
Serotonin syndrome, potentially life-threatening, has been reported with serotonergic antidepressants (SNRIs, SSRIs, and others), including TRINTELLIX, both when
used alone but especially when coadministered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan,
buspirone, and St. John’s Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and others,
such as linezolid and intravenous methylene blue). If such symptoms occur, discontinue TRINTELLIX and any concomitant serotonergic agents, and initiate supportive
treatment. If concomitant use of TRINTELLIX with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for
serotonin syndrome, particularly during treatment initiation and dose increases.
Treatment with serotonergic antidepressants (SSRIs, SNRIs, and others) may increase the risk of abnormal bleeding. Patients should be cautioned about the increased
risk of bleeding when TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that affect coagulation.
Activation of mania/hypomania can occur. Screen patients for bipolar disorder prior to initiating antidepressant treatment. Use cautiously in patients with a history or
family history of bipolar disorder, mania, or hypomania.
Angle-closure glaucoma has occurred with antidepressant treatment in patients with anatomically narrow angles who did not have patent iridectomy.
Hyponatremia, which may be severe, can occur in association with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and patients
taking diuretics or who are otherwise volume-depleted can be at greater risk. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and initiate
appropriate medical intervention.
Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo in 6- to 8-week studies) were nausea, constipation, and vomiting.
Coadministration with strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX.
Please see Brief Summary of full Prescribing Information on the following pages.
BRINTELLIX is a trademark of H. Lundbeck A/S registered with the U.S. Patent and Trademark Office,
TRINTELLIX is a trademark of H. Lundbeck A/S, trademarks are used under license by Takeda Pharmaceuticals America, Inc.
©2016 Takeda Pharmaceuticals U.S.A., Inc. USD/VOR/16/0041 06/2016
BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION
TRINTELLIX (vortioxetine) tablets, for oral use
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in
children, adolescents, and young adults in short-term studies. These
studies did not show an increase in the risk of suicidal thoughts and
behavior with antidepressant use in patients over age 24; there was a
trend toward reduced risk with antidepressant use in patients aged 65
and older [see Warnings and Precautions].
In patients of all ages who are started on antidepressant therapy,
monitor closely for worsening, and for emergence of suicidal thoughts
and behaviors. Advise families and caregivers of the need for close
observation and communication with the prescriber [see Warnings
and Precautions].
TRINTELLIX has not been evaluated for use in pediatric patients
[see Use in Specific Populations].
Major Depressive Disorder
TRINTELLIX is indicated for the treatment of major depressive disorder
(MDD). The efficacy of TRINTELLIX was established in six 6 to 8 week studies
(including one study in the elderly) and one maintenance study in adults.
CONTRAINDICATIONS
@ >5*78*38.9.;.9>94;479.4=*9.3*47&3>(42543*3984+9-*+472:1&9.43
Angioedema has been reported in patients treated with TRINTELLIX.
@ !-*:8*4+8.39*3)*)9497*&958>(-.&97.().847)*78<.9-!!#
or within 21 days of stopping treatment with TRINTELLIX is contraindicated
because of an increased risk of serotonin syndrome. The use of TRINTELLIX
within 14 days of stopping an MAOI intended to treat psychiatric disorders
is also contraindicated [see Warnings and Precautions].
Starting TRINTELLIX in a patient who is being treated with MAOIs such as
linezolid or intravenous methylene blue is also contraindicated because of
an increased risk of serotonin syndrome [see Warnings and Precautions].
Clinical Worsening and Suicide Risk
Patients with major depressive disorder (MDD), both adult and pediatric, may
experience worsening of their depression and/or the emergence of suicidal
ideation and behavior (suicidality) or unusual changes in behavior, whether
or not they are taking antidepressant medications, and this risk may persist
until significant remission occurs. Suicide is a known risk of depression and
certain other psychiatric disorders, and these disorders themselves are the
strongest predictors of suicide. There has been a long-standing concern,
however, that antidepressants may have a role in inducing worsening of
depression and the emergence of suicidality in certain patients during the early
phases of treatment. Pooled analyses of short-term placebo-controlled studies
of antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs] and
others) showed that these drugs increase the risk of suicidal thinking and
behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24)
with MDD and other psychiatric disorders. Short-term studies did not show
an increase in the risk of suicidality with antidepressants compared to
placebo in adults beyond age 24; there was a trend toward reduction with
antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled studies in children and adolescents
with MDD, obsessive-compulsive disorder (OCD), or other psychiatric
disorders included a total of 24 short-term studies of nine antidepressant
drugs in over 4,400 patients. The pooled analyses of placebo-controlled
studies in adults with MDD or other psychiatric disorders included a total of
295 short-term studies (median duration of two months) of 11 antidepressant
drugs in over 77,000 patients. There was considerable variation in risk of
suicidality among drugs, but a tendency toward an increase in the younger
patients for almost all drugs studied. There were differences in absolute risk
of suicidality across the different indications, with the highest incidence in
MDD. The risk differences (drug vs. placebo), however, were relatively stable
within age strata and across indications. These risk differences (drug-placebo
difference in the number of cases of suicidality per 1000 patients treated)
are provided in Table 1.
Table 1. Drug-Placebo Difference in Number of Cases of Suicidality per
1000 Patients Treated
Age Range
Increases Compared to Placebo
<18
14 additional cases
18-24
5 additional cases
Decreases Compared to Placebo
25-64
1 fewer case
≥65
6 fewer cases
No suicides occurred in any of the pediatric studies. There were suicides in
the adult studies, but the number was not sufficient to reach any conclusion
about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e.,
beyond several months. However, there is substantial evidence from placebocontrolled maintenance studies in adults with depression that the use of
antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should
be monitored appropriately and observed closely for clinical worsening,
suicidality, and unusual changes in behavior, especially during the initial
few months of a course of drug therapy, or at times of dose changes, either
increases or decreases.
The following symptoms anxiety, agitation, panic attacks, insomnia, irritability,
hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness),
hypomania, and mania have been reported in adult and pediatric patients
being treated with antidepressants for MDD as well as for other indications,
both psychiatric and nonpsychiatric. Although a causal link between the
emergence of such symptoms and either the worsening of depression and/or
the emergence of suicidal impulses has not been established, there is concern
that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including
possibly discontinuing the medication, in patients whose depression is
persistently worse, or who are experiencing emergent suicidality or symptoms
that might be precursors to worsening depression or suicidality, especially if
these symptoms are severe, abrupt in onset, or were not part of the patient’s
presenting symptoms.
Families and caregivers of patients being treated with antidepressants for
MDD or other indications, both psychiatric and nonpsychiatric, should be
alerted about the need to monitor patients for the emergence of agitation,
irritability, unusual changes in behavior, and the other symptoms
described above, as well as the emergence of suicidality, and to report
such symptoms immediately to healthcare providers. Such monitoring
should include daily observation by families and caregivers.
Screening Patients for Bipolar Disorder
A major depressive episode may be the initial presentation of bipolar disorder.
It is generally believed (though not established in controlled studies) that
treating such an episode with an antidepressant alone may increase the
likelihood of precipitation of a mixed/manic episode in patients at risk for
bipolar disorder. Whether any of the symptoms described above represent
such a conversion is unknown. However, prior to initiating treatment with
an antidepressant, patients with depressive symptoms should be adequately
screened to determine if they are at risk for bipolar disorder; such screening
should include a detailed psychiatric history, including a family history of
suicide, bipolar disorder, and depression. It should be noted that TRINTELLIX
is not approved for use in treating bipolar depression.
Serotonin Syndrome
The development of a potentially life-threatening serotonin syndrome has
been reported with serotonergic antidepressants including TRINTELLIX, when
used alone but more often when used concomitantly with other serotonergic
drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,
tryptophan, buspirone, and St. John’s Wort), and with drugs that impair
metabolism of serotonin (in particular, MAOIs, both those intended to treat
psychiatric disorders and also others, such as linezolid and intravenous
methylene blue).
Serotonin syndrome symptoms may include mental status changes
(e.g., agitation, hallucinations, delirium, and coma), autonomic instability
(e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing,
hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus,
hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms
(e.g., nausea, vomiting, diarrhea). Patients should be monitored for the
emergence of serotonin syndrome.
The concomitant use of TRINTELLIX with MAOIs intended to treat psychiatric
disorders is contraindicated. TRINTELLIX should also not be started in a
patient who is being treated with MAOIs such as linezolid or intravenous
methylene blue. All reports with methylene blue that provided information
on the route of administration involved intravenous administration in the
dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of
methylene blue by other routes (such as oral tablets or local tissue injection)
or at lower doses. There may be circumstances when it is necessary to initiate
treatment with a MAOI such as linezolid or intravenous methylene blue in
a patient taking TRINTELLIX. TRINTELLIX should be discontinued before
initiating treatment with the MAOI [see Contraindications].
If concomitant use of TRINTELLIX with other serotonergic drugs, including
triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone,
tryptophan, and St. John’s Wort is clinically warranted, patients should be
made aware of a potential increased risk for serotonin syndrome, particularly
during treatment initiation and dose increases.
Treatment with TRINTELLIX and any concomitant serotonergic agents
should be discontinued immediately if the above events occur and supportive
symptomatic treatment should be initiated.
Abnormal Bleeding
The use of drugs that interfere with serotonin reuptake inhibition, including
TRINTELLIX, may increase the risk of bleeding events. Concomitant use of
aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other
anticoagulants may add to this risk. Case reports and epidemiological studies
(case-control and cohort design) have demonstrated an association between
use of drugs that interfere with serotonin reuptake and the occurrence of
gastrointestinal bleeding. Bleeding events related to drugs that inhibit
serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis,
and petechiae to life-threatening hemorrhages.
Patients should be cautioned about the increased risk of bleeding when
TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that
affect coagulation or bleeding [see Drug Interactions].
Activation of Mania/Hypomania
Symptoms of mania/hypomania were reported in <0.1% of patients treated
with TRINTELLIX in pre-marketing clinical studies. Activation of mania/
hypomania has been reported in a small proportion of patients with major
affective disorder who were treated with other antidepressants. As with all
antidepressants, use TRINTELLIX cautiously in patients with a history or
family history of bipolar disorder, mania, or hypomania.
Angle Closure Glaucoma
Angle Closure Glaucoma: The pupillary dilation that occurs following use
of many antidepressant drugs, including TRINTELLIX, may trigger an angle
closure attack in a patient with anatomically narrow angles who does not
have a patent iridectomy.
Hyponatremia
Hyponatremia has occurred as a result of treatment with serotonergic drugs.
In many cases, hyponatremia appears to be the result of the syndrome
of inappropriate antidiuretic hormone secretion (SIADH). One case with
serum sodium lower than 110 mmol/L was reported in a subject treated
with TRINTELLIX in a pre-marketing clinical study. Elderly patients may be at
greater risk of developing hyponatremia with a serotonergic antidepressant.
Also, patients taking diuretics or who are otherwise volume-depleted can be
at greater risk. Discontinuation of TRINTELLIX in patients with symptomatic
hyponatremia and appropriate medical intervention should be instituted. Signs
and symptoms of hyponatremia include headache, difficulty concentrating,
memory impairment, confusion, weakness, and unsteadiness, which can lead
to falls. More severe and/or acute cases have included hallucination, syncope,
seizure, coma, respiratory arrest, and death.
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other
sections of the label.
G E<1>?1:?5@5B5@E[see Contraindications]
G 85:5/-8+;>?1:5:3-:0(A5/501'5?7[see Warnings and Precautions]
G (1>;@;:5:(E:0>;91[see Warnings and Precautions]
G .:;>9-881105:3[see Warnings and Precautions]
G /@5B-@5;:;2#-:5-E<;9-:5-[see Warnings and Precautions]
G E<;:-@>195-[see Warnings and Precautions]
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials of a drug cannot be directly
compared to rates in the clinical studies of another drug and may not reflect
the rates observed in clinical practice.
Patient Exposure
TRINTELLIX was evaluated for safety in 4746 patients (18 years to 88 years of
age) diagnosed with MDD who participated in pre-marketing clinical studies;
2616 of those patients were exposed to TRINTELLIX in 6 to 8 week, placebocontrolled studies at doses ranging from 5 mg to 20 mg once daily and
204 patients were exposed to TRINTELLIX in a 24 week to 64 week placebocontrolled maintenance study at doses of 5 mg to 10 mg once daily. Patients
from the 6 to 8 week studies continued into 12-month open-label studies. A
total of 2586 patients were exposed to at least one dose of TRINTELLIX in
open-label studies, 1727 were exposed to TRINTELLIX for six months and
885 were exposed for at least one year.
Adverse Reactions Reported as Reasons for Discontinuation of Treatment
In pooled 6 to 8 week placebo-controlled studies the incidence of patients who
received TRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day and 20 mg/day and
discontinued treatment because of an adverse reaction was 5%, 6%, 8% and
8%, respectively, compared to 4% of placebo-treated patients. Nausea was
the most common adverse reaction reported as a reason for discontinuation.
Common Adverse Reactions in Placebo-Controlled MDD Studies
The most commonly observed adverse reactions in MDD patients treated with
TRINTELLIX in 6 to 8 week placebo-controlled studies (incidence ≥5% and
at least twice the rate of placebo) were nausea, constipation and vomiting.
