CONTRAINDICATIONS
Finasteride 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 5a-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.
(See also WARNINGS, Exposure of Women — Risk to Male Fetus and PRECAUTIONS,
Information for the Patient, and PRECAUTIONS, Pregnancy, Teratogenic Effects, Pregnancy
Category X.) 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.
WARNINGS
Finasteride is not indicated for use in pediatric patients (see INDICATIONS AND USAGE and
PRECAUTIONS, Pediatric Use) or women (see also Exposure of Women — Risk to Male Fetus;
PRECAUTIONS, Information for the Patient, and PRECAUTIONS, Pregnancy, Teratogenic
Effects, Pregnancy Category X; and HOW SUPPLIED, Storage and Handling).
Exposure of Women — Risk to Male Fetus: Women should not handle crushed or broken
finasteride 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. Finasteride 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 also CONTRAINDICATIONS; PRECAUTIONS,
Information for the Patient, and PRECAUTIONS, Pregnancy, Teratogenic Effects, Pregnancy
Category X and HOW SUPPLIED, Storage and Handling.)
PRECAUTIONS
General
1-mg Tablets
Caution should be used in the administration of finasteride in patients with liver function
abnormalities, as finasteride is metabolized extensively in the liver.
5-mg Tablets
Prior to initiating therapy with finasteride, appropriate evaluation should be performed to identify
other conditions such as infection, prostate cancer, stricture disease, hypotonic bladder or other
neurogenic disorders that might mimic BPH.
Patients with large residual urinary volume and/or severely diminished urinary flow should be
carefully monitored for obstructive uropathy. These patients may not be candidates for finasteride
therapy.
Caution should be used in the administration of finasteride in those patients with liver function
abnormalities, as finasteride is metabolized extensively in the liver.
Effects on PSA and Prostate Cancer Detection: No clinical benefit has been demonstrated in
patients with prostate cancer treated with finasteride. Patients with BPH and elevated PSA were
monitored in controlled clinical studies with serial PSAs and prostate biopsies. In these studies,
finasteride did not appear to alter the rate of prostate cancer detection. The overall incidence of
prostate cancer was not significantly different in patients treated with finasteride or placebo.
Finasteride causes a decrease in serum PSA levels by approximately 50% in patients with BPH,
even in the presence of prostate cancer. This decrease is predictable over the entire range of PSA
values, although it may vary in individual patients. Analysis of PSA data from over 3000 patients in
PLESS confirmed that in typical patients treated with finasteride for six months or more, PSA
values should be doubled for comparison with normal ranges in untreated men. This adjustment
preserves the sensitivity and specificity of the PSA assay and maintains its ability to detect prostate
cancer.
Any sustained increases in PSA levels while on finasteride should be carefully evaluated, including
consideration of non-compliance to therapy with finasteride.
Information for the Patient
1-mg Tablets
Women should not handle crushed or broken finasteride 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. Finasteride 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
also CONTRAINDICATIONS; WARNINGS, Exposure of Women — Risk to Male Fetus;
Pregnancy, Teratogenic Effects, Pregnancy Category X and HOW SUPPLIED, Storage and
Handling)
See also the PATIENT PACKAGE INSERT.
5-mg Tablets
Women should not handle crushed or broken finasteride tablets when they are pregnant or may
potentially be pregnant because of the possibility of absorption of finasteride and the subsequent
potential risk to the male fetus (see CONTRAINDICATIONS; WARNINGS, Exposure of Women
— Risk to Male Fetus; Pregnancy, Teratogenic Effects, Pregnancy Category X and HOW
SUPPLIED).
Physicians should inform patients that the volume of ejaculate may be decreased in some patients
during treatment with finasteride. This decrease does not appear to interfere with normal sexual
function. However, impotence and increased libido may occur in patients treated with finasteride
(see ADVERSE REACTIONS).
Physicians should instruct their patients to read the PATIENT PACKAGE INSERT before starting
therapy with finasteride and to reread it each time the prescription is renewed so that they are
aware of current information for patients regarding finasteride.
