Manufacturer:

GlaxoSmithKline Pharmaceuticals

Pharmacological Class:

Type I and II 5α-reductase inhibitor + α1A-blocker.

Active Ingredient(s):

Dutasteride 0.5mg, tamsulosin HCl 0.4mg; caps.

Indication(s):

Benign prostatic hyperplasia (BPH).

Pharmacology:

The development and enlargement of the prostate gland is largely controlled by the androgen, dihydrotestosterone. It is formed by the conversion of testosterone through the action of the enzyme steroid 5α-reductase. The type 2 isoform of this enzyme is primarily active in reproductive tissues, while the type 1 also works in the skin and the liver. Dutasteride is a selective inhibitor of both type 1 and type 2 5α-reductase. By inhibiting the formation of dihydrotestosterone, dutasteride reduces prostate enlargement.

Smooth muscle tone is controlled by the sympathetic nervous system via stimulation of α₁-adrenergic receptors. Most (70%) of the α₁-adrenergic receptors in the prostate are of the type α1A subtype. Tamsulosin is an α1A-antagonist that is selective for those receptors. It improves urine flow rates and reduces the symptoms of BPH by relaxing the smooth musculature in the bladder neck and prostate.

Dutasteride is metabolized by CYP3A4 and CYP3A5, and tamsulosin is metabolized mainly by CYP3A4 and CYP2D6. In making decisions regarding drug therapy, potential interactions with other drugs that affect these metabolic enzymes should be considered.

Clinical Trials:

A 4-year, multicenter, randomized, double-blind study investigated the efficacy of dutasteride + tamsulosin compared to either drug alone in relieving the symptoms of BPH. The primary efficacy endpoint for this parallel group study was based on the change in the International Prostate Symptom Score (IPSS). The results of this study indicated that coadministration therapy (dutasteride 0.5mg/day + tamsulosin HCl 0.4mg/day) was statistically superior to each of the monotherapy treatments in reducing the symptom score at month 24. Also, coadministration of both drugs was superior to monotherapy in increasing maximum urine flow rates. Prostate volume was reduced by both dual therapy and monotherapy with dutasteride, but not for tamsulosin.

Legal Classification:

Rx

Adults:

Swallow whole. Take ½ hour after same meal each day. 1 capsule daily.

Children:

Not recommended.

Contraindication(s):

Not for use in children or women. Pregnant women and those of childbearing potential should avoid handling capsules. Pregnancy (Cat.X). Nursing mothers.

Warnings/Precautions:

Rule out prostate cancer. Monitor prostate specific antigen (PSA) values (set new baseline PSA after 3–6 months of treatment); double PSA levels to compare with normal values. Monitor for prostate cancer, obstructive uropathy. Syncope. End-stage renal disease. Severe hepatic impairment. Cataract surgery (intraoperative floppy iris syndrome possible). Poor metabolizers (low CYP2D6 activity). Sulfa allergy. Avoid donating blood until at least 6 months after last dose.

Interaction(s):

Concomitant strong inhibitors of CYP3A4 (eg, ketoconazole): not recommended; caution with strong CYP2D6 inhibitors (eg, paroxetine). Do not use with other alpha-blockers. Potentiated by cimetidine. Dutasteride may be potentiated by moderate CYP3A4/5 inhibitors (eg, diltiazem, erythromycin). Tamsulosin may be potentiated by a concomitant combination of CYP3A4 and CYP2D6 inhibitors (eg, terbinafine). Caution with PDE-5 inhibitors (may increase orthostatic hypotension). Monitor warfarin.

Adverse Reaction(s):

Ejaculation disorders, impotence, decreased libido, dizziness, breast disorders, orthostatic hypotension and/or syncope; rare: priapism.

How Supplied:

Caps—30, 90

Last Updated:

9/9/2010