AHFS Class:

• Cell Stimulants and Proliferants 84:16

Generic Name(s):

• Finasteride

Finasteride is a competitive and specific inhibitor of Type II 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT).1

Androgenetic Alopecia

Finasteride is used orally for the treatment of male pattern hair loss (androgenetic alopecia) in men.1 Finasteride does not appear to affect nonscalp hair.1 The drug should be used in men only and is not indicated for use in women or pediatric patients.1

In clinical trials, oral finasteride therapy was effective in promoting hair regrowth in young and middle-aged men (18-41 years of age) with mild to moderate androgenetic alopecia and hair loss on the vertex of the scalp and/or anterior mid-scalp area; the effects of finasteride on bitemporal recession have not been established.1 Improvement in both objective (scalp hair count) and subjective (individuals' self-assessment of appearance) measures of hair regrowth has been demonstrated as early as 3 months following initiation of oral finasteride therapy, and objective improvement was at its maximum during the first 2 years of treatment.1 Continuation or maintenance of hair regrowth (based on scalp hair count) beyond 2 years of treatment has not been demonstrated; however, slowing of further progression of hair loss has been demonstrated in clinical trials with follow-up periods of up to 5 years.1 Current evidence indicates that oral finasteride therapy must be continued to sustain initial regrowth and subsequent slowing of hair loss; however, benefit of the drug should be reevaluated periodically.1

Evidence of clinical benefit of finasteride is based principally on the results of 3 randomized, double-blind, placebo-controlled clinical trials in men with mild to moderate androgenetic alopecia.1 Two of the trials were conducted in men with predominantly vertex hair loss, and the third trial involved men with hair loss in the anterior mid-scalp, with or without vertex balding.1 In these trials, efficacy of finasteride therapy was evaluated objectively using hair counts (e.g., number of hairs in a 1-inch diameter circle) and subjectively by investigators' and treated individuals' assessments of cosmetic benefit.1 All individuals in these clinical trials (both active drug and placebo groups) were instructed to use a specific, medicated, tar-based shampoo (Neutrogena T/Gel® shampoo) to prevent seborrheic dermatitis that potentially could influence assessment of hair growth.1

The 2 trials in men with predominantly vertex hair loss were 1-year controlled trials with 1-year, controlled extension periods.1 The trials were extended for an additional 3 years in some men.1 As a result, some men who received finasteride during the first year of the trial continued to receive the drug for periods up to 5 years total, while others were switched to placebo for the second year and then were switched back to finasteride for years 3-5.1 Of the men who received placebo during the first year of the trial and participated in the extension trials, some continued to receive placebo and some were switched to finasteride during the extension trials.1 In these trials, hair regrowth (as indicated by increases in hair counts) with finasteride therapy was demonstrated at 6 months and 1 year and was maintained with continued finasteride therapy for up to a total of 2 years, while men receiving placebo continued to have progressive hair loss.1 Men receiving finasteride for up to 5 years experienced a maximum improvement in hair count during the first 2 years; a gradual decline in hair count occurred in these men after the second year, although hair counts remained above baseline during up to 5 years of finasteride therapy.1 Men receiving placebo for up to 5 years experienced a decline in hair count that was more rapid than that observed in men receiving finasteride.1 At 1 year, 14% of men treated with finasteride had further hair loss (defined as any decrease in hair count from baseline) compared with 58% of men receiving placebo.1 In men treated for up to 2 years, 17% of those receiving finasteride had hair loss compared with 72% of those receiving placebo.1 At 5 years, 35% of those receiving finasteride had hair loss compared with all of those receiving placebo.1 In men receiving finasteride for the first year who were switched to placebo for the second year, reversal of the increase in hair count was demonstrated at the end of the second year; those switched back to finasteride for years 3-5 experienced an increase in hair count to above baseline during the third year, and hair counts for years 3-5 remained above baseline.1 Men who were switched from placebo during the first year to finasteride during the second year had a decline in hair count during placebo therapy followed by an increase in hair count to above baseline after 1 year of treatment with finasteride; with continued finasteride therapy during years 3-5 of the trial, a gradual decline in hair count occurred.1 Individuals' subjective perceptions of hair growth, hair loss, and appearance were obtained at each clinic visit using a self-administered questionnaire.1 Evaluation of these self-assessments was consistent with an increase in the amount of hair, a decrease in and slowing of the rate of hair loss, and improvement in appearance in men treated with finasteride.1 Overall improvement according to individuals' self-assessments was observed as early as 3 months following initiation of finasteride therapy and maintained for up to 5 years.1 Self-assessments of finasteride therapy generally showed improvement in hair growth across racial groups (i.e., in whites, Asians, blacks, and Hispanics); black men reported dissatisfaction with hair growth in the frontal hairline and vertex but were satisfied with overall therapy.1 Investigators' assessments of clinical efficacy were based on a 7-point scale evaluating increases or decreases in scalp hair at each clinic visit.1 At 1 year, investigators determined that hair growth had increased in 65% of men treated with finasteride compared with 37% of those receiving placebo, while increased hair growth at 2 years occurred in 80 or 47% of men receiving finasteride or placebo, respectively.1 At 5 years, investigators determined that hair growth had increased in 77% of men receiving finasteride, compared with 15% of men receiving placebo.1 Increased hair growth as determined by investigators occurred as early as 3 months after initiation of finasteride therapy.1 Based on blinded evaluation of standardized photographs of the head, an independent panel determined that increased hair growth had occurred in 48 or 66% of men treated with oral finasteride for 1 or 2 years, respectively, compared with 7% of men receiving placebo for both time periods.1 The panel also determined that, at 5 years, 48 or 6% of men receiving finasteride or placebo, respectively, had experienced an increase in hair growth; 42 or 19%, respectively, had experienced no chan and 10 or 75%, respectively, had experienced hair loss.1 While most men with vertex baldness had some response to finasteride in clinical trials, treatment failures occurred in 17% of men treated for up to 2 years with the drug.1

