Document 6426566

DRUG THERAPY IN
PREGNANCY, NEONATES,
AND PEDIATRICS
Amber Lucas, PharmD
Saint Luke’s Hospital of Kansas City
Causes of Infant Mortality
Birth defects are the most common
cause of infant mortality in countries
with a low infant mortality rate
Overall risk of 3%
Cause for the majority of cases is
unknown
Environment (drug exposures) accounts
for 3%
What is a Teratogen?
A substance, organism, or physical agent that
is capable of causing abnormal development
A teratogen can cause abnormalities of
structure or function, growth retardation, or
death of the organism.
Classic teratogens – isotretinoin (Accutane®)
or thalidomide
GOALS
Learn background for prescribing for
pregnant and lactating patients.
2. Understand differences in prescribing for
pediatric patients.
3. Learn current treatment recommendations
for common pediatric illnesses.
4. Develop understanding for use of vaccines
in pediatrics and pregnancy.
1.
Drugs and the Fetus
Extension of drug’s pharmacologic
activity
Absorption across the placenta
Metabolism by the fetus
Teratogenicity
FDA Classification of
Teratogens
Category
Category
Category
Category
Category
A
B
C
D
X
1
Category A
Category B
No evidence of risk in humans
Controlled studies show no risk
Safe for use in pregnancy
Examples: folic acid, levothyroxine
Category C
Risk cannot be ruled out – risk has been
demonstrated in animals but no controlled
studies are available in women
Benefit may justify risk
Examples: albuterol, aspirin, TMP/SMX,
ß-blockers, phenothiazines, loop diuretics,
guaifenesin, ACE inhibitors (1)
Category X
Contraindicated in pregnancy
Risk clearly outweighs benefit
Examples: finasteride, misoprostil,
retinoids, warfarin, thalidomide, alcohol,
cocaine
Either no evidence of risk in animal
studies
or animal studies reveal risk and risk not
demonstrated in well controlled trials
Examples: acetaminophen, cephalosporins,
penicillins, NSAIDs (1,2), insulin,
H-2 blockers
Category D
Positive evidence of risk
Risk usually outweighs benefitexception maybe made for certain
situations
Examples: benzodiazepines, thiazides,
certain oral hypoglycemic agents,
lithium, phenytoin, ACE inhibitors (2,3),
valproic acid, NSAIDs (3)
Routes of Administration
Route of administration may influence
use of medication
Examples inhaled steroids, vaginal
creams, topical creams
Flagyl® vs Metrogel®
Gynazole® vs Diflucan®
Flonase® vs prednisone
2
Sources of Drug Information
Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs
in Pregnancy and Lactation, 7th ed.
Baltimore: Lippincott, Williams and Wilkins
(2005)
PDR
Package insert
Epocrates and Lexi-Drug (PDA reference)
Drug Therapy of Pregnancy
Vitamin / Mineral Supplementation
Nausea / Vomiting
Diabetes in Pregnancy
Depression
Asthma
Rhinitis
Antibiotic Use
Folic Acid and Pregnancy
A supplement of 0.4 mg of folic acid
has been recommended to decrease the
risk of neural tube defects
Should be started 3 months prior to
intended conception and continued
throughout pregnancy
Patients with a history of affected
offspring should take 4 mg/day
Drug exposure during pregnancy
Many drug exposures occur prior to
knowledge of pregnancy – fetus most
susceptible
Need information – what medication was
used, verify pregnancy and gestational age
Use appropriate reference material to
determine risk
Report to pharmaceutical companies
Appropriate referral for diagnostic ultrasound
Vitamins and Minerals in
Pregnancy
Prenatal vitamin supplement is
recommended – formulation adjusted
for needs of and safety in pregnancy
Some contain an iron supplement
30 mg elemental iron recommended
Most contain additional calcium
Non-Pharmacologic Therapies
for Nausea / Vomiting
