Duagen

Duagen (dutasteride) is a synthetic 4-azasteroid compound that is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5α-reductase (5AR), an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT).

Dutasteride is chemically designated as (5α, 17β)-N-{2, 5 bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-l-ene-17-carboxamide. The empirical formula of dutasteride is C27H30F6N2O2, representing a molecular weight of 528.5.

Dutasteride is a white to pale yellow powder with a melting point of 242 to 250°C. It is soluble in ethanol (44 mg/mL), methanol (64 mg/mL) and polyethylene glycol 400 (3 mg/mL), but it is insoluble in water.

Duagen (dutasteride) Soft Gelatin Capsules for oral administration contain 0.5 mg of the active ingredient dutasteride in yellow capsules with red print. Each capsule contains 0.5 mg dutasteride dissolved in a mixture of mono-di-glycerides of caprylic/capric acid and butylated hydroxytoluene. The inactive excipients in the capsule shell are gelatin (from certified BSE-free bovine sources), glycerin, and ferric oxide (yellow). The soft gelatin capsules are printed with edible red ink.

Duagen (dutasteride) Soft Gelatin Capsules 0.5 mg are oblong, opaque, dull yellow, gelatin capsules imprinted with "GX CE2" in red ink on one side packaged in bottles of 100 (NDC 0173-0712-00) with child-resistant closures and unit dose blister packs of 70 capsules (NDC 0173-0712-01).

Storage and Handling: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Dutasteride is absorbed through the skin. Duagen (dutasteride) Soft Gelatin capsules should not be handled by women who are pregnant or who may become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus (see CLINICAL PHARMACOLOGY: Pharmacokinetics, WARNINGS: Exposure of Women†?Risk to Male Fetus, and PRECAUTIONS: Information For Patients and Pregnancy).

Manufactured by:

RP Scherer Beinheim, France for

GlaxoSmithKline

GlaxoSmithKline

Research Triangle Park, NC 27709

©2001 ,GlaxoSmithKline All rights reserved.

(Updated Sep 05, 2003)

Adverse reactions were generally mild and transient. The most common adverse events leading to withdrawal in both treatment groups were associated with the reproductive system.

The data described below reflect exposure to Duagen (dutasteride) in 2166 male subjects, including 1772 exposed for one year. Over 4300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of Duagen (dutasteride) in three identical, placebo-controlled Phase in treatment studies. The population was aged 47 to 94 years (mean age 66 years) and greater than 90% Caucasian. A total of 267 subjects (6% of each treatment group) were withdrawn from the studies due to adverse experiences, usually associated with the reproductive system. Withdrawals due to adverse events considered by the investigator to have a reasonable possibility of being caused by the study medication occurred in 3% of the subjects receiving Duagen (dutasteride) and in 2% of the subjects receiving placebo. Table 1 summarizes clinical adverse reactions that were reported by the investigator as drug-related in at least 1% of subjects receiving Duagen (dutasteride) and at a higher incidence than subjects receiving placebo.

Table 1: Drug-related Adverse Events* Reported in >1% Subjects and More Frequently in the

Duagen (dutasteride) Group than the Placebo Group Pivotal Studies Pooled