The trial in patients with mild-to-moderate anterior mid-scalp area hair loss was a 1-year controlled trial.1 In this trial, hair counts also increased and were accompanied by patient-rated improvements in appearance in men who received finasteride compared to placebo; investigator assessments and ratings based on standardized photographs also demonstrated improvements.1,2

Additional placebo-controlled studies evaluating the efficacy of finasteride in male patients with androgenetic alopecia have been conducted.13 In all studies, treatment with finasteride 1 mg daily resulted in significant increases in total hair counts compared with placebo.13 Long-term results up to 120 months showed that the mean changes from baseline were significantly higher with finasteride compared to placebo at all time points evaluated.13

Finasteride is not effective for treatment of hair loss in postmenopausal women with androgenetic alopecia and is not indicated for use in women.1 In a 1-year study in postmenopausal women with androgenetic alopecia, there was no improvement in hair counts, investigators' or treated individuals' assessments of benefit, or ratings based on standardized photographs of the head in women receiving finasteride versus those receiving placebo.1

Clinical Perspective

Based on the current evidence demonstrating efficacy in the treatment of androgenetic alopecia in men, finasteride is recommended as a first-line treatment for this use.13 Response to treatment should be assessed at 6 months, although in some men, response may not become evident until 12 months.13 If treatment is successful, continued therapy is required to maintain efficacy.13 For greater efficacy, the combination of oral finasteride and topical minoxidil can be considered.13

Some studies comparing the efficacy of oral finasteride to topical minoxidil have shown superiority of finasteride in the treatment of male patients with androgenetic alopecia; however, other comparison studies have shown contradictory results.13

General

Dispensing and Administration Precautions

Handling and Disposal

• Females who are pregnant or who may become pregnant should not handle crushed or broken finasteride tablets because of the possibility of drug absorption and subsequent potential risk to a male fetus.1

Administration

Finasteride is administered orally without regard to meals.1

Dosage

Androgenetic Alopecia

The recommended dosage of finasteride for the treatment of men with androgenetic alopecia is 1 mg once daily.1 Daily administration of the drug for 3 months or longer is generally necessary before benefit is observed.1 Continued use is recommended to sustain benefit, which should be reevaluated periodically; reversal of clinical benefit occurs within 1 year after discontinuance of finasteride.1

Special Populations

Hepatic Impairment

Use caution in patients with hepatic impairment; the manufacturer makes no specific dosage adjustment recommendations.1

