Benign Prostatic Hyperplasia and the Medication

7/30/2019 Benign Prostatic Hyperplasia and the Medication

1/9

http://www.medscape.com/viewarticle/745454

www.medscape.com

Authors and Disclosures

Emily L. Knezevich, PharmD, BCPS, CDE

Assistant Professor of Pharmacy Practice

Jon T. Knezevich, PharmD, BCPS

Assistant Professor of Pharmacy Practice

Mikayla L. Spangler, PharmD, BCPS

Assistant Professor of Pharmacy Practice Creighton University School of Pharmacy and Health

Professions, Omaha, Nebraska

FromU.S. Pharmacist

Benign Prostatic Hyperplasia and the Medication

Management of Associated Lower Urinary Tract SymptomsEmily L. Knezevich, PharmD, BCPS, CDE; Jon T. Knezevich, PharmD, BCPS; Mikayla L. Spangler, PharmD,

BCPS

Posted: 07/11/2011; US Pharmacist 2011 Jobson Publishing

Abstract and Introduction

Introduction

Benign prostatic hyperplasia (BPH) is the most common benign tumor in men. [1] By age 50 years, up to

50% of men may have histologically distinguished BPH with reported prevalence increasing to90% by

age 90.[2] Histology indicating the presence of BPH includes proliferation of prostatic tissue around the

urethra. Despite the high prevalence of histologic diagnosis, symptoms of the disorder do not affect all

men presenting with BPH. Prostatic tissue overgrowth combined with poor glandular elasticity may lead

to urethral opening constriction. This may then become severe enough to negatively affect men's quality

of life (QOL)due to increased frequency of BPH-associated urinary symptoms. It has been reported that

50% of men diagnosed with histologic changes indicating BPH demonstrate urinary symptoms at age 80

years.[3]

Symptomatic BPH is generally recognized as including the presence of lower urinary tract symptoms

(LUTS). These symptoms may include problems with either storage or ability to void urine, or both. [3]

Symptoms are progressive with age and become significant if prostatic tissue growth results in urethral

constriction.[3] Symptoms are often measured with a tool developed by the American Urological

Association (AUA), known as the International Prostate Symptoms Score (IPSS). Table 1 describes

symptoms of BPH assessed by this tool, which are related to both storage and voiding dysfunction.
http://www.medscape.com/http://www.medscape.com/http://www.medscape.com/index/list_4891_0http://www.medscape.com/index/list_4891_0http://www.medscape.com/index/list_4891_0http://www.uspharmacist.com/home/http://www.medscape.com/index/list_4891_0http://www.medscape.com/


2/9

Table 1. Symptoms Assessed by International Prostate Symptoms Score (IPSS)a

Sensation of not emptying bladder

Frequency of urination

Interruption of urine stream

Difficulty postponing urination

Weakness of urine stream Need to strain to begin urination

Frequency of urination overnight (nocturia)

aSymptoms are assessed by the patient from a range of not at all (0 points) to almost always (5 points).

Nocturia is measured as a frequency of 05 or more times and receives a corresponding point value

(maximum of 5). Total score: 07 points = mild symptoms; 819 points = moderate symptoms; 2035

points = severe symptoms. Source: Reference 7.

Two main mechanisms can cause bladder obstruction. With prostatic tissue growth, the prostate

becomes enlarged. This, in turn, results in a narrowing of the urethral lumen. [4] A second mechanism is

related to smooth muscle tone mediated by alpha-adrenergic receptors.[4]

This smooth muscleencapsulates the prostate, urethra, and prostate stoma. Over stimulation of alpha-adrenergic receptors

located within the smooth muscle can increase muscle tone, worsening symptoms of obstruction and

retention of urine and decreasing the urinary flow rate. [4] Commonly used drug classes for BPH (alpha-

antagonists, 5-alpha-reductase inhibitors) focus on reversing these mechanisms.

