Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3854
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Finasteride (Tablet, Film Coated)
|
| dailymed-instance:dosage |
The recommended dose is
5 mg orally once a day. Finasteride 5 mg tablets can be administered alone or in combination
with the alpha-blocker doxazosin (see CLINICAL PHARMACOLOGY, Clinical
Studies). Finasteride 5 mg tablets may be administered with or without meals. No dosage adjustment is necessary
for patients with renal impairment or for the elderly .
|
| dailymed-instance:descripti... |
Finasteride, a synthetic
4-azasteroid compound, is a specific inhibitor of steroid Type II5��-reductase, an
intracellular enzyme that converts the androgen testosterone into
5��-dihydrotestosterone (DHT). Finasteride is 4-azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3-oxo-,(5��,17��)-.
The empirical formula of finasteride is CHNOand 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. Finasteride 5 mg tablets for oral administration are film-coated
tablets that contain 5 mg of finasteride and the following inactive
ingredients: hydrous lactose, microcrystalline cellulose, pregelatinized
starch, sodium starch glycolate, hydroxypropyl cellulose LF, hydroxypropyl
methylcellulose, titanium dioxide, magnesium stearate, talc, docusate
sodium, FD&C Blue 2 aluminum lake and yellow iron oxide.
|
| dailymed-instance:clinicalP... |
The development and enlargement
of the prostate gland is dependent on the potent androgen, 5��-dihydrotestosterone
(DHT). Type II 5��-reductase metabolizes testosterone to DHT
in the prostate gland, liver and skin. DHT induces androgenic effects
by binding to androgen receptors in the cell nuclei of these organs. Finasteride is a competitive
and specific inhibitor of Type II 5��-reductase with which it
slowly forms a stable enzyme complex. Turnover from this complex is
extremely slow (t~ 30 days). This has been
demonstrated both in vivo and in vitro. Finasteride has no affinity
for the androgen receptor. In man, the 5��-reduced steroid metabolites
in blood and urine are decreased after administration of finasteride. In man, a single 5-mg oral dose
of finasteride produces a rapid reduction in serum DHT concentration,
with the maximum effect observed 8 hours after the first dose. The
suppression of DHT is maintained throughout the 24-hour dosing interval
and with continued treatment. Daily dosing of finasteride at 5 mg/day
for up to 4 years has been shown to reduce the serum DHT concentration
by approximately 70%. The median circulating level of testosterone
increased by approximately 10-20% but remained within the physiologic
range. Adult males with
genetically inherited Type II 5��-reductase deficiency also have
decreased levels of DHT. Except for the associated urogenital defects
present at birth, no other clinical abnormalities related to Type
II 5��-reductase deficiency have been observed in these individuals.
These individuals have a small prostate gland throughout life and
do not develop BPH. In patients with BPH treated with finasteride (1-100 mg/day)
for 7-10 days prior to prostatectomy, an approximate 80% lower
DHT content was measured in prostatic tissue removed at surgery, compared
to placebo; testosterone tissue concentration was increased up to
10 times over pretreatment levels, relative to placebo. Intraprostatic
content of prostate-specific antigen (PSA) was also decreased. In healthy male volunteers treated
with finasteride 5mg tablets for 14 days, discontinuation of
therapy resulted in a return of DHT levels to pretreatment levels
in approximately 2 weeks. In patients treated for three months,
prostate volume, which declined by approximately 20%, returned to
close to baseline value after approximately three months of discontinuation
of therapy.<br/>Pharmacokinetics:<br/>Absorption: In a study of 15
healthy young subjects, the mean bioavailability of finasteride 5-mg
tablets was 63% (range 34-108%), based on the ratio of area under
the curve (AUC) relative to an intravenous (IV) reference dose. Maximum
finasteride plasma concentration averaged 37 ng/mL (range, 27-49 ng/mL)
and was reached 1-2 hours postdose. Bioavailability of finasteride
was not affected by food.<br/>Distribution: Mean steady-state
volume of distribution was 76 liters (range, 44-96 liters). Approximately
90% of circulating finasteride is bound to plasma proteins. There
is a slow accumulation phase for finasteride after multiple dosing.
