Therapeutic Class Review Urology Medication Update February 2012

Therapeutic Class ReviewSM
Urology Medication Update
Benign Prostatic Hyperplasia
February 2012
Confidential
Executive Summary
Conclusion (Product Value)
• Tadalafil (Cialis) improves BPH symptoms; however the clinical significance is uncertain. It
is unknown how it compares to generically available alpha-1 adrenergic blockers (“alphablockers”) and 5-alpha-reductase inhibitors (“5ARIs”).
• Generic alpha-1-adrenergic blockers (alpha-blockers) and generic 5ARIs remain the best
value in the treatment of BPH, with no evidence of superiority of branded options.
Evidence of Efficacy
Key Evidence Question
Assessment
Does tadalafil (Cialis) improve BPH symptoms?
Does the evidence allow for comparisons between tadalafil (Cialis)
and other medications in the treatment of BPH?
Evidence
Quality
Modest
improvement
Moderate
Certainty
Insufficient
Evidence
Low
Certainty
Considerations of BPH medications in Subpopulations:
• Pediatrics: The safety and effectiveness in pediatrics have not been established.
• Geriatrics: BPH is prevalent in aging men. There is dose adjustment warranted based on age alone.
However, a greater sensitivity to medications in some older individuals should be considered such
as postural hypotension and risk of falls with alpha-blockers.
• Race, ethnicity: There is no apparent treatment difference due to race, or ethnicity.
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Formulary Considerations for tadalafil (Cialis)
Consideration
Efficacy
Practical Considerations
Other
Treatment
Options
Safety
Cost
Description
- There is moderate certainty that tadalafil (Cialis) provides a modest reduction in BPH
symptoms. However, the improvement might not be clinically meaningful.
- There is insufficient information as to how tadalafil (Cialis) compares with other BPH
medications, as it has not been studied in head-to-head trials.
- Alpha-blockers, 5ARIs, and their combinations have been mainstay of therapy for lower
urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS). Most are
available generically.
- Alpha-blockers have a relatively rapid onset with regard to improving BPH symptoms
- 5-alpha-reductase inhibitors reduce prostate size, to relieve BPH symptoms over time.
- Alpha-blockers and 5ARIs have a long track record for safety. Common adverse events
include postural hypotension and impotence, respectively.
- While tadalafil (Cialis) has a long track record for safety for on-demand use in erectile
dysfunction, long-term safety for daily use in BPH is unknown.
- Safety of tadalafil (Cialis) in combination with alpha-blockers or 5ARIs has not been
established.
Tadalafil (Cialis) for BPH is significantly more costly than generic alternatives.
Disease
Treatment
Aspects
Benign prostatic hyperplasia is a very common chronic and progressive disease in aging men.
Symptoms include increased frequency of urination, nocturia, hesitancy urgency and weak
urinary stream. [1] Treatments are aimed at short-term symptom relief and long-term avoidance
of urinary retention and the need for surgery.
Standard of
Care
The American Urological Association (AUA) recommends alpha-blockers and 5ARIs in
moderate to severe BPH symptoms. The AUA does not differentiate between the clinical
efficacy among medications within each drug class.[2]
Clinical
Burden
All existing BPH medications are dosed once daily. Tadalafil (Cialis) does not reduce clinical
barriers to treatment.
Commercial Formulary Decision
Recommendation
Maintain tadalafil
(Cialis) nonpreferred/
non-formulary
Rationale:
See Appendix H, Table 1, “Scenario 3”
When there is not high certainty in the evidence of effectiveness (U/P or I evidence)
and there are other established treatment options available, the medication must be
non-preferred / non-formulary unless there is uncertain confidence (or lacking
confidence) in the other available treatment options AND:
□ There are profound, proven safety advantages over established treatment
options. OR
□ Multiple treatment options are needed because established treatments are
clearly insufficient for most affected patients AND there are no significant
safety concerns AND overall costs are not raised.
Medicare Part D Formulary Decision
Do not add tadalafil (Cialis) to the formulary.
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Product Information and Cost
A. Current products for benign prostatic hyperplasia (BPH)
Drug Products
FDA
approval
a
Patent
Expiration(s)b
Phosphodiesterase 5 (PDE5) Inhibitor
tadalafil (Cialis®)[3]
11/21/03 11/21/2017
[Eli Lilly and
Company]
Alpha-1 Adrenergic Blockers (Alpha-Blockers)
alfuzosin HCl XL[4]
06/2003
Expired
[generic]
doxazosin mesylate[5]
[generic]
BPH: 5 mg PO
once daily
$135c
for
BPH
None listed.