Serious complications can arise from untreated BPH. Acute urinary retention, nephropathy, infections,

and bladder stones have all been reported outcomes of uncontrolled disease.[2] In addition, much QOL

research on BPH management has been done. Severity of symptoms is commonly related to QOL.[2] Men

with BPH report having concerns over sleep, their condition, mobility, leisure, activities of daily living, and

sexual activities.[2] Goals of therapy include measureable improvement in QOL through use of the IPSS,

amelioration of LUTS, and prevention of serious complications.[5]

Despite the great prevalence of BPH in today's society, many patients remain untreated. In an analysis of

1,500 men with BPH surveyed in a 1999 study completed in the United Kingdom, only 11% were aware

of treatment options that could treat or manage their disease. [6] Due to the vital role pharmacists play on

the health care team, involvement in the education of patients with BPH is essential in promotion of

therapy to manage their disease appropriately. As accessible health care professionals, pharmacists are

also well suited to recognize urinary symptoms as cause for alarm and advocate for referral to a health

care provider for evaluation to rule out other possible diagnoses (i.e., prostatitis, prostate cancer).

Medication Management of BPH

The use of drugs in the treatment of BPH is based upon disease severity as well as the underlyingcause. As previously mentioned, the AUA's IPSS can stage a patient's disease. For mild-to-moderate

symptoms, a period of watchful waiting is sometimes recommended in which no pharmacotherapy is

prescribed. As symptoms progress, alpha-antagonists are typically the first-line agents due to their

efficacy and rapid response seen upon initiation.[4] If symptoms persist despite optimization of alpha-

antagonists, or a patient is unable to tolerate side effects related to their use, 5-alpha-reductase inhibitors

may be added to the regimen. Other agents have shown possible benefit as well when used in

combination with standard treatment, or as monotherapy if patients are unable to tolerate usual


3/9

treatment. Table 2 reviews the available FDA-approved options for treating BPH, their dosing

recommendations, and their generic availability.[7]

Table 2. FDA-Approved Medications Used to Treat BPH

Medication Receptor Selectivity Dosing Range Generically Available

Alpha Antagonists

Alfuzosin 10 mg daily No

Doxazosin 18 mg daily Yes

Silodosin + 8 mg daily No

Tamsulosin + 0.40.8 mg daily Yes

Terazosin 110 mg daily Yes

5-Alpha-Reductase Inhibitors

Dutasteride + 0.5 mg daily No

Finasteride + 5 mg daily Yes

+: selective;: not selective; BPH: benign prostatic hyperplasia.

Source: References 3, 4.

Alpha-antagonists

The five alpha-antagonists currently available in the United States for the treatment of BPH are alfuzosin,

doxazosin, silodosin, tamsulosin, and terazosin. Alpha-antagonists are a useful option in the

management of moderate-to-severe LUTS secondary to BPH. Alpha-antagonists are the most effective

agents used to treat the moderate-to-severe and bothersome symptoms associated with bladder outlet

obstruction (BOO) secondary to BPH.[4] Symptoms related to urinary storage including frequency,

nocturia, urgency, and incontinence are generally reported as the most bothersome with the largestimpact on QOL. These symptoms are lessened by the use of alpha-antagonists. The alpha-antagonists

reduce BOO by decreasing the alpha-adrenergic tone of the smooth muscle within the prostate. [4]

There are three subtypes of alpha-receptors identified within the prostate (1A, 1B, and 1D), with about

70% of the subtypes being 1A.[8,9] The 1B subtype is located primarily in the peripheral vasculature and is

vital to blood pressure regulation, with very little effect on BPH. All available alpha-antagonists have

activity at all receptors, with only two being semiselective for the 1A subtype, tamsulosin and silodosin.

Tamsulosin is more selective for all subtypes, but the ratio of selectivity for the 1A subtype to 1B or1D is

greater for silodosin than tamsulosin. Despite this higher receptor affinity, all alpha-antagonists with the

exception of silodosin seem to have equal clinical efficacy, though clinical studies comparing all agents

are currently lacking.[3]

As silodosin was approved in 2008, it has only been compared head to head in a 12-week clinical trial

with tamsulosin.[10] Silodosin was found to be noninferior to tamsulosin; however, it must be noted that the

dose of tamsulosin used in the study (0.2 mg/day) is half the dose approved for clinical use in the U.S.

(0.4 mg/day). Most of the alpha-antagonists must be titrated slowly to effective doses with the exception

of alfuzosin and silodosin, which can be started at their recommended dose on day 1.[3]


4/9

The main difference between the various alpha-antagonists appears to be their side-effect profiles. The

second-generation alpha-antagonists (alfuzosin, doxazosin, terazosin) are all likely to have hypotensive

and other syncopal events associated with their use, with alfuzosin causing less hypotension than the

other two second-generation medications.[11] These adverse effects are dose related, so the lowest

effective dose should be used. Alfuzosin may also cause abnormal ejaculations; however, the newer

generation agents, tamsulosin and silodosin, are more likely to cause abnormal ejaculations, with

silodosin causing more retrograde ejaculation than tamsulosin. [12,13] Dizziness has been associated with

all agents.

