Propecia (Finasteride)
Propecia®, Proscar®
Classification:
Genitourinary Agents
- Benign Prostatic Hyperplasia (BPH) Agents
- 5-Alpha reductase inhibitors
Hormones and Hormone Modifiers
- Antiandrogens
- 5-Alpha reductase inhibitors
Description: Finasteride is used in the treatment of symptomatic benign prostatic hyperplasia (BPH), a condition found in the majority of men over the age of 50. Finasteride has been shown to increase and maintain maximum urine flow rate in men with BPH, although less than 50% of men show improvement despite a reduction in prostate size. Although there was a concern of finasteride altering the level of prostate specific antigen (PSA) used to detect prostate cancer, this does not appear to be the case. The percent free PSA (free to total PSA ratio) is not significantly decreased by finasteride. If clinicians use the percent free PSA as an aid in the detection of prostate cancer in men receiving finasteride, no adjustment in PSA values appear to be necessary. In one long-term study, finasteride prevented or delayed the appearance of prostate cancer; however, a higher rate of high-grade prostate cancer was noted with finasteride treatment relative to placebo but the association to finasteride therapy could not be determined. Finasteride is also effective for treating hair loss in men and has been shown to be effective for mild to moderate hair loss of the vertex and anterior mid-scalp area; efficacy in bitemporal recession has not been established. Finasteride (Proscar®) was approved by the FDA in June 1992 for the treatment of BPH. Another finasteride oral dosage form, Propecia®, was approved by the FDA in December 1997 for the treatment of male pattern baldness (i.e., androgenetic alopecia).
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.
Pharmacokinetics: Finasteride is administered orally in the treatment of either BPH or male pattern baldness. 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 - 6 months after beginning therapy. The mean bioavailability following a single dose of finasteride is about 63 - 65%; however, bioavailability is highly variable. Approximately 90% is bound to plasma proteins; yet the drug has been found to cross the blood-brain barrier. This is not problematic, since finasteride generally does not affect other hormones. Daily dosing causes accumulation to occur, with plasma concentrations increasing by 50% over those observed from a single dose. 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%). The mean plasma elimination half-life of finasteride is 4.8 - 6 hours (range, 3 - 16 hours); however, the turnover rate for the type II 5alpha-reductase enzyme complex is slow, with a turnover half-life of approximately 30 days.
Propecia Tablets(Tab 1 mg) 
Special Populations: Elimination of finasteride is reduced somewhat in the elderly, but no dosage adjustment is necessary. Normal doses may also be used in patients with renal impairment. The effect of hepatic impairment on finasteride pharmacokinetics has not been studied.
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References
. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003:349:213 - 22.
[ Revised 3/2/2005 7:51:00 PM ]
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