Finasteride

372.54

372.54

1308068-626-2

57GNO57U7G

741485

DTXSID3020625

C1099

White to off-white crystalline solid

G04CB01|D - Dermatologicals|G - Genito urinary system and sex hormones

29379000

58.2

3

white to beige solid

1.065±0.06 g/cm3(Predicted)

252-254 °C

576.6°C at 760 mmHg

177.4ºC

1.524

H2O: insoluble ;DMSO: 32 mg/mL, soluble

Store at RT

405 -59° (c = 1 in methanol)

200 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

MP approx 257 °C (dried to anhydrous under nitrogen)

3

22-61-60-36/37/38

36/37/39-45-53-36-26-24/25

CL5245000

Xn,T,Xi

P201, P202, P260, P264, P270, P273, P281, P301+P312, P308+P313, P314, P330, P391, P405, P501

H302

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Danger|H302 (98.9%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P281, P301+P312, P308+P313, P314, P330, P391, P405, and P501|Aggregated GHS information provided by 91 companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

**LD50** Oral LD50 is about 418 mg/kg in rats[MSDS] and there have been cases of lethality in rats receiving a single oral dose of 400 mg/kg in males and 1000 mg/kg in females. **Nonclinical toxicology** In a 24-month rat study, there were no signs of the tumorigenic potential of finasteride. In a 19-month carcinogenicity study in CD-1 mice, high doses of finasteride, at 1824 times the human exposure (250 mg/kg/day), resulted in an increase in the incidence of testicular Leydig cell adenomas and an increase in serum LH levels. _In vitro_ mutagenesis assays demonstrated no evidence of mutagenicity. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations with much higher doses of finasteride. **Overdose** There were no reported significant adverse events in clinical trials of male patients receiving single oral doses of finasteride up to 400 mg and multiple doses of finasteride up to 80 mg/day for three months. As there have been no cases of overdose or clinically significant toxicity with finasteride, there are no specific recommendations in case of an overdose. **Significant adverse events** Common reproductive adverse events seen with finasteride therapy include erectile dysfunction, ejaculatory dysfunction, and loss of libido. These adverse events tend to disappear after discontinuation or chronic use of the drug. Only causal adverse event occurring at the male reproductive system that is caused by finasteride is decreased ejaculatory volume because of the predominant action of DHT on the prostate. **Special populations** Finasteride can be safely used in elderly patients or those with renal impairment with no specific dosing adjustment recommendations. Finasteride is indicated for male patients only, and it is advised that exposure to finasteride is avoided in pregnant women carrying male fetuses as it may lead to abnormal development of external genitalia in male fetuses.

Finasteride has been associated with a low rate of serum aminotransferase elevations that, in controlled trials, was no higher than with placebo therapy. These elevations were transient and rarely required dose modification, and have occurred with both the 5 mg dose for prostatic hypertrophy and the 1 mg dose for hair growth. There have been published reports of transient serum enzyme elevations occurring during finasteride therapy, but none of clinically apparent liver injury.

Approximately 90% of circulating finasteride is bound to plasma proteins.

Indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy. Indicated for the treatment of male pattern hair loss (androgenetic alopecia, hereditary alopecia, or common male baldness) in male patients.|Treatment of androgenetic alopecia

Finasteride is a 5-alpha reductase inhibitor used to treat symptoms of benign prostatic hypertrophy and male pattern baldness. Finasteride is associated with a low rate of transient serum aminotransferase elevations, but has yet to be linked to instances of clinically apparent, acute liver injury.

Benign Prostatic Hypertrophy Agents

Enzyme Inhibitors|Treatment of benign prostatic hypertrophy|Antiandrogen therapy appears to produce a 30 to 40% decrease in the volume of the hyperplastic prostate after 3 to 6 months of therapy. Longer treatment may result in further prostatic regression, although this remains to be seen. Biopsy studies suggest that epithelial regression occurs to a much more significant degree than does stromal regression, but this finding may simply reflect the relatively longer turnover of the stromal cell population. The significant placebo effect of oral medication in patients with benign prostatic hyperplasia makes interpretation of clinical symptomatology and uro-flow data difficult. Analysis of symptom improvement is further complicated by the relatively slow improvement of patients on antiandrogen therapy, in contrast to surgery, in which relief is immediate. In addition to limited stromal involution and inadequate treatment duration, other biologic factors may limit the clinical efficacy of antiandrogen therapy. Most importantly, prostatic involution may not necessarily decrease urethral resistance. In addition, obstruction induced detrusor dysfunction may persist after relief of outflow obstruction in some patients, as it does after surgery. Incomplete antiandrogen action of the compounds, as well as compliance issues, may likewise limit efficacy. Although there are no data to suggest that the 5 alpha-reductase inhibitor finasteride will be more effective than other antiandrogen compounds in the treatment of benign prostatic hyperplasia, preliminary studies suggest that it has less toxicity. If long-term studies validate a modest but significant clinical response rate and preservation of sexual function, then finasteride therapy may well be acceptable to a subgroup of men presenting with the symptoms of benign prostatic hyperplasia.