After dosing with 5 mg/day of finasteride for 17 days, plasma
concentrations of finasteride were 47 and 54% higher than after the
first dose in men 45-60 years old (n=12) and���70 years
old (n=12), respectively. Mean trough concentrations after 17 days
of dosing were 6.2 ng/mL (range, 2.4-9.8 ng/mL) and 8.1 ng/mL
(range, 1.8-19.7 ng/mL), respectively, in the two age groups.
Although steady state was not reached in this study, mean trough plasma
concentration in another study in patients with BPH (mean age, 65 years)
receiving 5 mg/day was 9.4 ng/mL (range, 7.1-13.3 ng/mL;
n=22) after over a year of dosing. Finasteride has been shown to cross the blood brain barrier but does
not appear to distribute preferentially to the CSF. In 2 studies of healthy subjects (n=69) receiving finasteride 5 mg/day
for 6-24 weeks, finasteride concentrations in semen ranged from
undetectable (<0.1 ng/mL) to 10.54 ng/mL. In an earlier
study using a less sensitive assay, finasteride concentrations in
the semen of 16 subjects receiving finasteride 5 mg/day ranged
from undetectable (<1.0 ng/mL) to 21 ng/mL. Thus, based on a 5-mL ejaculate volume, the
amount of finasteride in semen was estimated to be 50- to 100-fold
less than the dose of finasteride (5��g) that had no effect
on circulating DHT levels in men .<br/>Metabolism: Finasteride is extensively
metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme
subfamily. Two metabolites, the t-butyl side chain monohydroxylated
and monocarboxylic acid metabolites, have been identified that possess
no more than 20% of the 5��-reductase inhibitory activity of
finasteride.<br/>Excretion: In healthy young
subjects (n=15), mean plasma clearance of finasteride was 165 mL/min
(range, 70-279 mL/min) and mean elimination half-life in plasma was
6 hours (range, 3-16 hours). Following an oral dose ofC-finasteride in man (n=6), 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 mean terminal half-life of finasteride in subjects���70 years
of age was approximately 8 hours (range, 6-15 hours; n=12), compared
with 6 hours (range, 4-12 hours; n=12) in subjects 45-60 years
of age. As a result, mean AUCafter 17 days
of dosing was 15% higher in subjects���70 years of age
than in subjects 45-60 years of age (p=0.02).<br/>Special Populations: Pediatric: Finasteride
pharmacokinetics have not been investigated in patients<18 years
of age. Gender:
Finasteride pharmacokinetics in women are not available. Geriatric: No dosage adjustment
is necessary in the elderly. Although the elimination rate of finasteride
is decreased in the elderly, these findings are of no clinical significance.
See also Pharmacokinetics, Excretion, PRECAUTIONS, Geriatric Use and DOSAGE AND ADMINISTRATION. Race: The
effect of race on finasteride pharmacokinetics has not been studied. Renal Insufficiency: No
dosage adjustment is necessary in patients with renal insufficiency.
In patients with chronic renal impairment, with creatinine clearances
ranging from 9.0 to 55 mL/min, AUC, maximum plasma concentration,
half-life, and protein binding after a single dose ofC-finasteride were similar to values 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). However, finasteride has
been well tolerated in BPH patients 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. Hepatic Insufficiency: The effect of hepatic
insufficiency on finasteride pharmacokinetics has not been studied.
Caution should be used in the administration of finasteride 5 mg tablets
in those patients with liver function abnormalities, as finasteride
is metabolized extensively in the liver.<br/>Drug Interactions: No drug interactions
of clinical importance have been identified. Finasteride does not
appear to affect the cytochrome P450-linked drug metabolism enzyme
system. Compounds that have been tested in man have included antipyrine,
digoxin, propranolol, theophylline, and warfarin, and no clinically
meaningful interactions were found.<br/>Clinical Studies: Finasteride 5 mg/day
was initially evaluated in patients with symptoms of BPH and enlarged
prostates by digital rectal examination in two 1-year, placebo-controlled,
randomized, double-blind studies and their 5-year open extensions. Finasteride 5 mg tablets
were further evaluated in the PROSCAR (Finasteride) Long-Term Efficacy
and Safety Study (PLESS), a double-blind, randomized, placebo-controlled,
4-year, multicenter study. 3040 patients between the ages of 45 and
78, with moderate to severe symptoms of BPH and an enlarged prostate
upon digital rectal examination, were randomized into the study (1524
to finasteride, 1516 to placebo) and 3016 patients were evaluable
for efficacy. 1883 patients completed the 4-year study (1000 in the
finasteride group, 883 in the placebo group).<br/>Effect on Symptom Score: Symptoms were quantified
using a score similar to the American Urological Association Symptom
Score, which evaluated both obstructive symptoms (impairment of size
and force of stream, sensation of incomplete bladder emptying, delayed
or interrupted urination) and irritative symptoms (nocturia, daytime
frequency, need to strain or push the flow of urine) by rating on
a 0 to 5 scale for six symptoms and a 0 to 4 scale for one symptom,
for a total possible score of 34. Patients in PLESS had moderate to severe symptoms at baseline (mean
of approximately 15 points on a 0-34 point scale). Patients randomized
to finasteride 5 mg tablets who remained on therapy for 4 years had
a mean (��1 SD) decrease in symptom score of 3.3 (��5.8)
points compared with 1.3 (��5.6) points in the placebo group.
