Binfin 1

Binfin 1

finasteride

Manufacturer:

Hetero Labs

Distributor:

Medicell Pharma
Full Prescribing Info
Contents
Finasteride.
Description
Each Film coated tablet contains: 1 mg Finasteride.
Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of steroid Type II 5α-reduclase, an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT).
Finasteride is 4-azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3-oxo-,(5α,17β)-. The empirical formula of Finasteride is C22H36N2O2 and its molecular weight is 372.54.
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 tablets for oral administration are film-coated tablets that contain 1 mg of finasteride.
Excipients/Inactive Ingredients: Lactose monohydrate, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, docusate sodium, magnesium stearate, opadry brown 03A86790.
Action
Pharmacology: Pharmacodynamics: Finasteride is a competitive and specific inhibitor of Type II 5α-reductase. Finasteride has no affinity for androgen receptor and has no androgenic, antiandrogenic, estrogenic, antiestrogenic or progestational effects. Inhibition of this enzyme blocks the peripheral conversion of testosterone to the androgen dihydrotestosterone (DHT), resulting in significant decreases in serum and tissue DHT concentrations. Circulating levels of testosterone were increased by approximately10-15% compared with placebo yet remained within the physiologic range. Finasteride produces a rapid reduction in serum DHT concentration, reaching significant suppression within 24 hours of dosing.
Hair follicles contain Type II 5α-reductase. In men with male pattern hair loss, the balding scalp contains miniaturized hair follicles and increased amounts of DHT. Administration of finasteride decreases scalp and serum DHT concentration in these men. Men with a genetic deficiency of Type II 5α-reductase do not suffer from male pattern hair loss. These data and the results of the clinical studies confirm that finasteride inhibits the process responsible for miniaturization of the scalp hair follicles, leading to reversal of the balding process.
Studies in men: The efficacy of Finasteride was demonstrated in three studies in 1879, men 18 to 41 years of age with mild to moderate, but not complete, vertex and frontal/mid-area hair loss. In these studies, hair growth was assessed using four separate measures including hair count, rating of photographs of the head by an expert panel of dermatologists, investigator assessment, and patient self-assessment.
In the two studies in men with vertex hair loss, treatment with Finasteride was continued for 5 years, during which time patients improved compared to both baseline and placebo beginning as early as 3 months. Treatment with Finasteride for 5 years resulted in stabilization of hair loss in 90% of men based in photographic assessment and in 93% based on investigator assessment. In addition, increased hair growth was reported in 65% of men treated with Finasteride based on hair counts (vs 0% of the placebo group), in 48% based on photographic assessment (vs 6% of the placebo group), and in 77% based on investigator assessment (vs 15% of the placebo group). In contrast, in the placebo group, gradual hair loss over time was observed in 100% of men based on hair counts (vs 35% of men treated with Finasteride), in 75% based on photographic assessment (vs 10% of men treated with Finasteride, and in 38% based on investigator assessment (vs 7% of men treated with Finasteride). In addition, patient self-assessment demonstrated significant increases in hair density, decreases in hair loss, and improvement in appearance of hair over 5 years of treatment with Finasteride. White hair improvement measures compared to baseline were greatest in men treated with Finasteride at 2 years and gradually declined thereafter (e.g. increase of 88 hairs in a representative 5.1 cm2 area at 2 years and increase of 38 hairs at 5 years), hair loss in the placebo group progressively worsened compared to baseline (decrease of 50 hairs at 2 years and 239 hairs at 5 years). Thus, based on all four measures, the difference between treatment groups continued to increase throughout the 5 years of the studies.
The 12-month study in men with frontal/mid-area hair loss also demonstrated significant improvements in scalp hair growth and appearance as evaluated by the same measures as those described in the previous texts.
A 48-week placebo-controlled study designed to assess the effect of Finasteride on the phases of hair-growth cycle (growing phase [anagen] and resting phase [telogen]) in vertex baldness enrolled 212 men with androgenetic alopecia. At baseline and 48 weeks, total telogen, and anagen hair counts were obtained in a 1-cm2 target area of the scalp. Treatment with Finasteride led to improvements in anagen hair counts, while men in the placebo group lost anagen hair counts of 17 hairs and 27 hairs, respectively, compared to placebo. This increase in anagen hair count, compared to total hair count, led to a net improvement in the anagen-to-telogen ratio of 47% at 48 weeks for men treated with Finasteride, compared to placebo. These data provide direct evidence that treatment with Finasteride promotes the conversion of hair follicles into the actively growing phase.
