FDA Approves Dutasteride/Tamsulosin Combo Pill for Benign Prostatic Hyperplasia

Yael Waknine

June 18, 2010

June 18, 2010 (UPDATED June 21, 2010) — The US Food and Drug Administration (FDA) has approved a single-capsule formulation of 0.5-mg dutasteride and 0.4-mg tamsulosin (Jalyn; GlaxoSmithKline) for symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate. The prescription product is expected to be available during the second half of 2010.

BPH is a progressive disease that affects nearly half of all men aged 50 years and older, and more than 90% of those older than 80 years. Common urinary symptoms are classified as irritative (frequency, urgency, and nocturia) or obstructive (hesitancy, incomplete emptying, intermittency, and weak stream).

Dutasteride (Avodart; GlaxoSmithKline) is a 5-α-reductase inhibitor that treats BPH symptoms and can shrink the prostate over time; it is currently approved by the FDA to reduce the risk for acute urinary retention and prostate-related surgery. Tamsulosin (Flomax; Astellas Pharma, Inc, marketed by Boehringer Ingelheim) is an alpha1a-adrenergic blocker that relaxes bladder and prostate muscles and is indicated for the symptomatic treatment of BPH.

"This is the first time these therapies will be available together in a once-daily capsule," said Anne Phillips, MD, vice president, R&D Medicine Development Leader, GlaxoSmithKline, in a company news release. "Jalyn offers two mechanisms of action to provide symptom improvement and the ability shrink the prostate over a sustained time."

FDA approval was based on 2-year data from the Combination of Avodart and Tamsulosin 4-year study of 4884 men aged 50 years and older with a serum prostate-specific antigen level of 1.5 to 10 ng/mL; maximal urinary flow rate (Qmax) ranging from more than 5 mL/second to 15 mL/second with a minimum voided volume of 125 mL; and International Prostate Symptom scores of 12 or higher associated with moderate to severe BPH symptoms.

Primary results showed that daily use of the drug combination yielded significantly greater relief of BPH symptoms compared with either 0.5 mg dutasteride or 0.4 mg tamsulosin alone, as measured by point changes on the International Prostate Symptom scale from baseline (mean Δ, −6.2 vs −4.9 and −4.3; P < .001 for both). The difference was observed by month 9 and continued through month 24.

On secondary endpoints, dutasteride–tamsulosin was shown to significantly improve maximal urinary flow rate from baseline compared with either drug alone (mean Δ Qmax, 2.4 mL/second vs 1.9 mL/second and 0.9 mL/second; P = .003 and P < .0001, respectively) — a difference that was observed by month 6 and continued through month 24.

Adverse events reported in the study were consistent with the known safety profiles of dutasteride and tamsulosin and most commonly included impotence, decreased libido, breast disorders (including enlargement and tenderness), ejaculation disorders, and dizziness.

The recommended dose of dutasteride–tamsulosin is a single 0.5 mg/0.4 mg capsule taken approximately 30 minutes after the same meal each day. The combination drug should not be used with strong inhibitors of cytochrome P 450 isoenzyme 3A4 (CYP 3A4) such as ketoconazole. Caution is advised when using moderate CYP 3A4 inhibitors, strong/moderate CYP 2D6 inhibitors, or warfarin, or when treating patients known to be poor metabolizers of CYP 2D6.

Because dutasteride–tamsulosin decreases total serum prostate-specific antigen concentrations by about 50%, patients with increased prostate-specific antigen levels during therapy should be evaluated for the presence of prostate cancer.

As with other alpha-1 blockers, tamsulosin may cause postural hypotension, dizziness, and vertigo. Patients should be cautioned to avoid situations in which syncope could result in injury. Concomitant treatment with other alpha-blockers or phosphodiesterase type 5 inhibitors should be avoided because of the increased risk for symptomatic hypotension.

Patients should also be advised that alpha-1 blockers, including tamsulosin, have been associated with a risk for priapism and rare reports of intraoperative floppy iris syndrome during cataract surgery.

Dutasteride–tamsulosin capsules should not be handled by women who are, or may become, pregnant. Dutasteride is absorbed through the skin and could result in unintended fetal exposure, potentially inhibiting the normal development of external male genitalia. To protect pregnant women from transfusion-related exposure, men receiving dutasteride should not donate blood until 6 months after termination of therapy.