PROSCAR SIDE EFFECTS

SIDE EFFECTS

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 trials of another drug and may not reflect the rates observed in clinical practice.

4-Year Placebo-Controlled Study (PLESS)

In PLESS, 1524 patients treated with PROSCAR and 1516 patients treated with placebo were evaluated for safety over a period of 4 years. The most frequently reported adverse reactions were related to sexual function. 3.7% (57 patients) treated with PROSCAR and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions.

Table 1 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on PROSCAR was ≥1% and greater than placebo over the 4 years of the study. In years 2-4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder.

Table 1: Drug-Related Adverse Experiences

Phase III Studies And 5-Year Open Extensions

The adverse experience profile in the 1-year, placebo-controlled, Phase III studies, the 5-year open extensions, and PLESS were similar.

Medical Therapy Of Prostatic Symptoms (MTOPS) Study

In the MTOPS study, 3047 men with symptomatic BPH were randomized to receive PROSCAR 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of PROSCAR 5 mg/day and doxazosin 4 or 8 mg/day (n=786), or placebo (n=737) for 4 to 6 years.

The incidence rates of drug-related adverse experiences reported by ≥2% of patients in any treatment group in the MTOPS Study are listed in Table 2.

The individual adverse effects which occurred more frequently in the combination group compared to either drug alone were: asthenia, postural hypotension, peripheral edema, dizziness, decreased libido, rhinitis, abnormal ejaculation, impotence and abnormal sexual function (see Table 2). Of these, the incidence of abnormal ejaculation in patients receiving combination therapy was comparable to the sum of the incidences of this adverse experience reported for the two monotherapies.

Combination therapy with finasteride and doxazosin was associated with no new clinical adverse experience.

Four patients in MTOPS reported the adverse experience breast cancer. Three of these patients were on finasteride only and one was on combination therapy.

The MTOPS Study was not specifically designed to make statistiical comparisons between groups for reported adverse experiences. In addition, direct comparisons of safety data between the MTOPS study and previous studies of the single agents may not be appropriate based upon differences in patient population, dosage or dose regimen, and other procedural and study design elements.

Table 2: Incidence ≥2% in One or More Treatment Groups Drug-Related Clinical Adverse Experiences in MTOPS

Long-Term Data

High-Grade Prostate Cancer

The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 men ≥55 years of age with a normal digital rectal examination and a PSA ≤3.0 ng/mL. Men received either PROSCAR (finasteride 5 mg) or placebo daily. Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study. The incidence of Gleason score 8-10 prostate cancer was higher in men treated with finasteride (1.8%) than in those treated with placebo (1.1%). In a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART), similar results for Gleason score 8-10 prostate cancer were observed (1% dutasteride vs 0.5% placebo).

No clinical benefit has been demonstrated in patients with prostate cancer treated with PROSCAR.

Breast Cancer

During the 4-to 6-year placebo-and comparator-controlled MTOPS study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with finasteride but no cases in men not treated with finasteride. During the 4-year, placebo-controlled PLESS study that enrolled 3040 men, there were 2 cases of breast cancer in placebo-treated men but no cases in men treated with finasteride. During the 7year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with finasteride, and 1 case of breast cancer in men treated with placebo. The relationship between long-term use of finasteride and male breast neoplasia is currently unknown.

Sexual Function

There is no evidence of increased sexual adverse experiences with increased duration of treatment with PROSCAR. New reports of drug-related sexual adverse experiences decreased with duration of therapy.

Postmarketing Experience

The following additional adverse events have been reported in postmarketing experience with PROSCAR. Because these events 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:

• hypersensitivity reactions, such as pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face)
• testicular pain
• hematospermia
• sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, decreased libido and ejaculation disorders (e.g. reduced ejaculate volume). These events were reported rarely in men taking PROSCAR for the treatment of BPH. Most men were older and were taking concomitant medications and/or had co-morbid conditions. The independent role of PROSCAR in these events is unknown.
• male infertility and/or poor seminal quality were reported rarely in men taking PROSCAR for the treatment of BPH. Normalization or improvement of poor seminal quality has been reported after discontinuation of finasteride. The independent role of PROSCAR in these events is unknown.
• depression
• male breast cancer.

The following additional adverse event related to sexual dysfunction that continued after discontinuation of treatment has been reported in postmarketing experience with finasteride at lower doses used to treat male pattern baldness. Because the event is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure:

• orgasm disorders