In summary, these studies demonstrated that treatment with Finasteride increases hair growth and prevents further hair loss in men with androgenetic alopecia.
Studies in women: Lack of efficacy was demonstrated in postmenopausal women with androgenetic alopecia who were treated with Finasteride in a 12-month, placebo-controlled study (n=137). These women showed no improvement in hair count, patient self-assessment, investigator assessment, or ratings based on standardized photographs, compared with the placebo group (see Indications).
Pharmacokinetics: Absorption: Relative to an intravenous reference dose, the oral bioavailability of finasteride is approximately 80%. The bioavailability is not affected by food. Maximum finasteride plasma concentrations are reached approximately 2 hours after dosing and the absorption is complete after 6-8 hours.
Distribution: Protein binding is approximately 93%. The volume of distribution of finasteride is approximately 76 liters.
At steady state following dosing with 1 mg/day, maximum finasteride plasma concentration averaged 9.2 ng/mL and was reached 1-2 hours postdose; AUC(0-24 hr) was 53 ng•hr/mL.
Finasteride has been recovered in the cerebrospinal fluid (CSF) but the drug does not apperar to concentrate preferentially to the CSF. A very small amount of fiansteride has also been detected in the seminal fluid of subjects receiving finasteride.
Biotransformation: Finasteride is metabolized primarily via the cytochrome P450 3A4 enzyme subfamily. Following an oral dose of 14C-finasteridfe in man, two metabolites of finasteride were identified that possess only a small fraction of the 5α-reductase inhibitory activity of finasteride.
Elimination: Following an oral dose of 14C-finasteride in man, 39% of the dose was excreted in the urine in the form of metabolites (virtually no unchanged drug was excreted in the urine) and 57% of total dose was excreted in the feces.
Plasma clearance is approximately 165 mL/min.
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 older than 70 years of age. These finding are of no clinical significance and hence, a reduction in dosage in the elderly is not warranted.
Characteristics in Patients: No adjustment in dosage is necessary in nondialyzed patients with renal impairment.
Special Populations: Pediatric: Finasteride pharmacokinetics have not been investigated in patients <18 years of age.
Gender: Finasteride is not indicated for use in women.
Geriatric: Clinical studies with Finasteride have not been conducted in elderly men with male pattern hair loss.
Race: The effect of race on finasteride pharmacokinetics has not been studied.
Renal Insufficiency: No dosage adjustment is necessary in patients with renal insufficiency.
Hepatic Insufficiency: The effect of hepatic insufficiency on finasteride pharmacokinetics has not been studied. Caution should be used in the administration of finasteride in patients with liver function abnormalities, as finasteride is metabolized extensively in the liver.
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 clinically meaningful interactions were found.
Clinical Studies: Studies in men: The efficacy of Finasteride 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, all men, whether treated with finasteride or placebo, were instructed to use a specified, medicated, tar-based shampoo (Neutrogena T/Gel Shampoo) during the first 2 years of studies.
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. In addition, information was collected regarding sexual function (based on a self-administered questionnaire) and non-scalp body hair growth.
Studies in Men with Vertex Baldness: In order to evaluate the effect of discontinuation of therapy, men who received Finasteride for the initital 12 months followed by placebo in the first 12-month extension period.
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 Finasteride, while significant hair loss from baseline was demonstrated in those treated with placebo. In men treated with Finasteride, the maximum improvement in hair count compared to baseline was achieved during the first 2 years. Although the initial improvement was followed by a slow decline, hair count was maintained above baseline throughout the 5 years of the studies.
Patients who switched from placebo to Finasteride had a decrease in hair count at the end of the initial 12-month placebo period, followed by an increase in hair count after 1 year of treatment with Finasteride. This increase in hair count was less (56 hairs above original baseline) than the increase (91 hairs above original baseline) observed after 1 year of treatrnent in men initially randomized to Finasteride. Although the increase in hair count relative to when therapy was initiated, was comparable between these two groups, a higher absolute hair count was achieved. In patients who were started on treatment with Finasteride in the initial study. This advantage was maintained through the remaining 3 years of the studies. A change of treatment from Finasteride to placebo at the end of the initial 12 months resulted in reversal of the increase in hair count 12 months later, at 24 months.
At 12 months, 58% of men in the placebo group had further hair loss (defined as any decrease in hair count from baseline), compared with 14% of men treated with Finasteride. In men treated for up to 2 years, 72% of men in the placebo group demonstrated hair loss, compared with 17% of men treated with Finasteride. At 5 years, 100% of men in the placebo group demonstrated hair loss, compared with 35% of men treated with Finasteride.
