PROSTACARE

Finasteride is a synthetic 4-azasteroid compound and specific inhibitor of steroid Type II 5α-reductase, which is an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT).

It works in a similar fashion as dutasteride, which is another 5-alpha-reductase inhibitor, by exerting antiandrogenic effects.

Finasteride is an Oral active drug that was first approved by the FDA in for the treatment of benign prostatic hyperplasia to improve symptoms and reduce the risk for acute urinary retention or the need for surgical procedures. 12, 13 In 1998, it was approved by the FDA to treat male pattern hair loss.

Finasteride is commonly marketed under the brand names Propecia and Proscar to be used aloneo or in combination with doxazosin, an alpha-blocker.

Both benign prostatic hyperplasia and androgenic alopecia are androgen-dependent disorders that are characterized by in situ high levels of DHT.

In the treatment of benign prostate hyperplasia, alpha-blockers such as tamsulosin and terazosin are also used.

Compared to alpha-blockers that focus on providing the rapid relief of symptoms, 5α-reductase inhibitors aim to target the underlying disease by blocking the effects of the primary androgen involved in benign prostate hyperplasia and androgenic alopecia, thus reducing the risk for secondary complications while providing symptom control.

Finasteride is 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.

A with tadalafil is also used for the symptomatic treatment of BPH for up to 26 weeks.

Finasteride is also indicated for the treatment of male pattern hair loss (androgenetic alopecia, hereditary alopecia, or common male baldness) in male patients.

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. 5.

There is evidence from early clinical observations and controlled studies that finasteride may reduce bleeding of prostatic origin.

3-oxo-5-alpha-steroid 4-dehydrogenase 2 Inhibitor Polyprenal reductase Inhibitor 3-oxo-5-alpha-steroid 4-dehydrogenase 1 Inhibitor.

Finasteride is well absorbed following oral administration and displays a slow accumulation phase after multiple dosing.

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 26-170% for 1 mg dose and from 34-108% for 5 mg dose, respectively. 11, 13 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.

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.

The volume of distribution is 76 L at steady state, ranging from 44-96 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.

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. 5, 13 Theses metabolites retain less than 20% of the pharmacological activity of the parent compound.

Hover over products below to view reaction partners Finasteride omega-hydroxyfinasteride.

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.

In healthy young subjects receiving finasteride, the mean elimination half-life in plasma was 6 hours ranging from 3-16 hours.

In elderly patients over the age of 70 years, the half-life is prolonged to 8 hours.

In healthy young subjects (n=15), the mean plasma clearance of finasteride was 165 mL/min with the range between and 279 mL/min.

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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.

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 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 5α-dihydrotestosterone (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.

• Hypersensitivity to any components of this product.

& ADMINISTRATION Finasteride tablets USP may be administered with or without meals.

The recommended dose of finasteride tablets

USP is one tablet (1 mg) taken once daily.

In general, daily use for 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.

• Finasteride tablets USP may be administered with or without meals.

• One tablet (1 mg) taken once daily.

• In general, daily use for three months or more is necessary before benefit is observed.

Finasteride tab le t s

USP, 1 mg, is brown color, round film coated tablets, debossed with ‘H’ on one side and ‘36’ on other side.

They are supp lied as f o llo w s: NDC 31722-526-30 bottles of 30 NDC 31722-526-90 bottles of 90 NDC 31722-526-10 bottles of 1000 Storage and Handling Store at 20° to 25° C (68° to 77° F) .

Keep container closed and protect from moisture.

Women should not handle crushed or broken finasteride tablets USP 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 USP are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed.

Finasteride tablets

USP is contraindicated for use in women who are or may become pregnant.

Finasteride tablets USP are Type

II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia.

In animal studies, finasteride caused abnormal development of external genitalia in male fetuses.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus.

Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors.

These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency.

Women could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride tablets USP.

With regard to finasteride exposure through the skin, finasteride tablets USP are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken.

Women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets USP because of possible exposure of a male fetus.

If a pregnant woman comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water.

With regard to potential finasteride exposure through semen, a study has been conducted in men receiving finasteride tablets USP 1 mg/day that measured finasteride concentrations in semen.

In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days to 17).

At maternal doses of oral finasteride approximately to 684 times the recommended human dose ( RHD ) of 1 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring.

Exposure multiples were estimated using data from nonpregnant rats.

Days to 17 of gestation are a critical period in male fetal rats for differentiation of the external genitalia.

At oral maternal doses approximately 0.2 times the RHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development.

Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the RHD (based on AUC at animal dose of 0.003 mg/kg/day).

No abnormalities were observed in female offspring exposed to any dose of finasteride in utero.

No developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the RHD (based on AUC at animal dose of 80 mg/kg/day).

Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation.

No effects on fertility were seen in female offspring under these conditions.

No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days to 18) at maternal doses up to 100 mg/kg/day (finasteride exposure levels were not measured in rabbits).

However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit.

The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits.

Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 930 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day) resulted in no abnormalities in male fetuses.

In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 120,000 times the highest estimated blood levels of finasteride from semen of men taking 1 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses.

No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose.

Finasteride tablets

USP are not indicated for use in women.

It is not known whether finasteride is excreted in human milk.

Finasteride tablets

USP are not indicated for use in pediatric patients.

Safety and effectiveness in pediatric patients have not been established.

Clinical efficacy studies with finasteride tablets

USP did not include subjects aged and over.

Based on the pharmacokinetics of finasteride 5 mg, no dosage adjustment is necessary in the elderly for finasteride tablets USP.

However the efficacy of finasteride tablets

USP in the elderly has not been established.