Finasteride (hair growth) (monograph)

Finasteride (hair growth) (monograph)

introduction

Uses for Finasteride (Hair Growth)

Androgenetic alopecia

Finasteride is used orally to stimulate hair regrowth in men with mild to moderate androgenetic alopecia (male alopecia, hereditary alopecia, male pattern baldness). Androgenetic alopecia in men is primarily manifested by baldness of the vertex (vertex) of the scalp. In clinical trials, oral finasteride therapy has been shown to be effective in promoting hair growth in young and middle-aged men (18-41 years) with mild to moderate androgenetic alopecia and hair loss at the vertex of the scalp and/or anterior middle age. scalp area; The effects of finasteride on bitemporal recession have not been established. Improvement in both objective (scalp hair count) and subjective (individual self-assessment of appearance) measures of hair growth was demonstrated as early as three months after starting oral finasteride therapy, and objective improvement reached its maximum in the first two years of treatment. Continuation or maintenance of hair growth (based on scalp hair count) beyond two years of treatment has not been demonstrated; However, in clinical studies with follow-up periods of up to 5 years, a slowing of the further progression of hair loss was demonstrated. Current evidence suggests that oral finasteride therapy must be continued to maintain initial regrowth and subsequent slowing of hair loss. However, the benefits of the drug should be reassessed regularly. If there is no improvement within the first year of finasteride therapy, further treatment with the drug is unlikely to provide benefit. Discontinuation of the drug results in reversal of clinical benefit within one year.

Evidence of the clinical benefit of finasteride is based primarily on the results of three randomized, placebo-controlled clinical trials in men with mild to moderate androgenetic alopecia. Two of the studies were conducted in men with predominantly vertex hair loss, and the third study included men with hair loss in the front center of the scalp, with or without hair loss at the vertex. In these studies, the effectiveness of finasteride therapy was assessed objectively by hair count (e.g., number of hairs in a 1-inch diameter circle) and subjectively by assessment of cosmetic benefit by investigators and treated subjects. All subjects in these clinical trials (both active and placebo groups) were instructed to use a specific medicated tar-based shampoo (Neutrogena T/Gel Shampoo) to prevent seborrheic dermatitis, which could potentially affect hair growth assessment. The two studies in men with predominantly parietal hair loss were 1-year controlled studies with 1-year controlled extension periods. For some men, the trials were extended for another three years. As a result, some men who received finasteride in the first year of the study continued to receive the drug for a total of up to five years, while others were switched to placebo in the second year and then switched back to finasteride for three years. 5. Of the men who received placebo in the first year of the study and participated in the extension studies, some continued to receive placebo and some were switched to finasteride during the extension studies. The study involving patients with mild to moderate anterior midhead hair loss was a one-year controlled study.

In the studies of men with parietal hair loss, hair regrowth (indicated by an increase in hair count) with finasteride therapy was demonstrated at 6 months and 1 year and was maintained for a total of up to 2 years with continued finasteride therapy, while in men hair regrowth (indicated by an increase in hair count) continued to occur in patients receiving placebo. Men who received finasteride for up to 5 years experienced maximum improvement in hair count in the first 2 years; These men experienced a gradual decline in hair count after the second year, although hair count remained above baseline for up to 5 years of finasteride therapy. Men who received a placebo for up to 5 years experienced a faster decline in hair number than those who received finasteride. After one year, 14% of men treated with finasteride experienced hair loss (defined as any decrease in hair count from baseline), compared to 58% of men who received placebo. In men treated for up to two years, 17% of those who received finasteride experienced hair loss, compared to 72% of those who received placebo. After 5 years, 35% of those who received finasteride experienced hair loss, compared to all people who received placebo. In men who received finasteride in the first year and were switched to placebo in the second year, a reversal in the increase in hair count was noted at the end of the second year; Those who switched back to finasteride in years 3–5 experienced an increase in hair count above baseline in year 3, and in years 3–5 hair count remained above baseline. Men who switched from placebo in the first year to finasteride in the second year experienced a decrease in hair count during placebo therapy, followed by an increase in hair count above baseline after one year of treatment with finasteride; With continued finasteride therapy in the third to fifth year of the study, there was a gradual decrease in hair count.

Individuals' subjective perceptions of hair growth, hair loss, and appearance were collected at each clinic visit using a self-completed questionnaire. Evaluation of these self-assessments revealed an increase in the amount of hair, a reduction and slowing of hair loss, and an improvement in appearance in men treated with finasteride. According to individual self-assessment, general improvement was observed as early as 3 months after starting finasteride therapy and lasted up to 5 years.

