(Finasteride)
DESCRIPTION
CLINICAL PHARMACOLOGY
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
OVERDOSAGE
DOSAGE AND ADMINISTRATION
HOW SUPPLIED
PROPECIA* (finasteride), a synthetic 4-azasteroid compound,
is a specific inhibitor of steroid Type II 5a-reductase, an intracellular enzyme that converts the androgen
testosterone into 5a-dihydrotestosterone
(DHT).
Finasteride is 4-azaandrost-1-ene-17-carboxamide,N-(1,1-dimethylethyl)-3-oxo-,(5a,17b)-. The empirical formula of finasteride
is C23H36N2O2 and its molecular weight is
372.55. Its structural formula is:
Finasteride is a white crystalline powder with a melting
point near 250°C. It is freely soluble in chloroform and in lower alcohol solvents but is
practically insoluble in water.
PROPECIA tablets for oral administration are film-coated
tablets that contain 1 mg of finasteride and the following inactive ingredients:
lactose monohydrate, microcrystalline cellulose, pregelatinized starch, sodium starch
glycolate, docusate sodium, magnesium stearate, hydroxypropyl methylcellulose 2910,
hydroxypropyl cellulose, titanium dioxide, talc, yellow ferric oxide, and red ferric
oxide.
*Registered trademark of MERCK & CO., Inc.
Finasteride is a competitive and specific inhibitor of Type
II 5a-reductase, an
intracellular enzyme that converts the androgen testosterone into DHT. Two distinct
isozymes are found in mice, rats, monkeys, and humans: Type I and II. Each of these
isozymes is differentially expressed in tissues and developmental stages. In humans, Type
I 5a-reductase is
predominant in the sebaceous glands of most regions of skin, including scalp, and liver.
Type I 5a-reductase
is responsible for approximately one-third of circulating DHT. The Type II 5a-reductase isozyme is primarily
found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver,
and is responsible for two-thirds of circulating DHT.
In humans, the mechanism of action of finasteride is based
on its preferential inhibition of the Type II isozyme. Using native tissues (scalp and
prostate), in vitro binding studies examining the potential of finasteride to
inhibit either isozyme revealed a 100-fold selectivity for the human Type II 5a-reductase over Type I isozyme
(IC50=500 and 4.2 nM for Type I and II, respectively). For both isozymes,
the inhibition by finasteride is accompanied by reduction of the inhibitor to
dihydrofinasteride and adduct formation with NADP+. The turnover for the enzyme complex is
slow (t1/2 approximately 30 days for the Type II enzyme complex and 14 days for
the Type I complex).
Finasteride has no affinity for the androgen receptor and
has no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational effects.
Inhibition of Type II 5a-reductase blocks the peripheral conversion of testosterone to DHT, resulting
in significant decreases in serum and tissue DHT concentrations. Finasteride produces a
rapid reduction in serum DHT concentration, reaching 65% suppression within 24 hours of
oral dosing with a 1-mg tablet.
In men with male pattern hair loss (androgenetic alopecia),
the balding scalp contains miniaturized hair follicles and increased amounts of DHT
compared with hairy scalp. Administration of finasteride decreases scalp and serum DHT
concentrations in these men. The relative contributions of these reductions to the
treatment effect of finasteride have not been defined. By this mechanism, finasteride
appears to interrupt a key factor in the development of androgenetic alopecia in those
patients genetically predisposed.
Finasteride had no effect on circulating levels of
cortisol, thyroid-stimulating hormone, or thyroxine, nor did it affect the plasma lipid
profile (e.g., total cholesterol, low-density lipoproteins, high-density lipoproteins and
triglycerides) or bone mineral density. In studies with finasteride, no clinically
meaningful changes in luteinizing hormone (LH) or follicle-stimulating hormone (FSH) were
detected. 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. Mean circulating levels of
testosterone and estradiol were increased by approximately 15% as compared to baseline,
but these remained within the physiologic range.
Pharmacokinetics
Following an oral dose of 14C-finasteride in man, a mean
of 39% (range, 32-46%) of the dose was excreted in the urine in the form of metabolites;
57% (range, 51-64%) was excreted in the feces. The major compound isolated from urine was
the monocarboxylic acid metabolite; virtually no unchanged drug was recovered. The t-butyl
side chain monohydroxylated metabolite has been isolated from plasma. These metabolites
possessed no more than 20% of the 5a–reductase inhibitory activity of finasteride.
In a study in 15 healthy male subjects, the mean
bioavailability of finasteride 1-mg tablets was 65% (range 26-170%), based on the ratio of
AUC relative to a 5-mg intravenous dose infused over 60 minutes. Following intravenous
infusion, mean plasma clearance was 165 mL/min (range, 70-279 mL/min) and mean
steady-state volume of distribution was 76 liters (range, 44-96 liters). In a
separate study, the bioavailability of finasteride was not affected by food.