Renal Impairment

No dosage adjustment is necessary in patients with renal impairment.1

Geriatric Patients

No dosage adjustment is necessary in geriatic patients.1

Contraindications

• Pregnancy.1
• Hypersensitivity to any component of the medication.1

Warnings/Precautions

Risk to Male Fetus

Finasteride is not indicated for use in women.1 Based on animal findings and the drug's mechanism of action, finasteride may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female.1 (See Pregnancy under Cautions.) Women should not handle crushed or broken finasteride tablets if they are pregnant or potentially pregnant because of the possibility of absorption of finasteride and the potential riskto a male fetus.1 Finasteride tablets are coated and will prevent contact with the active ingredient during normal handling, provided the tablets have not been broken orcrushed.1 If a pregnant woman comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water.1

Effects on Prostate Specific Antigen

Oral finasteride therapy has been associated with small reductions (from 0.7 ng/mL at baseline to 0.5 ng/mL at month 12) in serum prostate-specific antigen (PSA) levels in men 18-41 years of age receiving finasteride 1 mg daily for androgenetic alopecia.1 PSA reductions of approximately 50% have been demonstrated in older men receiving the drug at a dosage of 5 mg daily for benign prostatic hyperplasia (BPH).1 Such reductions should be considered when interpreting serum PSA values in men receiving finasteride.1

Any confirmed increase from the lowest PSA concentration during finasteride therapy may signal the presence of prostate cancer and should be evaluated carefully, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor.1 Noncompliance to therapy with finasteride may also affect PSA results.1

Increased Risk of High-grade Prostate Cancer with 5-Reductase Inhibitors

5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer. 1,14 In 2 placebo-controlled trials evaluating finasteride (5 mg daily for 7 years) or dutasteride (0.5 mg daily for 4 years) for prevention of prostate cancer in men at least 50 years of age, 5α-reductase inhibitor therapy was associated with an overall reduction in prostate cancer occurrence, which reflected a reduction in lower-grade (Gleason score of 6 or less) tumors; however, the incidence of high-grade tumors (Gleason score of 8-10) was increased in men receiving finasteride or dutasteride.1,14

Specific Populations

Pregnancy

Finasteride is contraindicated in women who are or may become pregnant.1

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.1 If finasteride is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the male fetus.1

In animal studies, finasteride caused abnormal development of external genitalia in male fetuses.1 A dose-dependent increase in hypospadias was observed in 3.6 to 100% of male offspring in an embryo-fetal development study where pregnant rats received oral finasteride at maternal doses of approximately 1 to 684 times the recommended human dose (RHD) of 1 mg/day during the period of major organogenesis (gestation days 6 to 17); days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia.1 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.1 Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the RHD.1 No abnormalities were observed in female offspring exposed to any dose of finasteride in utero.1 In addition, no developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the RHD.1 In another study in rhesus monkeys, administration of an oral 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.1

Lactation

Finasteride is not indicated for use in women.1 It is not known whether the drug is distributed into human milk.1

Females and Males of Reproductive Potential

Finasteride is not indicated for use in women.1 The drug is contraindicated in women who are or may become pregnant.1

Pediatric Use

Finasteride is not indicated for use in pediatric patients; safety and efficacy have not been established.1

Geriatric Use

Clinical studies of finasteride for androgenetic alopecia did not include patients 65 years of age and older.1 Based on the pharmacokinetics of finasteride 5 mg, the manufacturer states that no dosage adjustment is necessary in the elderly; however, efficacy of the drug has not been established in this population.1

The elimination rate of finasteride decreases slightly with increasing age of the patient, with a half-life ranging from approximately 5-6 hours in men 18-60 years of age to 8 hours in men older than 70 years of age.1

Hepatic Impairment

Because finasteride is extensively metabolized in the liver, mainly via cytochrome P-450 (CYP) isoenzyme 3A4, and the effect of hepatic impairment on finasteride pharmacokinetics has not been established, the drug should be used with caution in patients with liver dysfunction.1

Renal Impairment

Values for finasteride AUC, peak plasma concentrations, elimination half-life, and protein binding in patients with chronic renal failure (creatinine clearance 9-55 mL/minute) were similar to those in healthy individuals, and the manufacturer recommends no dosage adjustment for finasteride in patients with renal insufficiency.1