Table 2 shows the incidence of common adverse reactions that occurred in
≥2% of MDD patients treated with any TRINTELLIX dose and at least 2%
more frequently than in placebo-treated patients in the 6 to 8 week placebocontrolled studies.
Table 2. Common Adverse Reactions Occurring in ≥2% of Patients
Treated with any TRINTELLIX Dose and at Least 2% Greater
than the Incidence in Placebo-treated Patients
System Organ
Class Preferred
Term
TRINTELLIX TRINTELLIX TRINTELLIX TRINTELLIX
Placebo
5 mg/day 10 mg/day 15 mg/day 20 mg/day
N=1013
%
N=699
%
N=449
%
N=455
%
N=1621
%
21
26
32
32
9
Gastrointestinal
disorders
Nausea
Diarrhea
7
7
10
7
6
Dry mouth
7
7
6
8
6
Constipation
3
5
6
6
3
Vomiting
3
5
6
6
1
Flatulence
1
3
2
1
1
6
6
8
9
6
<1
<1
2
3
1
1
2
3
3
1
Nervous system
disorders
Dizziness
Psychiatric
disorders
Abnormal
dreams
Skin and
subcutaneous
tissue disorders
Pruritus*
*
includes pruritus generalized
Nausea
Nausea was the most common adverse reaction and its frequency was
dose-related (Table 2). It was usually considered mild or moderate in
intensity and the median duration was 2 weeks. Nausea was more common
in females than males. Nausea most commonly occurred in the first week of
TRINTELLIX treatment with 15 to 20% of patients experiencing nausea after
1 to 2 days of treatment. Approximately 10% of patients taking TRINTELLIX
10 mg/day to 20 mg/day had nausea at the end of the 6 to 8 week placebocontrolled studies.
Sexual Dysfunction
Difficulties in sexual desire, sexual performance and sexual satisfaction
often occur as manifestations of psychiatric disorders, but they may also be
consequences of pharmacologic treatment.
In the MDD 6 to 8 week controlled trials of TRINTELLIX, voluntarily reported
adverse reactions related to sexual dysfunction were captured as individual
event terms. These event terms have been aggregated and the overall
incidence was as follows. In male patients the overall incidence was 3%,
4%, 4%, 5% in TRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day,
respectively, compared to 2% in placebo. In female patients, the overall
incidence was <1%, 1%, <1%, 2% in TRINTELLIX 5 mg/day, 10 mg/day,
15 mg/day, 20 mg/day, respectively, compared to <1% in placebo.
Because voluntarily reported adverse sexual reactions are known to be
underreported, in part because patients and physicians may be reluctant
to discuss them, the Arizona Sexual Experiences Scale (ASEX), a validated
measure designed to identify sexual side effects, was used prospectively in
seven placebo-controlled trials. The ASEX scale includes five questions that
pertain to the following aspects of sexual function: 1) sex drive, 2) ease of
arousal, 3) ability to achieve erection (men) or lubrication (women), 4) ease
of reaching orgasm, and 5) orgasm satisfaction.
The presence or absence of sexual dysfunction among patients entering
clinical studies was based on their ASEX scores. For patients without sexual
dysfunction at baseline (approximately 1/3 of the population across all
treatment groups in each study), Table 3 shows the incidence of patients
that developed treatment-emergent sexual dysfunction when treated with
TRINTELLIX or placebo in any fixed dose group. Physicians should routinely
inquire about possible sexual side effects.
Table 3. ASEX Incidence of Treatment Emergent Sexual Dysfunction*
TRINTELLIX TRINTELLIX TRINTELLIX TRINTELLIX
Placebo
5 mg/day
10 mg/day 15 mg/day 20 mg/day
N=135:162†
N=65:67†
N=94:86†
N=57:67†
N=67:59†
Females
22%
23%
33%
34%
20%
Males
16%
20%
19%
29%
14%
*Incidence based on number of subjects with sexual dysfunction during the study /
number of subjects without sexual dysfunction at baseline. Sexual dysfunction
was defined as a subject scoring any of the following on the ASEX scale at two
consecutive visits during the study: 1) total score ≥19; 2) any single item ≥5;
3) three or more items each with a score ≥4
†
Sample size for each dose group is the number of patients (females:males) without
sexual dysfunction at baseline
Adverse Reactions Following Abrupt Discontinuation of TRINTELLIX Treatment
Discontinuation symptoms have been prospectively evaluated in patients
taking TRINTELLIX 10 mg/day, 15 mg/day, and 20 mg/day using the
Discontinuation-Emergent Signs and Symptoms (DESS) scale in clinical trials.
Some patients experienced discontinuation symptoms such as headache,
muscle tension, mood swings, sudden outbursts of anger, dizziness, and runny
nose in the first week of abrupt discontinuation of TRINTELLIX 15 mg/day
and 20 mg/day.
Laboratory Tests
TRINTELLIX has not been associated with any clinically important changes in
laboratory test parameters in serum chemistry (except sodium), hematology
and urinalysis as measured in the 6 to 8 week placebo-controlled studies.
Hyponatremia has been reported with the treatment of TRINTELLIX
[see Warnings and Precautions]. In the 6-month, double-blind, placebocontrolled phase of a long-term study in patients who had responded to
TRINTELLIX during the initial 12-week, open-label phase, there were no
clinically important changes in lab test parameters between TRINTELLIX and
placebo-treated patients.
Weight
TRINTELLIX had no significant effect on body weight as measured by the
mean change from baseline in the 6 to 8 week placebo-controlled studies.
In the 6-month, double-blind, placebo-controlled phase of a long-term study
in patients who had responded to TRINTELLIX during the initial 12-week,
open-label phase, there was no significant effect on body weight between
TRINTELLIX and placebo-treated patients.
Vital Signs
TRINTELLIX has not been associated with any clinically significant effects on
vital signs, including systolic and diastolic blood pressure and heart rate, as
measured in placebo-controlled studies.
Other Adverse Reactions Observed in Clinical Studies
The following listing does not include reactions: 1) already listed in previous
tables or elsewhere in labeling, 2) for which a drug cause was remote,
3) which were so general as to be uninformative, 4) which were not considered
to have significant clinical implications, or 5) which occurred at a rate equal
to or less than placebo.
Ear and labyrinth disorders — vertigo
Gastrointestinal disorders — dyspepsia
Nervous system disorders — dysgeusia
Vascular disorders — flushing
DRUG INTERACTIONS
CNS Active Agents
Monoamine Oxidase Inhibitors
Adverse reactions, some of which are serious or fatal, can develop in
patients who use MAOIs or who have recently been discontinued from an
MAOI and started on a serotonergic antidepressant(s) or who have recently
had SSRI or SNRI therapy discontinued prior to initiation of an MAOI
[see Contraindications and Warnings and Precautions].
Serotonergic Drugs
Based on the mechanism of action of TRINTELLIX and the potential for
serotonin toxicity, serotonin syndrome may occur when TRINTELLIX
is coadministered with other drugs that may affect the serotonergic
neurotransmitter systems (e.g., SSRIs, SNRIs, triptans, buspirone, tramadol,
and tryptophan products etc.). Closely monitor symptoms of serotonin
syndrome if TRINTELLIX is co-administered with other serotonergic drugs.
Treatment with TRINTELLIX and any concomitant serotonergic agents should
be discontinued immediately if serotonin syndrome occurs [see Warnings
and Precautions].
Other CNS Active Agents
No clinically relevant effect was observed on steady state lithium exposure
following coadministration with multiple daily doses of TRINTELLIX.
Multiple doses of TRINTELLIX did not affect the pharmacokinetics or
pharmacodynamics (composite cognitive score) of diazepam. A clinical study
has shown that TRINTELLIX (single dose of 20 or 40 mg) did not increase
the impairment of mental and motor skills caused by alcohol (single dose
of 0.6 g/kg). Details on the potential pharmacokinetic interactions between
TRINTELLIX and bupropion can be found in the section titled: Potential for
Other Drugs to Affect TRINTELLIX.
Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin)
Serotonin release by platelets plays an important role in hemostasis.
Epidemiological studies of case-control and cohort design have demonstrated
an association between use of psychotropic drugs that interfere with
serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
These studies have also shown that concurrent use of an NSAID or aspirin
may potentiate this risk of bleeding. Altered anticoagulant effects, including
increased bleeding, have been reported when SSRIs and SNRIs are
coadministered with warfarin.
Following coadministration of stable doses of warfarin (1 to 10 mg/day)
with multiple daily doses of TRINTELLIX, no significant effects were
observed in INR, prothrombin values or total warfarin (protein bound
plus free drug) pharmacokinetics for both R- and S-warfarin [see Drug
Interactions]. Coadministration of aspirin 150 mg/day with multiple
daily doses of TRINTELLIX had no significant inhibitory effect on platelet
aggregation or pharmacokinetics of aspirin and salicylic acid [see Drug
Interactions]. Patients receiving other drugs that interfere with hemostasis
should be carefully monitored when TRINTELLIX is initiated or discontinued
[see Warnings and Precautions].
Potential for Other Drugs to Affect TRINTELLIX
Reduce TRINTELLIX dose by half when a strong CYP2D6 inhibitor (e.g.,
bupropion, fluoxetine, paroxetine, quinidine) is coadministered. Consider
increasing the TRINTELLIX dose when a strong CYP inducer (e.g., rifampicin,
carbamazepine, phenytoin) is coadministered. The maximum dose is not
recommended to exceed three times the original dose (Figure 1).
Figure 1. Impact of Other Drugs on Vortioxetine PK
Potential for TRINTELLIX to Affect Other Drugs
No dose adjustment for the comedications is needed when TRINTELLIX
is coadministered with a substrate of CYP1A2 (e.g., duloxetine), CYP2A6,
CYP2B6 (e.g., bupropion), CYP2C8 (e.g., repaglinide), CYP2C9 (e.g.,
S-warfarin), CYP2C19 (e.g., diazepam), CYP2D6 (e.g., venlafaxine), CYP3A4/5
(e.g., budesonide), and P-gp (e.g., digoxin). In addition, no dose adjustment
for lithium, aspirin, and warfarin is necessary.
Vortioxetine and its metabolites are unlikely to inhibit the following CYP
enzymes and transporter based on in vitro data: CYP1A2, CYP2A6, CYP2B6,
CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, and P-gp. As
such, no clinically relevant interactions with drugs metabolized by these CYP
enzymes would be expected.
In addition, vortioxetine did not induce CYP1A2, CYP2A6, CYP2B6, CYP2C8,
CYP2C9, CYP2C19, and CYP3A4/5 in an in vitro study in cultured human
hepatocytes. Chronic administration of TRINTELLIX is unlikely to induce the
metabolism of drugs metabolized by these CYP isoforms. Furthermore, in a
series of clinical drug interaction studies, coadministration of TRINTELLIX
with substrates for CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin),
and CYP2C19 (e.g., diazepam), had no clinical meaningful effect on the
pharmacokinetics of these substrates (Figure 2).
Because vortioxetine is highly bound to plasma protein, coadministration
of TRINTELLIX with another drug that is highly protein bound may increase
free concentrations of the other drug. However, in a clinical study with
coadministration of TRINTELLIX (10 mg/day) and warfarin (1 mg/day to
10 mg/day), a highly protein-bound drug, no significant change in INR was
observed [see Drug Interactions].
Figure 2. Impact of Vortioxetine on PK of Other Drugs
Pregnancy
Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies of TRINTELLIX in pregnant
women. Vortioxetine caused developmental delays when administered
during pregnancy to rats and rabbits at doses 15 and 10 times the maximum
recommended human dose (MRHD) of 20 mg, respectively. Developmental
delays were also seen after birth in rats at doses 20 times the MRHD of
vortioxetine given during pregnancy and through lactation. There were
no teratogenic effects in rats or rabbits at doses up to 77 and 58 times,
the MRHD of vortioxetine, respectively, given during organogenesis. The
incidence of malformations in human pregnancies has not been established
for TRINTELLIX. All human pregnancies, regardless of drug exposure, have
a background rate of 2 to 4% for major malformations, and 15 to 20% for
pregnancy loss. TRINTELLIX should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Clinical Considerations
Neonates exposed to SSRIs or SNRIs, late in the third trimester have developed
complications requiring prolonged hospitalization, respiratory support and
tube feeding. Such complications can arise immediately upon delivery.
Reported clinical findings have included respiratory distress, cyanosis, apnea,
seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia,
hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability and
constant crying. These features are consistent with either a direct toxic
effect of these classes of drugs or possibly, a drug discontinuation syndrome.
It should be noted that in some cases, the clinical picture is consistent
with serotonin syndrome [see Warnings and Precautions]. When treating a
pregnant woman with TRINTELLIX during the third trimester, the physician
should carefully consider the potential risks and benefits of treatment.
Neonates exposed to SSRIs in pregnancy may have an increased risk for
persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in
one to two per 1,000 live births in the general population and is associated
with substantial neonatal morbidity and mortality. Several recent epidemiologic
studies suggest a positive statistical association between SSRI use in pregnancy
and PPHN. Other studies do not show a significant statistical association.
A prospective longitudinal study was conducted of 201 pregnant women
with a history of major depression, who were either on antidepressants or
had received antidepressants less than 12 weeks prior to their last menstrual
period, and were in remission. Women who discontinued antidepressant
medication during pregnancy showed a significant increase in relapse of their
major depression compared to those women who remained on antidepressant
medication throughout pregnancy. When treating a pregnant woman with
TRINTELLIX, the physician should carefully consider both the potential risks
of taking a serotonergic antidepressant, along with the established benefits
of treating depression with an antidepressant.