Small, frequent high CBH meals
Avoid triggers
Bedrest
Bio-Bands (Sea-bands)
Emetrol® – cola syrup
Ginger root
3
Pharmacological Treatment
Mild Nausea and Vomiting
pyridoxine (vitamin B-6)
meclizine (Antivert®, Bonine®)
dimenhydrinate (Dramamine®)
doxylamine (OTC Unisom®)
H2 blockers (ranitidine)
metoclopramide (Reglan®)
Hyperemesis
Severe nausea and vomiting resulting in
weight loss, electrolyte abnormalities
May require hospitalization
Can become life-threatening if
untreated
IV fluids, IV medication
Consider vitamin supplements (thiamine
and vitamin K) if protracted
Diabetes in Pregnancy
White’s Classification (cont)
D - Diabetes diagnosed before age 10 or
length of disease > 20 years or benign
retinopathy
EF - disease w/ nephropathy
H - presence of cardiac disease
R - proliferative retinopathy
RT - disease with a renal transplant
Pharmacologic Treatment
(cont)
promethazine (Phenergan®)
prochlorperazine (Compazine®)
ondansetron (Zofran®)
droperidol – associated with EKG
changes – used only as an inpatient on
a telemetry unit
Diabetes in Pregnancy
White’s Classification
A – Gestational Diabetes
A1: managed by diet alone
A2: managed by diet and insulin
B - Diabetes diagnosed after age 20 or
length of disease < 10 years
C - Diabetes diagnosed between age 10-19
or length of disease for 10-19 years
Gestational Diabetes
Treatment is definitely indicated for
elevated blood sugars that do not
respond to modification of diet
Insulin is the drug of choice
Glyburide has recently been shown to
be safe and effective
NEJM 10/19/2000
4
Depression
Asthma
SSRI’s - most common drug class used
Asthma course may worsen, improve or
remain unchanged during pregnancy
Poor asthma control biggest factor leading to
poor outcomes
OK to use:
Prozac®, Paxil®, Zoloft®, Celexa®, Lexapro®
Cymbalta®
Many cases of neonatal withdrawal reported
Start with lowest possible dose
Caution with Paxil® use
Breastfeeding helps
Post-partum depression & breastfeeding
Consider Zoloft® or Paxil®
Beta-agonists (Albuterol, Salmeterol, Fometerol)
Inhaled Corticosteroids (Budesonide, Fluticasone)
Theophylline
Cromolyn-decocromil
Antibiotic Use During
Pregnancy
Rhinitis (Allergies)
Complicates up to 20% of pregnancies
Avoid environmental triggers
1st generation antihistamines
Chlorpheniramine
Tripelennamine
2nd generation antihistamines
Loratadine (Claritin®)
Cetirizine (Zyrtec®)
Fexofenadine (Allegra®)
Safe
penicillins
cephalosporins
erythromycin
nitrofurantoin
Intranasal corticosteroids appear to be safe
Antibiotics and Pregnancy
contraindications
Sulfonamides can displace bilirubin from
binding sites and affect folic acid metablolism
Do not use in 3rd trimester
Tetracyclines cause staining of fetal teeth and
bones
Fluoroquinolones are associated with joint
malformations in animal studies
UTI in Pregnancy
Common infection during pregnancy
Risk of pyelonephritis, sepsis if
untreated
Benefit of culture and sensitivity
Treat with macrodantin, penicillins,
cephalosporins, Bactrim® (not third
trimester)
5
Parting thoughts #1
Prior to prescribing medication, ask your
female patients if they are attempting
pregnancy
May need to verify with pregnancy testing!!!
Use medications with safety information
Educate your patients
Drugs and Lactation
Drug Use During Lactation
Overview
“Safe” Drugs
Drugs to Avoid
“Safe” Drugs for use during
lactation
Most drugs are safe during lactation
Typically only 1-2 percent of the
maternal dose is secreted in breast milk
Again, utilize appropriate references
before prescribing to lactating patients
Many antibiotics
Antihistamines
Vitamins
Antidepressants – Paxil® with shortest
t½ and no active metabolite
Domperidone?