Although rare, another adverse effect of the alpha-antagonists is intraoperative floppy iris syndrome (a

complication of cataract surgery). When offered alpha-antagonist treatment, men should be asked if

cataract surgery is planned, and therapy should be delayed until after the procedure is completed.

Tamsulosin has the most reported cases of floppy iris syndrome. [14]

All agents should be started at the lowest dose if the patient is concurrently taking a phosphodiesterase

type 5 (PDE-5) inhibitor and vice versa because of the possibility of a systemic hypotensive reaction with

concurrent use.[1517] Alfuzosin and silodosin are contraindicated in use with concurrent potent CYP3A4

inhibitors, and silodosin is not recommended for use with potent P-glycoprotein inhibitors.[18,19]

5-alpha-reductase Inhibitors

The 5-alpha-reductase inhibitor class has been shown to improve LUTS in the presence of BPH.[4] Two

drugs currently available within this class are finasteride and dutasteride (Table 2). These medications

differ in the extent that they are able to block the 5-alpha-reducatase conversion of testosterone to

dihydrotestosterone (DHT) within the body. By inhibiting the formation of DHT, 5-alpha-reducatase

inhibitors are able to mitigate the effects that androgens have on the prostate. Androgenic effects include

proliferation of prostate cells, decrease in prostate cell apoptosis, and elevation of rate of angio-genesis

within the prostate.[3] Finasteride works solely on the 5-alpha-reductase type II enzyme by inhibiting about

70% of the conversion of testosterone to DHT within the body, while dutasteride has been shown to

inhibit both 5-alpha-reductase type I and type II, preventing 95% conversion of testosterone to DHT. [4] As

a result of the high prevalence of 5-alpha-reductase type II enzymes present within the prostate and

genital tissue, any clinical benefits seen from dutasteride's inhibition of both 5-alpha-reductase enzymes

have not been evident. However, no comparative trials have been reported. [20]

Table 2. FDA-Approved Medications Used to Treat BPH

Medication Receptor Selectivity Dosing Range Generically Available

Alpha Antagonists

Alfuzosin 10 mg daily No

Doxazosin 18 mg daily Yes

Silodosin + 8 mg daily No

Tamsulosin + 0.40.8 mg daily Yes

Terazosin 110 mg daily Yes

5-Alpha-Reductase Inhibitors

Dutasteride + 0.5 mg daily No

Finasteride + 5 mg daily Yes


5/9

+: selective;: not selective; BPH: benign prostatic hyperplasia.


Meta-analyses have demonstrated an improved IPSS and peak urinary flow rate in patients who have

prostate volumes 30 mL upon initiating therapy.[21] Individuals with lower prostate volumes have not

shown statistically significant improvement in their symptom scores or peak urinary flow rates and will

most likely not benefit from a 5-alpha-reductase inhibitor.[21] Additionally, when using an agent in this

class, if prostate specific antigen (PSA) levels are monitored for the detection of prostate cancer, one

must understand that 5-alpha-reductase inhibitors typically decrease a patient's PSA by about 50%. [4]

Because of delayed prostatic response to this class of medications, after 3 to 6 months of therapy

practitioners should double the PSA level drawn if a patient is on a 5-alphareductase inhibitor in order to

appropriately assess the patient's true level.[2] If PSA levels increase or do not follow this trend, further

urologic workup is warranted. [4] In addition, dutasteride dosage reductions may be warranted in patients

concurrently taking CYP3A4 and CYP3A5 inhibitors. [22]

It should also be noted that 5-alpha-reductase inhibitors differ in their reported length of activity, with

finasteride's half-life estimated to be around 6 to 8 hours while dutasteride's is estimated to be 5

weeks.[20]

Appropriate treatment duration of at least 6 months should be allowed before a response isevaluated. Clinically important adverse effects in this class are decreased libido, decreased semen

quantity during ejaculation, and impotence. [21] Furthermore, gynecomastia is reported as a potential,

though infrequent, adverse event. Finally, it should be noted that all adverse effects have been shown to

diminish after the first year of treatment.[20]