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 Finasteride. Overall improvement compared with placebo was seen as early as 3 months (p<0.05) with improvement maintained over 5 years.
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 Finasteride compared with placebo as early as 3 months (p<0.001). At 12 months, the investigators rated 65% of men treated with Finasteride as having increased hair growth compared with 37% in the placebo group. At 2 years, the Investigators rated 80% of men treated with Finasteride as having increased hair growth compared with 47% of men treated with placebo. At 5 years, the investigators rated 77% of men treated with Finasteride as having increased hair growth, compared with 15% of men treated with placebo.
An independent panel rated standardized photographs of the head in a blinded fashion based on increases or decreases in scalp hair using the same 7-point scale as the investigator assessment. At 12 months, 48% of men treated with Finasteride had an increase as compared with 7% of men treated with placebo. At 2 years, an increase in hair growth was demonstrated in 66% of men treated with Finasteride, compared with 7% of men treated with placebo. At 5 years, 48% of men treated with Finasteride dernonstrated an increase in hair growth, 42% ware rated as having no change (no further visible progression of hair loss from baseline) and 10% were rated as having lost hair when compared to baseline. In comparison, 6% of men treated with placebo demonstrated an increase in hair growth, 19% were rated as having no change and 75% were rated as having lost hair when compared to baseline.
Other Results In Vertex Baldness Studies: 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 .
In one of the two vertex baldness studies, patients were questioned on non-scalp body hair growth. Finasterlde did not appear to affect non-scalp body hair.
Study in Men with Hair Loss In the Anterior Mid-Scalp Area: A study of 12-month duration, designed to assess the efficacy of Finasteride 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 patients 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 in Men: All men treated with Finasteride or placebo received a tar-based shampoo (Neutrogena T/Gel Shampoo) during the first 2 years of the studies. Clinical improvement was seen as early as 3 months in the patients treated with Finasteride and led to a net increase in scalp hair count and hair regrowth. In clinical studies for up to 5 years, treatment with Finasteride slowed the further progression of hair loss observed in the placebo group. In general, the difference between treatment groups continued to increase throughout the 5 years of the studies.
Ethnic Analysis of Clinical Data from Men: In a combined analysis of the two studies on vertex baldness, mean hair count changes from baseline were hairs (Finasteride vs placebo) among Caucasians hairs among Blacks hairs among Asians hairs among Hispanics and hairs among other ethnic groups. Patient self-assessment showed improvement across racial groups with Finasteride treatment, except for satisfaction of the frontal hairline and vertex in Black men who were satisfied overall.
Study in Women: In a study involving postmenopausal women with androgenetic alopecia who were treated with Finasteride or placebo for 12 months, effectiveness could not be demonstrated. There was no improvement in hair counts, patient self-assessment, investigator assessment or ratings of standardized photographs in the women treated with Finasteride when compared with the placebo group.
Indications/Uses
Finasteride is indicated for the treatment of male pattern hair loss (androgenetic alopecia) in men only.
Finasteride is not indicated in women. Finasteride is not indicated in children.
Dosage/Direction for Use
The recommended dosage is 1 mg orally once a day.
Finasteride may be administered with or without meals.
In general, daily use for the three months or more is necessary before benefit is observed. Continued use is recommended to sustain benefit , which should be re-evaluated periodically. Withdrawal of treatment leads to reversal of effect within 12 months.
Overdosage
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 side effects.
No specific treatment for overdosage with finasteride is recommended.
Contraindications
Finasteride is contraindicated in the following: Finasteride is not indicated for use in women or children.
Pregnancy, Finasteride use is contraindicated in women when they are or may potentially be pregnant. Because of the ability of Type II 5α-reductase inhibitors to inhibit the conversion of testosterone to DHT, finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives finasteride. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. In female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring.
Hypersensitivity to any component of this medication.
Warnings
Finasteride is not indicated for use in women and pediatric patients.
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.
Special Precautions
General: Caution should be used in the administration of Finasteride in patients with liver function abnormalities, as finasteride is metabolized extensively in the liver.
Information for Patients: 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.
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.
Use in Pregnancy: Finasteride is contraindicated for use in women when they are or may potentially be pregnant.Because of the ability of Type II 5α-reductase inhibitors to inhibit conversion of testosterone to DHT in some tissues, these drugs, including finasteride, may cause abnormalities of the external genitalia of a male fetus when administered to a pregnant woman.Women should not handle crushed or broken tablets of Finasteride when they are 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.