Treatment of Mastitis
Contraceptives and Lactation
Dicloxacillin, cephalexin
Encourage breastfeeding or pumping
No need to pump and discard
Infant treated via breastmilk
Estrogen containing contraceptives may
decrease milk supply
Progesterone-only-pills, Depo-Provera®, IUD’s
would be appropriate alternatives
Breast-feeding alone not adequate for
contraception
6
Medications Contraindicated
during Breast-feeding
Bromocriptine
Cocaine, Alcohol, PCP
Antineoplastic Agents
Cyclophosphamide
Methotrexate
Radioactive Iodine
Lithium, Ergotamine
Immunosuppresive Agents
Parting thoughts #2
Verify the appropriateness of treatment
prior to prescribing medication
Verify safety of the medication in
question
Typically, 1% of medications are
excreted in breast milk
Counsel your patient regarding risks
and benefits
Drug Dosing Principles
Individualize the dose!
mg/kg for most drugs
mg/m2 for chemotherapy
Make sure that you prescribe the correct
units (mg, mcg)
Make sure that the parent or caregiver
knows how to measure the dose
Educate the parents or caregiver
Sources of Drug Information for
Lactation
Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs
in Pregnancy and Lactation, 7th ed.
Baltimore: Lippincott, Williams and Wilkins
(2005)
Hale, TW. Medications and Mothers’ Milk,
Amarillo: Pharmasoft Medical Publishing,
11th ed. (2004)
Package insert
Epocrates or Lexi-Drug (PDA reference)
Drug Therapy in
Neonates and Pediatrics
Principles of Drug Dosing
Sources of Information
Routes of Administration
Treatment of Common Illnesses
Immunizations
Sources of Pediatric Drug /
Dosing Information
Gunn VL, Nechyba C, Barone NA, eds. Harriet
Lane Handbook, 17th ed. St. Louis: Mosby,
(2005).
Taketomo CK, et al., eds. Pediatric Dosage
Handbook, 12th ed. Hudson, OH: Lexi-Comp,
Inc. (2005).
Young TE, Mangum B. Neofax, 18th ed.
Raleigh, NC: Acorn Publishing, Inc. (2005)
7
Sources of Pediatric Drug /
Dosing Information
a Children’s Hospital pharmacy
National Poison Control Center:
1-800-222-1222
Dosing Conversion Factors
1 ml = 1 cc
1 tsp =5 ml
1/4 tsp = 1.25 ml
1/2 tsp = 2.5 ml
3/4 tsp = 3.75 ml
Routes of Administration
Oral
Solutions / Suspensions vs Elixirs
“Sprinkles”
Chewable tablets
Rectal
Make sure to specify “pediatric”
suppositories
Pediatric Drug Dosing
Look in more than one source if:
You are unfamiliar with the drug
The drug has a narrow therapeutic range
If you can’t find a pediatric drug
dosage, perhaps the drug shouldn’t be
used.
Don’t rely on adult formulas!
Pediatric Drug Dosing
When writing drug orders for pediatric
patients, BE EXPLICIT!
Good: 375 mg PO q12h
Bad: 37.5 mg/kg q12h
Awful: 75 mg/kg/d in 2 divided doses
Write legibly
ex: ampicillin vs. aminophylline
Routes of Administration
Topical
Increased absorption of topical drugs
(proportionately larger skin surface area;
increased with inflammation, plastic
diapers)
Special care with groin and face
Parenteral
IV preferred in neonates
8
Acetaminophen dosing
Treatment of Fever
Acetaminophen (Tylenol, Tempra, generics)
Drops
Elixer
Chewable
Weight (lbs) 80 mg/0.8 mls 160 mg/tsp 80 mg/tab
6-10
0.4 mls
11-15
0.8 mls
1/2 tsp
1 tab
16-20
1.2 mls
3/4 tsp
1.5 tabs
21-25
1.6 mls
1 tsp
2 tabs
26-30
2.0 mls
1 1/4 tsp
2.5 tabs
31-40
2.4 mls
1 1/2 tsp
3 tabs
41-50
3.2 mls
2 tsp
4 tabs
Note: Dosage is every 4 hours not to exceed 5 doses/ 24 hrs
Junior chewable tablets are 160 mg/tab
Acetaminophen: 10-15 mg/kg/dose
max 60 mg/kg/d
Ibuprofen: 5-10 mg/kg/dose
max 40 mg/kg/day
NO ASPIRIN!!!