(See Figure 1.) A statistically significant improvement in symptom
score was evident at 1 year in patients treated with finasteride
5 mg tablets vs placebo (���2.3 vs���1.6), and this improvement
continued through Year 4. Results seen in earlier studies were comparable to those seen in
PLESS. Although an early improvement in urinary symptoms was seen
in some patients, a therapeutic trial of at least 6 months was
generally necessary to assess whether a beneficial response in symptom
relief had been achieved. The improvement in BPH symptoms was seen
during the first year and maintained throughout an additional 5 years
of open extension studies.<br/>Effect on Acute Urinary Retention and the Need for Surgery: In PLESS, efficacy
was also assessed by evaluating treatment failures. Treatment failure
was prospectively defined as BPH-related urological events or clinical
deterioration, lack of improvement and/or the need for alternative
therapy. BPH-related urological events were defined as urological
surgical intervention and acute urinary retention requiring catheterization.
Complete event information was available for 92% of the patients.
The following table (Table 1) summarizes the results. Compared with placebo, finasteride 5 mg tablets was associated with
a significantly lower risk for acute urinary retention or the need
for BPH-related surgery [13.2% for placebo vs 6.6% for finasteride
5 mg tablets; 51% reduction in risk, 95% CI: (34 to 63%)]. Compared
with placebo, finasteride 5 mg tablets were associated with a significantly
lower risk for surgery [10.1% for placebo vs 4.6% for finasteride
5 mg tablets; 55% reduction in risk, 95%CI: (37 to 68%)] and with
a significantly lower risk of acute urinary retention [6.6% for placebo
vs 2.8% for finasteride 5 mg tablets; 57% reduction in risk, 95% CI:
(34 to 72%)]; see Figures 2 and 3.<br/>Effect on Maximum Urinary Flow Rate: In the patients
in PLESS who remained on therapy for the duration of the study and
had evaluable urinary flow data, finasteride 5 mg tablets increased
maximum urinary flow rate by 1.9 mL/sec compared with 0.2 mL/sec in
the placebo group. There was a clear difference between treatment groups in maximum
urinary flow rate in favor of finasteride 5 mg tablets by month 4
(1.0 vs 0.3 mL/sec) which was maintained throughout the study. In
the earlier 1-year studies, increase in maximum urinary flow rate
was comparable to PLESS and was maintained through the first year
and throughout an additional 5 years of open extension studies.<br/>Effect on Prostate Volume: In PLESS, prostate
volume was assessed yearly by magnetic resonance imaging (MRI) in
a subset of patients. In patients treated with finasteride 5 mg tablets
who remained on therapy, prostate volume was reduced compared with
both baseline and placebo throughout the 4-year study. Finasteride
5 mg tablets decreased prostate volume by 17.9% (from 55.9 cc
at baseline to 45.8 cc at 4 years) compared with an increase
of 14.1% (from 51.3 cc to 58.5 cc) in the placebo group
(p<0.001). (See Figure 4.) Results seen in earlier studies were comparable
to those seen in PLESS. Mean prostate volume at baseline ranged between
40-50 cc. The reduction in prostate volume was seen during the
first year and maintained throughout an additional five years of open
extension studies.<br/>Prostate Volume as a Predictor of Therapeutic Response: A meta-analysis
combining 1-year data from seven double-blind, placebo-controlled
studies of similar design, including 4491 patients with symptomatic
BPH, demonstrated that, in patients treated with finasteride 5 mg
tablets, the magnitude of symptom response and degree of improvement
in maximum urinary flow rate were greater in patients with an enlarged
prostate at baseline.<br/>Medical Therapy of Prostatic Symptoms: The Medical Therapy
of Prostatic Symptoms (MTOPS) Trial was a double-blind, randomized,
placebo-controlled, multicenter, 4- to 6-year study (average 5 years)
in 3047 men with symptomatic BPH, who were randomized to receive finasteride
5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination
of finasteride 5 mg/day and doxazosin 4 or 8 mg/day (n=786),
or placebo(n=737). All participants underwent weekly titration of
doxazosin (or its placebo) from 1 to 2 to 4 to 8 mg/day. Only
those who tolerated the 4 or 8 mg dose level were kept on doxazosin
(or its placebo) in the study. The participant's final tolerated
dose (either 4 mg or 8 mg) was administered beginning at
end-Week 4. The final doxazosin dose was administered once per day,
at bedtime. The mean patient age at randomization was 62.6 years (��7.3 years).
