finasteride (Rx)

1-10%

Erectile dysfunction (1.3-8.1%)

Decrease libido (1.8-6.4%)

Breast enlargement (0.5-1.8%)

Ejaculation disorder (0.8-1.2%)

<1%

Breast tenderness (0.4-0.7%)

Rash (0.5%)

Postmarketing Reports

Neoplasms: Male breast cancer

Breast disorders: Breast tenderness and enlargement

Nervous system/psychiatric: Depression

Hypersensitivity reactions: 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

Contraindications

Hypersensitivity

Women of childbearing potential

Cautions

Use with caution with obstructive uropathy; carefully monitor patients with large residual urinary volume or severely diminished urinary flow

Use caution in liver disease

May cause decreased serum PSA in presence of prostate cancer; increases in PSA levels from nadir while on finasteride may signal the presence of prostate cancer and should be carefully evaluated (even if PSA value within normal range)

Pregnant and potentially pregnant women should not handle crushed or broken tablets or semen of male partner; may have negative impact in fetal development

Rare reports of male breast cancer observed with use; any breast tenderness, enlargement, pain, lumps, nipple discharge or any other type of breast changes should be reported immediately to healthcare provider

5-ARIs and prostate cancer risk

• June 9, 2011: Recent data from 2 large, randomized, controlled trials observed a reduction in overall incidence of prostate cancer but an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer) in trial participants taking 5-alpha reductase inhibitors (5-ARIs)
• The 2 trials are the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial
• The revised prescribing information recommends that prior to initiating therapy with 5-ARIs, appropriate evaluation should be performed to rule out other urologic conditions, including prostate cancer, that might mimic benign prostatic hyperplasia (BPH)
• A minimum of 6 months may be necessary to assess response in BPH

Pregnancy

Therapy is contraindicated in pregnant females and not indicated for use in females; based on animal studies and mechanism of action, drug may cause abnormal development of external genitalia in a male fetus if administered to pregnant female

Animal data

• In an embryo-fetal development study in rats, there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring of pregnant rats administered oral finasteride during period of major organogenesis at doses approximately 0.1 to 86 times the maximum recommended human dose (MRHD) of 5 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day)
• Decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development were also observed in male offspring at oral maternal doses approximately 0.03 times the MRHD (based on AUC at animal dose of 0.03 mg/kg/day), along with decreased anogenital distance in male offspring at oral maternal doses approximately 0.003 times the MRHD (based on AUC at animal dose of 0.003 mg/kg/day)
• Finasteride is a Type II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia
• If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of potential hazard to male fetus
• Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors
• These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency; females could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride
• With regard to finasteride exposure through skin, finasteride tablets are coated and will prevent skin contact with finasteride during normal handling if tablets have not been crushed or broken
• Females who are pregnant or may potentially be pregnant should not handle crushed or broken tablets because of possible exposure of a male fetus; with regard to potential finasteride exposure through semen
• Three studies have been conducted that measured finasteride concentrations in semen in men receiving 5 mg/day finasteride; in these studies the highest amount of finasteride in semen was estimated to be 50-to 100-fold less than dose of finasteride (5 μg) that had no effect on circulating DHT levels in men

Reproductive potential

• Females: Drug not indicated for use in females
• Males: Treatment for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or pH. A 0.6 mL (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed
• These parameters remained within normal range and were reversible upon discontinuation of therapy with average time to return to baseline of 84 weeks
• There have been postmarketing reports of male infertility and/or poor seminal quality; normalization or improvement of seminal quality has been reported after discontinuation of finasteride

Lactation

Drug is not indicated for use in females

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Selective inhibitor of type 1 & type 2 isoforms of 5-alpha-reductase; suppresses serum dihydrotestosterone levels by inhibiting the conversion of testosterone to dihydrotestosterone

Absorption

Bioavailability: 65%

Onset: 6 months (BPH); >3 months (hair loss)

Peak plasma time: 2-6 hours

Distribution

Protein bound: 90%

Vd: 76 L

Metabolism

Hepatic CYP3A4

Metabolites: t-butyl side chain monohydroxylate, monocarboxylic acid metabolite (active)

Elimination

Half-life: 6 hours

Excretion: Feces (57%); urine (39%)