Propecia Indications and Usage

Propecia is indicated for the treatment of male pattern hair loss (androgenetic alopecia) in MEN ONLY . Safety and efficacy were demonstrated in men between 18 to 41 years of age with mild to moderate hair loss of the vertex and anterior mid-scalp area.

Efficacy in bitemporal recession has not been established.

Propecia is not indicated in women.

Propecia is not indicated in children.

Propecia Contraindications

Propecia is contraindicated in the following:

Pregnancy. Finasteride use is contraindicated in women when they are or may potentially be pregnant. Because of the ability of 5(alpha)-reductase inhibitors to inhibit the conversion of testosterone to DHT, finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives finasteride. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. In female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring.

Hypersensitivity to any component of this medication.

Propecia Warnings

Propecia is not indicated for use in pediatric patients.

EXPOSURE OF WOMEN - RISK TO MALE FETUS

Women should not handle crushed or broken Propecia tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Propecia tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed.

Propecia Precautions

General

Caution should be used in the administration of Propecia in patients with liver function abnormalities, as finasteride is metabolized extensively in the liver.

Information for Patients

Women should not handle crushed or broken Propecia tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Propecia tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. Drug/Laboratory Test Interactions

In clinical studies with Propecia in men 18-41 years of age, the mean value of serum prostate-specific antigen (PSA) decreased from 0.7 ng/mL at baseline to 0.5 ng/mL at Month 12. When finasteride is used in older men who have benign prostatic hyperplasia (BPH), PSA levels are decreased by approximately 50%. Until further information is gathered in men >41 years of age without BPH, consideration should be given to doubling the PSA level in men undergoing this test while taking Propecia.

Drug Interactions

No drug interactions of clinical importance have been identified. Finasteride does not appear to affect the cytochrome P450-linked drug metabolizing enzyme system. Compounds that have been tested in man include antipyrine, digoxin, propranolol, theophylline, and warfarin and no interactions were found.

Other concomitant therapy:   Although specific interaction studies were not performed, finasteride doses of 1 mg or more were concomitantly used in clinical studies with acetaminophen, (alpha)-blockers, analgesics, angiotensin-converting enzyme (ACE) inhibitors, anticonvulsants, benzodiazepines, beta blockers, calcium-channel blockers, cardiac nitrates, diuretics, H ₂ antagonists, HMG-CoA reductase inhibitors, prostaglandin synthetase inhibitors (NSAIDs), and quinolone anti-infectives without evidence of clinically significant adverse interactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of a tumorigenic effect was observed in a 24-month study in Sprague-Dawley rats receiving doses of finasteride up to 160 mg/kg/day in males and 320 mg/kg/day in females. These doses produced respective systemic exposure in rats of 888 and 2,192 times those observed in man receiving the recommended human dose of 1 mg/day. All exposure calculations were based on calculated AUC _{(0-24 hr)} for animals and mean AUC _{(0-24 hr)} for man (0.05 µg·hr/mL).

In a 19-month carcinogenicity study in CD-1 mice, a statistically significant (p</=0.05) increase in the incidence of testicular Leydig cell adenomas was observed at a dose of 250 mg/kg/day (1,824 times the human exposure). In mice at a dose of 25 mg/kg/day (184 times the human exposure, estimated) and in rats at a dose of >/=40 mg/kg/day (312 times the human exposure) an increase in the incidence of Leydig cell hyperplasia was observed. A positive correlation between the proliferative changes in the Leydig cells and an increase in serum LH levels (2-3 fold above control) has been demonstrated in both rodent species treated with high doses of finasteride. No drug-related Leydig cell changes were seen in either rats or dogs treated with finasteride for 1 year at doses of 20 mg/kg/day and 45 mg/kg/day (240 and 2,800 times, respectively, the human exposure) or in mice treated for 19 months at a dose of 2.5 mg/kg/day (18.4 times the human exposure).