Combination Therapy

The AUA guidelines for BPH state that with an enlarged prostate, the use of a combination alpha-

antagonist and 5-alpha-reductase inhibitor is effective and appropriate.[3] In short-term studies, the alpha-

antagonists were equally efficacious and safe compared with combination therapy but were better than

5-alpha-reductase inhibitor therapy alone.[23,24] However, in long-term studies in men with enlarged

prostates, combination therapy with both alpha-antagonist and 5-alpha-reductase inhibitor has

demonstrated clear benefit when compared to either agent alone in preventing disease progression and

improving symptoms.[25] In addition, combination therapy significantly reduces the risk of acute urinary

retention as well as the need for invasive procedures to correct the disorder. [25]

Recently, clinical evidence has emerged for using tolterodine, an anticholinergic, in the treatment of over-

active bladder and BPH if symptoms are not controlled with monotherapy with an alpha-antagonist.

Current literature evaluates combination therapy only with an alpha-antagonist.[26] Tolterodine works by

blocking the effects of acetylcholine on the central and peripheral nervous system, thus blunting the

bladder contraction effects known to occur when acted upon by the cholinergic nervous system. [26]

Clinical trials have demonstrated improvements in patients who did not have an overactive bladder but

suffered from LUTS that were irritative in nature (i.e., frequency, urgency, and nocturia). [3] Tolterodine isthe only anticholinergic to date that has been studied in combination treatment of BPH. [26] It is important

to note that tolterodine should only be used in combination with alpha-antagonists in patients with BPH

who have a postvoid residual volume of less than 250 to 300 mL because of the risk of urinary retention

with anticholinergic medications.[3] The most common adverse effect that has been reported with

tolterodine for this indication is dry mouth, with a reported incidence of up to 24%. [3] Other adverse events

described were similar to placebo.[3]


6/9

Complementary and Alternative Medicine

The AUA does not recommend the use of complementary and alternative medicine (CAM) to treat LUTS

caused by BPH.[3] This is related to the unavailability of clinical research demonstrating clear benefit with

its use as well as the lack of standardization of available products. [3]

The most well-studied CAM used for treatment of BPH is saw palmetto, which has been described in

some clinical trials as "likely safe" and "possibly effective" in treating LUTS associated with BPH.[27] In

clinical studies, saw palmetto has demonstrated mild improvements in LUTS and urinary flow measures

in patients with BPH; however, data from other studies are conflicting, questioning benefit in symptomatic

relief with long-term use.[4,27,28] Saw palmetto is well tolerated, with minimal adverse effects reported;

however, concern over increased risk of bleeding exists with its use, so caution should be used when

combining it with other medications that may prolong bleeding time.[28] Safety has been established with

the use of saw palmetto for up to 1 year. [27] Other CAM treatments marketed for LUTS associated with

BPH are listed in Table 3.[21,2729]

Table 3. CAM Therapies Used to Treat LUTS

CAM Therapy Possible Benefit Possible Risk

Urtica dioica(stinging nettle)

May decrease LUTS when combinedwith saw palmetto

Long-term safety unknown; risk ofhypoglycemia, hypotension, CNSdepression, decreased effect of warfarin

Cucurbita pepo(pumpkin seed oilextract)

May decrease prostate epitheliumwhen combined with saw palmettoand other herbal products

May decrease ejaculatory volume; maycause diuresis

Hypoxis rooperi(South African stargrass)

May decrease LUTS and improveQOL given alone or in combination

Possibly safe for up to 18 months of use;may cause bone marrow suppression andventricular tachycardia

Pygeum africanum

(African plum tree)

May decrease LUTS and increase

urine flow Likely safe

Opuntia (pricklypear cactus)

May decrease urgency and bladderfullness

Possibly safe up to 8 months of use; mayincrease risk of hypoglycemia

CAM: complementary and alternative medicine; CNS: central nervous system; LUTS: lower urinary tract

symptoms; QOL: quality of life.