Finasteride is an antiandrogenic compound that works by suppressing the production of serum and intraprostatic dihydrotestosterone (DHT) in men via inhibiting the enzyme responsible for the biosynthesis of DHT. The maximum effect of a rapid reduction in serum DHT concentration is expected to be observed 8 hours following administration of the first dose. In a single man receiving a single oral dose of 5 mg finasteride for up to 4 years, there was a reduction in the serum DHT concentrations by approximately 70% and the median circulating level of testosterone increased by approximately 10-20% within the physiologic range. In a double-blind, placebo-controlled study, finasteride reduced intraprostatic DHT level by 91.4% but finasteride is not expected to decrease the DHT levels to castrate levels since circulating testosterone is also converted to DHT by the type 1 isoenzyme expressed in other tissues. It is expected that DHT levels return to normal within 14 days upon discontinuation of the drug. In a study of male patients with benign prostatic hyperplasia prior to prostatectomy, the treatment with finasteride resulted in an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery compared to placebo. While finasteride reduces the size of the prostate gland by 20%, this may not correlate well with improvement in symptoms. The effects of finasteride are reported to be more pronounced in male patients with enlarged prostates (>25 mL) who are at the greatest risk of disease progression. In phase III clinical studies, oral administration of finasteride in male patients with male pattern hair loss promoted hair growth and prevented further hair loss by 66% and 83% of the subjects, respectively, which lasted during two years' treatment. The incidences of these effects in treatment groups were significantly higher than that of the group receiving a placebo. Following finasteride administration, the levels of DHT in the scalp skin was shown to be reduced by more than 60%, indicating that the DHT found in scalp is derived from both local DHT production and circulating DHT. The effect of finasteride on scalp DHT is likely seen because of its effect on both local follicular DHT levels as well as serum DHT levels.. There is evidence from early clinical observations and controlled studies that finasteride may reduce bleeding of prostatic origin.

Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION. (See all compounds classified as Urological Agents.)|Drugs that inhibit 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE. They are commonly used to reduce the production of DIHYDROTESTOSTERONE. (See all compounds classified as 5-alpha Reductase Inhibitors.)

Finasteride is well absorbed following oral administration and displays a slow accumulation phase after multiple dosing.[lablel] In healthy male subjects receiving oral finasteride, the mean oral bioavailability was 65% for 1 mg finasteride and 63% for 5 mg finasteride, and the values ranged from 26 to 170% for 1 mg dose and from 34 to 108% for 5 mg dose, respectively. It is reported that food intake does not affect the oral bioavailability of the drug. The peak plasma concentrations (Cmax) averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours post administration. The AUC(0-24 hr) was 53 ngxhr/mL (range, 20-154 ngxhr/mL). The plasma concentrations and AUC are reported to be higher in elderly male patients aged 70 years or older.|In healthy subjects, about 32-46% of total oral dose of finasteride was excreted in the urine in the form of metabolites while about 51-64% of the dose was excreted in the feces. In patients with renal impairment, the extent of urinary excretion of finasteride is expected to be decreased while the fecal excretion is increased.|The volume of distribution is 76 L at steady state, ranging from 44 to 96 L. Finasteride has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF. It is not known whether finasteride is excreted in human milk.|In healthy young subjects (n=15), the mean plasma clearance of finasteride was 165 mL/min with the range between 70 and 279 mL/min.

Finasteride undergoes extensive hepatic metabolism predominantly mediated by the cytochrome P450 3A4 (CYP3A4) enzyme to form the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites. Theses metabolites retain less than 20% of the pharmacological activity of the parent compound.|Finasteride has known human metabolites that include N-(1-Hydroxy-2-methylpropan-2-yl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide.