Animal Data
In pregnant rats and rabbits, no teratogenic effects were seen when
vortioxetine was given during the period of organogenesis at oral doses up to
160 and 60 mg/kg/day, respectively. These doses are 77 and 58 times, in rats
and rabbits, respectively, the maximum recommended human dose (MRHD)
of 20 mg on a mg/m2 basis. Developmental delay, seen as decreased fetal body
weight and delayed ossification, occurred in rats and rabbits at doses equal to
and greater than 30 and 10 mg/kg (15 and 10 times the MRHD, respectively) in
the presence of maternal toxicity (decreased food consumption and decreased
body weight gain). When vortioxetine was administered to pregnant rats at
oral doses up to 120 mg/kg (58 times the MRHD) throughout pregnancy and
lactation, the number of live-born pups was decreased and early postnatal pup
mortality was increased at 40 and 120 mg/kg. Additionally, pup weights were
decreased at birth to weaning at 120 mg/kg and development (specifically
eye opening) was slightly delayed at 40 and 120 mg/kg. These effects were
not seen at 10 mg/kg (5 times the MRHD).
Nursing Mothers
It is not known whether vortioxetine is present in human milk. Vortioxetine is
present in the milk of lactating rats. Because many drugs are present in human
milk and because of the potential for serious adverse reactions in nursing
infants from TRINTELLIX, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the importance of the
drug to the mother.
Pediatric Use
Clinical studies on the use of TRINTELLIX in pediatric patients have not been
conducted; therefore, the safety and effectiveness of TRINTELLIX in the
pediatric population have not been established.
Geriatric Use
No dose adjustment is recommended on the basis of age (Figure 3). Results
from a single-dose pharmacokinetic study in elderly (>65 years old) vs. young
(24 to 45 years old) subjects demonstrated that the pharmacokinetics were
generally similar between the two age groups.
Of the 2616 subjects in clinical studies of TRINTELLIX, 11% (286) were 65 and
over, which included subjects from a placebo-controlled study specifically
in elderly patients. No overall differences in safety or effectiveness were
observed between these subjects and younger subjects, and other reported
clinical experience has not identified differences in responses between the
elderly and younger patients.
Serotonergic antidepressants have been associated with cases of clinically
significant hyponatremia in elderly patients, who may be at greater risk for
this adverse event [see Warnings and Precautions].
Use in Other Patient Populations
No dose adjustment of TRINTELLIX on the basis of race, gender, ethnicity,
or renal function (from mild renal impairment to end-stage renal disease) is
necessary. In addition, the same dose can be administered in patients with
mild to moderate hepatic impairment (Figure 3). TRINTELLIX has not been
studied in patients with severe hepatic impairment. Therefore, TRINTELLIX
is not recommended in patients with severe hepatic impairment.
Figure 3. Impact of Intrinsic Factors on Vortioxetine PK
DRUG ABUSE AND DEPENDENCE
TRINTELLIX is not a controlled substance.
OVERDOSAGE
Human Experience
There is limited clinical trial experience regarding human overdosage with
TRINTELLIX. In pre-marketing clinical studies, cases of overdose were limited
to patients who accidentally or intentionally consumed up to a maximum dose
of 40 mg of TRINTELLIX. The maximum single dose tested was 75 mg in men.
Ingestion of TRINTELLIX in the dose range of 40 to 75 mg was associated
with increased rates of nausea, dizziness, diarrhea, abdominal discomfort,
generalized pruritus, somnolence, and flushing.
Management of Overdose
No specific antidotes for TRINTELLIX are known. In managing over dosage,
consider the possibility of multiple drug involvement. In case of overdose,
call Poison Control Center at 1-800-222-1222 for latest recommendations.
Distributed and Marketed by:
Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015
Marketed by:
Lundbeck
Deerfield, IL 60015
TRINTELLIX is a trademark of H. Lundbeck A/S and used under license by
Takeda Pharmaceuticals America, Inc.
All other trademarks are the property of their respective owners.
©2013-2016 Takeda Pharmaceuticals America, Inc.
LUN205 R7_Brf. May 2016
L-LUN-0316-8
PRODUCT UPDATES
EYES AND EARS
1
2
3
PRODUCT IMAGES COURTESY OF BURT’S BEES / PRESTIGE BRANDS HOLDINGS INC. / ABBOTT LABORATORIES
OTC
Revive tired, dry eyes; safely
clear ears of wax buildup
Some patients need help to improve the
appearance of puffiness and dark circles
in the eye area. Others may be looking
for relief from worrisome fine lines and
crow’s feet. And some may be experiencing burning, itchy, reddened eyes.
Do you have what they need? Here are
some options.
For tired eyes
Burt’s Bees Sensitive Eye Cream 1 , a
lightweight,fragrance-free,hypoallergenic
cream used under the eye, is formulated
with cotton, eyebright, and olive fruit oil
to help sustain moisture and reduce the
appearance of puffiness, hydrating and
smoothing the delicate skin around the
eye. (burtsbees.com)
REN Vita Mineral Active 7 Eye Gel
is a light cooling gel that can reduce puffy
eyes and dark circles. The gel contains
arnica flavonoids, rose anthocyanins,
and vitamin P to help alleviate redness;
its Rumex extract (from a plant related to
Canadian field dock) reduces the produc-
tion of melanin and hemoglobin, causes
of hyperpigmentation; pectins and hyaluronic bioextracts help to hydrate the
skin. Store the gel in the refrigerator for a
greater cooling effect. (feelunique.com).
JustNaturalAnti-AgingEyeSerum
provides nutrients to nourish and protect
delicate skin that is prone to fine lines.
Camellia seed, argan oils, and antioxidants contained in the serum are useful
in slowing the aging process, the manufacturer says. This product contains no
mineral oil, petrolatum, silicone, artificial fragrance, or artificial color. (justnaturalskincare.com)
For dry eyes and more
In April, Prestige Brands Holdings Inc.
introduced a new line of preservativefree drops in a multidose bottle: Clear
Eyes Pure Relief for Dry Eyes 2 and
Clear Eyes Pure Relief Multi-Symptom.
The bottle has a built-in purifying filter at its tip that blocks bacteria and
allows only a one-way flow of fluid
during dispensing. The multisymptom artificial tears are formulated to
treat eyes that are dry, red, itchy, and
irritated. (cleareyes.com)
Blink Tears Lubricating Eye Drops
by Abbott Laboratories can help relieve
mild-to-moderate dry eye by replenishing the tear film and improving tear film
stability. Patients who cannot tolerate any
preservative can try Blink Tears Preservative Free Lubricating Eye Drops 3
, available in sterile, single-use vials. For
more severe dry eye, patients can turn to
Blink Gel Tears Lubricating Eye Drops,
which has a more viscous formula for
moderate-to-severe dry eye sufferers.
(abbottmedicaloptics.com/products)
Another eye gel, Refresh Optive Gel
DropsExtendedTherapy, is a new addition to the Refresh brand. Indicated for
burning, irritation, and discomfort due to
dryness of the eye or exposure to wind or
sun, the extended therapy gel drops are
said to significantly reduce dry-eye sympC O N T I N U E D O N P A G E 68 >
51
VANCOMYCIN
Time-Saving Convenience
pre-weighed, pre-measured ingredients
Streamlined Process
single NDC # eases reimbursement
NEW ED
IMPROEVLS
LAB
Great Flavor
XIJUFHSBQFƌBWPSFEPSBMTPMVUJPO
IT’S ALL IN
THE KIT!
KITS contain everything you need to compound
individual prescriptions quickly and easily.
Additional concentration and sizes available through all major wholesalers.
To learn more about how FIRST® KITS are transforming compounding, call
1-800-461-7449
or visit: www.CutisPharma.com
MKT-11 042716
CLINICAL
MEDICATION SAFETY
New kidney warning on popular diabetes drugs
Soon after FDA warned about a potential increased risk of foot and leg amputations with the use of the type 2 diabetes medication canagliflozin (Invokana
and Invokamet; Janssen Biotech), the
agency strengthened the existing warning about the risk of acute kidney injury
with Invokana and Invokamet, as well
as with dapagliflozin (Farxiga and Xigduo XR, AstraZeneca).
“Based on recent reports, we have
revised the warnings in the drug labels
to include information about acute kidney injury and added recommendations to minimize this risk,” FDA said
in a statement.
Acute kidney injury
FDA strengthened the kidney warning
after finding that, from March 2013, when
canagliflozin was approved, to October 2015, the agency received reports of
101 confirmable cases of acute kidney
injury, some requiring hospitalization
and dialysis, following canagliflozin or
dapagliflozin use. “This number includes
only reports submitted to FDA, so there
are likely additional cases about which
we are unaware,” FDA said.
Foot and leg amputations
In late May, FDA warned that interim
safety results from an ongoing clinical trial
found an increase in foot and leg amputations with the Invokana and Invokamet.
“We have not determined whether
canagliflozin increases the risk of leg and
foot amputations,” FDA said in a Drug
Safety Communication. “We are currently investigating this new safety issue
and will update the public when we have
more information.”
With the strengthened kidney warning, healthcare professionals should con-
sider factors that may predispose patients to
acute kidney injury prior to starting them
oncanagliflozinordapagliflozin,FDAsaid.
“These include decreased blood volume;
chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure
medications called angiotensin-converting
enzyme (ACE) inhibitors and angiotensin
receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs).”
“Assess kidney function prior to starting
canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue
the drug and treat the kidney impairment,” FDA added.
Patients should seek medical attention
immediately if they experience signs
and symptoms of acute kidney injury,
FDA said.
Diabetes drug may be linked to heart failure, FDA warns
Type 2 diabetes drugs containing saxagliptin and alogliptin may increase the risk
of heart failure, particularly in patients
who already have heart or kidney disease, according to an FDA Drug Safety
Communication.
FDA is adding new warnings to labels
of the drugs in question, including: Onglyza and Kombiglyze XR (AstraZeneca),
and Nesina, Kazano, and Oseni (Takeda).
ness, weakness or fatigue; and weight
gain with swelling in the ankles, feet,
legs, or stomach.
However, patients should not stop taking medication without first talking to
their healthcare professionals. FDA is
also urging healthcare professionals and
patients to report side effects involving
saxagliptin, alogliptin, or other drugs to
the FDA MedWatch program.
Saxagliptin, alogliptin
Metformin recommendations
Patients taking saxagliptin- or alogliptin-containing drugs should contact their healthcare professionals right
away if they develop signs and symptoms of heart failure, according to FDA,
Symptoms include unusual shortness
of breath during daily activities; trouble breathing when lying down; tired-
FDA also is requiring labeling changes
for metformin-containing medications.
“FDA concluded, from the review of
studies published in the medical literature, that metformin can be used safely
in patients with mild impairment in kidney function and in some patients with
moderate impairment in kidney func-
52
tion,” the agency said in a statement.
However, “FDA is requiring changes to
the metformin labeling to reflect this
new information and provide specific
recommendations on the drug’s use in
patients with mild to moderate kidney
impairment.”
Testing renal function
FDA is also requiring manufacturers to
revise the labeling to recommend that
the measure of kidney function used to
determine whether a patient can receive
metformin be changed from one based
on a single laboratory parameter (blood
creatinine concentration) to one that provides a better estimate of renal function
(i.e., glomerular filtration rate estimating equation [eGFR]).
I CHOOSE A
RELIABLE
WHOLESALER
hdsmith.com | 866.232.1222
Helping You Care For Your Community
ISSUES & TRENDS
Innovations
Point-of-care testing opens
door to new patient-care model
Pharmacy is a second career for Patrick Adams, RPh, who at age 45 became a pharmacist in his home state
of Hawaii. With a view to expanding the services that his community pharmacy offered, he set out to persuade
HMSA, a major health plan in his state, to allow him to offer a point-of-care service such as the Timed Up and Go (TUG)
test to assess an older person’s mobility function.
In spite of the fact that the annual cost
of falls to the healthcare system in
Hawaii totaled $250 million, neither
HMSA nor any healthcare provider
wanted to support the service through
a collaborative practice agreement.
As director of pharmacy at Foodland Pharmacy for 12 years, Adams
also understands the benefits of offering laboratory tests for glycosylated
hemoglobin (HbA1c) and cholesterol
screenings for patients.
But how could a pharmacy be paid
directly for point-of-care tests?
Then he heard a fellow pharmacist talking about CLIA-waived tests.
These tests are waived under the Clinical Laboratory Improvement Amendments (CLIA) of 1988, allowing pharmacists to charge the patient directly or
bill through a third-party payer.
Turn your pharmacy into a lab
Adams again approached HMSA, an
independent licensee of the Blue Cross
and Blue Shield Association and one
of the largest health plans in his state,
and asked about reimbursement for
CLIA-waived tests.
HMSA agreed that these tests were
within the scope of pharmacy practice
for his state, although the health plan
did not have any contracts demonstrating that a pharmacist could provide these
assessments.
When HMSA asked about his expertise with CLIA-waived tests, Adams
explained that “this testing doesn’t
require any more expertise than if you
were to go to a lab and have a technician
swab your throat or nose,” he recounted.