Pharmacoeconomic Considerations

Economic considerations include direct medication and resource utilization costs. Other factors

considered include severity of symptoms, morbidities resulting from the disease, and patient QOL while

on therapy.[5] Appropriate patient selection for pharmacotherapy in treating BPH is essential when

considering cost of the disease. Watchful waiting is recommended in patients with low symptom severity

scores, whereas treatment is indicated in patients who have IPSS scores above 7 and are generally

considered to have moderate-to-severe LUTS.[5] Symptom severity at this level has demonstrated

significantly higher costs, more utilization of health care resources, and decreased QOL of patients,

indicating that cost of the disease would outweigh the cost of treatment. Because therapeutic options for

treatment of BPH differ in cost, efficacy, and potential for adverse effects, each class must be analyzed

separately to determine cost-effectiveness.


7/9

Alpha-antagonists

Though often quite effective in treating LUTS associated with BPH, alpha-antagonists can cause many

vasodilatory adverse effects, specifically the second-generation agents. [3] Patients taking these types of

alpha-antagonists may experience dizziness and hypotension and have increased risk of falling, all of

which may negatively impact their QOL in addition to increasing health utilization costs to treat any of

these adverse events. However, use of terazosin has demonstrated efficacy in treating LUTS with asignificant increase in QOL compared to placebo. [30]

Alfuzosin and tamsulosin both demonstrate improvement in QOL related to amelioration of LUTS without

significant adverse effects. However, compared to earlier generation alpha-antagonists, the direct cost of

these medications is generally higher.[5]

There are currently few comparisons regarding cost-efficacy analysis within the class; however, a study

published in 2004 compared cost-efficacy among tamsulosin, terazosin, and doxazosin use over 3

years.[31] Data from the comparison showed that direct medical costs were highest with tamsulosin;

however, tamsulosin was also associated with a higher success rate in limiting the need for transurethral

resection of the prostate (TURP), demonstrating a large cost savings. [31] In addition, at the time of this

study, tamsulosin was not generically available.

5-alpha-reductase Inhibitors

A number of studies have described the pharmacoeconomic benefit of using finasteride for periods of

time less than 3 years.[5] When comparing cost efficacy to other therapeutic options, and taking into

account the long-term risk reduction provided by 1 year of finasteride therapy, data show finasteride to

be less favored than doxazosin, but more cost-efficient than watchful waiting in patients not undergoing

surgery.[32] Common side effects of sexual dysfunction impair QOL and may impact cost-benefit analysis

of these agents, though long-term studies addressing cost efficacy have not been published to date, so it

is difficult to make conclusions at this time.

Combination Therapy

Because of its efficacy in halting symptoms and progression of BPH with use of combination therapy,

cost-effectiveness has also been demonstrated. Despite the likelihood of sexual side effects with

combination therapy and the resultant potential impact on QOL, analytic models demonstrate benefit in

men with moderate-to-severe LUTS.[32]

Conclusion

The medication management of BPH should be focused on improving LUTS associated with the disease

while limiting side effects of medications used to treat them. Alpha-antagonists remain the mainstay of

therapy, while patients with moderate-to-severe symptoms and enlarged prostates may see additional

benefit from 5-alpha-reductase inhibitors. Additional therapies, including herbal remedies and

combinations of available pharmacotherapy, may benefit some patients in reducing LUTS.

References

1. Scher HI. Chapter 91. Benign and malignant diseases of the prostate. In: Fauci AS, Braunwald

E, Kasper DL, et al, eds. Harrison's Principles of InternalMedicine. 17th ed.


8/9

www.accessmedicine.com.cuhsl.creighton.edu/content.aspx?aID=2893170. Accessed February

24, 2011.

2. McVary KT. BPH: epidemiology and comorbidities.Am J Manag Care. 2006;12(suppl 5):S122-

S128.

3. Chapter 1: AUA guideline on the management of benign prostatic hyperplasia: diagnosis and

treatment recommendations. American Urological Association.

www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/bph-

management/chapt_1_appendix.pdf. Accessed February 24, 2011.

4. Burnett AL, Wein AJ. Benign prostatic hyperplasia in primary care: what you need to know. J

Urol. 2006;175:S19-S24.

5. Nickel JC. BPH: costs and treatment outcomes.Am J Manag Care. 2006;12(suppl 5):S141-

S148.

6. Trueman P, Hood SC, Nayak US, Mrazek MF. Prevalence of lower urinary tract symptoms and

self reported diagnosed "benign prostatic hyperplasia," and their effect on quality of life in a

community-based survey of men in the UK. BJU Int. 1999;83:410415.

7. 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;148:15491557.