The researchers' assessment of clinical effectiveness was based on a 7-point scale that assessed the increase or decrease in scalp hair at each clinic visit. After one year, researchers found that hair growth increased in 65% of men treated with finasteride compared to 37% of men who received placebo, while after two years, increased hair growth occurred in 80 and 47% of men who received finasteride and placebo, respectively. After five years, researchers found that hair growth increased in 77% of men who received finasteride, compared to 15% of men who received placebo. The increased hair growth noted by the researchers occurred as early as 3 months after starting finasteride therapy. Based on a blinded review of standardized head photographs, an independent panel found that increased hair growth occurred in 48 and 66% of men treated with oral finasteride for 1 and 2 years, respectively, compared with 7 and 7% of men who received placebo for the same periods. The panel also found that after 5 years, 48 ​​and 6% of men who received finasteride and placebo, respectively, experienced an increase in hair growth; 42 or 19% had experienced no change; and 10 and 75%, respectively, had experienced hair loss.

In the year-long study of patients with mild to moderate hair loss in the anterior midhead region, hair count also increased and was associated with patient-rated improvement in appearance.

In the studies of subjects with predominantly vertex baldness, self-assessments of finasteride therapy generally showed improvement in hair growth in all racial groups (ie, whites, Asians, blacks, and Hispanics); Black men reported dissatisfaction with hair growth at the front hairline and vertex but were satisfied with overall therapy.

While most men with crown baldness showed some response to finasteride in clinical trials, 17% of men treated with the drug for up to two years experienced treatment failure. Finasteride does not appear to have any effect on hair outside the scalp.

Finasteride is not effective for the treatment of hair loss in postmenopausal women with androgenetic alopecia and is not indicated for use in women. In a one-year study of postmenopausal women with androgenetic alopecia, there was no improvement in hair count, investigator or treated person assessments of benefit, or assessments based on standardized head photographs in women who received finasteride compared to women who received placebo.

In clinical trials of men with parietal hair loss, people who received oral finasteride therapy were significantly more likely to report problems with sexual interest, erections, and sexual perception at the end of one year than those who received a placebo; However, no significant difference was reported between finasteride and placebo in overall satisfaction with sex life. Breast enlargement and breast tenderness were reported during clinical trials in men receiving finasteride 5 mg daily for benign prostatic hyperplasia (BPH) and during postmarketing surveillance in men receiving finasteride 1 mg daily for androgenetic alopecia. Breast neoplasia has been reported in clinical trials over a period of 4 to 7 years in men receiving finasteride 5 mg daily and during postmarketing surveillance in men receiving finasteride 1 mg daily. Whether there is a causal relationship between long-term use of finasteride and breast neoplasia in men has not been established. Men receiving the medication should be instructed to report any breast changes (e.g., lumps, pain, nipple discharge) to their doctor.

In men aged 18-41 years who received the drug at a dosage of 1 mg daily for androgenetic alopecia, oral finasteride therapy was associated with a small reduction (from 0.7 to 0.5 ng/ml) in serum prostate specific antigen (PSA). In older men who received the drug at a dosage of 5 mg daily for BPH, a PSA reduction of approximately 50% was demonstrated. Such reductions should be considered when interpreting serum PSA values ​​in men receiving finasteride. Any confirmed increase in serum PSA concentration during finasteride therapy should be carefully evaluated.

5α-reductase inhibitors may increase the risk of developing high-grade prostate cancer. In two placebo-controlled trials evaluating finasteride (5 mg daily for 7 years) or dutasteride (0.5 mg daily for 4 years) for the prevention of prostate cancer in men at least 50 years of age, 5α-reductase inhibitor therapy was associated with an overall reduction in the incidence of prostate cancer, reflecting a reduction in lower grade tumors (Gleason score 6 or less); However, the incidence of high-grade tumors (Gleason score 8-10) was increased in men receiving finasteride or dutasteride. Finasteride is not approved by the U.S. Food and Drug Administration (FDA) to prevent prostate cancer.

Finasteride is contraindicated in women who are or may be pregnant. Because finasteride inhibits the conversion of testosterone to dihydrotestosterone, the drug could cause abnormalities in the external genitalia of a male fetus if a pregnant woman receives the drug, and female patients should be informed of the potential danger to the fetus. In addition, pregnant women should not handle crushed or broken finasteride tablets because of the possibility of absorption and resulting danger to the male fetus.

For use in the treatment of benign prostatic hyperplasia, see Finasteride 92:08.

Dosage and administration of finasteride (hair growth).

Administration

Finasteride is administered orally; The drug can be administered regardless of meals.

dosage

Finasteride is only recommended for use in men. The manufacturer states that the drug is not suitable for use in women or children.

Patients should be instructed to read the patient information provided by the manufacturer before starting finasteride treatment and each time their prescription is renewed.