Ibuprofen dosing
Cough / Cold
Ibuprofen (Motrin, Advil, generics)
Weight
Pounds
12-17
18-23
24-35
36-47
48-59
60-71
72-95
Age
Dose every 6-8 hours--Do not give if child has diarrhea or has been vomiting
Oral drops
Suspension
Chewable
Chewable
50 mg/1.25 mls
100 mg/5 mls
tablets 50 mg
tablets 100 mg
Fever
Fever
Kilos
<102.5
>102.5
5.5-7.9 6-11 mos 0.675 mls 1.25 mls
8-10.9 12-23 mos 1.25 mls 2.5 mls
11-15.9 2-3 yrs
2 mls
3.75 mls
16-21.9 4-5 yrs
22-26.9 6-8 yrs
27-31.9 9-10 yrs
32-43.9 11 yrs
Fever
<102.5
1/4 tsp
1/2 tsp
3/4 tsp
1 tsp
1 1/4 tsp
1 1/2 tsp
2 tsp
Fever
>102.5
1/2 tsp
1 tsp
1 1/2 tsp
2 tsp
2 1/2 tsp
3 tsp
4 tsp
Fever
<102.5
Fever
>102.5
1 tab
1 1/2 tab
2 tab
2 1/2 tab
3 tab
4 tab
2 tab
3 tab
4 tab
5 tab
6 tab
8 tab
Fever
<102.5
Fever
>102.5
Fever
<102.5
Fever
>102.5
1/2 tab 1 tab
3/4 tab 1 1/2 tab
1 tab
2 tab
1 cap
2 cap
1 1/4 tab 2 1/2 tab 1 1/4 cap 2 1/2 cap
1 1/2 tab 3 tab 1 1/2 cap 3 cap
2 tab
4 tab
2 cap
4 cap
Treatment of Otitis Media
Antibiotics
Drug selection
Duration of therapy
Chronic, suppressive therapy
Antihistamines / Decongestants
No evidence of value
Caplets
100 mg
Antihistamines
Decongestants
Expectorants
Cough suppressants
Treatment of Otitis Media
New criteria for treatment of otitis
media
Mild and moderate cases to be followed
expectantly to decrease overuse of
antibiotics
High-dose amoxicillin x 10 days
Single-dose azithromycin (30 mg/kg)
9
Primary Care Associates
1234 Wellness Road
Resume Speed, Kansas
Phone: 999-1212
Amoxicillin for 25 lb child
40 mg/kg/day in 3 divided doses
25 pounds = 11.4 kg
Daily dose = 40 x 11.4 = 456 mg = 450
450 mg/3 doses = 150 mg/dose
150 mg/dose / 125 mg/5 ml = 6 ml
Dose: 6 ml tid
Name ___Ear infection Emily____________________ Date ____________
Address ____123 Mulberry Ln________________ Age/Wt _18mo/25lbs
Rx
Amoxicillin susp. 125mg/5ml
Disp: 150 ml
Sig: 6 ml po tid x 5 days
____________________________
Dispense as Written
______________________
Substitution Permissible
Refills __________
Pharyngitis (Strep throat)
Usually caused by Group A beta-hemolytic
streptococcus
Only treat if rapid-screen is positive
10 day antibiotic course
1st choice: Pen-VK or Amoxicillin
2nd choice or PCN allergic: Macrolides or
Cephalosporins
Acute Bacterial Rhinosinusitis
Supportive Therapy
Hydration
Nasal saline spray and/or gel
Steam
Rest
Analgesia
Decongestants
Mucolytics
Acute Bacterial Rhinosinusitis
Initial therapy for mild disease w/o previous
abx use:
High-dose Augmentin®
High-dose amoxicillin
Cefpodoxime (Vantin®)
Cefuroxime (Ceftin®)
Cefdinir (Omnicef®)
With prior abx use in previous 4-6 weeks
High-dose Augmentin®
Ceftriaxone (50 mg/kg/day x 5 days by inj)
Allergic Rhinitis
Affects 40% of children
Risk factors
Pollution, maternal smoking, higher social class,
non-white race, early intro of foods
Environmental control measures
Decrease exposure to dander and pollens
Filtered vacuum
Air conditioner and dehumidifier
Wash bedding in hot water every 2 weeks
10
Allergic Rhinitis
Pharmacologic treatment
Antihistamines (1st gen vs 2nd gen)
Inhaled corticosteroids
Decongestants
Anticholinergic agents
Mast cell stabilizers
Leukotriene antagonist
Oral Corticosteroids
Childhood Asthma