Patients were Caucasian (82%), African American (9%), Hispanic (7%),
Asian (1%) or Native American (<1%). The mean duration of BPH symptoms
was 4.7 years (��4.6 years). Patients had moderate to
severe BPH symptoms at baseline with a mean AUA symptom score of approximately
17 out of 35 points. Mean maximum urinary flow rate was 10.5 mL/sec (��2.6 mL/sec).
The mean prostate volume as measured by transrectal ultrasound was
36.3 mL (��20.1 mL). Prostate volume was���20 mL
in 16% of patients,���50 mL in 18% of patients and between
21 and 49 mL in 66% of patients. The primary endpoint was a composite measure of the first occurrence
of any of the following five outcomes: a���4 point confirmed
increase from baseline in symptom score, acute urinary retention,
BPH-related renal insufficiency (creatinine rise), recurrent urinary
tract infections or urosepsis, or incontinence. Compared to placebo,
treatment with finasteride 5 mg tablets, doxazosin, or combination
therapy resulted in a reduction inthe risk of experiencing one of
these five outcome events by 34% (p=0.002), 39% (p<0.001), and
67% (p<0.001), respectively. Combination therapy resulted in a
significant reduction in the risk of the primary endpoint compared
to treatment with finasteride 5 mg tablets alone (49%; p���0.001)
or doxazosin alone (46%; p���0.001). (See Table 2.) The majority of the events (274 out of 351; 78%) was a confirmed���4 point increase in symptom score, referred to as symptom
score progression. The risk of symptom score progression was reduced
by 30% (p=0.016), 46% (p<0.001), and 64% (p<0.001) in patients
treated with finasteride 5 mg tablets, doxazosin, or the combination,
respectively, compared to patients treated with placebo (see Figure
5). Combination therapy significantly reduced the risk of symptom
score progression compared to the effect of finasteride 5 mg tablets
alone (p<0.001) and compared to doxazosin alone (p=0.037). Treatment with finasteride 5 mg tablets, doxazosin
or the combination of finasteride 5 mg tablets with doxazosin, reduced
the mean symptom score from baseline at year 4. Table 3 provides the
mean change from baseline for AUA symptom score by treatment group
for patients who remained on therapy for four years. The results of MTOPS are consistent with the findings of the 4-year,
placebo-controlled study PLESS (see CLINICAL PHARMACOLOGY, Clinical
Studies) in that treatment with finasteride 5 mg tablets
reduces the risk of acute urinary retention and the need for BPH-related
surgery. In MTOPS, the risk of developing acute urinary retention
was reduced by 67% in patients treated with finasteride 5 mg tablets
compared to patients treated with placebo (0.8% for finasteride 5
mg tablets and 2.4% for placebo). Also, the risk of requiring BPH-related
invasive therapy was reduced by 64% in patients treated with finasteride
5 mg tablets compared to patients treated with placebo (2.0% for finasteride
5 mg tablets and 5.4% for placebo).<br/>Summary of Clinical Studies: The data from these
studies, showing improvement in BPH-related symptoms, reduction in
treatment failure (BPH-related urological events), increased maximum
urinary flow rates, and decreasing prostate volume, suggest that finasteride
5 mg tablets arrests the disease process of BPH in men with an enlarged
prostate.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:supply |
No. 8356 Finasteride
5 mg Tablets, USP are blue, modified apple-shaped, film-coated
tablets, with the 72 on one side and plain on the other. They
are supplied as follows: NDC 55111-554-30 unit of use bottles of
30 NDC 55111-554-90 unit of use bottles of 90<br/>Storage and Handling: Store at room temperatures below 30��C (86��F). Protect from
light and keep container tightly closed. Women should not handle crushed or broken Finasteride 5 mg Tablets,
USP 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 (see WARNINGS, EXPOSURE OF WOMEN���RISK TO MALE FETUS, and PRECAUTIONS, Information
for Patients and Pregnancy). Manufactured by: MERCK&CO., Inc.,Whitehouse Station, NJ 08889, USA Distributed by:Dr. Reddy's Laboratories Inc.Bridgewater, NJ 08807, USA COPYRIGHT��MERCK&CO., Inc., 1992, 1995, 1998All rights reserved Issued February 2006 Printed in USA 9714400
|
| dailymed-instance:genericDr... | |
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:FD&C_Blue_2_aluminum_lake,