For the treatment of androgenetic alopecia in men, the usual dosage of finasteride is 1 mg once daily. In general, daily administration of the drug for 3 months or longer is required before benefit is observed. To maintain benefit, continued use is recommended and should be reassessed periodically; Reversal of clinical benefit occurs within one year of discontinuation of finasteride.

The elimination rate of finasteride decreases slightly as the patient ages, ranging from approximately 5-6 hours in men aged 18-60 years to 8 hours in men over 70 years old. The manufacturer states that these results are not clinically significant and that reducing the dosage of finasteride in geriatric individuals is not warranted.

Dosage for impaired kidney and liver function

Finasteride area under the plasma concentration-time curve (AUC), maximum plasma concentration, elimination half-life, and protein binding values ​​in patients with chronic renal failure (creatinine clearance: 9-55 mL/minute) were similar to those in healthy individuals, and the manufacturer does not recommend dose adjustment for finasteride in patients with renal insufficiency.

Because finasteride is extensively metabolized in the liver, primarily via the cytochrome P-450 (CYP) isoenzyme 3A4, and the effect of hepatic impairment on the pharmacokinetics of finasteride has not been established, the drug should be used with caution in patients with hepatic impairment.

Description

Finasteride is a synthetic 4-azasteroid compound. The drug is a specific, competitive inhibitor of steroid type II 5α-reductase, an intracellular enzyme present in high concentrations in the liver, skin and prostate. The conversion of testosterone to the active metabolite 5α-dihydrotestosterone (DHT) depends on the presence of this enzyme.

In humans and certain animals, 5α-reductase exists in the form of two different isoenzymes, type I and type II. Type I 5α-reductase is found primarily in the sebaceous and sweat glands of the skin, including the scalp, follicular and epidermal keratinocytes, and dermal papilla cells, as well as in the liver; This isoenzyme is responsible for about a third of circulating DHT. The type II isoenzyme is predominantly found in the prostate, seminal vesicles, epididymis and liver and is detectable in the inner root sheath of hair follicles and epidermal keratinocytes; This isoenzyme is responsible for two-thirds of circulating DHT. Although testosterone is the major circulating androgen, conversion to DHT enhances androgenic effects in androgen-sensitive target tissues such as skin and scalp.

In men with androgenetic hair loss, increased levels of DHT and 5α-reductase result in miniaturized hair follicles and a shortened hair growth cycle; These changes do not occur on the hairy scalp in men with androgenetic hair loss and in patients without alopecia. Evidence that testosterone (and DHT) and steroid 5α-reductase may be involved in androgenetic hair loss comes from clinical observations in men with congenital 5α-reductase deficiency and in hypogonadal men. Androgenetic hair loss is not observed in these men, and hair loss in hypogonadal men can be induced by the administration of testosterone. In men with congenital 5α-reductase deficiency (pseudohermaphroditism), the gene for type II 5α-reductase activity is defective, while the gene for type I isoenzyme activity is unaffected. These data suggest that although the type II isoenzyme is not as abundant in the human scalp as the type I isoenzyme, the type II isoenzyme is involved in the development of androgenetic alopecia.

The exact mechanism of action of finasteride in patients with androgenetic alopecia is not fully understood, as the role of 5α-reductase and DHT in male pattern hair loss is not fully understood. In vitro binding studies indicate that finasteride inhibits type II 5α-reductase by binding tightly to the enzyme and is 100-fold more selective for this isoenzyme than for the type I isoenzyme. Inhibition of 5α-reductase by finasteride is accompanied by a reduction of finasteride to dihydrofinasteride and adduct formation with nicotinamide adenine dinucleotide phosphate (NADP+). This enzyme complex has a slow turnover rate in the body (half-life of about 30 days for the type II isoenzyme complex and 14 days for the type I complex). Although in vitro studies suggest that finasteride acts primarily through type II 5α-reductase, some doctors suspect that chronic treatment with finasteride may also have some effect on the type I isoenzyme.

Inhibition of type II 5α-reductase by finasteride blocks the peripheral conversion of testosterone to DHT, resulting in significant reductions in serum and tissue DHT concentrations. In men with androgenetic alopecia, high-dose oral finasteride (5 mg) reduces scalp DHT concentrations to hairy scalp levels, reduces serum DHT, increases hair regrowth, and slows hair loss. Finasteride may affect hair growth on the scalp by reducing local and systemic DHT because the scalp is highly vascularized. The relative contributions of reductions in serum and scalp concentrations to the observed increase in scalp hair have not been elucidated.

Finasteride has no affinity for the androgen receptor and has no androgenic, antiandrogenic, estrogenic, antiestrogenic or progestin effects.

Preparations

Excipients in commercial drug preparations may have clinically significant effects in some individuals; Details can be found on the respective product labeling.

For information about shortages of one or more of these drugs, visit the ASHP Drug Shortages Resource Center.

Finasteride

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