5-Alpha Reductase Inhibitors
Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.
Finasteride may be administered without regard to meals.
Women who are pregnant or may get pregnant must not handle/administer broken or crushed finasteride tablets; the active ingredient could harm the unborn baby. Exposure to whole tablets is not expected to cause harm as long as they are not swallowed.
new primary malignancy / Delayed / Incidence not known
breast cancer / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
teratogenesis / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / 1.3-1.3
ejaculation dysfunction / Delayed / 1.2-1.2
depression / Delayed / Incidence not known
infertility / Delayed / Incidence not known
libido decrease / Delayed / 1.8-1.8
decreased ejaculate volume / Delayed / 1.2-1.2
rash / Early / 0.5-0.5
gynecomastia / Delayed / 10.0
breast enlargement / Delayed / 10.0
hematospermia / Delayed / Incidence not known
testicular pain / Early / Incidence not known
orgasm dysfunction / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
oligospermia / Delayed / Incidence not known
spermatogenesis inhibition / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
Common Brand Names
5-alpha reductase inhibitor
Used for symptomatic treatment of BPH and male pattern baldness (i.e., androgenetic alopecia)
May decrease risk of low-grade prostate cancer; but, may increase risk of more serious high-grade prostate cancer
Dosage And Indications
5 mg PO once daily.
1 mg PO once daily. Daily use for 3 months or more is necessary before benefit is observed. Continued use is recommended to sustain benefit. Withdrawal of treatment leads to reversal of effect within 12 months.
5 mg PO once daily either alone or in combination with oral contraceptives was shown to reduce hirsutism in women with mild hirsutism. Women with moderate to severe hirsutism either do not respond or only respond initially. Adverse effects from finasteride were minimal compared to other antiandrogens such as cyproterone, flutamide, and spironolactone.
The risks of finasteride for prostate cancer prevention outweigh the benefits. In a 7-year placebo-controlled study, finasteride 5 mg PO once daily was shown to prevent or delay the development of prostate cancer in healthy men (>= 55 years of age) with a low risk of prostate cancer (PSA <= 3 ng/mL). Prostate specific antigen (PSA) levels, digital rectal exams, and biopsies were used to aid in the diagnosis of prostate cancer. Results showed that men receiving finasteride had a 26% decreased risk of being diagnosed with prostate cancer compared to placebo (p < 0.0001); however, the risk reduction was limited to Gleason score (GS) <= 6 cancers. There was an increased incidence of high-grade prostate cancer (GS 7—10) with finasteride compared to placebo (6.4% vs. 5.2%, respectively, p = 0.005). Finasteride was also associated with a higher incidence of sexual side effects versus placebo.
†Indicates off-label use
Finasteride should be initiated with caution in patients with hepatic disease. Since finasteride is metabolized extensively in the liver, reduced metabolism is possible. The effect of hepatic impairment on finasteride pharmacokinetics has not been studied.Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Saw Palmetto, Serenoa repens: (Moderate) Saw palmetto may inhibit 5 alpha-reductase, preventing the conversion of testosterone to dihydrotestosterone. This action is similar to the action of 5-alpha reductase inhibitors, such as dutasteride and finasteride. Co-use is likely to be common by patients, but the effects of co-use are not known. In theory, the effects could be additive, but it is not known if the added effects would be beneficial or harmful. Clinicians should be alert for any unusual effects if patients ingest saw palmetto supplements while taking 5-alpha reductase inhibitors.
Soy Isoflavones: (Minor) Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may have additive effects with other 5-alpha reductase inhibitors.
Terazosin: (Minor) Terazosin has been reported to increase peak concentrations of finasteride by 16% and AUC by 31% when the two agents are coadministered. The interaction is of minor importance.