dailymed-ingredient:docusate_sodium,
dailymed-ingredient:hydrous_lactose,
dailymed-ingredient:hydroxypropyl_cellulose_LF,
dailymed-ingredient:hydroxypropyl_methylcellulose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:pregelatinized_starch,
dailymed-ingredient:sodium_starch_glycolate,
dailymed-ingredient:talc,
dailymed-ingredient:titanium_dioxide,
dailymed-ingredient:yellow_iron_oxide
|
| dailymed-instance:possibleD... | |
| dailymed-instance:precautio... |
General: Prior to initiating
therapy with finasteride 5 mg tablets, 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 5 mg tablets in those patients
with liver function abnormalities, as finasteride is metabolized extensively
in the liver.<br/>Effects on PSA and Prostate Cancer Detection: No clinical benefit
has been demonstrated in patients with prostate cancer treated with
finasteride 5 mg tablets. Patients with BPH and elevated PSA were
monitored in controlled clinical studies with serial PSAs and prostate
biopsies. In these BPH studies, finasteride 5 mg tablets did not appear
to alter the rate of prostate cancer detection, and the overall incidence
of prostate cancer was not significantly different in patients treated
with finasteride 5 mg tablets or placebo. Finasteride 5 mg tablets cause 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 5 mg tablets 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 5 mg tablets should be carefully evaluated,
including consideration of non-compliance to therapy with finasteride
5 mg tablets. Percent free PSA (free to total PSA ratio) is not significantly decreased
by finasteride 5 mg tablets. The ratio of free to total PSA remains
constant even under the influence of finasteride 5 mg tablets. If
clinicians elect to use percent free PSA as an aid in the detection
of prostate cancer in men undergoing finasteride therapy, no adjustment
to its value appears necessary.<br/>Information for Patients: Women should not
handle crushed or broken finasteride 5 mg 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; PRECAUTIONS, Pregnancy and HOW SUPPLIED). Physicians should inform patients that the volume of ejaculate may
be decreased in some patients during treatment with finasteride 5
mg tablets. This decrease does not appear to interfere with normal
sexual function. However, impotence and decreased libido may occur
in patients treated with finasteride 5 mg tablets . 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 . Physicians should instruct
their patients to read the patient package insert before starting
therapy with finasteride 5 mg tablets and to reread it each time the
prescription is renewed so that they are aware of current information
for patients regarding finasteride 5 mg tablets.<br/>Drug/Laboratory Test Interactions: In patients with
BPH, finasteride 5 mg tablets have 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
5 mg tablets, but levels remained within the normal range. In healthy
volunteers, treatment with finasteride 5 mg tablets 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
5 mg tablets 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.<br/>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 have included antipyrine,
digoxin, propranolol, theophylline, and warfarin and no clinically
meaningful interactions were found. Other
Concomitant Therapy: Although specific interaction studies
were not performed, finasteride 5 mg tablets were concomitantly used
in clinical studies with acetaminophen, acetylsalicylic acid,��-blockers,
angiotensin-converting enzyme (ACE) inhibitors, analgesics, anti-convulsants,
beta-adrenergic blocking agents, diuretics, calcium channel blockers,
cardiac nitrates, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory
drugs (NSAIDs), benzodiazepines, Hantagonists and quinolone
anti-infectives without evidence of clinically significant adverse
interactions.<br/>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 111 and 274 times those observed in man
receiving the recommended human dose of 5 mg/day. All exposure
calculations were based on calculated AUCfor animals and mean AUCfor man (0.4��g���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 (228 times the human exposure). In mice
at a dose of 25 mg/kg/day (23 times the human exposure, estimated)
