Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia.
OBJECTIVE
The objective of this paper is to examine safety and tolerability data from a number of recently completed clinical trials with the novel, dual 5alpha-reductase inhibitor, dutasteride.


METHODS
Intent-to-treat analyses were conducted on data for dutasteride 0.5 mg/day for drug-related adverse events, clinical laboratory test results, and prostate-specific antigen (PSA) levels derived from four large, randomised, double-blind clinical trials (n=5655). Further data were derived from a randomised, double-blind combination study of dutasteride 0.5 mg/day and tamsulosin 0.4 mg/day (n=327), and several safety studies conducted in healthy volunteers.


RESULTS
Data from two-year blinded clinical studies demonstrate that dutasteride is well tolerated, with a profile comparable with that of placebo. The exception is a modestly elevated incidence of impotence, decreased libido, ejaculation disorders, and gynaecomastia. Clinical laboratory test abnormalities were reported by <1% of patients treated with dutasteride, and abnormal values occurred with similar frequency versus placebo-treated patients. In a healthy volunteer study, when dutasteride was administered daily for 1 year, it did not significantly affect bone metabolism markers, bone mineral density or lipid profiles. Dutasteride reduced total serum PSA concentrations by approximately 50% following 6, 12, and 24 months of treatment but had no effect on free-to-total PSA levels. The safety profile of dutasteride did not differ from that of finasteride in a large, parallel-group, comparator trial. Additionally, when dutasteride was used in combination with an alpha(1)-blocker, the drug-related adverse event profiles were as would be expected for the individual agents.


CONCLUSIONS
Considered together, these data demonstrate dutasteride to be well-tolerated.
Andriole
Gerald L
GL
Division of Urologic Surgery, Washington University School of Medicine, 4960 Children's Place, Campus Box 8242, St. Louis, MO 63110, USA. andrioleg@msnotes.wustl.edu
Kirby
Roger
R
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D001378:Azasteroids / Q000627:therapeutic use*; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000068538:Dutasteride; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016896:Treatment Outcome
D001378:Azasteroids; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000068538:Dutasteride