“I said, ‘You pay the labs,’ and they
said, ‘Yes.’ So I said, ‘If I were a lab, you
would pay me.’ And they said, ‘Yes.’”
Adams decided to take the next step
and turn his pharmacies into labs. He
contracted with HMSA to offer — and
be paid for — CLIA-waived tests. This
contract allows him to bill as a medical provider, because his pharmacies are now operating as laboratories.
So if a patient comes in with a prescription for oseltamivir phosphate
(Tamiflu), Foodland pharmacists can
I said, ‘You pay the labs,’ and
they said, ‘Yes.’ So I said, ‘If I were
a lab, you would pay me.’ And they
said, ‘Yes.’”
PATRICK ADAMS
RPH
54
perform an assessment to determine
whether the patient really has the flu.
“I may make $5 for a nose swab,
which costs a total of $15. [The reimbursement] is lousy, but it’s important.
The assessment allows me to either dispense or not dispense Tamiflu, which
costs about $130,” Adams said.
“HMSA is very interested in the savings. In fact, their online providers
can provide online care through the
pharmacy as opposed to the urgent
care or emergency room.”
All Foodland pharmacies have an
iPad, so patients can access doctors at
the pharmacy. This patient-care model
works well in Hawaii, which has a limited number of primary care providers,
as do other rural settings throughout
the United States.
Point-of-care certificate program
In 2015, Adams set about obtaining
training for himself and the pharmacists employed in his nine pharmacies.
He found his opportunity when, during a multi-city tour, the National Association of Chain Drug Stores launched
a national certificate program to train
pharmacists to perform “point-of-care
testing” and other health assessments.
To qualify for the program, pharmacists had to be willing to participate in
a two-day program and learn how to
teach other pharmacists interested in
performing point-of-care testing, also
known as CLIA-waived tests.
ISSUES & TRENDS
First, Adams took the 20-hour continuing educationaccredited program, which included 12 hours of home
study and eight hours of live training in disease states.
Then he trained all 20 pharmacists, who practice at Foodland Pharmacy. The pharmacy now offers a select number of CLIA-waived tests, including influenza, Streptococcal infections, tuberculosis, and croup.
“Point-of-care testing is a term that pharmacies are using
for about five basic tests, but there are many more,” Adams
said. [See accompanying list.]
POINT-OF-CARE TESTS
At its website, the National Community Pharmacists
Association lists the following point-of-care tests:
` Calcium
` Helicobacter pylori
` HIV
` Liver function tests
` Renal function (e.g., BUN and serum creatinine)
` Thyroid stimulating hormone (TSH)
Pharmacogenomics testing
In addition, Foodland Pharmacy offers pharmacogenomic
testing to determine how fast an individual metabolizes
medications. The pharmacy is paid for data collection — performed by means of a cheek swab — plus a fee for the data it
supplies, at a total of $50, he said.
“Every pharmacy has patients who either undermetabolize or overmetabolize certain drugs,” said Adams.
Using a cheek swab test, he can do the testing in 15 minutes, Adams said. “First you identify the patient” by the medications the patient is taking and collect some information
about any side effects the patient has experienced while taking the medication.
“You swab the cheek and send the sample to the lab,” he
continued. “You get paid, and you supply the doctor with
some information about the results through a fax.”
The patient is directed to his physician to discuss the results.
The pharmacist does not make any medication adjustments
based on the results of the cheek swab, a difference in practice from medication therapy management. The physician
makes the decision to adjust the medication after reading the
pharmacogenomic test results, Adams said.
` Opioids
` Respiratory syncytial virus
` INR
` Serum chemistries (e.g., sodium, potassium)
` B-Type natriuretic peptide (BNP)
1
# TRUSTED FORMULA
TREATING PINWORM SINCE 1986
Great
Low Price
)#%
)
#$!"'!##
#'##
!('#
)''!##
$%##(
!!$
The EMR connection
Foodland Pharmacy will soon be connected to HMSA’s platform, known as Cozeva, which houses patients’ electronic
medical records, according to Adams.
This platform allows the pharmacist to go into the dashboard and determine possible gaps in patient care.
“Filling the gaps in care is really important to the Medicare STAR rating program and to the health plan,” Adams
said.
“I can do A1c tests, conduct medication therapy management, and then test again to see if there is any improvement,” he added.
To be paid under a healthcare capitation plan, pharmacists must be able to show outcomes.
“That is the reason that assessments are so important,”
he said.
55
)"*"&!1(
UPC 0-23513-61801-2
)"*"&!2(
UPC 0-23513-61821-0
PRODUCT UPDATES
NEW PRODUCTS
Julianne Stein, Managing Editor
RX CARE: New drugs
UCB has announced that its new
epilepsy treatment brivaracetam 1
(Briviact) is now available in pharmacies around the country. FDA approved
it in February as adjunctive therapy to
treat partial-onset seizures in patients
16 years of age and older. Product literature states that brivaracetam can be
taken at therapeutic doses from day
one, serving a need among epilepsy
patients. (www.briviact.com)
FDA has approved Gilead’s combination drug sofosbuvir/velpatasvir (Epclusa),
for adults with chronic hepatitis C virus
(HCV) infection, both with and without cirrhosis. Adults with cirrhosis may
receive concomitant ribavirin therapy.
This product treats all six strains of
HCV, including the hard-to-treat genotype 3, and has a 90% cure rate after a
12-week course. (www.gilead.com)
FDA has granted accelerated approval
to obeticholic acid 2 (Ocaliva; Intercept
Pharmaceuticals), indicated to treat
primary biliary cholangitis, previously
known as primary biliary cirrhosis,
in combination with ursodeoxycholic
acid(UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate
UDCA. This product will be distrib-
56
2
3
uted through a specialty pharmacy
network. (https://ocaliva.com)
Opko Health has announced FDA
approval of calcifediol (Rayaldee)
extended-release capsules, indicated
for secondary hyperparathyroidism
associated with vitamin D insufficiency in stage 3-4 chronic kidney
disease. The manufacturer says this
product offers an alternative to the
current standard of care — high-dose
vitamin D supplementation that is not
FDA-approved. U.S. launch is planned
for the second half of 2016. (www.
opkorenal.com)
The first U.S. cholera vaccine has been
approved by FDA. Vaxchora, from PaxVax
Bermuda Ltd, is formulated to prevent
cholera caused by serogroup 01, for use
in adults ages 18-64. The company states
that a single dose of the live weakened
vaccine is especially beneficial to individuals traveling to a cholera-affected
region on short notice. FDA awarded
this product fast-track designation, priority review status, and tropical disease
priority review. (paxvax.com)
New generics
Amneal has launched its AB-rated levonorgestrel/ethinyl estradiol tablets, USP 3
0.1 mg/0.02 mg (Larissia), generic for
4
Lutera 28, the reference listed drug for
Wyeth’s discontinued Alesse brand. The
combination oral contraceptive product carries a boxed warning stating that
cigarette smoking increases the risk of
serious cardiovascular side effects from
oral- contraceptive use. (amneal.com)
FDA has approved and awarded 180
days’ marketing exclusivity to Mayne
Pharma’s dofetilide 4 , the generic version of Pfizer’s Tikosyn, in capsules of
125 mcg, 250 mcg, and 500 mcg. Dofetilide is indicated to treat atrial fibrillation and atrial flutter. FDA recently
canceled the dofetilide REMS program.
This product still carries a medication
guide and a boxed warning stating that
patients initiating on dofetilide be hospitalized and monitored for a minimum
of 3 days. (www.maynepharma.com)
Greenstone has launched its own
authorized generic dofetilide in 125mcg, 250-mcg, and 500-mcg capsules.
(http://greenstonellc.com)
Mylan has announced the U.S. launch
of dutasteride capsules 0.5 mg, its generic
version of GlaxoSmithKline’s Avodart
capsules, to treat symptomatic benign
prostatic hyperplasia (BPH), reduce the
risk of acute urinary retention, and
reduce the risk of the need for BPHrelated surgery. (www.mylan.com)
PRODUCT IMAGES COURTESY OF UCB / INTERCEPT PHARMACEUTICALS / AMNEAL / MAYNE PHARMA
1
REGULATORY & LEGAL
LEGAL COMPLIANCE
Ned Milenkovich, PharmD, JD
DEA to consider rescheduling
marijuana — for the fourth time
On April 4, 2016, the Drug Enforcement Administration (DEA) wrote a letter to several U.S. Senators signaling
its plan to decide whether marijuana should be reclassified under federal law in “the first half of 2016.” The
DEA letter came in response to a 2015 letter drafted by Senator Elizabeth Warren (D-Mass.) and seven other Democratic senators asserting that the federal government should provide for research into marijuana’s medical benefits.
The DEA, in its response letter, does not
conclusively indicate whether it will reclassify marijuana out of Schedule I.
Acting DEA Administrator Chuck
Rosenberg signed the letter, as did Sylvia Burwell, the current secretary of the
DepartmentofHealthandHumanServices
(HHS), and Michael Botticelli, director of
the Office of National Drug Control Policy.
Besides Sen. Warren, seven other Democratic senators received the response letter. In 2015, these seven senators sponsored a bill that would reduce the federal
government’s ability to enforce against
state-legalized medical marijuana programs, while also encouraging more
research on marijuana.
The DEA letter describes in detail the
marijuana supply available at the University of Mississippi, which is where
the federal government houses its only
sanctioned marijuana cultivation center.
Deliberations past and present
This is not the first time that DEA has
been asked to look in to the reclassifica-
SENATORS SUPPORT MEDICAL
MARIJUANA RESEARCH
> Sen. Cory Booker (D-N.J.)
> Sen. Barbara Boxer (D-Calif.)
> Sen. Kirsten Gillibrand (D-N.Y.)
> Sen. Edward Markey (D-Mass.)
> Sen. Jeffrey Merkley (D-Ore.)
> Sen. Barbara Mikulski (D-Md.)
> Sen. Elizabeth Warren (D-Mass.)
> Sen. Ron Wyden (D-Ore.)
NEW POSSIBILITIES
The rescheduling of marijuana into a different category is likely to generate several
consequences. Among them, it would:
` Provide opportunities for research
` Pave the way for the development of cannabis-based prescription drugs
` Open the discussion for banking access
` Create new implications for taxation, depending upon the reclassification category
tion of marijuana. In 2001 and 2006, and
again in 2011, DEA considered petitions
requesting that marijuana be reclassified,
but each time DEA decided to keep marijuana a Schedule I substance.
Schedule I is reserved for drugs DEA
considers to have the highest potential for abuse and for which there is no
currently acceptable medical use. Marijuana has been classified as Schedule I
for decades, along with other drugs such
as heroin and LSD.
In its letter, DEA indicates that it has
received recommendations about reclassification of marijuana from other agencies, such as HHS. Allegedly, the agency
looked into making an in-depth review
of the medical evidence supporting marijuana’s safety and efficacy. Of interest,
DEA’s letter does not disclose the recommendation that resulted.
Once DEA makes its decision, the public may request an administrative hearing
to voice opinions about the decision. After
the hearing, the DEA would then review
its decision and make a final determination, which then could be challenged again
in court by those who disagree with it.
A bumpy ride
The possibility of a change in category for
marijuana gives rise to the prospect of some
turbulence, since many states have already
provided for the passage of disparate laws
that relegate the growing and dispensing
of marijuana to specified licensees without
regard to existing federal laws; a change
in classification means that the licensees
may be exposed to a new level of competition and federal regulation.
Although it is largely unclear whether
DEA will move away from its traditional
position maintaining the present classification of marijuana, there has been an
unprecedented movement from industry
stakeholders to bring political pressure
on DEA to reschedule marijuana. This
has included asking President Obama
to make such reclassification a priority
before he leaves office.
Ned Milenkovich is chair of the healthcare
law practice at Much Shelist PC, and vice chair
of the Illinois State Board of Pharmacy. Call him
at 312-521-2482 or [email protected].
This article is not intended as legal advice and should not be used
as such. When legal questions arise, pharmacists should consult
with attorneys familiar with the relevant drug and pharmacy laws.
57
AND
AN ONGOING CE PROGRAM
OF THE UNIVERSITY OF CONNECTICUT
SCHOOL OF PHARMACY AND DRUG TOPICS
2
CPE
CREDITS
EARN CE CREDIT
FOR THIS ACTIVITY AT
WWW.DRUGTOPICS.COM/CPE
EDUCATIONAL OBJECTIVES
GOAL: The goal of this program is to educate
pharmacists and pharmacy technicians about
current vaccine recommendations so that they
can identify adolescent and adult patients who
may need vaccinations. Readers will also gain
knowledge about where to obtain information
about current vaccine recommendations.
After participating in this activity,
pharmacists will be able to:
> Discuss the human and economic burden
of major vaccine-preventable diseases
> Identify recent changes in vaccine
recommendations and be able to locate
reputable sources for the most current
vaccine recommendations
> Outline the pharmacist’s role in identifying
patients who are least likely to be
vaccinated and identifying high-risk
adolescents and adults who require
immunizations
> Apply knowledge to determine which
vaccines a patient may need
After participating in this activity,
pharmacy technicians will be able to:
> Recall the basic principles behind
vaccinations
> Locate reputable sources for the most
current vaccine recommendations
> Discuss proper storage temperatures for
vaccinations
> Recognize when to refer patients to the
pharmacist for recommendations on
vaccinations
The University of Connecticut School
of Pharmacy is accredited by the
Accreditation Council for Pharmacy
Education as a provider of continuing
pharmacy education.