Treatment of
the signs and
symptoms of
BPH
10 mg PO
once daily
after a meal
$98d
-Treatment of
the signs and
symptoms of
BPH
-Hypertension
Treatment of
the signs and
symptoms of
BPH
2 mg to 8 mg
PO once daily
$9d
4 mg to 8 mg
PO once daily
$58d
- Bladder neck obstruction,
Primary - LUTS
- Chronic prostatitis chronic pelvic pain
syndrome
- ED - LUTS
- Hypertension
- Spinal cord injury
- Cardiac syndrome X
- Congestive heart failure
- Disorder of the urinary
system
- ED; Diagnosis
- Pheochromocytoma
- Ureteric stone
Expired
10/2008
12/2013
Treatment of
the signs and
symptoms of
BPH
8 mg PO once
daily with a
meal
$121d
None listed.
04/1997
Expired
Treatment of
the signs and
symptoms of
BPH
0.4 mg to 0.8
mg PO once
daily
$20d
08/1987
Expired
- Treatment of
the signs and
symptoms of
BPH
- Hypertension
2 mg to 10 mg
PO once daily
at bedtime
$9d
- Chronic prostatitis
- Pelvic pain syndrome
- Disorder of the urinary
system - Spinal cord injury
- LUTS
- Neurogenic bladder
- Radiation-induced disorder
- Urethritis
- Ureteric stone
- Carcinoma of prostate
- Chronic prostatitis chronic pelvic pain
syndrome
- Congestive heart failure
- Hyperlipidemia
- Nocturia
- Oligozoospermia
- Radiation-induced
urethritis
- Spinal cord injury
[generic]
terazosin HCl[9]
- Treatment of
the signs and
symptoms of
BPH
- ED
Potential Off-label Uses
02/2005
[Watson]
tamsulosin HCl[8]
Cost
Expired
[Pfizer]
silodosin (Rapaflo®)[7]
Usual
Dose/Route
11/1990
[generic]
doxazosin mesylate
XL (Cardura XL®)[6]
FDA
approved
indications
Page 3 of 6
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5-Alpha Reductase Inhibitors (5ARIs)
dutasteride
11/2001
11/2015
(Avodart®)[10]
[GlaxoSmithKline]
finasteride[11]
06/1992
Expired
[generic]
Combination Products
dutasteride/tamsulosin
(Jalyn®)[12]
06/2010
11/2015
- Symptomatic
BPH, alone
or with
tamsulosin
- To reduce
the risk of
AUR and
BPH-related
surgery
- Symptomatic
BPH, alone
or with
doxazosin
- To reduce
the risk of
AUR and
BPH-related
surgery
- Alopecia
0.5 mg PO
once daily
$112d Male pattern alopecia
5 mg PO once
daily
$19d
Treatment of
symptomatic
BPH
One capsule
(dutasteride
0.5
mg/tamsulosin
0.4 mg) PO
once daily
$117d
[GlaxoSmithKline]
- Carcinoma of prostate
- Carcinoma of prostate;
prophylaxis
- Hidradenitis suppurativa
- Hirsutism
- Male pattern alopecia
None listed.
ED: erectile dysfunction; LUTS: lower urinary tract symptoms; AUR: acute urinary retention.
a
b
c
d
e
Date applies to approval date for the original brand name medication where there are now generics available.
Based on patents listed in Orange Book as of 10/24/2011.
Estimated cost per prescription for 30-day supply from AWP as of 10/24/2011, considering a dosing range, based on the prescribing information.
Average cost per prescription based on RegenceRx claims data as listed on RegenceRx PriceGuide for 30 day supply as of 10/24/2011.
As listed in © 1974 – 2011 Thomson MICROMEDEX database or as referenced.
B. Pipeline products
No pipeline products were identified.
Page 4 of 6
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References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (BPH).
Revised, 2010. [cited 11/9/2011]; Available from: http://www.auanet.org/content/clinical-practiceguidelines/clinical-guidelines.cfm?sub=bph
McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign
prostatic hyperplasia. J Urol. 2011 May;185(5):1793-803. PMID: 21420124
Cialis® [prescribing information]. Indianapolis, IN: Lilly USA, LLC; October 2011
sanofi-aventis U.S. LLC. Uroxatral (alfuzosin HCl) prescribing information. [cited 10/25/2011];
Available from: http://products.sanofi.us/uroxatral/uroxatral.html
Cardura® [product information]. New York, NY: Pfizer; July 2009
Cardura® XL [product information]. New York, NY: Pfizer; July 2011
Watson Pharma, Inc. Rapaflo® (silodosin) prescribing information. [cited 10/24/2011]; Available from:
http://pi.watson.com/data_stream.asp?product_group=1630&p=pi&language=E
Flomax® [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.;
January 2011
Hytrin® [presccribing information]. North Chicago, IL: Abbott Laboratories; July 2009
Avodart® [prescribing information]. Research Triangle Park, NC GlaxoSmithKline; June 2011
Proscar® [prescribing information] Whitehouse Station, NJ: Merck & CO., INC.; June 2011
Jalyn™ [prescribing information]. Research Triangle Park, NC GlaxoSmithKline June 2011
McNicholas T, Kirby R. Benign prostatic hyperplasia and male lower urinary tract symptoms (LUTS).