Beta-agonists
Albuterol / Levalbuterol
Salmeterol
Formoterol (Foradil®)
Inhaled corticosteroids
Fluticasone (Flovent®)
Budesonide (Pulmicort®)
Theophylline - children metabolize faster
LT modifiers - (Singulair®) vs. Steroids
MDIs - for children > 4 yrs
Gastroesophageal Reflux
presenting symptoms and signs
Infants
Prednisone
Tablets
Liquid: 5mg/5ml
Prednisolone
Tablets
Liquid: 5 mg/5 ml and 15 mg/5 ml
Older child / adolescent
Fussy feedings
Arching
Irritability
Recurrent vomiting
Poor weight gain
Apnea
Poor sleeping
Recurrent vomiting
Heartburn
Esophagitis
Dysphagia or refusal to
eat
Asthma
Recurrent pneumonia
Upper airway symptoms
Gold, BD. Management Algorithm #1…Medscape Pediatrics.12/2004
Reflux
True reflux vs spitting up
Risk of aspiration in infancy
Goals of treatment:
eliminate symptoms
heal esophagitis
manage or prevent complications
maintain remission
Reflux
Non-pharmacologic therapy
Feed in upright position
Elevate crib mattress
Drug therapy
Motility agent – Metoclopramide (Reglan®)
H2 blockers – Ranitidine (Zantac®)
Proton Pump Inhibitors – Prilosec®,
Prevacid®
11
Vaccines - CDC 2007
Recommended Childhood Immunization Schedule
Benefits of vaccines
Prevention of acute illness
Prevention of complications of illnesses
Improvement in quality of life
Prevention of death
Herd immunity
Prevention of disease outbreaks
Reduction in health care costs
Contraindications to ALL
Vaccines
History of anaphylactic reaction to
vaccine
Concurrent moderate / severe illness
+/- fever
vomiting, diarrhea, otitis media
Vaccines - CDC 2007
Recommended Adolescent Immunization Schedule
Simultaneous Administration
Increases likelihood that child will be fully
immunized
No effect on ability of vaccine to confer
immunity
If not administered simultaneously, live
vaccines should be given 4 weeks apart
Inactivated vaccines do not interfere with
other vaccines and can be given at any time
interval
Contraindications to live,
attenuated vaccines
Immunocompromised individuals
Pregnancy
Receipt of antibody containing products
(blood or immunoglobulin) within the
last 3-5 months
12
Hepatitis B
Perinatal Transmission
Perinatal transmission a serious risk for
infants born to mothers with hepatitis B
90% of affected infants develop chronic
hepatitis
95% of cases acquired at delivery
Immunoglobulin available
Screening of all pregnant women for
hepatitis B - a practice standard
Vaccine 85-95% effective
Diphtheria, Pertussis,
and Tetanus
Diphtheria - acute infection that affects
tonsillar tissues
Pertussis – Whooping cough
high morbidity and mortality
Tetanus – infects wounds
Tetanus vaccine indicated at time of exposure if
greater than five years since last booster
Haemophilus Influenza type b
(HIb)
Leading cause of invasive bacterial
disease in the US
66% of cases affected children age <15
months
Prior to vaccination, 1/200 developed
invasive disease by age 5
60% had meningitis and 3-6% died
20-30% with permanent sequelae
Hepatitis B and delivery
First vaccine dose given to infants
before discharge
Infants born to HBsAg-positive /
HBsAg status unknown mothers receive
vaccine plus HBIG at delivery
Measles, Mumps, and Rubella
Measles
