Efficacy and safety of long-term treatment with the dual 5α-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia

Objectives: Dutasteride, a dual inhibitor of Type 1 and Type 2 5alpha-reductase, has been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomised, placebo-controlled, large-scale, 2-year Phase III clinical studies. This paper reports the pooled results of a 2-year open-label extension of the three randomised studies assessing the long-term efficacy and safety of dutasteride. Methods: Patients randomised to dutasteride or placebo in the double-blind portion of the Phase III studies were eligible for a 2-year open-label extension, where all patients received dutasteride 0.5 mg daily (dutasteride/dutasteride [D/D] group and placebo/dutasteride [P/D group]). Results: Significant improvements in AUA-SI score and Q(max) were observed from Month 24 to 48 in both study groups. At Month 48, patients in the D/D group had significantly greater improvements in AUA-SI score and Qmax, and significantly greater reductions in prostate volume, than those in the P/D group. Acute urinary retention and BPH-related surgery occurred in a small percentage of patients during the open-label phase. No new safety issues were noted with long-term therapy. Onset of new drug-related adverse events were reported most frequently at the start of therapy and declined over time in patients receiving dutasteride. Conclusions: Long-term treatment with dutasteride results in continuing improvements in urinary symptoms and flow rate, and further reductions in TPV, in men with symptomatic BPH. The reduction in risk of AUR and BPH-related surgery, seen in the double-blind phase, was durable over 4-year treatment. Dutasteride was also well tolerated in long-term use. (C) 2004 Elsevier B.V. All rights reserved.