Finasteride/Propecia/Proscar Oral Tab: 1mg, 5mg
Males: 5 mg/day PO for benign prostatic hyperplasia (BPH); the manufacturer literature states that patients have received up to 80 mg/day PO for three months without adverse effects; however, it is not clear if the dose was used therapeutically or provided additional benefit over the usual dose range. Maximum dose-response is 1 mg/day PO for alopecia.Elderly
Males: 5 mg/day PO for benign prostatic hyperplasia (BPH); the manufacturer literature states that patients have received up to 80 mg/day PO for three months without adverse effects; however, it is not clear if the dose was used therapeutically or provided additional benefit over the usual dose range. Maximum dose-response is 1 mg/day PO for alopecia.Adolescents
Mechanism Of Action
Finasteride is a synthetic 4-aza analog of testosterone that acts as a competitive, specific inhibitor of type II 5-alpha-reductase, an intracellular enzyme that converts testosterone to the potent androgen 5-alpha-dihydrotestosterone (DHT). The type II 5alpha-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles, as well as liver. The type II isozyme is responsible for two-thirds of circulating DHT. DHT is the primary androgen that stimulates the development of prostate tissue. When used for the treatment of benign prostatic hyperplasia, as the enzymatic conversion from testosterone to DHT is inhibited, a desirable reduction in prostate hypertrophy is achieved, and urine flow should be improved. In male pattern hair loss, the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Finasteride decreases scalp and serum DHT concentrations, thus interrupting a key factor in the development of androgenetic alopecia in those patients genetically predisposed. Finasteride does not appear to affect circulating concentrations of cortisol, estradiol, prolactin, thyroid-stimulating hormone, thyroxine or cholesterol. Research to date also suggests that finasteride does not affect the hypothalamic-pituitary-testicular-axis.
Finasteride is administered orally in men. Approximately 90% is bound to plasma proteins; yet the drug has been found to cross the blood-brain barrier. Finasteride generally does not affect other hormones. Finasteride has minimal distribution into semen. Data from 2 studies found semen drug concentrations ranged from undetectable (less than 0.1 ng/mL) to 10.54 ng/mL following daily treatments for 6 to 24 weeks. Daily dosing causes accumulation to occur, with plasma concentrations increasing by 50% over those observed from a single dose. The mean plasma elimination half-life of finasteride is 6 hours (range, 3 to 16 hours); however, the turnover rate for the type II 5-alpha-reductase enzyme complex is slow, with a turnover half-life of approximately 30 days. After oral dosing, about half of the unchanged drug is excreted in the feces, and one-third is metabolized in the liver to the 17-carboxylic acid, which is then excreted in the urine (39%) and the feces (57%).
A single 5 mg oral dose rapidly reduces serum DHT concentrations by as much as 70%, with the maximum reduction occurring at about 8 hours. The effect lasts for at least 24 hours, so once daily dosing is appropriate. Actual clinical effects, however, are not realized for 3 to 6 months after beginning therapy.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, UGT1A4
While finasteride is metabolized by hepatic CYP3A4 isoenzymes, no drug interactions of clinical importance have been identified, likely due to the hormonal mechanisms of action and relatively large therapeutic window of effect. Finasteride does not appear to affect the CYP450-linked drug metabolizing enzyme system. Compounds that have been tested in man have included antipyrine, digoxin, propranolol, theophylline, and warfarin and no clinically meaningful interactions were found. Finasteride has not been associated with clinically important drug interactions during clinical trials, including a 4-year safety trial of 3,040 males aged 45 to 78 years. Finasteride markedly inhibited UGT1A4 activity in vitro in a drug transporter study; however, the data strongly suggested that finasteride is unlikely to cause clinically significant drug-drug interactions mediated via inhibition of the hepatic UGT enzymes involved in drug metabolism in vivo.
The mean bioavailability following a single dose of finasteride is about 63%; however, bioavailability is highly variable (range, 34% to 108%). Bioavailability is not affected by food, and maximum plasma concentrations (Cmax) are attained within 1 to 2 hours post dose.
Pregnancy And Lactation
Finasteride is not FDA-approved for use in females of childbearing potential and is contraindicated during pregnancy. Finasteride may cause fetal harm. Finasteride and other 5-alpha-reductase inhibitors, by inhibiting the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT), have the ability to cause abnormalities in the external genitalia of the male fetus if administered to pregnant females. Pregnant women or females trying to conceive should not handle crushed or broken finasteride tablets. The distribution of finasteride into human semen has been assessed and appears to be well below the threshold concentration associated with fetal anomalies in animals.