Finasteride

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Abstract
Finasteride inhibits type 25α-reductase activity, significantly reducing dihydrotestosterone levels. Consequent reductions in prostate volume, increases in urinary flow rates and improvements in symptoms compared with placebo have been observed in trials of up to 4 years’ duration and in noncomparative extensions (for up to 6 years). Results from the 4-year placebo-controlled PLESS trial show finasteride to significantly reduce the risk of benign prostatic hypertrophy (BPH)-related acute urinary retention and the requirement for surgical intervention. Finasteride has significantly greater efficacy in patients with a large prostate (≥40ml) than in patients with a small prostate. However, the predictive value of prostate size has been questioned. Results of an earlier comparative 1-year trial show terazosin monotherapy and terazosin plus finasteride therapy to be significantly more effective than both finasteride monotherapy and placebo in reducing symptom scores and improving maximum urinary flow rates. Prostatic volume was significantly reduced by finasteride monotherapy and combination therapy only. The overall efficacy of finasteride in patients with mild to moderate symptomatic BPH tended to be greater than that of serenoa repens (Permixon®)1 in a 6-month trial. A US cost analysis model indicates that finasteride and terazosin are less expensive than transurethral resection of the prostate (TURP) during the first 2 years of initiation. Canadian cost-effectiveness and cost-utility analyses using decision analysis modelling have shown primary intervention with finasteride to provide more quality-adjusted life years (QALYs) at lesser cost than watchful waiting or TURP in patients with moderate symptoms who receive the drug for ≤3 years and ≤14 years, respectively, but fewer QALYs at a higher cost in patients with severe symptoms needing therapy for ≥4 years. Confirmatory prospective economic studies are required. Finasteride appears to improve overall quality of life to a similar extent to serenoa repens; patient satisfaction appears similar with finasteride and TURP. Finasteride is generally well tolerated. Most commonly reported adverse effects are sexually related (1 to 2.1%). Gynaecomastia has been reported in 0.4% of patients. Conclusions: Despite modest improvements in maximum urinary flow rates and symptom scores, finasteride is a first-line treatment option in those with moderate uncomplicated BPH, especially in patients with a large prostate (≥40ml). It is also an option in patients with more severe symptoms who are unable or unwilling to undergo surgery and in those awaiting surgery. Importantly, finasteride appears to reduce disease progression, significantly decreasing the incidence of acute urinary retention and the requirement for surgical intervention; to date, no other pharmacological agent has been shown to reduce these outcomes. Finasteride is a 4-azasteroid which selectively and competitively inhibits the activity of 5α-reductase. This nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzyme is necessary for converting testosterone to dihydrotestosterone. The drug specifically inhibits the type 2 isoenzyme of 5α-reductase, the predominant form in prostatic tissue. Dose-dependent inhibition of 5α-reductase results in significant reductions in prostatic (by up to >90%) and circulating (by up to 60 to 80%) dihydrotestosterone levels. Prostatic testosterone levels are increased by finasteride (by approximately 85%) in patients with benign prostatic hypertrophy (BPH); however, these levels do not appear to affect prostatic growth or morphology. The drug has no significant affinity for the androgen receptor. Finasteride significantly reduces serum prostate-specific antigen (PSA) levels by 41 to 71% in patients with symptomatic BPH. However, the mean free-to-total PSA ratio is unaffected by the drug (see also Dosage and Administration summary). Prostate size is reduced by finasteride by a combination of atrophy and apoptosis. Drug-induced histological changes have been observed after 6 months’ treatment; glandular elements of prostatic tissue are the most sensitive to finasteride. Finasteride reduces detrusor pressure in patients with bladder outlet obstruction due to BPH. Finasteride is well absorbed from the gastrointestinal tract, with food slowing the rate but not the extent of absorption. The drug appears to accumulate after multiple doses. Time to steady state appears to be longer than 17 days; the exact time is unknown. The volume of distribution of finasteride is large (76Lat steady state); the drug crosses the blood-brain barrier and small amounts are found in semen. The drug may be absorbed through the skin on contact with crushed tablets (see Dosage and Administration summary). Finasteride is extensively metabolised in the liver to essentially inactive metabolites. Elimination is mainly via the faeces and bile and, to a lesser extent, in the urine. The overall pharmacokinetic profile of the drug appears generally unaffected by increased age or renal impairment (see also Dosage and Administration summary). The effects of hepatic impairment on the pharmacokinetics of finasteride are not known. In a 4-year placebo-controlled trial of patients with moderate to severe disease (PLESS study), finasteride 5 mg/day had significantly superior effects on maximum urinary flow rates (Qmax), prostate volume and symptom scores to those of placebo. Between-treatment differences were usually observed within 4 months of treatment initiation. These findings confirm those of previous trials of up to 2 years’ duration, in which finasteride 5 mg/day, compared with placebo, significantly reduced total symptom scores (by 13 to 23%), increased Qmax(by 12.5 to 22%) and decreased prostate volume (by 15 to 47%) in...