Pharmacists and pharmacy technicians are eligible
to participate in the application-based activity, and will
receive up to 0.2 CEUs (2 contact hours) for completing
the activity, passing the quiz with a grade of 70% or better,
and completing an online evaluation. Statements of credit
are available via the CPE Monitor online system and your
participation will be recorded with CPE Monitor within 72
hours of submission.
ACPE# 0009-9999-16-030-H01-P
ACPE# 0009-9999-16-030-H01-T
Grant funding: This activity is supported by an
educational grant from Sanofi Pasteur US.
Expanding
vaccination rates
through pharmacistinitiated patient
identification and
assessment
Jennifer E. Girotto, PharmD
ASSOCIATE CLINICAL PROFESSOR OF PHARMACY PRACTICE, UNIVERSITY OF CONNECTICUT; ANTIMICROBIAL STEWARDSHIP
CO-DIRECTOR, CONNECTICUT CHILDREN’S MEDICAL CENTER
Abstract
As the number of vaccines available for adolescents and adults continues to increase,
pharmacists can serve as a useful resource by providing data and administering vaccines
to patients. This module discusses the burden of vaccine-preventable diseases in adults and
adolescents, summarizes information about vaccine administration, and offers reliable
resources for further facts about vaccines. This article specifically addresses vaccines that
pharmacists can administer to patients, with a focus on recent changes in recommendations
for these vaccines and ways in which pharmacists can identify patients who may be eligible
for vaccination.
Activity Fee: There is no fee for this activity.
To obtain CPE credit, visit www.drugtopics.com/cpe and
click on the “To Take the CE test, click here.” link. This will
direct you to the UConn/Drug Topics website, where you
will click on the Online CE Center. Use your NABP E-Profile
ID and the session code: 16DT30-VXB22 for pharmacists or the session code: 16DT30-AYE32 for
pharmacy technicians to access the online quiz and
evaluation. First-time users must pre-register in the Online
CE Center. Test results will be displayed immediately and
your participation will be recorded with CPE Monitor within
72 hours of completing the requirements.
For questions concerning the online CPE activities,
e-mail: [email protected].
Faculty: Jennifer E. Girotto, PharmD
Dr. Girotto is an associate clinical professor of Pharmacy Practice, University of Connecticut, Storrs, Conn.,
and antimicrobial stewardship co-director, Connecticut Children’s Medical Center, Hartford, Conn.
Faculty Disclosure: Dr. Girotto has no actual or potential conflicts of interest associated with this article.
Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion
of unlabeled/unapproved use of drugs in the United States. When unlabeled discussion occurs, it will be based
upon the Centers for Disease Control and Prevention recommendations. The content and views presented
in this educational program are those of the faculty and do not necessarily represent those of Drug Topics
or University of Connecticut School of Pharmacy. Please refer to the official information for each product for
discussion of approved indications, contraindications, and warnings.
58
IMAGE:GETTYIMAGES/ SUSAN CHIANG
INITIAL RELEASE DATE: JULY 10, 2016
EXPIRATION DATE: JULY 10, 2018-
PEER REVIEWED | CONTINUING EDUCATION
Introduction
In the United States, great strides
have been made in improving vaccination efforts, resulting in significant
reductions in the occurrence of vaccine-preventable diseases (VPD).1
Many of these improvements have
been the result of very successful
pediatric vaccination efforts. The
area that pharmacists have made
substantial improvements in vaccination of adolescents and adults have
been with influenza vaccines. Unfortunately, more work is needed, especially in the vaccination of adolescents and adults for vaccinations
other than just influenza.2, 3 Therefore, this review will not address
influenza vaccination in this population; instead, it will review other vaccines that should become a priority
for pharmacist vaccination programs
aimed at adolescents and adults.
In 2013, there were 26,639 cases
of pertussis, 17,193 cases of pneumococcal disease, 3050 cases of
hepatitis B, and 241 cases of meningococcal disease (strains ACYW or B)
in the United States that could potentially have been prevented by vaccination.4 These diseases are associated not only with significant morbidity
and mortality but also with significant
costs. In one study that evaluated the
cost of major VPD in adults aged 50
years and older, the annual expenses,
including medical and indirect costs,
were estimated to be $5.1 billion for
pneumococcal diseases, $5 billion
for herpes zoster (HZ), and $397.7
million for pertussis.5
The percentage of adults receiving
recommended vaccinations is generally low. For example, less than one-quarter of those indicated to receive hepatitis B or HZ vaccines do so. Further, few
patients receive the full schedule
of human papillomavirus (HPV) vaccine with only 5.9% to 37% of men and
women aged 19 to 26 years receiving even a single dose.3 Although overall tetanus vaccine rates in adults over
the past 10 years have been slightly
higher (ranging from 56%-63% depending on age), less than 20% of patients
aged 19 years and older have ever
received a dose of the tetanus-containing pertussis vaccine (Tdap) as recommended.3 The uptake of pneumococcal vaccine among adults is slightly better; however, goal rates have still
not been achieved, with only 60% of
patients aged 65 years and older having received any pneumococcal vaccine
despite recommendations.3
Although overall vaccination rates
are higher for adolescents than for
tered to immunosuppressed individuals, as these attenuated strains can
still cause significant disease in these
patients.1
Vaccine recommendations
The CDC routinely provides recommendations for vaccination.6,7 The
CDC’s advisory committee (the Advisory Committee on Immunization
Practices [ACIP]) meets quarterly to
discuss updated vaccine information
and to vote on changes to existing
recommendations. Information about
The percentage of adults receiving recommended
vaccinations is generally low; 25% or less of adults
receive the routinely recommended hepatitis B and
herpes zoster vaccinations.”
adults, they are still lower than recommended, with rates of only 29% for
completion of meningococcal (MenACWY) vaccination, 40% for completion
of HPV vaccination, and 88% for a single dose of Tdap.2
Basic vaccine principles
There are two general classes of vaccines: inactivated and live. Inactivated
vaccines cannot cause disease, even
if administered to patients with significant immunodeficiency, because they
contain either an inactivated whole
virus or bacterium or contain only protein, polysaccharide, or toxoid components of the pathogen.1 Most vaccines
routinely given to adults are inactivated. The only live vaccines recommended for adolescents and adults
are the measles, mumps, and rubella (MMR) vaccine; varicella (chickenpox or HZ) vaccines; and intranasal influenza vaccine.6,7 Live vaccines
contain a live virus or bacteria; however, they contain not the wild strain
but a weakened, or attenuated, strain
of the pathogen. Attenuated strains
do not cause disease in healthy individuals but should not be adminis-
these meetings, including agendas,
minutes, presentations, and full YouTube recordings, is available at www.
cdc.gov/vaccines/acip/meetings/
meetings-info.html. The CDC’s recommendations are considered enacted when they are formally published
in the Morbidity and Mortality Weekly Report (MMWR). Pharmacists may
wish to subscribe to a listserv (http://
www.cdc.gov/Other/emailupdates/)
that provides updates on immunizations (ACIP official recommendations) and/or MMWR subscription to
ensure that they are always following
current recommendations. To summarize the changes that occur over
the year, the CDC also provides an
annual update, usually in February, to
the vaccine schedules (both pediatric and adult).6,7 In the vaccine schedules, the CDC describes what vaccinations should still be “caught-up” or
administered if vaccines are missed,
minimum and maximum ages, and
what the minimum intervals between
doses of these vaccinations. Although the CDC is an excellent
resource for vaccine recommendations, additional resources are avail-
59
EXPANDING VACCINATION RATES
able for pharmacists. The Immunization Action Coalition website (www.
immunize.org) has a multitude of
resources for pharmacists, including vaccine information statements
in many different languages, clinic
resources, and question-and-answer
summaries about common topics
related to vaccination.
Vaccine storage
and administration
Pharmacists must be aware of key
points regarding storage and administration of vaccines.1 For vaccine storage, it is important to use
stand-alone refrigerator and freezer units with a temperature-monitoring device containing an alarm that
is activated if the temperature is outside of the required range. The temperature should be recorded at least
twice daily. As shown in Table 1, most
live vaccines should be stored in the
TABLE 1
ing on the patient’s weight is used.
The needle is inserted into the lower
half of the deltoid muscle at a 90°
angle.1,9,10 Choosing the correct needle length based on patient weight
and administering the vaccine in the
lower half of the deltoid muscle will
improve the likelihood that the vaccine reaches the muscle; if the vaccine instead enters the bursa space,
acromion, or synovial space (all of
which are located behind the upper
one-third of the deltoid muscle), this
can result in an increased risk of
local adverse reactions, some severe
enough to require surgery.1,9,10
Key VPD and vaccination
recommendations for
adolescents and adults
As discussed earlier, adolescent and
adult vaccination rates are often suboptimal, providing an opportunity for
pharmacists to work with patients to
Vaccine Storage and Administration Routes
TYPE OF VACCINE
STORAGE TEMPERATURE
ADMINISTRATION
ROUTE
Live (measles, mumps, and rubellaa;
varicella; zoster)
Freezer:
–58°F to 5°F
Subcutaneous
Inactivated (hepatitis A, hepatitis B,
hepatitis A and B, human papillomavirus,
polio, meningococcal, pneumococcal,
tetanus, diphtheria, and pertussis)
Refrigerator:
35°F to 46°F
Intramuscularb,c
a
Measles, mumps, and rubella vaccine can be stored in refrigerator or freezer as unreconstituted lyophilized vaccine.
The polysaccharide meningococcal vaccine (MPSV4) should be administered subcutaneously instead of intramuscularly.
Both polio and pneumococcal polysaccharide vaccines can be administered either intramuscularly or subcutaneously.
b
c
freezer, whereas inactivated vaccines
are kept in the refrigerator.1,8
Most live vaccines are administered subcutaneously (SC); inactivated vaccines are generally administered intramuscularly (IM) (Table 1).1,8
For administration of an SC vaccine,
a 23- to 35-gauge 5/8-inch needle
should be inserted at a 45° angle in
pinched fatty tissue below the dermis
but over the upper outer triceps muscle.1 For administration of an IM vaccine, a 22- to 25-gauge needle ranging from 5/8 inch to 1.5 inch depend-
60
Source: Ref 1,8
improve their protection against multiple pathogens. In this section, vaccines with recent changes or those
that offer a significant opportunity for
pharmacist vaccination programs are
highlighted.
Pneumococcus
Pneumococcal disease, or disease
caused by the bacteria Streptococcus
pneumoniae, has been reported to be
associated with four million infections
annually in the United States, half of
which occur in adults.11 It is also asso-
ciated with approximately 22,000
deaths annually from pneumonia,
acute exacerbation of chronic bronchitis, bacteremia/sepsis, and meningitis. Importantly, 60% of hospitalizations associated with pneumococcal disease occur in adults, and 95%
of deaths occur in patients aged 65
years and older, mostly from pneumococcal pneumonia.11
Adolescent and adult patients at
increased risk for serious pneumococcal disease include those who are
immunocompromised (eg, those with
cancer, transplant, chronic renal failure, HIV); those with anatomical or
functional asplenia (eg, sickle cell disease); and those who are immunocompetent but have other risk factors such as chronic heart disease
(eg, congestive heart failure, cardiomyopathies), chronic lung disease (eg, chronic obstructive pulmonary disease, emphysema, or asthma), diabetes mellitus, chronic liver
disease, cerebral spinal fluid leak,
cochlear implant, alcoholism, or a history of smoking.12,13 Additionally, all
patients aged 65 years and older are
at increased risk for severe pneumococcal disease.14
Two vaccines are currently available to provide protection against
pneumococcal disease. The 23-valent
pneumococcal polysaccharide vaccine (Pneumovax; PPSV23) has been
available since the 1980s and provides protection against 23 strains of
S pneumoniae.
However, PPSV23 has demonstrated efficacy results ranging from just
10% to 74% against various invasive
pneumococcal diseases. This vaccine
is still recommended despite its lack
of robust effect because of the significance of invasive pneumococcal disease and the number of strains it provides protection against.15
In 2010, a 13-valent pneumococcal conjugate vaccine (Prevnar13;
PCV13) was approved by the FDA for
patients aged 50 years and older. This
vaccine has demonstrated the abil-
THROUGH PHARMACIST-INITIATED PATIENT IDENTIFICATION AND ASSESSMENT
ity to provide immunologic responses that are at least as strong as those
seen with PPSV23. Furthermore, in a
study evaluating pneumococcal pneumonia in patients aged 65 years and
older, PCV13 demonstrated efficacy against first episode of communityacquired pneumonia (45%) and invasive pneumococcal disease (75%) that
was identified to be caused by a vaccine strain.16
Current recommendations for pneumococcal vaccination for adolescents
and adults include both of these vaccines (Table 2).12-14,17 Because many
patients are recommended to receive
both vaccines, the CDC has recently
clarified the spacing between vaccine
doses.12-14,17 When neither vaccine
has yet been given, PCV13 should be
administered first. Timing between the
administration of PCV13 and PPSV23
then depends on whether the patient
has risk factors (other than being aged
>65 years). If the patient has specific
risk factors (eg, immunocompromise,
asplenia, cochlear implants, cerebrospinal fluid leak) and both vaccines are
recommended, PPSV23 can be administered eight weeks after PCV13. In
adults who were administered PPSV23
first or in those without these risk factors, the spacing between the vaccines should be one year. In adolescents with risk factors, PCV13 can
be given as soon as eight weeks
after PPSV23.17 It is also important
to remember that any time more than
one dose of PPSV23 is indicated, the
doses should be separated by a minimum of five years.
