Propecia

Propecia

finasteride

Manufacturer:

Merck Sharp & Dohme

Distributor:

A. Menarini
Full Prescribing Info
Contents
Finasteride.
Description
Each film-coated tablet of FINASTERIDE (PROPECIA) contains 1 mg of finasteride.
FINASTERIDE (PROPECIA) is a synthetic 4-azasteroid compound that is a specific inhibitor of Type II 5α-reductase, an intracellular enzyme that metabolizes the androgen testosterone into dihydrotestosterone (DHT).
FINASTERIDE (PROPECIA) is described chemically as: N-(1,1-dimethylethyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide.
Its empirical formula is C23H36N2O2.
Finasteride is a white, crystalline solid with a molecular weight of 372.55. It is freely soluble in chloroform and in lower alcohol solvents but is practically insoluble in water.
Action
Pharmacology: Pharmacodynamics: 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), follicle-stimulating hormone (FSH), estradiol or prolactin were detected. Gonadotropin-releasing hormone (GnRH) stimulated levels of LH or FSH were not altered, indicating that regulatory control of the hypothalamic-pituitary-testicular axis was not affected. Circulating levels of testosterone were increased by approximately 10-15% compared with placebo, yet remained within the physiologic range. There was no effect on semen parameters in men treated with finasteride 1 mg/day for 48 weeks.
Finasteride appeared to inhibit both C19 and C21 steroid metabolism and hence appeared to have an inhibitory effect on both hepatic and peripheral Type II 5α-reductase activity. The serum DHT metabolites androstenediol glucuronide and androsterone glucuronide were also significantly reduced. This metabolic pattern is similar to that observed in individuals with a genetic deficiency of Type II 5α-reductase who have markedly decreased levels of DHT and who do not suffer from male pattern hair loss.
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 two 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.
There is modest accumulation of finasteride in plasma after multiple dosing. At steady state following dosing with 1 mg/day, maximum finasteride plasma concentration averaged 9.2 ng/mL and was reached 1 to 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 appear to concentrate preferentially to the CSF. A very small amount of finasteride has also been detected in the seminal fluid of subjects receiving finasteride.
Metabolism: Finasteride is metabolized primarily via the cytochrome P450 3A4 enzyme subfamily. Following an oral dose of 14C-finasteride 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 more than 70 years of age. These findings are of no clinical significance and hence, a reduction in dosage in the elderly is not warranted.
Characteristics in Patients: In patients with chronic renal impairment whose creatinine clearance ranged from 9 to 55 mL/min, the disposition of a single dose of 14C-finasteride was not different from that in healthy volunteers. Protein binding also did not differ in patients with renal impairment. A portion of the metabolites that normally is excreted renally was excreted in the feces. It therefore appears that fecal excretion increases commensurate to the decrease in urinary excretion of metabolites. No adjustment in dosage is necessary in nondialyzed patients with renal impairment.
Indications/Uses
FINASTERIDE (PROPECIA) is indicated for the treatment of men with male pattern hair loss (androgenetic alopecia) to increase hair growth and prevent further hair loss.
FINASTERIDE (PROPECIA) is not indicated for use in women (see USE IN PREGNANCY & LACTATION) or children.
FINASTERIDE (PROPECIA) is not effective in postmenopausal women with androgenetic alopecia.
Dosage/Direction for Use
The recommended dosage is one 1-mg tablet daily. FINASTERIDE (PROPECIA) may be taken with or without food.
In general, daily use for 3 months or more is necessary before increased hair growth and/or prevention of further hair loss is observed. Continued use is recommended to obtain maximum benefit. Withdrawal of treatment leads to reversibility of effect within 12 months.
Mode of Administration: FINASTERIDE (PROPECIA) is available for oral administration as tablet. It may be taken with or without food.
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 (PROPECIA) is recommended.
Contraindications
FINASTERIDE (PROPECIA) is contraindicated in the following: Use in women when they are or may potentially be pregnant (See USE IN PREGNANCY & LACTATION).
Hypersensitivity to any component of this product.
FINASTERIDE (PROPECIA) is not indicated for use in women or children.
Special Precautions
In clinical studies with FINASTERIDE (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 (PROPECIA) is used for treatment of male pattern hair loss in older men who also have benign prostatic hyperplasia (BPH), consideration should be given to the fact that, in older men with BPH, PSA levels are decreased by approximately 50%.
Use in Children: FINASTERIDE (PROPECIA) is not indicated for use in children.
Use in the Elderly: Clinical studies with FINASTERIDE (PROPECIA) have not been conducted in elderly men with male pattern hair loss.
Use In Pregnancy & Lactation
FINASTERIDE (PROPECIA) 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 (PROPECIA) 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 (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.
FINASTERIDE (PROPECIA) is not indicated for use in women.
It is not known whether finasteride is excreted in human milk.
Adverse Reactions
FINASTERIDE (PROPECIA) 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 than 3,200 men. In three 12-month, placebo-controlled, double-blind, multicenter studies of comparable design, the overall safety profiles of FINASTERIDE (PROPECIA) and placebo were similar. Discontinuation of therapy due to any clinical adverse experience occurred in 1.7% of 945 men treated with FINASTERIDE (PROPECIA) 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 (PROPECIA): decreased libido [FINASTERIDE (PROPECIA), 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 (PROPECIA) and 0.4% of men treated with placebo. Resolution of these side effects occurred in men who discontinued therapy with FINASTERIDE (PROPECIA) and in many who continued therapy. In a separate study, the effect of FINASTERIDE (PROPECIA) on ejaculate volume was measured and was not different from that seen with placebo.
The incidence of each of the above side effects decreased to ≤0.3% by the fifth year of treatment with FINASTERIDE (PROPECIA).
Breast Cancer: Finasteride has also been studied in men with prostate disease at 5 times the dosage recommended for the treatment of male pattern hair loss. During the 4- to 6-year placebo- and comparator-controlled Medical Therapy of Prostatic Symptoms (MTOPS) study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with finasteride 5 mg but no cases in men not treated with finasteride 5 mg. 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 in men treated with finasteride 5 mg. During the 7-year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with finasteride 5 mg, and 1 case of breast cancer in men treated with placebo. There have been postmarketing reports of male breast cancer with the use of finasteride 1 mg and 5 mg. The relationship between long-term use of finasteride and male breast neoplasia is currently unknown.
Postmarketing Experience: 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 disorders) that continued after discontinuation of treatment; breast tenderness and enlargement; testicular pain; hematospermia; 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 at temperatures not exceeding 30°C. Keep container closed and protect from moisture.
ATC Classification
D11AX10 - finasteride ; Belongs to the class of other dermatologicals.
Presentation/Packing
Tab 1 mg x 28's.
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