Common Adverse Effects

The most common adverse effects reported in ≥1% of patients receiving finasteride in clinical studies and more frequentlythan in patients treated with placebo include decreased libido, erectile dysfunction, and ejaculation disorder.1

Finasteride does not affect the cytochrome P-450 (CYP) enzyme system.1 No clinically meaningful drug interactions have been identified.1 Drugs that have been tested for drug interaction potential with finasteride include antipyrene, digoxin, propranolol, theophylline, and warfarin.1

Although specific drug interaction studies have not been performed, finasteride (administered at a dose of 1 mg or higher) was used concomitantly with acetaminophen, acetylsalicylic acid, α-blockers, analgesics, angiostensin-converting enzyme (ACE) inhibitors, anticonvulsants, benzodiazepines, beta-blockers, calcium-channel blockers, cardiac nitrates, diuretics, H₂ receptor antagonists, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory agents, and quinolone anti-infectives in clinical studies without evidence of clinically significant adverse interactions.1

Description

Finasteride is a synthetic 4-azasteroid compound.1,2,3,4 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 gland.1,2,3,4,5,6 The conversion of testosterone to the active metabolite 5α-dihydrotestosterone (DHT) depends on the presence of this enzyme.1,5,6

5α-Reductase is present as 2 distinct isoenzymes, type I and type II, in humans and certain animals.1,3,7 Type I 5α-reductase is found principally in the sebaceous and sweat glands of the skin, including scalp, follicular and epidermal keratinocytes, and dermal papilla cells, and also in the liver; this isoenzyme is responsible for approximately one-third of circulating DHT.1,3,7,8,9,10,11 The Type II isoenzyme is found predominantly in the prostate, seminal vesicles, epididymides, 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.1,3,7,8,9,10,11 Although testosterone is the principal circulating androgen, conversion to DHT amplifies the androgenic effect in androgen-sensitive target tissues such as the skin and scalp.2,7,9,10

In men with androgenetic hair loss, increased amounts of DHT and 5α-reductase lead to miniaturized hair follicles and a shortened hair growth cycle; these alterations are not seen in hairy scalp portions of men with androgenetic hair loss or in patients without alopecia.1,3,8 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.3,7,9 Androgenetic hair loss is not observed in these men, and hair loss in hypogonadal men can be induced by administration of testosterone.2,3,7,9 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 remains unaffected.3,7,8,9,10,11 These data suggest that while the Type II isoenzyme is not as prevalent in human scalp as the Type I isoenzyme, the Type II isoenzyme is involved in the development of androgenetic alopecia.7,8,11

The exact mechanism of action of finasteride in patients with androgenetic alopecia has not been fully elucidated since the role of 5α-reductase and DHT in male-pattern baldness has not been fully elucidated.3,8 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.3,7,8,9 Inhibition of 5α-reductase by finasteride is accompanied by reduction of finasteride to dihydrofinasteride and adduct formation with nicotinamide adenine dinucleotide phosphate (NADP⁺).1 This enzyme complex has a slow rate of turnover in the body (half-life of about 30 days for the Type II isoenzyme complex and 14 days for the Type I complex).1 Although in vitro studies suggest that finasteride acts principally through Type II 5α-reductase, some clinicians suggest that chronic treatment with finasteride also may have some effect on the Type I isoenzyme.3,9

Inhibition of Type II 5α-reductase by finasteride blocks the peripheral conversion of testosterone to DHT, resulting in substantial reductions in serum and tissue DHT concentrations.1 In men with androgenetic alopecia, high-dose oral finasteride (5 mg) decreases scalp DHT concentrations to levels found in hairy scalp, reduces serum DHT, increases hair regrowth, and slows hair loss.1,3,7,8,9,11 Finasteride may affect scalp hair growth through reductions in 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 has not been elucidated.1,2,3,8

Finasteride has no affinity for the androgen receptor and has no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational effects.1