Zoster
Varicella zoster virus is responsible for
both chickenpox and HZ diseases. The
virus initially causes chickenpox and
then hides in the dorsal root ganglia,
where it remains latent for a period of
time.18 It is believed that factors such
as increasing age cause a loss of cellular-mediated immunity, which allows
for the latent virus to become active
and spread along the nerve cells to
the skin, resulting in HZ infection.18
Before routine vaccination was recommended, patients with these infections were older than 50 years in 49%
of cases and older than 60 years in
68% of cases; a total of 60% of affected patients were women.19
Administering the
vaccine in the lower
half of the deltoid
muscle will improve
the likelihood that the
vaccine reaches the
muscle.”
Increased age and immunocompromised state increase the likelihood of
complications from zoster infections.
The most common complication is
postherpetic neuralgia (PHN), which
is the prolonged duration of persistent pain. This complication increases
in incidence as patient age increases,
with an incidence ranging from 5% in
patients aged 50 to 59 years to 20% in
patients aged at least 80 years.19 The
duration of PHN varies but can be very
prolonged, with 6% of those aged at
least 50 years having pain for one year
or more.19 Other complications of zoster disease include HZ oticus, Bell-like
palsy, motor nerve palsies, and skin
superinfections.19
Zoster infections are not isolated to a single episode; recurrence is
possible. Follow-up from a zoster epidemiology study showed that at eight
years, the estimated recurrence rate
was 6.2%.20 Factors associated with
increased risk of recurrence include
female sex (7.2% vs 4.5% male), immunocompromised status at initial episode (12% vs 5.7% immunocompetent), and the occurrence of PHN for
at least 30 days with the first episode
(hazard ratio, 2.8; 95% confidence
interval [CI], 1.8-4.3).20
One live attenuated vaccine is currently approved for the prevention
of zoster (Zostavax). This vaccine is
approved for patients aged 50 years
and older, but the CDC recommends
vaccination only for patients aged
at least 60 years.21 The CDC evaluated the limited follow-up data available from the original efficacy trials (in patients aged ≥60 years) and
found that estimated vaccine efficacy for preventing zoster infection was
reduced to 43.1% at five years and
21.1% at seven to 10 years.21 Additionally, vaccine efficacy for preventing
PHN was reduced to 60.1% at years
four to seven and to 35.4% at years
seven to 10.21 These data demonstrate that the vaccine loses its effectiveness over time and does not provide lifelong immunity. This is important as the ACIP and additional studies have not shown that administering
it at age 50 years is generally costeffective.21 Therefore, most patients
should wait to be vaccinated until age
60 years to ensure protection when
they are at highest risk for complications.21 Because many patients who
have had an episode of zoster will
have a recurrence, the CDC also recommends that the vaccine should be
administered even in patients who
have experienced a previous episode.21
The current zoster vaccine is a
live vaccine; as such, it should not
be administered to patients who are
immunocompromised (eg, malignant
PAUSE AND PONDER
Which patients have a routine recommendation
for MenB vaccination, and which have a permissive
recommendation?
61
disease or taking medications such
as biological modifiers), those who
are pregnant, or those receiving antiviral treatments with activity against
herpesviruses (eg, famciclovir, valacyclovir). That being said, patients
with many chronic conditions such as
chronic renal failure, diabetes, rheumatoid arthritis, and chronic pulmonary disease can receive the zoster
TABLE 2
had an efficacy of 97.2% (95% CI, 93.799.0) in a placebo-controlled study
that included 15,411 patients aged 50
years and older. Differences in vaccine
efficacy did not appear to be related to
age, so this vaccine may be promising
for patients of all ages, and those who
cannot receive the currently approved
live vaccine because of an immunocompromised status.
Pneumococcal Vaccination Overview
for Adolescents and Adults
INDICATION
VACCINE(S) INDICATED
VACCINE MINIMUM
SPACINGa
Immunocompromised
patients; patients with
asplenia
PCV13 and PPSV23
(1 additional PPSV23 dose
in patients aged <65 years;
follow appropriate spacing)
PCV13 to PPSV23: 8 weeks
PPSV23 to PCV13:
Ì Adolescents: 8 weeks
Ì Adults: 1 year
PPSV23 to PPSV23: 5 years
Patients with cerebrospinal
fluid leaks or cochlear
implants (aged <65 years)
PCV13 and PPSV23 only 1 time
in patients aged <65 years
PCV13 to PPSV23: 8 weeks
PPSV23 to PCV13:
Ì Adolescents: 8 weeks
Ì Adults: 1 year
Immunocompetent patients
with disease risk factors
(aged <65 years)
PPSV23 only 1 time in patients
aged <65 years
N/A
without risk factors
(aged <65 years)
None
N/A
aged ≥65 years
PCV13 and PPSV23
(1 time each)
PCV13 to PPSV23: 1 year
PPSV23 to PCV13: 1 year
PPSV23 to PPSV23: 5 years
a
Note that adolescent and adult patients can receive 1 PCV13 vaccine, whereas patients can receive up to 3 lifetime doses (2 before age 65 years and 1
after) of PPSV23 depending on risk factors. Appropriate spacing must be followed throughout.
Abbreviations: N/A, not applicable.
Source: Ref 12-14,17
vaccine. Additionally, patients who
receive nonimmunosuppressant dosing of corticosteroids (<20 mg/day or
≥20 mg/day for <2 weeks), low-dose
methotrexate (≤0.4 mg/kg/week), or
low-dose azathioprine (≤1.5 mg/kg/
day) are not considered to be significantly immunosuppressed and so can
receive the zoster vaccine.21
An inactivated zoster vaccine,
HZ/su, is currently in phase III trials.22
This vaccine, which is a two-dose
series given at zero and two months,
62
Hepatitis B
Hepatitis B virus is a double-stranded DNA virus that is usually acquired
via blood or mucosal routes, with most
infections occurring through blood
(eg, needles or lancets), perinatal, or
sexual exposure. Men who have sex
with men, patients who use intravenous drugs, and those who have multiple sexual partners continue to be the
largest identified populations with hepatitis B.23 Patients with diabetes who
use assisted blood glucose monitor-
ing are also at increased risk of infection.24 Hepatitis B infection can cause
acute hepatitis or chronic infection.1
Older patients are more likely to have
acute hepatitis. Acute disease presents similarly to other forms of hepatitis, with fever, jaundice, nausea, vomiting, right upper quadrant pain, and
a serum alanine aminotransferase
level higher than 100 IU/L.1,23 Those
who are infected at younger ages, are
immunocompromised, have diabetes,
or require hemodialysis are more likely
to have chronic infection.1,25 Patients
with chronic disease are able to transmit the infection, which is associated
with cirrhosis, liver failure, and hepatocellular carcinoma.1
Although there have been significant reductions since the early
2000s in hepatitis B rates in the United States, most recent estimates suggest that nearly 20,000 acute cases
still occur annually.23 Patients aged 30
to 39 years followed by those aged 40
to 49 years have the highest reported
incidence of acute hepatitis, and this
incidence increased from the previous
year in both groups.23 Among patients
whose data was submitted to the CDC,
only 37% had an identified risk factor
for hepatitis B acquisition.23
Multiple vaccines are approved to
provide protection against hepatitis B
infection in adolescents and adults.
Two general single-antigen hepatitis B
vaccines (Recombivax HB and EngerixB) are available, as well as a combination hepatitis A and B vaccine (Twinrix) and a formulation specifically for
patients currently undergoing or about
to undergo hemodialysis (Recombivax HB Dialysis formulation). The routine vaccination schedule for hepatitis B protection is one dose (0.5 mL
of single-antigen vaccine for patients
aged <20 years; 1.0 mL of single-antigen vaccine for patients aged ≥20
years; 40 mcg of dialysis formulation
for dialysis patients; 1 mL of combination vaccine in adults) administered at
zero, one, and six months.26 Alternative
schedules include three-dose sched-
ules with doses administered at zero,
one to two, and four months (adolescents and adults) or at zero, 12, and 24
months (adolescents) and a two-dose
schedule (for patients aged 11-15
years) with a dose of 10 mcg of the dialysis formulation administered at zero
and four to six months.26 The combination vaccine can also be administered
on a four-dose schedule, with doses
administered at zero days, seven days,
21 to 30 days, and 12 months.27
Most patients will respond to the
full vaccine series. Approximately
90% of adults aged younger than 40
years who receive the full three-dose
series attain protection against hepatitis B. This protection is reduced with
increasing age at vaccination, history of smoking, history of obesity, and
immunosuppresion.25 Because most
patients will respond to the vaccine
series, testing for vaccine response
is recommended in only a small number of patient populations. Healthcare and public safety workers who are
at risk for exposure, patients undergoing chronic hemodialysis, patients
with HIV, and immunocompromised
patients should be assessed for vaccination response through evaluation of surface antibody (anti-HBs) levels one to two months after completing the vaccine series. Seroprotection
is defined as ≥10 mIU/mL anti-HBs.25
When patients do not demonstrate
evidence of seroprotection (ie, antiHBs levels <10 mIU/mL), they should
receive another three-dose series
of the vaccine.25 If patients fail to
respond one to two months after the
second vaccine series, they should
be assessed for the presence of the
disease with HBsAg testing; if the
results are positive, patients are considered infected, but if the results are
negative, they are considered nonresponders who are not protected.25
Most patients can be considered to
have long-term (>20 years) immunity
after demonstrating adequate immune
response to vaccination. Patients who
undergo hemodialysis or are immun-
PAUSE AND PONDER
Which patients should receive both the PCV13
and PPSV23 vaccines?
compromised (including those with
HIV, those with hematopoietic stem
cell transplant, and those receiving chemotherapy) may have waning
responses; as such, anti-HBs levels
may need to be assessed annually in
these patients.25
Recently, questions have arisen regarding patients who were vaccinated previously (eg, as infants or
children) but did not have their vaccine response evaluated and are now
part of a group (eg, healthcare providers) who should have evidence of protection established. These patients
should undergo response testing. If
their anti-HBs level is <10 mIU/mL,
Incorporation
of vaccination into
the busy pharmacy
environment requires
strategies to incorporate
it into the general
workflow.”
they should receive a single dose of
hepatitis B vaccine as a challenge
dose followed by anti-HBs testing one
to two months later. If patients still
do not demonstrate an adequate vaccine response, they should receive two
additional hepatitis B vaccine doses
followed by additional anti-HBs testing one to two months after the final
dose.28
HPV
There are approximately 150 identified
strains of HPV.29 Approximately onequarter of these strains are associated with causing genital warts (lowrisk strains 6 and 11) or genital can-
cers (oncogenic strains 16, 18, 31,
33, 45, 52, and 58) at the mucosal
epithelia.1,29,30 Although most cases
of HPV infection are spontaneously cleared, HPV can cause cancers
when the infection persists over a
period of many years. In cervical cancer, the type of cancer most commonly associated with HPV infection, cervical intraepithelial neoplasia (CIN)
that progresses from stages 1 to 3 is
indicative of persistent and progressing infection.1 In addition to genital
warts and cervical cancer, HPV is also
associated with anal, vulvar, vaginal,
penile, and oropharyngeal cancers,
as well as recurrent respiratory papillomatosis (recurrent warts often on
the larynx).29 The 2vHPV (Cervarix) and
4vHPV (Gardasil) vaccines covering
HPV 16 and 18 are estimated to provide protection against 64% of HPVassociated invasive cancers; the use
of 9vHPV (Gardasil9) adds an additional 10% of protection.30
Certain populations are at higher
risk for HPV infection or at higher risk
for increased disease severity. Immunocompromised patients (those with
transplant, those with HIV, those taking immunosuppressant medications) are at higher risk for both disease occurrence and increased disease severity. Men who have sex with
men are at increased risk for HPV disease and the cancers associated with
this infection. Patients with a history of sexual abuse or assault are at
an increased risk of exposure to HPV
because of the potential for future
abuse and risky sexual behaviors.29,30
Three vaccines are currently
approved for the prevention of HPV
infection in adolescents and adults:
2vHPV, 4vHPV, and 9vHPV. 2vHPV
is approved for female patients aged
nine through 25 years, whereas
4vHPV is approved for both male and
63
female patients aged nine through 26
years. 9vHPV is approved for female
patients aged nine through 26 years
and male patients aged nine through
15 years.29,30 2vHPV and 4vHPV have
shown not only initial efficacy but also
significant persistence of protection. Recent data show that both of these
vaccines have sustained protection
for more than eight years with almost
100% efficacy at protection against CIN
2 or 3 caused by included strains.31
All HPV vaccines have the same
administration schedule: a threedose series administered at zero
months, one to two months, and six
months.29,30 HPV vaccination is recommended routinely for patients aged 11
or 12 years.29,30 The HPV vaccines can
be administered in patients as young
as nine years, especially in those with
Meningococcus
Neisseria meningitides is associated
with severe systemic diseases including meningitis, bacteremia, and bacteremic pneumonia.32 There are 13
strains of N meningitidis; the strains
are classified based on their polysaccharide capsule.1 Five strains—
A, B, C, W, and Y—are associated with most cases of invasive diseases.1 Patients who have complement deficiencies, have anatomic or
functional asplenia, are first-year college students living in dormitories,
or are microbiologists who work with
N meningitidis are at increased risk
for meningococcal disease.32 Adolescents and young adults also have an
increased risk of contracting the disease and are the most common carriers of the organism.32
TABLE 3
Meningococcal Vaccine Indications
VACCINE
COVERAGE
SPECIFIC
VACCINES
Strains A, C, Y,
and W
MenACWY-D
MenACWY-CRM
Strain B
INDICATIONS FOR VACCINATION
BOOSTING
Routine adolescent vaccination;
vaccination for high-risk
adolescents and adults
Adolescents, 1 time;
high-risk patients,
every 5 yearsa
MPSV4
Indicated based on risk in patients No
aged >55 years who have never
received a MenACWY vaccine
MenB-4C
Routine recommendation for
high-risk adolescents and adults;
permissive recommendation
for patients aged 16-23 years
(preference, patients aged 16-18
years)
MenB-FHbp
a
If still at high risk
a history of sexual assault or other risk
factors. Catch-up vaccinations should
be continued through age 21 years for
men not at high risk and through age
26 years for women and for men who
are immunocompromised, have sex
with other men, or want to be vaccinated. If the patient began with 2vHPV
or 4vHPV, he or she can finish out the
series with 9vHPV.30 Additionally, the
vaccine series can be finished after
the 27th birthday as long as the series
was initiated at the appropriate age.29
64
No
Source: Refs 31-33
Meningococcal vaccines can be confusing, as different vaccines cover different strains and have different indications. Three vaccines are approved
to cover strains A, C, Y, and W in adolescents and adults. The two conjugate vaccines (MenACWY) are MenACWY-D (Menactra) and MenACWY-CRM
(Menveo). MenACWY-D is approved for
patients aged nine months to 55 years,
whereas MenACWY-CRM is approved
for patients aged two to 55 years. Both
of these vaccines are recommended for
both primary (one- or two-dose series,
depending on the patient) and booster
dosing. The other vaccine is a polysaccharide vaccine (MPSV4; Menomune).
