Finasteride

6 ADVERSE REACTIONS The most common adverse reactions, reported in ≥1% of patients treated with finasteride tablets and greater than in patients treated with placebo are: decreased libido, erectile dysfunction and ejaculation disorder ( 6.1 ).To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. Clinical Studies for finasteride tablets 1 mg in the Treatment of Male Pattern Hair Loss In three controlled clinical trials for finasteride tablets of 12-month duration, 1.4% of patients taking finasteride tablets (n=945) were discontinued due to adverse experiences that were considered to be possibly, probably or definitely drug-related (1.6% for placebo; n=934). Clinical adverse experiences that were reported as possibly, probably or definitely drug-related in > 1% of patients treated with finasteride tablets or placebo are presented in Table 1. TABLE 1: Drug-Related Adverse Experiences for Finasteride tablets 1 mg (finasteride 1 mg) inYear 1 (%) MALE PATTERN HAIR LOSS Finasteride N=945 Placebo N=934 Decreased Libido 1.8 1.3 Erectile Dysfunction 1.3 0.7 Ejaculation Disorder (Decreased Volume of Ejaculate) 1.2 (0.8) 0.7 (0.4) Discontinuation due to drug-related sexual adverse experiences 1.2 0.9 Integrated analysis of clinical adverse experiences showed that during treatment with finasteride tablets, 36 (3.8%) of 945 men had reported one or more of these adverse experiences as compared to 20 (2.1%) of 934 men treated with placebo (p=0.04). Resolution occurred in men who discontinued therapy with finasteride tablets due to these side effects and in most of those who continued therapy. The incidence of each of the above adverse experiences decreased to < 0.3% by the fifth year of treatment with finasteride tablets. In a study of finasteride 1 mg daily in healthy men, a median decrease in ejaculate volume of 0.3 mL (-11%) compared with 0.2 mL (-8%) for placebo was observed after 48 weeks of treatment. Two other studies showed that finasteride at 5 times the dosage of finasteride tablets (5 mg daily) produced significant median decreases of approximately 0.5 mL (-25%) compared to placebo in ejaculate volume, but this was reversible after discontinuation of treatment. In the clinical studies with finasteride tablets, the incidences for breast tenderness and enlargement, hypersensitivity reactions, and testicular pain in finasteride-treated patients were not different from those in patients treated with placebo . Controlled Clinical Trials and Long-Term Open Extension Studies for finasteride tablets (finasteride 5 mg) and AVODART (dutasteride) in the Treatment of Benign Prostatic Hyperplasia In the finasteride tablets 5 mg Long-Term Efficacy and Safety Study (PLESS), a 4-year controlled clinical study, 3,040 patients between the ages of 45 and 78 with symptomatic BPH and an enlarged prostate were evaluated for safety over a period of 4 years (1,524 on finasteride tablets 5 mg/day and 1,516 on placebo). 3.7% (57 patients) treated with finasteride tablets 5 mg 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 2 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on finasteride tablets 5 mg was > 1% and greater than placebo over the 4 years of the study. In years 2 to 4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder. TABLE 2: Drug-Related Adverse Experiences for finasteride tablets 5 mg BENIGN PROSTATIC HYPERPLASIA Year 1 (%) Years 2, 3 and 4* (%) Finasteride 5 mg Placebo Finasteride 5 mg Placebo Impotence 8.1 3.7 5.1 5.1 Decreased Libido 6.4 3.4 2.6 2.6 Decreased Volume of Ejaculate 3.7 0.8 1.5 0.5 Ejaculation Disorder 0.8 0.1 0.2 0.1 Breast Enlargement 0.5 0.1 1.8 1.1 Breast Tenderness 0.4 0.1 0.7 0.3 Rash 0.5 0.2 0.5 0.1 *Combined Years 2 to 4 N = 1,524 and 1,516, finasteride vs placebo, respectively The adverse experience profiles in the 1-year, placebo-controlled, Phase III BPH studies and the 5-year open extensions with finasteride tablets 5 mg and PLESS were similar. There is no evidence of increased sexual adverse experiences with increased duration of treatment with finasteride tablets 5 mg. New reports of drug-related sexual adverse experiences decreased with duration of therapy. During the 4- to 6-year placebo- and comparator-controlled Medical Therapy of Prostatic Symptoms (MTOPS) study that enrolled 3,047 men, there were 4 cases of breast cancer in men treated with finasteride tablets 5 mg but no cases in men not treated with finasteride tablets 5 mg. During the 4-year placebo-controlled PLESS study that enrolled 3,040 men, there were 2 cases of breast cancer in placebo-treated men, but no cases were reported in men treated with finasteride tablets 5 mg. During the 7-year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with finasteride tablets, 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. The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 healthy men ≥55 years of age with a normal digital rectal examination and a PSA ≤3.0 ng/mL. Men received either finasteride tablets 5 mg (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 to 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 [AVODART (dutasteride)], similar results for Gleason score 8 to 10 prostate cancer were observed (1% dutasteride vs 0.5% placebo). The clinical significance of these findings with respect to use of finasteride tablets by men is unknown. No clinical benefit has been demonstrated in patients with prostate cancer treated with finasteride tablets. Finasteride tablets is not approved to reduce the risk of developing prostate cancer. Sexual Function Questionnaire A sexual function questionnaire was self-administered by patients participating in the two vertex baldness trials to detect more subtle changes in sexual function. At Month 12, statistically significant differences in favor of placebo were found in 3 of 4 domains (sexual interest, erections, and perception of sexual problems). However, no significant difference was seen in the question on overall satisfaction with sex life. In one of the two vertex baldness studies, patients were questioned on non-scalp body hair growth. Finasteride tablets did not appear to affect non-scalp body hair. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of finasteride tablets. 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: Hypersensitivity Reaction: hypersensitivity reactions such as rash, pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face); Reproductive System: sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders; male infertility and/or poor seminal quality (normalization or improvement of seminal quality has been reported after discontinuation of finasteride); testicular pain; hematospermia. Neoplasms: male breast cancer; Breast disorders: breast tenderness and enlargement; Nervous System/Psychiatric: depression, suicidal ideation and behavior.