8. Caine M, Raz S, Zeigler M. Adrenergic and cholinergic receptors in the human prostate,

prostatic capsule and bladder neck. Br J Urol. 1975;47:193202.

9. Price DT, Schwinn DA, Lomasney JW, et al. Identification, quantitation, and localization of

mRNA for three distinct alpha 1 adrenergic receptor subtypes in human prostate. J Urol.

1993;150:546551.

10. Kawabe K, Yoshida M, Homma Y, for the Silodosin Clinical Study Group. Silodosin, a new alpha

1A-adrenoreceptor selective antagonist for treating benign prostatic hyperplasia: results of a

phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int.

2006;98:10191024.

11. Lee M. Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia.Am J Health

Syst Pharm. 2003;60:14261439.12. Andersson KE, Gratzke C. Pharmacology of alpha1-adrenoceptor antagonists in the lower

urinary tract and central nervous system. Nat Clin Pract Urol. 2007;4:368378.

13. Van Dijk MM, de la Rosette JJ, Michel MC. Effects of alpha1-adrenoceptor antagonists on male

sexual function. Drugs. 2006;66:287301.

14. Chatziralli IP, Sergentanis TN. Risk factors for intraoperative floppy iris syndrome: a meta-

analysis. Ophthalmology. 2011;118:730735.

15. Viagra (sildenafil) package insert. New York, NY: Pfizer Inc; March 2011.

16. Levitra (vardenafil) package insert. Westhaven, CT: Bayer Healthcare; March 2011.

17. Cialis (tadalafil) package insert. Indianapolis, IN: Eli Lilly; March 2011.

18. Uroxatral (alfuzosin) package insert. New York, NY: Sanofi-aventis Inc; May 2011.

19. Rapaflo (silodosin) package insert. Morristown, NJ: Watson Pharma; May 2011.

20. Kumar VL, Wahane VD. Current status of 5-alpha reductase inhibitors in the treatment of benign

hyperplasia of prostate. Indian J Med Sci. 2008;62:167175.

21. Chapple CR. Pharmacological therapy of benign prostatic hyperplasia/lower urinary tract

symptoms: an overview for the practicing clinician. BJU Int. 2004;94:738744.

22. Dolder CR. Dutasteride: a dual 5-alpha reductase inhibitor for the treatment of symptomatic

benign prostatic hyperplasia.Ann Pharmacother. 2006;40:658665.


9/9

23. Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign

prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study

Group. N Engl J Med. 1996;33:533539.

24. Kirby RS, Roehrborn C, Boyle P, et al. Efficacy and tolerability of doxazosin and finasteride,

alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the

Prospective European Doxazosin and Combination Therapy (PREDICT) trial.Urology.

2003;61:119126.

25. McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride,

and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J

Med. 2003;349:23872398.

26. Gallegos PJ, Frazee LA. Anticholinergic therapy for lower urinary tract symptoms associated

with benign prostatic hyperplasia. Pharmacotherapy. 2008;28:356365.

27. Natural Medicines Comprehensive Database.

http://naturaldatabase.therapeuticresearch.com.cuhsl.creighton.edu/home.aspx?cs=schoolnopl&

s=ND. Accessed February 24, 2011.

28. Berardi RR, Ferreri SP, Hume AL, et al. Handbook of Nonprescription Drugs: An Interactive

Approach to Self-Care. 16th ed. Washington, DC: American Pharmacists Association; 2009.

29. Levin RM, Das AK. A scientific basis for the therapeutic effects ofPygeum africanum and

Serenoa repens Urol Res. 2000;28:201209.

30. Hillman AL, Schwartz JS, Willian MK, et al. The cost-effectiveness of terazosin and placebo in

the treatment of moderate to severe benign prostatic hyperplasia. Urology. 1996;47:169178.

31. Ohsfeldt RL, Kreder KJ, Klein RW, Chrischilles EA. Cost-effectiveness of tamsulosin, doxazosin,

and terazosin in the treatment of benign prostatic hyperplasia. J Manag Care Pharm.

2004;10:412422.

32. McDonald H, Hux M, Brisson M, et al. An economic evaluation of doxazosin, finasteride and

combination therapy in the treatment of benign prostatic hyperplasia. Can J Urol. 2004;11:2327

2340.

US Pharmacist 2011 Jobson Publishing

Documents

Benign Prostatic Hyperplasia and the Medication