MPSV4 is approved for patients aged
at least two years but is recommended
only for some patients aged more than
55 years.32
Another two vaccines provide protection against the B strain of meningococcus: MenB-4C (Bexsero; twodose series) and MenB-FHbp (Trumenba; three-dose series). Both of these
vaccines are approved for patients
aged 10 to 25 years; however, the CDC
recommendation is for patients aged
at least 10 years old with no maximum
age.33
The CDC routinely recommends
vaccination with a MenACWY vaccine
for all patients aged 11 to 12 years
with a booster at 16 years of age, with
catch-up through age 21 years for
those who have not received a dose
since their 16th birthday.32 Additionally, the CDC recommends vaccination
with ACWY or B in cases of meningococcal outbreaks, with vaccine choice
depending on the strain of the current outbreak.32,33 The CDC has also
added a permissive recommendation
allowing a MenB vaccine series to
be administered to patients aged 16
to 23 years (with preference for age
16-18 years) when there is no current
outbreak.34
High-risk patients such as those
with complement component deficiency, those with asplenia, and microbiologists who work with N meningitidis
require both an ACWY and B strain vaccine for optimal protection (Table 3).32-34
Currently, all patients (high-risk or
permissive) who receive MenB vaccines receive the same recommended series for the vaccine; there is no
recommendation for boosting at this
time.33 However, some patients who
are indicated to receive MenACWY
may need dose modifications. Specifically, patients with immune issues (ie,
complement component deficiency,
asplenia, or HIV) should receive a two-
dose primary series of MenACWY, separated by eight to 12 weeks.32 Additionally, booster doses of MenACWY
are then needed every five years for
those who remain at increased risk.
Patients aged greater than 55 years
who are indicated to receive meningococcal vaccination and have never
received a dose of MenACWY should
instead receive MPSV4.32
Tetanus, Diphtheria, and Pertussis
Tetanus, diphtheria, and pertussis are all toxin-mediated diseases, meaning that although they are
caused by bacteria, their specific effects are due to the toxin that
these bacteria produce.1 For this reason, the vaccine is designed to target the toxins, not the bacteria. The
incidences of tetanus and diphtheria have significantly decreased
because of routine vaccination, making these diseases very uncommon.1
The incidence of pertussis, however,
continues to have periodic outbreaks,
partially because of increased recognition of this condition in adolescents
and adults, and partially because of
a change in the vaccine in the early
1990s (from a whole-cell vaccine
to an acellular vaccine) intended to
reduce the occurrence of adverse
effects.
There are currently three categories of vaccines that cover these diseases in adults: tetanus toxoid (TT;
generic); tetanus and diphtheria (Td;
Decavac, Tenivac and generic) and tetanus, diphtheria, and pertussis (Tdap;
Adacel and Boostrix).1 TT is generally not recommended for any patients
whereas both Td and Tdap are recommended for routine immunization in
adolescents and adults. Specifically,
patients should receive a tetanus- and
diphtheria-containing vaccine every 10
years (or five years after last tetanus
containing vaccine in cases of significant wound infection).35 Patients who
have not yet received a single dose
PAUSE AND PONDER
Why does the CDC not recommend the zoster vaccine
for patients as young as 50 years old?
of Tdap should be administered the
Tdap vaccine rather than Td. Emphasis should also be placed on ensuring vaccination of patients who plan
to have direct contact with infants. In
these cases, it is best to provide Tdap
two weeks before the patient plans to
interact with the infant to allow for full
protection. Additionally, Tdap should
be administered to every pregnant
woman between weeks 27 and 36 of
gestation.36 When Tdap is not administered during pregnancy, it should be
administered immediately after the
patient gives birth.36
Generally, immunizers can administer any brand of vaccine, however, for Tdap administered to patients
aged at least 65 years, more evidence
exists to support the use of Boostrix,
and this agent is therefore preferred
over Adacel. However, the CDC clearly
states that if Adacel is the only version
available to the provider, it would be
better to provide Adacel than to miss a
vaccination opportunity.37
Strategies to identify patients
needing vaccination
Incorporation of vaccination into the
busy pharmacy environment requires
various strategies, such as posting
current immunization schedules, creation of age-specific targeting (eg,
for pneumococcal, zoster, Tdap/Td,
meningococcal, HPV vaccines), and
disease-state targeting. To incorporate disease-state strategies, pharmacists can target specific medications that would generally only be prescribed for specific indications (eg,
metformin for diabetes) to alert for
potential vaccination opportunities
(eg, pneumococcal and hepatitis B
vaccination) and then put an alert on
those prescriptions. See http://pharmacy.uconn.edu/academics/ce/
immunization/, Medications and Disease Based Immunization Recommendations for Adults, for an example). Technicians can help with this
process by tagging prescriptions that
they are filling with a note stating that
the patient may need vaccination
Tdap should be
administered to every
pregnant woman
between weeks 27 and
36 of gestation.”
and that the patient should speak
with the pharmacist. The technician
can then alert the pharmacist when
the patient is picking up the prescription so that the pharmacist can discuss whether the vaccine is indicated
for that particular patient. Additionally, when time permits, the pharmacist
can sit down with the patient to learn
more about any additional potential
indications for vaccination such as
work or sexual exposures.
Conclusion
In conclusion, pharmacists are an
important provider of vaccines for adolescent and adult patients. Pharmacists must use the resources available to remain updated on information
regarding vaccine recommendations
and administration, as well as ways to
effectively identify patients in need of
these vaccines.r
» References are available online at
www.drugtopics.com/cpe.
For CPE credit, take the test now online at > www.drugtopics.com/cpe ONCE THERE, CLICK ON THE LINK BELOW FREE PEER-REVIEWED CPE ACTIVITIES
65
TEST QUESTIONS
For Pharmacists
1. A lack of vaccination in adolescents and adults
can lead to:
a. Loss of time at work
b. Increased medical utilization
c. Increased direct and indirect costs to patients
d. All of the above
2. For an otherwise healthy 18-year-old college
student who plays competitive softball and does
not smoke, which of the following vaccines could
be given based on recent changes in vaccine
recommendations?
a. PCV13
b. IPV
c. MenB
d. Zoster
3. Which of the following is a reliable site to
confirm current vaccine recommendations?
a. CDC.org
b. Immunize.org
c. MMWR.org
d. All of the above
4. Which pneumococcal vaccine(s) is/are indicated
for a patient who is aged 65 years and has never
received a pneumococcal vaccine?
a. PCV13 only
b. PPSV23 only
c. PCV13 and PPSV23, spaced appropriately
5. Which group of adults account for 95% of
deaths caused by pneumococcal pneumonia?
a. 18- to 49-year-old patients
b. 50- to 64-year-old patients
c. >65-year-old patients
6. Which of the following 19-year-old patients
would be indicated to receive the PCV13
vaccine?
a. Patient who smokes
b. Patient with cancer
c. Patient with diabetes
d. Patient with hypertension
7. What can be done in the pharmacy to make the
pharmacist more effective at identifying patients
who may need vaccines?
a. Tag prescriptions when they are filled based on the
likely indication, and talk to these patients when they
come in for the prescription.
b. Target prescriptions based on age, and talk with
patients when they come in.
c. A and B
8. Which of the following represents ACIP’s
recommendations on when patients should
receive the zoster vaccine?
a. Age ≥50 years
b. Age ≥60 years
c. Age ≥70 years
9. You are working at your pharmacy and are
targeting patients to receive HPV9 based
on age. Which of the following ages is
recommended by ACIP to receive the HPV9
vaccine?
a. Age 11 to 26 years
b. Age eight to 15 years
c. Age 15 to 30 years
10. You have a 30-year-old patient who recently
had a car accident that required his spleen
to be removed. He was told he would need a
meningococcal vaccine. Which meningococcal
vaccine(s) should he receive based on CDC
recommendations?
a. MenACWY only
b. MenB only
c. Both MenACWY and MenB
For Pharmacy Technicians
1. Can an inactivated vaccine cause disease?
a. Yes
b. Yes, but only in immunosuppressed patients
c. No
2. Which organization produces vaccine
recommendations?
a. Medscape
b. CDC
c. ASHP
3. Which site has clinic resources on its website
that the technician can use to ensure that
vaccines are stored appropriately?
a. ASHP.org
b. AAP.org
c. Immunize.org
4. Which of the following vaccines should always be
stored in the freezer?
a. PCV13
b. MenB
c. Tdap
d. Zoster
5. At what temperature should the PCV13 vaccine
be stored?
a. Between 35ºF and 46ºF
b. Between –58ºF and 5ºF
c. Between 68ºF and 78ºF
8. In what month are updated immunization
schedules usually published by the CDC?
a. February
b. April
c. September
6. What is included in a live virus vaccine such as
MMR?
a. An inactivated virus
b. Protein fragments of the virus
c. A weakened strain of the naturally occurring virus
9. The pharmacist has a patient who speaks only
Spanish; this patient needs to be given the
vaccine information statement in his native
language. Where can you go to obtain this for the
pharmacist?
a. CDC Pink Book
b. Immunization Action Coalition
c. CDC Morbidity and Mortality Weekly Report
7. A patient comes to the pharmacy, and there is
a note on her prescription stating that she may
be indicated to receive a particular vaccine. You
talk to the patient and learn that she has not
received that vaccine in the past. What should be
the next step?
a. Refer the patient to the pharmacist to determine
whether she can receive the vaccine.
b. Ask the patient clinical questions to determine
whether she is eligible for vaccination.
c. Tell the patient to come back another day for the
vaccine.
10. How often should the temperature of the
refrigerator and freezer that store vaccines be
recorded (at a minimum)?
a. Daily
b. Twice daily
c. Hourly
d. Twice weekly
For CPE credit, take the test now online at > www.drugtopics.com/cpe ONCE THERE, CLICK ON THE LINK BELOW FREE CPE PEER-REVIEWED ACTIVITIES
66
REMEMBER WHEN
160th Anniversar y
Pharmacists overwhelmingly
support Reagan re-election bid
Do you remember voting in the 1984 presidential race? If you answered yes, you probably remember that President Ronald Reagan won by a landslide, with 54.4 million votes (58.5% of the popular vote) and 525 electoral votes (97.58%). Former Vice President Walter Mondale was able to win only his home state of Minnesota and the
District of Columbia.
Pharmacists throughout the country had
already predicted Reagan as the winner, as the Sept. 17, 1984, edition of Drug
Topics reveals. More than 600 pharmacists from the journal’s national circulation were randomly surveyed, and 247
usable responses (41%) were tallied. Of
the 247 participants, 81% indicated that
they would vote for Reagan.
Most of the pharmacists (56.9%) who
completed the survey considered themselves to be “conservative” politically;
36.2% had marked that they were “moderates”; and 6.5% claimed the “liberal”
designation. Almost half (48.1%) were
Republicans. Only about 20.2% identified as Democrats, and almost 30% were
independents.
Top pharmacy issues
Thirty-two years later, the top pharmacy
issues haven’t changed drastically.