Approximately 90% of circulating finasteride is bound to
plasma proteins. Finasteride has been found to cross the blood-brain barrier.
There is a slow accumulation phase for finasteride after
multiple dosing. At steady state following dosing with 1 mg/day, maximum finasteride
plasma concentration averaged 9.2 ng/mL (range, 4.9-13.7 ng/mL) and was reached
1 to 2 hours postdose; AUC(0-24 hr) was 53 ng•hr/mL (range, 20-154 ng•hr/mL) and
mean terminal half-life of elimination was 4.8 hours (range, 3.3-13.4 hours).
Semen levels have been measured in 35 men taking
finasteride 1 mg daily for 6 weeks. In 60% (21 of 35) of the samples, finasteride levels
were undetectable. The mean finasteride level was 0.26 ng/mL and the highest level
measured was 1.52 ng/mL. Using this highest semen level measured and assuming 100%
absorption from a 5-mL ejaculate per day, human exposure through vaginal absorption would
be up to 7.6 ng per day, which is 750 times lower than the exposure from the no-effect
dose for developmental abnormalities in Rhesus monkeys (see PRECAUTIONS, Pregnancy).
The elimination rate of finasteride decreases somewhat with
age. Mean terminal half-life is approximately 5-6 hours in men 18-60 years of age and 8
hours in men more than 70 years of age. These findings are of no clinical significance,
and a reduction in dosage in the elderly is not warranted.
No dosage adjustment is necessary in patients with renal
insufficiency. In patients with chronic renal impairment (creatinine clearance ranging
from 9.0 to 55 mL/min), the values for AUC, maximum plasma concentration, half-life,
and protein binding after a single dose of 14C-finasteride were similar to those obtained in healthy volunteers.
Urinary excretion of metabolites was decreased in patients with renal impairment. This
decrease was associated with an increase in fecal excretion of metabolites. Plasma
concentrations of metabolites were significantly higher in patients with renal impairment
(based on a 60% increase in total radioactivity AUC). Furthermore, finasteride has been
well tolerated in men with normal renal function receiving up to 80 mg/day for 12
weeks where exposure of these patients to metabolites would presumably be much greater.
Clinical Studies
The efficacy of PROPECIA was demonstrated in men (88%
Caucasian) with mild to moderate androgenetic alopecia (male pattern hair loss) between 18
and 41 years of age. In order to prevent seborrheic dermatitis which might confound the
assessment of hair growth in these studies (controlled phase and extensions), all men,
whether treated with finasteride or placebo, were instructed to use a specified,
medicated, tar-based shampoo (Neutrogena T/Gel®** Shampoo).
There were three double-blind, randomized,
placebo-controlled studies of 12-month duration. The two primary endpoints were hair count
and patient self-assessment; the two secondary endpoints were investigator assessment and
ratings of photographs. The three studies were conducted in 1,879 men with mild to
moderate, but not complete, hair loss. Two of the studies enrolled men with predominantly
mild to moderate vertex hair loss (n=1,553). The third enrolled men having mild to
moderate hair loss in the anterior mid-scalp area with or without vertex balding (n=326).
Two studies on Vertex Baldness
Of the men who completed the first 12 months of the two
vertex baldness trials, 1,215 elected to continue in double-blind, placebo-controlled,
12-month extension studies. There were 547 men receiving PROPECIA for both the initial and
extension periods (up to 24 months) and 60 men receiving placebo for the same periods. Inaddition, there were 65 men who received PROPECIA for the initial 12 months followed by
placebo in the 12-month extension period, and 543 men who received placebo for the initial
12 months followed by PROPECIA in the 12-month extension period (See Figure below).
Hair counts were assessed by photographic enlargements of a
representative area of active hair loss. In these two studies in men with vertex baldness,
significant increases in hair count were demonstrated at 6 and 12 months in men treated
with PROPECIA, while significant hair loss from baseline was demonstrated in those treated
with placebo. At 12 months there was a 107-hair difference from placebo (p<0.001,
PROPECIA [n=679 evaluable men] vs placebo [n=672 evaluable men]) within a 1-inch diameter
circle (5.1 cm2). Hair count was maintained in those men taking PROPECIA (n=433
evaluable men) for up to 24 months, while the placebo group (n=47 evaluable men) continued
to show progressive hair loss. At 24 months, this resulted in a 138-hair difference
between treatment groups (p<0.001) within the same area. Patients who switched from
placebo to PROPECIA (n=426 evaluable men) at the end of the initial 12 months had an
increase in hair count at 24 months. A change of treatment from PROPECIA to placebo (n=48
evaluable men) at the end of the initial 12 months resulted in reversal of the increase in
hair count 12 months later, at 24 months. See figure below for combined study results.
| Effect on Hair Count† Number of Hairs in a 1-Inch Diameter Circle Mean Change + 1 S.E. 
|
At 12 months, 14% of men treated with PROPECIA had hair
loss (defined as any decrease in hair count from baseline) compared with 58% of men in the
placebo group. In men treated for up to 24 months, 17% of those treated with PROPECIA
demonstrated hair loss compared with 72% of those in the placebo group.