In healthy young subjects receiving finasteride, the mean elimination half-life in plasma was 6 hours ranging from 3 to 16 hours. In elderly patients over the age of 70 years, the half-life is prolonged to 8 hours.

Finasteride acts as a competitive and specific inhibitor of Type II 5α-reductase, a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, 5α-dihydrotestosterone (DHT). DHT is considered to be the primary androgen playing a role in the development and enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland. DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation. Responsible for the production of DHT together with type I 5α-reductase, the type II 5α-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver. Although finasteride is 100-fold more selective for type II 5α-reductase than for the type I isoenzyme, chronic treatment with this drug may have some effect on type I 5α-reductase, which is predominantly expressed in sebaceous glands of most regions of skin, including the scalp, and liver. It is proposed that the type I 5α-reductase and type II 5α-reductase is responsible for the production of one-third and two-thirds of circulating DHT, respectively. The mechanism of action of Finasteride is based on its preferential inhibition of Type II 5α-reductase through the formation of a stable complex with the enzyme _in vitro_ and _in vivo_. Finasteride works selectively, where it preferentially displays a 100-fold selectivity for the human Type II 5α-reductase over type I enzyme. Inhibition of Type II 5α-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations, minimal to moderate increase in serum testosterone concentrations, and substantial increases in prostatic testosterone concentrations. As DHT appears to be the principal androgen responsible for stimulation of prostatic growth, a decrease in DHT concentrations will result in a decrease in prostatic volume (approximately 20-30% after 6-24 months of continued therapy). It is suggested that increased levels of DHT can lead to potentiated transcription of prostaglandin D2, which promotes the proliferation of prostate cancer cells. In men with androgenic alopecia, the mechanism of action has not been fully determined, but finasteride has shown to decrease scalp DHT concentration to the levels found in the hairy scalp, reduce serum DHT, increase hair regrowth, and slow hair loss. Another study suggests that finasteride may work to reduce bleeding of prostatic origin by inhibiting vascular endothelial growth factor (VEGF) in the prostate, leading to atrophy and programmed cell death. This may bestow the drug therapeutic benefits in patients idiopathic prostatic bleeding, bleeding during anticoagulation, or bleeding after instrumentation.

Finasteride (Proscar, an orally active 5 alpha-reductase enzyme inhibitor) blocks the conversion of testosterone to dihydrotestosterone. The effects of finasteride in patients with benign prostatic hyperplasia were investigated in 2 double blind, placebo controlled studies. In study 1, 86 patients were treated with placebo or finasteride (5 to 80 mg/day) for 12 wk, followed by a 12 wk drug free period. After 12 wk of treatment all doses of finasteride showed significant decreases in prostate volume. However, 12 wk after discontinuation of finasteride prostate volume returned to near baseline values. In study 2, 104 patients were treated with placebo or finasteride (0.2 to 40 mg/day) for 24 wk. After 24 wk of finasteride treatment prostate volume showed a mean decrease of 24% and 28% (p less than 0.01) in the 1 and 5 mg groups, respectively. Lower doses had a lesser effect on prostate shrinkage. Maximum urinary flow showed a mean increase of 3.7 cc/second when the 1 and 5 mg groups were combined. Symptom improvement was observed in the 1 and 5 mg groups, although this was not statistically different from the placebo group due to the small sample size.

Chibro Proscar

High-performance liquid chromatographic method with ultraviolet detection for the determination of finasteride in human plasma at therapeutic doses.|A sensitive and selective high performance liquid chromatography method was developed for the quant. detn of N-(2-methyl-2-propyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide in human plasma. The 4-N-Methyl analog of the drug was used as the internal std and calibration curves were developed at 2 levels of sensitivity to cover a large dynamic range of plasma concn. I was isolated from biological fluids with a solid-phase C18 extn. column; the analyte was further purified by adsorption and desorption from a 2nd extn. column (CN cartridge). Evaluation of the isolation method revealed that it was reproducible and recoveries were approx 90%. Chromatography was carried out on a C8 column (5 mum). The detection limit was approx 10 ng/ml. Human plasma levels are reported for N-(2- methyl-2-propyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide following single-dose oral administration of 50,200 and 400 mg of N-(2- methyl-2-propyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide; urinary excretion data are reported for a single volunteer given 400 mg of N-(2-methyl-2-propyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide.

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