Clin Evid (Online). 2011;2011. PMID: 21871136
Tacklind J, Fink HA, Macdonald R, Rutks I, Wilt TJ. Finasteride for benign prostatic hyperplasia.
Cochrane Database Syst Rev. 2010(10):CD006015. PMID: 20927745
Porst H, Kim ED, Casabe AR, et al. Efficacy and Safety of Tadalafil Once Daily in the Treatment of
Men With Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Results of an
International Randomized, Double-Blind, Placebo-Controlled Trial. Eur Urol. 2011 Nov;60(5):1105-13.
PMID: 21871706
Egerdie RB, Auerbach S, Roehrborn CG, et al. Tadalafil 2.5 or 5 mg Administered Once Daily for 12
Weeks in Men with Both Erectile Dysfunction and Signs and Symptoms of Benign Prostatic
Hyperplasia: Results of a Randomized, Placebo-Controlled, Double-Blind Study. J Sex Med. 2011 Oct 7.
PMID: 21981682
Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower
urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol. 2008
Oct;180(4):1228-34. PMID: 18722631
Roehrborn CG, Siami P, Barkin J, et al. The effects of dutasteride, tamsulosin and combination therapy
on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2year results from the CombAT study. J Urol. 2008 Feb;179(2):616-21; discussion 21. PMID: 18082216
Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and
tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results
from the CombAT study. Eur Urol. 2010 Jan;57(1):123-31. PMID: 19825505
FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a
more serious form of prostate cancer. 6-9-2011. [cited 11/28/2011]; Available from:
http://www.fda.gov/drugs/%20drugsafety/ucm258314.htm
Centers for Medicare & Medicaid Services (CMS). Part D Patient Safety Measures-Updated NDC lists
(July 16, 2010). [cited 11/21/2011]; Available from:
https://www.cms.gov/PrescriptionDrugCovContra/Downloads/MemoPatientSafetyMeasures_07.16.10.p
df
FDA: Postmarket Drug Safety Information for Patients and Providers. Cialis (tadalafil) Information
[11/2007]. [cited 11/29/2011]; Available from:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm1
18686.htm
Page 5 of 6
© 2012 RegenceRx. All rights reserved.
23.
24.
25.
26.
27.
28.
29.
30.
Donatucci CF, Brock GB, Goldfischer ER, et al. Tadalafil administered once daily for lower urinary
tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study. BJU Int.
2011 Apr;107(7):1110-6. PMID: 21244606
Kramer BS, Hagerty KL, Justman S, et al. Use of 5-alpha-reductase inhibitors for prostate cancer
chemoprevention: American Society of Clinical Oncology/American Urological Association 2008
Clinical Practice Guideline. J Clin Oncol. 2009 Mar 20;27(9):1502-16. PMID: 19252137
Siami P, Roehrborn CG, Barkin J, et al. Combination therapy with dutasteride and tamsulosin in men
with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT
(Combination of Avodart and Tamsulosin) trial rationale and study design. Contemp Clin Trials. 2007
Nov;28(6):770-9. PMID: 17761460
Barry MJ, Fowler FJ, Jr., O'Leary MP, et al. The American Urological Association symptom index for
benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J
Urol. 1992 Nov;148(5):1549-57; discussion 64. PMID: 1279218
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile
function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997
Jun;49(6):822-30. PMID: 9187685
Rosen RC, Cappelleri JC, Gendrano N, 3rd. The International Index of Erectile Function (IIEF): a stateof-the-science review. Int J Impot Res. 2002 Aug;14(4):226-44. PMID: 12152111
Barry MJ, Fowler FJ, Jr., O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK. Measuring diseasespecific health status in men with benign prostatic hyperplasia. Measurement Committee of The
American Urological Association. Med Care. 1995 Apr;33(4 Suppl):AS145-55. PMID: 7536866
National Cancer Institute (NCI), U.S. National Institutes of Health [webpage]. Prostate-Specific Antigen
(PSA) Test. [cited 12/13/2011]; Available from:
http://www.cancer.gov/cancertopics/factsheet/Detection/PSA
Disclaimer: The information contained within this document best reflects the current state of medication information at the
date of publication. Conclusions may be subject to change over time because of many factors, including but not limited to:
emerging scientific evidence for safety and efficacy, evolving best-practices for critical appraisal of scientific evidence,
market availability of medications, medication cost information, and evolving medical practice standards.
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