and in rats at a dose of���40 mg/kg/day (39 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- 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 doses of 20 mg/kg/day and 45 mg/kg/day (30 and 350 times,
respectively, the human exposure) or in mice treated for 19 months
at a dose of 2.5 mg/kg/day (2.3 times the human exposure, estimated). 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. These concentrations correspond to 4000-5000
times the peak plasma levels in man given a total dose of 5 mg. 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
(228 times the human exposure) as determined in the carcinogenicity
studies. In
sexually mature male rabbits treated with finasteride at 80 mg/kg/day
(543 times the 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 (61
times the human exposure), there were no significant effects on fertility
after 6 or 12 weeks of treatment; however, when treatment wascontinued 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 and is
not relevant in man.<br/>Pregnancy:<br/>Pregnancy Category X: See CONTRAINDICATIONS. Finasteride 5 mg tablets
are not indicated for use in women. Administration of finasteride to pregnant rats at doses ranging from
100��g/kg/day to 100 mg/kg/day (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���30��g/kg/day (���3/10
of the recommended human dose of 5 mg/day) and decreased anogenital
distance when given finasteride at���3��g/kg/day
(���3/100 of 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 5��-reductase inhibitors and are similar to
those reported in male infants with a genetic deficiency of Type II
5��-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) male or female offspring resulting from
mating finasteride-treated male rats (80 mg/kg/day; 61 times
the human exposure) with untreated females. Administration of finasteride
at 3 mg/kg/day (30 times the recommended human dose of 5 mg/day)
during the late gestation and lactation period resulted in slightly
decreased fertility in Fmale 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 (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 60 to 120 times the highest estimated
exposure of pregnant women to finasteride from semen of men taking
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 dose of finasteride (2 mg/kg/day; 20
times the recommended human dose of 5 mg/day or approximately
1-2 million times the highest estimated exposure to finasteride from
semen of men taking 5 mg/day) to pregnantmonkeys 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.<br/>Nursing Mothers: Finasteride 5 mg
tablets are not indicated for use in women. It is not known whether finasteride is excreted in human milk.<br/>Pediatric Use: Finasteride 5 mg
tablets are not indicated for use in pediatric patients. Safety and effectiveness
in pediatric patients have not been established.<br/>Geriatric Use: Of the total number
of subjects included in PLESS, 1480 and 105 subjects were 65 and over
and 75 and over, respectively. No overall differences in safety or
effectiveness were observed between these subjects and younger subjects,
and other reported clinical experience has not identified differencesin responses between the elderly and younger patients. No dosage adjustment
is necessary in the elderly .
|
| dailymed-instance:overdosag... |
Patients have received single
doses of finasteride 5 mg tablets up to 400 mg and multiple doses
of finasteride 5 mg tablets up to 80 mg/day for three months
without adverse effects. Until further experience is obtained, no
specific treatment for an overdose with finasteride 5 mg tablets can
be recommended. Significant
lethality was observed in male and female mice at single oral doses
of 1500 mg/m(500 mg/kg) and in female and male rats at
single oral doses of 2360 mg/m(400 mg/kg) and 5900 mg/m(1000 mg/kg), respectively.
|
| dailymed-instance:genericMe... |
finasteride
|
| dailymed-instance:fullName |
Finasteride (Tablet, Film Coated)
|
| dailymed-instance:adverseRe... |
Finasteride 5 mg tablets
are generally well tolerated; adverse reactions usually have been
mild and transient.<br/>4-Year Placebo-Controlled Study: In PLESS, 1524 patients
treated with finasteride 5 mg tablets and 1516 patients treated with
placebo were evaluated for safety over a period of 4 years. The most
frequently reported adverse reactions were related to sexual function.