presents with cough, fever and rash
high morbidity and mortality
Mumps
infection of parotid and salivary glands,
encephalitis and meningitis
Rubella - viral infection
presents as a rash with fever, lymphadenopathy,
and arthralgias
congenital rubella can interfere with fetal
development
Polio Vaccine
Trivalent inactivated virus – IPV
Oral OPV no longer used
Contraindications
Avoid during pregnancy unless exposure
occurs
History of anaphylactic reaction to
streptomycin, bacitracin, neomycin
13
Streptococcus pneumoniae
(Prevnar®)
Varicella Zoster
Most common cause of community acquired
pneumonia in young children
Also causes septicemia and meningitis (5%)
mortality rate
Causative agent in 30-50% of otitis media
Carrier state – 30-50% of preschool children
Contraindicated if pt has h/o anaphylactic
reaction to gelatin or neomycin
Prior to vaccination, 90% of population
infected
Can result in severe complications and
hospitalizations
May cause congenital malformations
Neonatal infection caused by maternal
perinatal infection can be severe (35%
mortality)
Varicella Zoster (Varivax®)
Vaccination Guidelines
Influenza Vaccine
Live attenuated virus
Administer to any susceptible child at or
greater than 12 months of age
Susceptible children greater than age 13
should receive 2 doses 4 weeks apart
MMR-Varicella combo vaccine now available
70 to 90% effective in preventing disease
Influenza Vaccine
Fluzone®, Fluvirin®
For IM administration
Contain thimerosal
Flumist®
Intranasal administration
For ages 5-49 yrs
Often not covered by insurance ($23.50)
Contraindicated if severe allergy to eggs
Recommended for all children > 6 mo
Administered annually Oct – Dec
Dose
6-35 mos: 0.25 ml
3-8 yrs: 0.5 ml
Repeat dose in 1 mo if not previously
immunized
Hepatits A vaccine
Recommended for all children at 1yr
Should be given to children /
adolescents in regions of high risk
2 dose series – at least 6 months
between injections
VAQTA® - 12 mo or Havrix® - 2 yrs
14
Hepatits A cases in KS
Hepatits A cases in MO
Hepatits A Cases in the U.S.
Vaccines in Pregnancy
If indicated, you can give
Tetanus
Influenza (IM only)
Hepatitis B
If indicated, give the following before or after
pregnancy
MMR
Varicella
Hepatits A
Vaccines in the pipeline
Human Papillomavirus
Gardasil®, Cervarix®
Rotavirus
Rotateq®, Rotarix®
Invasive meningococcal disease
Menactra®
Immunization Standards
Vaccines should be readily available
Available for free or nominal charge
Immunization screening should be done
at all clinical encounters
Follow only “true” contraindications
Question and educate parents
www.immunize.org
15
Reporting Vaccine Adverse
Events
Health care providers should report
serious adverse events to the Vaccine
Adverse Event Reporting System
(VAERS) at 1-800-822-7967.
For more information, visit the following
site: http://www.vaers.org/
Other information and updates go to
www.cdc.gov/nip
Parting thought #3
Double check dosing and
appropriateness of medication choice
Verify references for medication use – if
you are unable to find references, the
medication probably should not be used
Follow CDC guidelines and
manufacturers instructions regarding
use of vaccines
Conclusion
16