Patient self-assessment was obtained at each clinic visit
from a self-administered questionnaire, which included questions on their perception of
hair growth, hair loss, and appearance. This self-assessment demonstrated an increase in
amount of hair, a decrease in hair loss, and improvement in appearance in men treated with
PROPECIA. Overall improvement compared with placebo was seen as early as 3 months
(p<0.05), with continued improvement over 24 months.
Investigator assessment was based on a 7-point scale
evaluating increases or decreases in scalp hair at each patient visit. This assessment
showed significantly greater increases in hair growth in men treated with PROPECIA
compared with placebo as early as 3 months (p<0.001). At 12 months, the investigators
rated 65% of men treated with PROPECIA as having increased hair growth compared with 37%
in the placebo group. At 24 months, the investigators rated 80% of men treated with
PROPECIA as having increased hair growth compared with 47% of men treated with placebo.
Standardized photographs of the head were assessed in a
blinded fashion, at the beginning of the study and at 6, 12, 18 and 24 months. An
independent panel rated increases or decreases in scalp hair on the same 7-point scale as
the investigator assessment. At 12 months, 48% of men treated with PROPECIA had an
increase as compared with 7% of men treated with placebo. At 24 months, an increase in
hair growth was demonstrated in 66% of men treated with PROPECIA compared with 7% of men
treated with placebo. Based on this assessment, continued treatment with PROPECIA resulted
in further improvement. These results were observed in the context of no further increase
in hair count between month 12 and month 24.
In one of the two vertex baldness studies, patients were
questioned on non-scalp body hair growth. PROPECIA did not appear to affect non-scalp body
hair.
Study on Hair Loss in the Anterior Mid-Scalp Area
A third study of 12-month duration, designed to assess the
efficacy of PROPECIA in men with hair loss in the anterior mid-scalp area, also
demonstrated significant increases in hair count compared with placebo. Increases in hair
count were accompanied by improvements in patient self-assessment, investigator
assessment, and ratings based on standardized photographs. Hair counts were obtained in
the anterior mid-scalp area, and did not include the area of bitemporal recession or the
anterior hairline.
Summary of Clinical Studies
Clinical studies were conducted in men aged 18 to 41 with
mild to moderate degrees of androgenetic alopecia. All men treated with PROPECIA or
placebo received a tar-based shampoo (Neutrogena T/Gel®** Shampoo). Clinical improvement was seen
as early as 3 months in the patients treated with PROPECIA and led to a net increase in
scalp hair count and hair regrowth. In addition, clinical studies demonstrated slowing of
hair loss with PROPECIA by patient self-assessment. These effects were maintained through
the second year of treatment. Maintenance of or improvement in clinical efficacy has also
been demonstrated in controlled and open-extension studies for up to 3 years.
Ethnic Analysis of Clinical Data
In a combined analysis of the two studies on vertex
baldness, mean hair count changes from baseline were 91 vs –19 hairs (PROPECIA vs
placebo) among Caucasians (n=1,185), 49 vs –27 hairs among Blacks (n=84), 53 vs
–38 hairs among Asians (n=17), 67 vs 5 hairs among Hispanics (n=45) and
67 vs -15 hairs among other ethnic groups (n=20). Patient self-assessment showed
improvement across racial groups with PROPECIA treatment, except for satisfaction of the
frontal hairline and vertex in Black men, who were satisfied overall.
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.
** Registered trademark of Johnson & Johnson
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 (See
CLINICAL PHARMACOLOGY, Clinical Studies).
Efficacy in bitemporal recession has not been established.
PROPECIA is not indicated in women (see CONTRAINDICATIONS).
PROPECIA is not indicated in children (see PRECAUTIONS, Pediatric
Use).
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 5alpha-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 Patients and Pregnancy.) 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 is not indicated for use in pediatric patients (See
INDICATIONS AND USAGE; and PRECAUTIONS, Pediatric Use) or
women (See also PRECAUTIONS, Information for Patients and
Pregnancy; and HOW SUPPLIED, Storage and Handling).
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. (See also CONTRAINDICATIONS;
PRECAUTIONS, Information for Patients and Pregnancy; and HOW
SUPPLIED, Storage and Handling.)
