Clinical Trials Experience
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.
Monotherapy:
- The most common adverse reactions reported in subjects receiving Avodart were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), and ejaculation disorders.
- Study withdrawal due to adverse reactions occurred in 4% of subjects receiving Avodart and 3% of subjects receiving placebo. The most common adverse reaction leading to study withdrawal was impotence (1%).
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. Table 1 summarizes clinical adverse reactions reported in at least 1% of subjects receiving Avodart and at a higher incidence than subjects receiving placebo.
| * Includes breast tenderness and breast enlargement. | ||||
| Adverse Reactions | Adverse Reaction Time of Onset | |||
| Month 0-6 | Month 7-12 | Month 13-18 | Month 19-24 | |
| Avodart (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 | ||||
| Avodart | 4.7% | 1.4% | 1.0% | 0.8% |
| Placebo | 1.7% | 1.5% | 0.5% | 0.9% |
| Decreased libido | ||||
| Avodart | 3.0% | 0.7% | 0.3% | 0.3% |
| Placebo | 1.4% | 0.6% | 0.2% | 0.1% |
| Ejaculation disorders | ||||
| Avodart | 1.4% | 0.5% | 0.5% | 0.1% |
| Placebo | 0.5% | 0.3% | 0.1% | 0.0% |
| Breast disorders* | ||||
| Avodart | 0.5% | 0.8% | 1.1% | 0.6% |
| Placebo | 0.2% | 0.3% | 0.3% | 0.1% |
Long-Term Treatment (Up to 4 Years): There is no evidence of increased drug-related sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders with increased duration of treatment. The relationship between long-term use of Avodart and male breast neoplasia is currently unknown.
Combination with Alpha-Blocker Therapy (CombAT):
- The most common adverse reactions reported in subjects receiving combination therapy (Avodart plus tamsulosin) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Over 2 years of treatment, drug-related ejaculation disorders occurred more frequently in subjects receiving combination therapy (9%) compared to Avodart (2%) or tamsulosin (3%) as monotherapy.
- Study withdrawal due to adverse reactions occurred in 5% of subjects receiving combination therapy (Avodart plus tamsulosin) and 3% of subjects receiving Avodart or tamsulosin as monotherapy. The most common adverse reaction leading to study withdrawal in subjects receiving combination therapy was impotence (1%).
Over 4,800 male subjects with BPH were randomly assigned to receive either 0.5-mg Avodart, 0.4-mg tamsulosin, or combination therapy (0.5-mg Avodart plus 0.4-mg tamsulosin) administered once daily in a 4-year double-blind study. Adverse reaction information over the first 2 years of treatment is presented below; information for years 2 to 4 is not yet available as the study is ongoing. During the first 2 years, 1,623 subjects received monotherapy with Avodart; 1,611 subjects received monotherapy with tamsulosin; and 1,610 subjects received combination therapy. The population was aged 49 to 88 years (mean age, 66 years) and 88% Caucasian. Table 2 summarizes adverse reactions reported in at least 1% of subjects in any treatment group.
| * Combination = Avodart 0.5 mg once daily plus tamsulosin 0.4 mg once daily. | ||||
| † Includes breast tenderness and breast enlargement. | ||||
| Adverse Reactions | Adverse Reaction Time of Onset | |||
| Month 0-6 | Month 7-12 | Month 13-18 | Month 19-24 | |
| Combination (n)* | (n = 1,610) | (n = 1,524) | (n = 1,424) | (n = 1,345) |
| Avodart (n) | (n = 1,623) | (n = 1,547) | (n = 1,457) | (n = 1,378) |
| Tamsulosin (n) | (n = 1,611) | (n = 1,542) | (n = 1,468) | (n = 1,363) |
| Impotence | ||||
| Combination | 5.5% | 1.2% | 0.8% | 0.3% |
| Avodart | 3.9% | 1.2% | 0.6% | 0.7% |
| Tamsulosin | 2.7% | 0.8% | 0.4% | 0.4% |
| Decreased libido | ||||
| Combination | 4.5% | 0.9% | 0.4% | <0.1% |
| Avodart | 3.3% | 0.6% | 0.7% | 0.2% |
| Tamsulosin | 1.9% | 0.6% | 0.4% | 0.2% |
| Ejaculation disorders | ||||
| Combination | 7.6% | 1.6% | 0.4% | <0.1% |
| Avodart | 1.1% | 0.6% | 0.1% | 0.1% |
| Tamsulosin | 2.2% | 0.5% | 0.4% | 0.1% |
| Breast disorders† | ||||
| Combination | 1.0% | 1.1% | 0.7% | 0.3% |
| Avodart | 0.9% | 1.0% | 0.8% | 0.5% |
| Tamsulosin | 0.4% | 0.4% | 0.2% | 0.1% |
| Dizziness | ||||
| Combination | 1.1% | 0.4% | 0.2% | 0.0% |
| Avodart | 0.4% | 0.2% | <0.1% | <0.1% |
| Tamsulosin | 0.9% | 0.5% | 0.3% | 0.1% |
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 always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Avodart.
Immune System Disorders: Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema.
