Pharmacological Treatment Options for _____BPH______

Barry VanDenHeuvel, PharmD Candidate 2007

Therapeutic Class/Agents
5a-reductase Inhibitors / Therapeutic Class/Agents
a-Adrenergic Antagonist
Product Availability
Generic (Brand) / Finasteride (Proscar)
Dutasteride (Avodart) / Prazosin (Minipress) *not recommended by the AUA
Terazosin (Hytrin)
Doxazosin (Cardura)
Alfuzosin (UroXatral)
Tamsulosin (Flomax)
Mechanism
of Action / Competitive inhibitors of 5a-reductase. This inhibits the conversion of testosterone to dihydrotestosterone (DHT) and suppresses serum DHT levels. DHT is responsible for prostate growth. The inhibition of DHT restricts prostate growth and reverses an enlarged prostate. This reversal may take up to 6 months to occur. / Alpha-blocker therapy is based on the hypothesis that clinical BPH is partly caused by alpha1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in bladder outlet obstruction. Alpha-adrenergic receptor antagonists (blockers) such as doxazosin, tamsulosin, alfuzosin, and terazosin inhibit this process and thus relieve the bladder outlet obstruction.
EFFICACY
(Indication/Use, Clinical Data Support) / Only for use in patients with enlarged prostate.
Also indicated for use in patients with uncontrolled arrhythmias, poorly controlled angina, patients taking multiple antihypertensive agents, or those unable to tolerate hypotensive adverse effects of a-Adrenergic antagonist.
With finasteride, the average patient experiences a 3-point improvement in the AUA Symptom Index.
Finasteride is ineffective
in patients who do not have enlarged prostates / a-Adrenergic Antagonist are faster acting and more effective than 5a-Reductase Inhibitors. A-Adrenergic Antagonists are effective in reducing LUTS independent of prostate size, have no effect on serum levels of PSA, and are associated with less sexual dysfunction than 5a-Reductase Inhibitors.
The use of alfuzosin, doxazosin, tamsulosin, and terazosin has been extensively investigated for the treatment of LUTS. Efficacy is dose dependent for the titratable alpha blockers doxazosin and terazosin —the higher the dose, the greater the observed improvement. Maximum tolerable and effective doses have not been defined for any alpha blocker, but reported clinical data support the efficacy and safety of titrating patients to 8 mg of doxazosin, to 0.8 mg of tamsulosin (from 0.4 mg), and to 10 mg of terazosin.
Meta-analyzed data from evidence-based reviews suggest that alfuzosin, doxazosin, tamsulosin, and terazosin are similarly effective in partially relieving symptoms, producing on average a 4-to-6 point improvement in the AUA Symptom Index.
SAFETY
(Major Drug Interactions,
Pre-cautions, Contra-indications,
Adverse Effects,
Pregnancy Risk Category) / Reported adverse events are primarily sexually related and include decreased libido, ejaculatory dysfunction, and erectile dysfunction and are reversible and uncommon after the first year of therapy.
Pregnancy Category X
Women should not handle these medications. / Tamsulosin not for use as an antihypertensive.
Alfuzosin is contraindicated in severe hepatic impairment.
The primary adverse events reported with alpha-blocker therapy are orthostatic hypotension, dizziness, tiredness (asthenia), ejaculatory problems, and nasal congestion.
The adverse event profile appears slightly different between the four alpha-blocking agents, for example, tamsulosin appears to have a lower probability of orthostatic hypotension but a higher probability of ejaculatory dysfunction than the other alpha blockers.
In men with hypertension and cardiac risk factors, doxazosin monotherapy was associated with a higher incidence of congestive heart failure than seen with other antihypertensive agents.
CYP2D6, 3A4 substrate
Pregnancy Category B-C
Therapeutic Class/Agents / Therapeutic Class/Agents
Dosage & Administration
(Include renal and/or hepatic adjustments) / Finasteride- Tablet 5mg
5mg once daily
No adjustments necessary
Dutatsteride- Capsule, soft-gel 0.5mg
0.5mg once daily
No adjustments necessary / Terazosin- Capsules 1, 2, 5, 10mg
1mg at bedtime, increased as needed up to 10mg/day normal dose.
No adjustments necessary
Tamsulosin- Capsules 0.4mg
0.4mg once daily, taken 30 minutes after the same meal each day.
No adjustments necessary
Doxazosin- Tablet 1, 2, 4, 8mg
1mg once daily, titrated slowly as needed up to a max of 8mg/day.
No adjustments necessary
Alfuzosin- Tablet 10mg
10mg once daily, taken immediately after the same meal each day.
Contraindicated in severe hepatic impairment
Monitoring
(Efficacy and Toxicity Parameters) /

Efficacy

Urinary symptoms

Toxicity

Sexual symptoms /

Efficacy

Urinary symptoms

Toxicity

BP- standing and sitting
Patient Education / Do not take any new medication during therapy unless approved by prescriber. Results of therapy may take several months. Take with or without meals. May cause decreased libido or impotence during therapy. Report any changes in urinary pattern (significant increase or decrease in volume or voiding patterns). Pregnancy precautions: This drug will cause fetal abnormalities - use barrier contraceptives and do not allow women of childbearing age to touch or handle broken or crushed tablets. / Report weight gain, or painful, persistent erection. Fainting sometimes occurs after initial dose, rise slowly after sitting or lying. Take at bedtime.
Alfuzosin, Doxazosin XL, Tamsulozin- do not crush, chew or open capsules.
Take at the same time everyday.
Cost
(1-month) / Finasteride- $79.99
Dutasteride- $77.99 / Alfuzosin- $52.99
Tamsulozin- $68.99
Doxazosin- GenericCardura
1 mg (30): $38.60
2mg-$21.992 mg (30): $38.60
4mg- $19.994 mg (30): $40.87
8mg- $23.998 mg (30): $43.14
Terazosin-GenericHytrin
1 mg (30): $13.991 mg (30): $67.39
2 mg (30): $13.992 mg (30): $65.15
5 mg (30): $13.995 mg (30): $65.15
10 mg (30): $13.9910 mg (30): $67.39
References
(Guidelines, Drug Info Sources) / Crlonline (lexiComp online)
AUA clinical guidelines, management of BPH
Dipiro, et al. Pharmacotherapy, A Pathophysiologic Approach / Crlonline (lexiComp online)
AUA clinical guidelines, management of BPH
Dipiro, et al. Pharmacotherapy, A Pathophysiologic Approach

Barry VanDenHeuvel, PharmD Candidate 2007Pharmacotherapy Presentation – Pharmaceutical Care Rotation

University of Maryland School of PharmacyHappy Harry’s Pharmacy Patient Care Center, Perryville, MD