Drug/Laboratory Test Interactions
1-mg Tablets
In clinical studies with finasteride 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 finasteride.
5-mg Tablets
In patients with BPH, finasteride has no effect on circulating levels of cortisol, estradiol, prolactin,
thyroid-stimulating hormone, or thyroxine. no clinically meaningful effect was observed on the
plasma lipid profile (i.e., total cholesterol, low density lipoproteins, high density lipoproteins and
triglycerides) or bone mineral density. Increases of about 10% were observed in luteinizing hormone
(LH) and follicle-stimulating hormone (FSH) in patients receiving finasteride, but levels remained
within the normal range. In healthy volunteers, treatment with finasteride did not alter the response
of LH and FSH to gonadotropin-releasing hormone indicating that the
hypothalamic-pituitary-testicular axis was not affected.
Treatment with finasteride 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 the normal range and were reversible
upon discontinuation of therapy with an average time to return to baseline of 84 weeks.
Carcinogenesis, Mutagenesis, and 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 (111 and 274 for 5 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 mg·hr/ml for 1 mg and 0.4 mg·hr/ml for 5 mg).
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 (1824 times
the human exposure for 1-mg tablets and 228 times for 5-mg tablets). In mice at a dose of 25
mg/kg/day (184 times the human exposure, estimated for 1-mg tablets and 23 times for 5-mg
tablets) and in rats at a dose of ³40 mg/kg/day (312 times the human exposure for 1-mg tablets and
39 for 5-mg tablets) 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 2800 times,
respectively, the human exposure for 1-mg tablets and 30 and 350 times, respectively, for 5-mg
tablets) or in mice treated for 19 months at a dose of 2.5 mg/kg/day (18.4 times the human
exposure for 1-mg tablets and 2.3 times for 5-mg tablets).
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 mmol) of 1 mg 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, and 4000-5000 times the peak plasma levels in man given a total dose of
5 mg. Further, the concentrations (450-550 mmol) used in in vitro studies are not achievable in a
biological system for 1-mg tablets. 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, estimated for 1-mg
tablets, and 228 times for 5-mg tablets) as determined in the carcinogenicity studies.
In sexually mature male rabbits treated with finasteride at 80 mg/kg/day (4344 times the estimated
human exposure for 1-mg tablets and 543 times for 5-mg tablets) 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 for 1-mg tablets and 61 times for
5-mg tablets), 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
See CONTRAINDICATIONS.
Finasteride is not indicated for use in women.
Administration of finasteride to pregnant rats at doses ranging from 100 mg/kg/day to 100 mg/kg/day
(5-5000 times the recommended human dose of 1 mg/day and 1-1000 times the recommended
human dose of 5 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 ³30 mg/kg/day (³1.5 times the recommended human dose of 1 mg/day and ³3/10
times the recommended human dose of 5 mg/day) and decreased anogenital distance when given
finasteride at ³3 mg/kg/day (one-fifth the recommended human dose of 1 mg/day and ³3/100 the
recommended human dose of 5 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 5a-reductase
inhibitors and are similar to those reported in male infants with a genetic deficiency of Type II
5a-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 (F1) male or female
offspring resulting from mating finasteride-treated male rats (80 mg/kg/day; 488 times the human
exposure for 1-mg tablets and 61 times for 5-mg tablets) with untreated females. Administration of
finasteride at 3 mg/kg/day (150 times the recommended human dose of 1 mg/day and 30 times for 5
mg/day) during the late gestation and lactation period resulted in slightly decreased fertility in F1
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 and 1000 times the
recommended human dose of 5 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 and 60 to 120 times for 5 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 [20 times for 5 mg/day] or approximately 12 million times
the highest estimated exposure to finasteride from semen of men taking 1 mg/day [1-2 million times
for 5 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
Finasteride is not indicated for use in women.
It is not known whether finasteride is excreted in human milk.
Pediatric Use
Finasteride is not indicated for use in pediatric patients.
Safety and effectiveness in pediatric patients have not been established.