The mean bioavailability of finasteride 1-mg tablets is 65%.1 At steady-state dosing, peak plasma concentrations were reached in 1 to 2 hours post-dose.1 The bioavailability of finasteride is not affected by food.1 Approximately 90% of circulating finasteride is bound to plasma proteins.1 The drug crosses the blood-brain barrier.1 Finasteride is extensively metabolized in the liver, primarily via cytochrome P-450 (CYP) enzymes.1 The 2 metabolites that have been identified (t-butyl side chain monohydroxylated and monocarboxylic acid) exhibit no more than 20% of the 5α-reductase inhibitory activity of the parent drug.1 The mean terminal half-life of finasteride is approximately 5-6 hours in men 18-60 years of age and 8 hours in men >70 years of age.1 Following administration of an oral dose, approximately 39% of the dose is excreted in urine in the form of metabolites and 57% is excreted in feces.1

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information).1
• Inform patients that women who are pregnant or may potentially be pregnant should not handle crushed or broken finasteride tablets because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus.1 The tablets are coated and will prevent contact with the active ingredient during normal handling, provided the tablets have not been broken or crushed.1 If a woman who is pregnant or may potentially be pregnant comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water.1
• Inform patients that there was an increase in high-grade prostate cancer in men treated with 5α-reductase inhibitors indicated for BPH treatment, compared to those treated with placebo in clinical studies.1 The screening blood test for prostate cancer (prostate-specific antigen [PSA]) may be affected by finasteride.1 Advise patients to inform providers if they are taking finasteride or if they have not taken finasteride as prescribed prior to having a PSA test performed.1
• Inform patients that finasteride may cause symptoms of sexual dysfunction such as decreased libido, erectile dysfunction, and ejaculation disorder, including decreased ejaculate volume.1
• Breast changes including breast enlargement, tenderness and neoplasm have been reported.1 Advise patients to promptly report any changes in their breasts such as lumps, pain, or nipple discharge to their clinician.1
• Instruct patients to read the patient package insert before starting therapy with finasteride and to read it again each time the prescription is renewed so that they are aware of current information for patients regarding the drug.1
• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
• Inform patients of other important precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

1. Organon & Co. Propecia^® (finasteride) tablets prescribing information. Jersey City, NJ; 2022 Aug.

2. Anon. Propecia and Rogaine Extra Strength for alopecia. Med Lett Drugs Ther . 1998; 40:25-7. [PubMed 9505960]

3. Dallob AL, Sadick NS, Unger W. The effect of finasteride, a 5α-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. J Clin Endocrinol Metab . 1994; 79:703-6. [PubMed 8077349]

4. Stoner E. The clinical development of a 5α-reductase inhibitor, finasteride. J Steroid Biochem Mol Biol . 1990; 37:375-8. [PubMed 1701660]

5. Gormley GJ, Stoner E, Rittmaster RS et al. Effects of finasteride (MK-906), a 5 α- reductase inhibitor, on circulating androgens in male volunteers. J Clin Endocrinol Metab . 1990; 70:1136-41. [PubMed 2156887]

6. Rittmaster RS, Stoner E, Thompson DL et al. Effect of MK-906, a specific 5 alpha- reductase inhibitor, on serum androgens and androgen conjugates in normal men. J Androl . 1989; 10:259-62. [PubMed 2550402]

7. Rittmaster RS. Finasteride. New Engl J Med . 1994; 330:120-5. [PubMed 7505051]

8. Walsh DS, Dunn CL, James WD. Improvement in androgenetic alopecia (stageV) using topical minoxidil in a retinoid vehicle and oral finasteride. Arch Dermatol . 1995; 131:1373-5. [PubMed 7492124]

9. Chen W, Zouboulis CC, Orfanos CE. The 5α-reductase system and its inhibitors: recent development and its perspective in treating androgen-dependent skin disorders. Dermatology . 1996; 193:177-84. [PubMed 8944337]

10. Gormley GJ. Finasteride: a clinical review. Biomed Pharmacother . 1995; 49:319-24. [PubMed 8562856]

11. Amichai B, Grunwald MH, Sobel R. 5α-reductase inhibitors—a new hope in dermatology. Int J Dermatol . 1997; 36:182-4. [PubMed 9158996]

13. Kanti V, Messenger A, Dobos G et al. Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men - short version. J Eur Acad Dermatol Venereol. 2018 Jan;32(1):11-22. doi: 10.1111/jdv.14624. Epub 2017 Nov 27. PMID: 29178529.

14. Food and Drug Administration. FDA drug safety communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. Rockville, MD; 2011 Jun 9. From FDA website. [Web]