Use in Lactation: Finasteride is not indicated for use in women.It is not known whether finasteride is excreted in human milk.
Use in Children: Finasteride is not indicated for use in children.
Use in the Elderly: Clinical studies with Finasteride have not been conducted in elderly men with male pattern hair loss.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy, Finasteride use is contraindicated in women when they are or may potentially be pregnant. Because of the ability of Type II 5α-reductase inhibitors to inhibit the conversion of testosterone to DHT, finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives finasteride. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. In female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring.
Finasteride is contraindicated for use in women when they are or may potentially be pregnant.
Because of the ability of Type II 5α-reductase inhibitors to inhibit conversion of testosterone to DHT in some tissues, these drugs, including finasteride, may cause abnormalities of the external genitalia of a male fetus when administered to a pregnant woman.
Women should not handle crushed or broken tablets of Finasteride when they are 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.
Nursing Mothers: Finasteride is not indicated for use in women.
It is not known whether finasteride is excreted in human milk.
Side Effects
Finasteride is generally well tolerated. Side effects, which usually have been mild, generally have not required discontinuation of therapy.
Finasteride for male pattern hair loss has been evaluated for safety in clinical studies involving more then 3,200 men. In three 12-month, placebo-controlled, double-blind, multicenter studies of comparable design, the overall safety profiles of Finasteride and placebo were similar. Discontinuation of therapy due to any clinical adverse experience occurred in 1.7% of 945 men treated with Finasteride and 2.1% of 934 men treated with placebo.
In these studies, the following drug-related adverse experiences were reported in =1% of men treated with Finasteride: decreased libido (Finasteride, 1.8% vs. placebo, 1.3%) and erectile dysfunction (1.3%, 0.7%). In addition, decreased volume of ejaculate was reported in 0.8% of men treated with Finasteride and 0.4% of men treated with placebo. Resolution of these side effects occurred in men who discontinued therapy with Finasteride and in many who continued therapy. In a separate study, the effect of Finasteride on ejaculate volume was measured and was not different from that seen with placebo.
The incidence of each of the previously mentioned side effects decreased to =0.3% by the fifth year of treatment with Finasteride.
Finasteride has also been studied for prostate cancer risk reduction at 5 times the dosage recommended for male pattern hair loss. In a 7-year placebo-controlled trial that enrolled 18,882 healthy men, of whom 9060 had prostate needle biopsy data available for analysis, prostate cancer was detected in 803 (18.4%) men receiving finasteride 5 mg and 1147 (24.4%) men receiving placebo. In the finasteride 5 mg 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. Additional analyses suggest that the increase in the prevalence of high-grade prostate cancer observed in the finasteride 5 mg group may be explained by a detection bias due to the effect of finasteride 5 mg on prostate volume. Of the total cases of prostate cancer diagnosed in this study, approximately 98% were classified as intracapsular (clinical stage T1 or T2) at diagnosis. The clinical significance of the Gleason 7-10 data is unknown.
Postmarketing Experience for finasteride 1 mg: The following additional adverse experiences have been reported in postmarketing use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Immune system disorders: hypersensitivity reactions such as rash, pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face).
Psychiatric disorders: depression: decreased libido that continued after discontinuation of treatment.
Reproductive system and breast disorders: sexual dysfunction (erectile dysfunction and ejaculation disorder) that continued after discontinuation of treatment: breast tenderness, breast enlargement and male breast cancer (see PRECAUTIONS); testicular pain: male infertility and/or poor seminal quality. Normalization or improvement of seminal quality has been reported after discontinuation of finasteride.
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, glyburide, propranolol, theophylline, and warfarin and no interactions were found.
Although specific interaction studies were not performed, in clinical studies finasteride doses of 1 mg or more were used concomitantly with ACE inhibitors, acetaminophen, alpha blockers, benzodiazepines, beta blockers, calcium-channel blockers, cardiac nitrates, diuretics, H2 antagonists, HMG-CoA reductase inhibitors, prostaglandin synthetase inhibitors (NSAIDs), and quinolones, without evidence of clinically significant adverse interactions.
Storage
Store below 30°C and protect from moisture.
ATC Classification
D11AX10 - finasteride ; Belongs to the class of other dermatologicals.
Presentation/Packing
FC tab 1 mg (brown colored, round, biconvex, debossed with 'H' on one side and '36' on other side) x 30's.
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