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Exposure of Women — Risk to Male Fetus
PROPECIA is not indicated for use in women. 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. [See INDICATIONS AND USAGE, CONTRAINDICATIONS, Use in Specific Populations, HOW SUPPLIED/Storage and Handling and PATIENT INFORMATION.]
Effects on Prostate Specific Antigen (PSA)
In clinical studies with PROPECIA (finasteride, 1 mg) 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. Further, in clinical studies with PROSCAR (finasteride, 5 mg) when used in older men who have benign prostatic hyperplasia (BPH), PSA levels are decreased by approximately 50%. Other studies with PROSCAR showed it may also cause decreases in serum PSA in the presence of prostate cancer. These findings should be taken into account for proper interpretation of serum PSA when evaluating men treated with finasteride. Any confirmed increase from the lowest PSA value while on PROPECIA may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor. Non-compliance to therapy with PROPECIA may also affect PSA test results.
Increased Risk of High-Grade Prostate Cancer with 5α-Reductase Inhibitors
Men aged 55 and over with a normal digital rectal examination and PSA ≤3.0 ng/mL at baseline taking finasteride 5 mg/day (5 times the dose of PROPECIA) in the 7-year Prostate Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8-10 prostate cancer (finasteride 1.8% vs placebo 1.1%). [See ADVERSE REACTIONS.] Similar results were observed in a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART) (1% dutasteride vs 0.5% placebo). 5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established.
PROPECIA is not indicated for use in pediatric patients [see Use In Specific Populations].
Patient Counseling Information
“See FDA-approved patient labeling (PATIENT INFORMATION)”
Exposure of Women — Risk to Male Fetus
Physicians should inform patients that women who are pregnant or may potentially be pregnant should not handle crushed or broken PROPECIA tablets 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. If a woman who is pregnant or may potentially be pregnant comes in contact with crushed or broken PROPECIA tablets, the contact area should be washed immediately with soap and water [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, Use in Specific Populations and HOW SUPPLIED/Storage and Handling].
Increased Risk of High-Grade Prostate Cancer
Patients should be informed that there was an increase in high-grade prostate cancer in men treated with 5αreductase inhibitors indicated for BPH treatment, compared to those treated with placebo in studies looking at the use of these drugs to prevent prostate cancer [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
Physicians should instruct their patients to promptly report any changes in their breasts such as lumps, pain or nipple discharge. Breast changes including breast enlargement, tenderness and neoplasm have been reported [see ADVERSE REACTIONS].
Physicians should instruct their patients to read the patient package insert before starting therapy with PROPECIA and to read it again each time the prescription is renewed so that they are aware of current information for patients regarding PROPECIA.
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 2192 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 1824 times the human exposure (250 mg/kg/day). In mice at 184 times the human exposure, estimated (25 mg/kg/day) and in rats at 312 times the human exposure (≥40 mg/kg/day) 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- to 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 240 and 2800 times (20 mg/kg/day and 45 mg/kg/day, respectively), or in mice treated for 19 months at 18.4 times the human exposure, estimated (2.5 mg/kg/day).
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, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations. 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 (1824 times the human exposure) as determined in the carcinogenicity studies.
In sexually mature male rabbits treated with finasteride at 4344 times the human exposure (80 mg/kg/day) for up to 12 weeks, no effect on fertility, sperm count, or ejaculate volume was seen. In sexually mature male rats treated with 488 times the human exposure (80 mg/kg/day), 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.
Use In Specific Populations
Pregnancy Category X [see CONTRAINDICATIONS].
PROPECIA is contraindicated for use in women who are or may become pregnant. PROPECIA 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. In animal studies, finasteride caused abnormal development of external genitalia in male fetuses. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus.
Abnormal male genital development is an expected consequence when conversion of testosterone to 5αdihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. Women could be exposed to finasteride through contact with crushed or broken PROPECIA tablets or semen from a male partner taking PROPECIA. With regard to finasteride exposure through the skin, PROPECIA tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. Women who are pregnant or may become pregnant should not handle crushed or broken PROPECIA tablets because of possible exposure of a male fetus. If a pregnant woman comes in contact with crushed or broken PROPECIA tablets, the contact area should be washed immediately with soap and water. With regard to potential finasteride exposure through semen, a study has been conducted in men receiving PROPECIA 1 mg/day that measured finasteride concentrations in semen [see CLINICAL PHARMACOLOGY].
In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral finasteride approximately 1 to 684 times the recommended human dose (RHD) of 1 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. Exposure multiples were estimated using data from nonpregnant rats. Days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.2 times the RHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the RHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring exposed to any dose of finasteride in utero.
No developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the RHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions.
No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6-18) at maternal doses up to 100 mg/kg/day (finasteride exposure levels were not measured in rabbits). However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit.
The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20-100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 930 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 dose of finasteride (2 mg/kg/day or approximately 120,000 times the highest estimated blood levels of 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.
PROPECIA is not indicated for use in women.
It is not known whether finasteride is excreted in human milk.
PROPECIA is not indicated for use in pediatric patients.
Safety and effectiveness in pediatric patients have not been established.
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 [see CLINICAL PHARMACOLOGY]. However the efficacy of PROPECIA in the elderly has not been established.
Caution should be exercised in the administration of PROPECIA in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see CLINICAL PHARMACOLOGY].
No dosage adjustment is necessary in patients with renal impairment [see CLINICAL PHARMACOLOGY].
Last reviewed on RxList: 4/19/2012
This monograph has been modified to include the generic and brand name in many instances.
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