In Drug Topics’ 1984 political poll, pharmacists ranked the following as pressing challenges for the chain drugstore
industry:
1. Third-party reimbursements (27.7%)
2. Competition from chain/discounters (10.9%)
3. Price increases by manufacturers
(9.8%)
4. Government regulation (7.6%)
5. Health maintenance organizations
(6%)
6. Other (mail order, price wars, and
the rapidly changing role of pharmacists) (<6%)
Today’s Poll? Drug Topics would like to hear from you about the upcoming 2016 presidential election. Please take a moment
to visit > www.drugtopics.com/presidentialpoll and complete our short survey. We will publish the results in the September
print edition of the magazine and online.
DRUG TOPICS’ 2 0 1 6 P O L I T I C A L P O L L
Donald Trump
(Republican Party)
Hillary Clinton
(Democratic Party)
Gary Johnson
(Libertarian Party)
Jill Stein
(Green Party)
Someone
else
Would
not vote
Don’t
know
67
PRODUCT UPDATES
EYES AND EARS
4
5
6
68
water, and/or sodium hydroxide. (alaway.com)
Earwax removal
FromMcKeonProductsInc.,Mack’sProRinse Earwax Removal Kit 6 offers
what the manufacturer describes as a
new tri-stream rinse tip and a steady-flow
bellows syringe. The easy-to-use syringe,
designed for adults and children over 12
years of age, works as follows. After complete compression of the bellows syringe,
the blue tip should be inserted into lukewarmwaterandthepressureonthesyringe
should be released, drawing water up into
the syringe bellow.Upon insertion of the
syringe into the ear opening, compression of the bellows releases water, rinsing the ear canal. The kit includes carbamide peroxide drops, an ear-wash rinse
tub, and earplugs that hold in the drops
during treatment. (www.macksearplugs.com)
Murine Ear Wax Removal Drops
with a new Sof Tip Dispenser, by Prestige
Brands, is a carbamide peroxide ear-wax
removal device with a flexible and angled
tip. For easy irrigation of the ear canal,
about five to 10 drops should be placed
into the ear; insertion of the tip into the
canal should be avoided. For any remaining wax, the ear can be flushed with a
soft bulb syringe. The Murine Ear Drops
can be used twice daily over a four-day
period. (prestigebrands.com)
Ototek Loop, an ear wax removal
device, was designed by Dr. Scot Estrem,
an ear specialist and faculty member
of the University of Missouri-Columbia School of Medicine. Its design was
based on the tools that doctors use to
remove ear wax. The device should be
used only on adults and teens age 16 and
older. (ototekloop.com)
Advertiser Index
BRAND NAME
ADVERTISER NAME
PAGE
Bendeka
Teva Oncology
Corporate
AmerisourceBergen
37A*
Corporate
Amneal Pharmaceuticals
31A*
Corporate
Camber Pharmaceuticals
41B*
Corporate
CutisPharma, Inc.
53B*
Corporate
EPIC Pharmacies
Corporate
H.D. Smith
Corporate
Tri State Distribution Inc.
Granix
Teva Oncology
MAVP
Merck & Co., Inc.
40B,T1-T4*
69
53A*
29
25B-26B*
MiraFIBER
Bayer
Mometasone Furoate
Nasal Spray
Apotex Inc.
Nexium 24hr
Pfizer Consumer Healthcare
9-11
21A*
CV4
CV2
Reese’s Pinworm
Reese Pharmaceutical Company
55
Tecnu
Tec Lab
33
Tresiba
Novo Nordisk
Trintellix
Takeda Pharmaceuticals America, Inc.45-50
*Indicates a demographic advertisement.
25A*
PRODUCT IMAGES COURTESY OF SIMILASAN USA / MCKEON PRODUCTS INC.
toms after only seven days’ use. The gel
contains carboxymethylcellulose sodium
1% and glycerin 0.9%, and is safe enough
to use as often as necessary, according to
Allergan, its manufacturer. (refreshbrand.com)
Similasan USA offers Allergy Eye
Relief 4 , Aging Eye Relief 5 , and
Complete Eye Relief drops to help relieve
allergy symptoms, dry eye, and redness,
burning, watering, and grittiness, respectively. The Allergy Eye Relief drops use
natural botanical extracts such as honeybee extract, eyebright, and Sabadilla
lily instead of vasoconstrictors to help
stimulate the immune system to alleviate symptoms. The Aging Eye Relief
drops are formulated with cineraria maritima, a botanical extract, to help maintain a clear crystalline lens, and herb-ofgrace to temporarily relieve dryness. The
Complete Eye Relief drops are formulated
for multisymptom relief and are gentle
enough to be used whenever symptoms
occur. (similasanusa.com)
Bausch & Lomb’s Alaway Eye Itch
Relief drops provide fast, long-lasting
relief for itchy eyes irritated by ragweed,
pollen,grass,animalhair,anddanderwith
the active ingredient ketotifen 0.025%.
The drops are approved for use in adults
and children 3 years and older. Inactive
ingredients include benzalkonium chloride 0.01%, glycerin, hydrochloric acid,
COUNTER POINTS
IN MY VIEW
M E DICA R E DRUG COSTS SHOU L D PA R A L L E L T HOSE OF M E DICA I D
ber of these expensive medications,
biologics, or any unique drugs lacking therapeutic alternatives. The proposal would include specific guidelines
involving scope of authority, processes
for price negotiation, pricing thresholds, formulary placement, drug market changes, and acceptable actions
for handling disagreements.
This solution is a first step towards
piloting a way out of the national Medicare drug problem. Medicare price negotiations must parallel those of Medicaid. All the supporting data indicate
that the American people endorse such
an initiative.
Medicare must have the same ability
as Medicaid to negotiate drug rebates to
improve spending and overall patient
care. We believe that the U.S. govern-
ment should have authority to negotiate
manufacturer drug prices for Medicare
as it has done for Medicaid, an approach
that has been proven effective.
8. Newkirk V. The election, on drugs. March 18, 2016. The Atlantic.
http://bit.ly/electionondrugs.
BIBLIOGRAPHY
1. American Public Health Association. Negotiations progress on
Medicare drug benefit. Nation’s Health. 2003;33(9):7.
10. Way WL, Mayer FS. Failures of Medicare Part D Delivery and Recommendations for Improvement. March 2008. www.ncbi.nlm.nih.gov.
http://bit.ly/partdfailures.
2. Angell M. The Truth About Drug Companies. Random House
Publishing Group; 2004.
11. Wechsler J. Congress stymied over Medicare drug discount
negotiations. Managed Healthcare Executive. May 1, 2007. http://
bit.ly/congressstymied.
3. Beasley B. Government negotiations on drug prices could reverse Medicare Part D. March 6, 2016. NC Spin, www.ncspin.com.
http://bit.ly/reversepartd.
4. Cubanski J, Neuman T. Searching for savings in Medicare drug
price negotiations. February 9, 2016. Kaiser Family Foundation.
http://bit.ly/searchingforsavings.
5. Hogberg D. Letting Medicare ‘negotiate’ drug prices: Myths vs. reality. January 2007. National Policy Analysis. http://bit.ly/rxpricemyths.
6. Leonard K. Not up for negotiation: Lowering drug prices is much
more complicated than candidates make it sound. February 26,
2016. usnews.com. http://bit.ly/unlikelyrxplans.
7. National Committee to Preserve Medicare and Social Security. Negotiating for lower drug Ccosts in Medicare Part D. April
22, 2014. http://bit.ly/entitledtoknow.
9. Shih C, Schwartz J, Coukell A. How would government negotiation of Medicare Part D drug prices work? February 1, 2016.
Health Affairs. http://bit.ly/negotiatepartd.
Genevieve Regal is director, Medicare Part
D Pharmacy Operations, Capital BlueCross,
Harrisburg, Penn. Contact her at [email protected].
Gail Bloom is professor, health policy and
health systems, at several universities. She
provides administrative and clinical occupational therapy consultation to mental health
programs and elder-care agencies. Contact her
at [email protected].
PRODUCTS & SERVICES
SHOWCASE
T BUY-SELL-BROKER
Contemplating the Sale of Your Pharmacy?
Select the largest, most experienced specialists to assist you.
15 YEARS EXPERIENCE
Successful completion of 400 sales
EIGHT REGIONAL SPECIALISTS
PROVIDING PERSONAL ATTENTION
KNOWLEDGE and EXPERIENCE
8 principals advising our clients
NATIONAL COVERAGE
Coast-to-coast personalized service
STRAIGHT TALK
Reality-based valuations; best outcomes
COMPLETE CONFIDENTIALITY
#VCNNVKOGUHQT[QWTDGPGƂV
COMPETITIVE FEES
Pay when you sell; no upfront fees
We Work Only For You!
www.buy-sellapharmacy.com | 877-360-0095
CONNECT
with qualified leads
and career professionals
Post a job today
www.modernmedicine.com/physician-careers
Joanna Shippoli
RECRUITMENT MARKETING ADVISOR
(800) 225-4569, ext. 2615
[email protected]
70
PRODUCTS & SERVICES
SHOWCASE
T BUY-SELL-BROKER
T FINANCING
Selling your
pharmacy?
KNOW
WE
PHARMACY
In fact, you could argue that we are
Pharmacy values are
currently very high.
Don’t sell yourself short.
If a chain or independent buyer has
contacted you, call immediately for a
free consultation.
the largest investor in community
pharmacies, lending close to $650
Million to the industry since 2010.
Contact your lending experts today.
COMMUNITY
S P E C I A LT Y
COMPOUNDING
L O N G - T E R M CA R E
ROBOTICS
FILE BUYS
9CVEJVJKUDTKGHOKPWVGXKFGQVQUGGJQY
QWTRTQXGPUCNGURTQEGUUYQTMU
YYYRJCTOCE[EDUEQOOQXKG
Daniel J. Lannon, RPh, Senior Pharmacy Broker
Pharmacy Consulting Broker Services
888.808.4774
[email protected]
ű'ZRGTKGPEGFű.KEGPUGFű+PUWTGF
Jimmy Neil
Pharmacy Loan Expert
[email protected]
910.212.4951
Mike Bollinger
Pharmacy Loan Expert
[email protected]
504.453.9726
www.pharmacycbs.com
liveoakbank.com/pharmacy
© 2016 Live Oak Banking Company. All rights reserved. Member FDIC
71
PRODUCTS & SERVICES
SHOWCASE
T EQUIPMENT FOR SALE
T GENERIC DISTRIBUTOR
FOR SALE
Script Pro SP 200
with collating center
This machine was purchased new in 2010, and the pharmacy
was recently closed. Will require refurbish, relocation, and
installation by Script Pro (which buyer is responsible for).
This would make the machine like new but at only a portion
of the cost of a new one. A cost quote from Script Pro is
available upon request. The refurbish is required by Script
Pro in order for them to continue supporting the equipment.
Asking 50,000 dollars or best offer.
Please contact Tom
Deutsch at 641-394-3913.
Content Licensing for
Every Marketing Strategy
Marketing solutions fit for:
Outdoor | Direct Mail | Print Advertising
Tradeshow/POP Displays | Social Media | Radio & TV
Leverage branded content from Drug Topics to create a more powerful and
sophisticated statement about your product, service, or company in your next
marketing campaign. Contact Wright’s Media to find out more about
how we can customize your acknowledgements and recognitions to
enhance your marketing strategies.
For information, call Wright’s Media at 877.652.5295
or visit our website at www.wrightsmedia.com
72
MARKETPLACE
PRODUCTS & SERVICES
T BROKERS
T EDUCATION
Need to Pass
®
NAPLEX ?
Do the NAPLEX
3 Step
with
2
®
1
3
NAPLEX® Review
QUICKCARDS®
with Memoronics®
plus Posters, Audio CD,
Math Practice, Telephone quizzing,
and Patient Profiles.
Using Memory Techniques of:
Visual
Auditory
Repetition
Self Testing
THE STUDY SYSTEM
IS THE SOLUTION
For details, please visit our website.
www.prontopass.com
T FOR SALE
For Sale
Script Pro SP-200
Medical Arts Pharmacy
San Angelo, TX
Call for pricing. 1-800-749-4383
MARKETPLACE ADVERTISING
FOR PRODUCTS AND SERVICES ADVERTISING:
PATRICK CARMODY at 440-891-2621
Email: [email protected]
FOR RECRUITMENT ADVERTISING:
JOANNA SHIPPOLI at (800) 225-4569 x 2615
E-mail: [email protected]
MARKETPLACE CAN WORK FOR YOU!
CV3
NOW AVAILABLE
Mometasone Furoate
Nasal Spray
Generic Equivalent to Nasonex®*
roate
u
F
e
n
o
s
Mometaal Spray
Nas
For more information, go to
www.apotexcorp.com/products or call 1-800-706-5575.
*Nasonex®is a registered trademark of Merck & Co., Inc.
Apotex is everywhere.
Making a difference. One life at a time.
www.ApotexCorp.com

Digital Edition

Transcription

Similar documents

Qmatic Pharmacy - Customer Flow Management

Harding Students Lobbied for Arkansas Therapeutic Substitution Law

It`s Digest Time Again

Pharmacies

Link to presentation - Leslie Dan Faculty of Pharmacy, University of

Pharmacy Daily for 250712

I`m helping to end MS by participating in the 2016 Jayman BUILT MS

PDF

St. Clare Pharmacy - St. Mary Medical Center

2014 Quarter 1 - Cooler Design, Inc.