3.7% (57 patients) treated with finasteride 5 mg tablets and 2.1%
(32 patients) treated with placebo discontinued therapy as a result
of adverse reactions related to sexual function, which are the most
frequently reported adverse reactions. Table 4 presents the only clinical adverse reactions considered possibly,
probably or definitely drug related by the investigator, for which
the incidence on finasteride 5 mg tablets were���1% and greater
than placebo over the 4 years of the study. In years 2-4 of the study,
there was no significant difference between treatment groups in the
incidences of impotence, decreased libido and ejaculation disorder.<br/>Phase III Studies and 5-Year Open Extensions: The adverse experience
profile in the 1-year, placebo-controlled, Phase III studies, the
5-year open extensions, and PLESS were similar.<br/>Medical Therapy of Prostatic Symptoms (MTOPS) Study: The incidence rates
of drug-related adverse experiences reported by���2% of patients
in any treatment group in the MTOPS Study are listed in Table 5. The individual adverse
effects which occurred more frequently in the combination group compared
to either drug alone were: asthenia, postural hypotension, peripheral
edema, dizziness, decreased libido, rhinitis, abnormal ejaculation,
impotence and abnormal sexual function (see Table 5). Of these, the
incidence of abnormal ejaculation in patients receiving combination
therapy was comparable to the sum of the incidences of this adverse
experience reported for the two monotherapies. Combination therapy with finasteride and doxazosin was associated
with no new clinical adverse experience. Four patients in MTOPS reported the adverse experience breast cancer.
Three of these patients were on finasteride only and one was on combination
therapy. (See ADVERSE
REACTIONS, Long-Term Data.) The MTOPS Study was not specifically designed to make statistical
comparisons between groups for reported adverse experiences. In addition,
direct comparisons of safety data between the MTOPS study and previous
studies of the single agents may not be appropriate based upon differences
in patient population, dosage or dose regimen, and other procedural
and study design elements.<br/>Long-Term Data: There is no evidence
of increased adverse experiences with increased duration of treatment
with finasteride 5 mg tablets. New reports of drug-related sexual
adverse experiences decreased with duration of therapy. During the 4- to 6-year
placebo- and comparator-controlled MTOPS study that enrolled 3047
men, there were 4 cases of breast cancer in men treated with finasteride
but no cases in men not treated with finasteride. During the 4-year,
placebo-controlled PLESS study that enrolled 3040 men, there were
2 cases of breast cancer in placebo-treated men, but no cases were
reported in men treated with finasteride. The relationship between
long-term use of finasteride and male breast neoplasia is currently
unknown. In a
7-year placebo-controlled trial that enrolled 18,882 healthy men,
9060 had prostate needle biopsy data available for analysis. In the
finasteride 5 mg tablets group, 280 (6.4%) men had prostate cancer
with Gleason scores of 7-10 detected on needle biopsy vs. 237 (5.1%)
men in the placebo group. Of the total cases of prostate cancer diagnosed
in this study, approximately 98% were classified as intracapsular
(stage T1 or T2). The clinical significance of these findings is unknown.
This information from the literature (Thompson IM, Goodman PJ, Tangen
CM, et al. The influence of finasteride on the development of prostatecancer. N Engl J Med 2003;349:213-22)
is provided for consideration by physicians when finasteride 5 mg
tablets are used as indicated (see INDICATIONS
AND USAGE). Finasteride 5 mg tablets are not approved to
reduce the risk of developing prostate cancer.<br/>Post-Marketing Experience: The following additional
adverse effects have been reported in post-marketing experience: - hypersensitivity
reactions, including pruritus, urticaria, and swelling of the lips
and face - testicular
pain.
|
| dailymed-instance:warning |
Finasteride 5 mg tablets
is not indicated for use in pediatric patients or women (see also WARNINGS, EXPOSURE OF WOMEN���RISK TO MALE FETUS; PRECAUTIONS,
Information for Patients and Pregnancy; and HOW SUPPLIED).<br/>EXPOSURE OF WOMEN���RISK TO MALE FETUS: Women should not
handle crushed or broken finasteride 5 mg 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 5 mg 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 CONTRAINDICATIONS; PRECAUTIONS, Information
for Patients and Pregnancy; and HOW SUPPLIED.)
|
| dailymed-instance:indicatio... |
Finasteride 5 mg Tablets,
USP are indicated for the treatment of symptomatic benign prostatic
hyperplasia (BPH) in men with an enlarged prostate to: Finasteride 5 mg Tablets,
USP administered in combination with the alpha-blocker doxazosin is
indicated to reduce the risk of symptomatic progression of BPH (a
confirmed���4 point increase in AUA symptom score).
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Finasteride
|