Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Most adverse reactions were mild or moderate and generally resolved while on treatment in both the AVODART and placebo groups. The most common adverse events leading to withdrawal in both treatment groups were associated with the reproductive system.

Over 4,300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of AVODART in 3 identical 2-year, placebo-controlled, double-blind, Phase 3 treatment studies, each with 2-year open-label extensions. During the double-blind treatment period, 2,167 male subjects were exposed to AVODART, including 1,772 exposed for 1 year and 1,510 exposed for 2 years. When including the open-label extensions, 1,009 male subjects were exposed to AVODART for 3 years and 812 were exposed for 4 years. The population was aged 47 to 94 years (mean age, 66 years) and greater than 90% Caucasian. Over the 2-year double-blind treatment period, 376 subjects (9% of each treatment group) were withdrawn from the studies due to adverse experiences, most commonly associated with the reproductive system, with similar findings during the 2-year open-label extensions. Withdrawals due to adverse events considered by the investigator to have a reasonable possibility of being caused by the study medication occurred in 4% of the subjects receiving AVODART and in 3% 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 AVODART and at a higher incidence than subjects receiving placebo.

Table 1. Drug-Related Adverse Events* Reported in ≥1% Subjects Over a 24-Month Period and More Frequently in the Dutasteride Group Than the Placebo Group (Pivotal Studies Pooled)
	Adverse Event Onset
Adverse Events	Month 0-6	Month 7-12	Month 13-18	Month 19-24
Dutasteride (n)	(n = 2,167)	(n = 1,901)	(n = 1,725)	(n = 1,605)
Placebo (n)	(n = 2,158)	(n = 1,922)	(n = 1,714)	(n = 1,555)
Impotence
Dutasteride	4.7%	1.4%	1.0%	0.8%
Placebo	1.7%	1.5%	0.5%	0.9%
Decreased libido
Dutasteride	3.0%	0.7%	0.3%	0.3%
Placebo	1.4%	0.6%	0.2%	0.1%
Ejaculation disorder
Dutasteride	1.4%	0.5%	0.5%	0.1%
Placebo	0.5%	0.3%	0.1%	0.0%
Gynecomastia†
Dutasteride	0.5%	0.8%	1.1%	0.6%
Placebo	0.2%	0.3%	0.3%	0.1%
*A drug-related adverse event is one considered by the investigator to have a reasonable possibility of being caused by the study medication. In assessing causality, investigators were asked to select from 1 of 2 options: reasonably related to study medication or unrelated to study medication.
† Includes breast tenderness and breast enlargement.

Long-Term Treatment (Up to 4 Years)

There is no evidence of increased drug-related sexual adverse events (impotence, decreased libido and ejaculation disorder) or gynecomastia with increased duration of treatment. The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of AVODART. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) potential causal connection to AVODART.

· allergic reactions, including rash, pruritus, urticaria, and localized edema.