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. (See also
CONTRAINDICATIONS; WARNINGS, EXPOSURE OF WOMEN – RISK TO MALE
FETUS; PRECAUTIONS, Pregnancy; and HOW SUPPLIED, Storage
and Handling.)
See also Patient Package Insert.
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, a-blockers,
analgesics, angiotensin-converting enzyme (ACE) inhibitors,
anticonvulsants, benzodiazepines, beta blockers, calcium-channel
blockers, cardiac nitrates, diuretics, H2 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 mg•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 mmol)
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 mmol) 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
See CONTRAINDICATIONS.
PROPECIA 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 (5-5,000 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 mg/kg/day
(>1.5
times the recommended human dose of 1 mg/day) and decreased
anogenital distance when given finasteride at >3 mg/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 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) 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 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). 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.
Clinical Studies for PROPECIA (finasteride 1 mg) in
the Treatment of Male Pattern Hair Loss
In controlled clinical trials for PROPECIA of 12-month
duration, 1.4% of the patients were discontinued due to adverse experiences that were
considered to be possibly, probably or definitely drug-related (1.6% for placebo); 1.2% of
patients on PROPECIA and 0.9% of patients on placebo discontinued therapy because of a
drug-related sexual adverse experience. The following clinical adverse reactions were
reported as possibly, probably or definitely drug-related in ³1% of patients treated for 12 months
with PROPECIA or placebo, respectively: decreased libido (1.8%, 1.3%), erectile
dysfunction (1.3%, 0.7%) and ejaculation disorder (1.2%, 0.7%; primarily decreased volume
of ejaculate:[0.8%, 0.4%]). Integrated analysis of clinical adverse experiences showed
that during treatment with PROPECIA, 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 all men who discontinued therapy with PROPECIA due to
these side effects and in 58% of those who continued therapy.
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 PROPECIA (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 PROPECIA, the incidences for
breast tenderness and enlargement, and for hypersensitivity reactions in
finasteride-treated patients were not different from those in patients treated with
placebo.
Controlled Clinical Trials and Long-Term Open Extension
Studies for PROSCAR* (finasteride 5 mg) in the Treatment of Benign Prostatic
Hyperplasia
In controlled clinical trials for PROSCAR of 12-month
duration, 1.3% of the patients were discontinued due to adverse experiences that were
considered to be possibly, probably or definitely drug-related (0.9% for placebo); only
one patient on PROSCAR (0.2%) and one patient on placebo (0.2%) discontinued therapy
because of a drug-related sexual adverse experience. The following clinical adverse
reactions were reported as possibly, probably or definitely drug-related in ³1% of patients treated for 12
months with PROSCAR or placebo, respectively: erectile dysfunction (3.7%, 1.1%), decreased
libido (3.3%, 1.6%) and decreased volume of ejaculate (2.8%, 0.9%). The adverse experience
profiles for patients treated with finasteride 1 mg/day for 12 months and those
maintained on PROSCAR for 24 to 48 months were similar to that observed in the 12-month
controlled studies with PROSCAR. Sexual adverse experiences resolved with continued
treatment in over 60% of patients who reported them.
Adverse Effects Reported in Post-Marketing Experience
for PROSCAR (finasteride 5 mg)
Breast tenderness and enlargement, as well as
hypersensitivity reactions, including lip swelling and skin rash have been reported.
* Registered trademark of MERCK & CO., Inc.
In clinical studies, single doses of finasteride up to 400 mg and multiple
doses of finasteride up to 80 mg/day for three months did not result in
adverse reactions. Until further experience is obtained, no specific
treatment for an overdose with finasteride can be recommended.
Significant lethality was observed in male and female mice at single oral
doses of 1,500 mg/m2 (500 mg/kg) and in female and male rats at single
oral doses of 2,360 mg/m2 (400 mg/kg) and 5,900 mg/m2 (1,000 mg/kg),
respectively.
The recommended dosage is 1 mg once a day.
PROPECIA may be administered with or without meals.
In general, daily use for three months or more is necessary before benefit
is observed. Continued use is recommended to sustain benefit.
Withdrawal of treatment leads to reversal of effect within 12 months.
No. 6550 — PROPECIA tablets, 1 mg, are tan,
octagonal, film-coated convex tablets with code MRK 71 on one side and PROPECIA 1 on the
other. They are supplied as follows:
NDC 0006-0071-31 unit of use bottles of 30.
NDC 0006-0071-61 ProPak™** – carton of 3 unit
of use bottles of 30.
Storage and Handling
Store at room temperature, 15-30°C (59-86°F). Keep
container closed and protect from moisture.
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 are not broken or crushed. (See WARNINGS, EXPOSURE OF
WOMEN – RISK TO MALE FETUS; and PRECAUTIONS, Information for Patients and Pregnancy.)
**Trademark of MERCK & CO., Inc.