No evidence of mutagenicity was observed in an in vitro bacterial mutagenesis assay, a mammalian cell mutagenesis assay, or in an in vitro alkaline elution assay. In an in vitro chromosome aberration assay, when Chinese hamster ovary cells were treated with high concentrations (450-550 µmol) of finasteride, there was a slight increase in chromosome aberrations. These concentrations correspond to 18,000-22,000 times the peak plasma levels in man given a total dose of 1 mg. Further, the concentrations (450-550 µmol) used in in vitro studies are not achievable in a biological system. In an in vivo chromosome aberration assay in mice, no treatment-related increase in chromosome aberration was observed with finasteride at the maximum tolerated dose of 250 mg/kg/day (1,824 times the human exposure, estimated) as determined in the carcinogenicity studies.

In sexually mature male rabbits treated with finasteride at 80 mg/kg/day (4,344 times the estimated human exposure) for up to 12 weeks, no effect on fertility, sperm count, or ejaculate volume was seen. In sexually mature male rats treated with 80 mg/kg/day of finasteride (488 times the estimated human exposure), there were no significant effects on fertility after 6 or 12 weeks of treatment; however, when treatment was continued for up to 24 or 30 weeks, there was an apparent decrease in fertility, fecundity, and an associated significant decrease in the weights of the seminal vesicles and prostate. All these effects were reversible within 6 weeks of discontinuation of treatment. No drug-related effect on testes or on mating performance has been seen in rats or rabbits. This decrease in fertility in finasteride-treated rats is secondary to its effect on accessory sex organs (prostate and seminal vesicles) resulting in failure to form a seminal plug. The seminal plug is essential for normal fertility in rats but is not relevant in man.

Pregnancy

Teratogenic Effects: Pregnancy Category X

Propecia is not indicated for use in women.

Administration of finasteride to pregnant rats at doses ranging from 100 µg/kg/day to 100 mg/kg/day (5-5,000 times the recommended human dose of 1 mg/day) resulted in dose-dependent development of hypospadias in 3.6 to 100% of male offspring. Pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation, and transient nipple development when given finasteride at >/=30 µg/kg/day (>/= 1.5 times the recommended human dose of 1 mg/day) and decreased anogenital distance when given finasteride at >/=3 µg/kg/day (one-fifth the recommended human dose of 1 mg/day). The critical period during which these effects can be induced in male rats has been defined to be days 16-17 of gestation. The changes described above are expected pharmacological effects of drugs belonging to the class of Type II 5(alpha)-reductase inhibitors and are similar to those reported in male infants with a genetic deficiency of Type II 5(alpha)-reductase. No abnormalities were observed in female offspring exposed to any dose of finasteride in utero .

No developmental abnormalities have been observed in first filial generation (F ₁ ) male or female offspring resulting from mating finasteride-treated male rats (80 mg/kg/day; 488 times the human exposure) with untreated females. Administration of finasteride at 3 mg/kg/day (150 times the recommended human dose of 1 mg/day) during the late gestation and lactation period resulted in slightly decreased fertility in F ₁ male offspring. No effects were seen in female offspring. No evidence of malformations has been observed in rabbit fetuses exposed to finasteride in utero from days 6-18 of gestation at doses up to 100 mg/kg/day (5000 times the recommended human dose of 1 mg/day). However, effects on male genitalia would not be expected since the rabbits were not exposed during the critical period of genital system development.

The in utero effects of finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20-100), a species more predictive of human development than rats or rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (at least 750 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day) resulted in no abnormalities in male fetuses. In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a very high dose of finasteride (2 mg/kg/day; 100 times the recommended human dose of 1 mg/day or approximately 12 million times the highest estimated exposure to finasteride from semen of men taking 1 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose.

Nursing Mothers

Propecia is not indicated for use in women.

It is not known whether finasteride is excreted in human milk.

Pediatric Use

Propecia is not indicated for use in pediatric patients.

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical efficacy studies with Propecia did not include subjects aged 65 and over. Based on the pharmacokinetics of finasteride 5 mg, no dosage adjustment is necessary in the elderly for Propecia. However the efficacy of Propecia in the elderly has not been established.