Optimizing the therapeutic approach of transurethral alprostadil

Objective To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 mu g and 500 mu g, MUSE(R), Vivus I nc., Menlo Park, CA, USA, and Astra Lakemedel AB, Sodertalje, Sweden) and t he need for dose titration in a general population with erectile dysfunctio n. Patients and methods In a 12-week randomized and open multicentre study wit h parallel groups, 166 patients were randomised to a starting dose of eithe r 250 or 500 mu g of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 mu g) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attaine d. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. Results The lowest dose of MUSE with which the patients achieved at least o ne EAS score of 4 or 5 was 125 mu g for 1% of participants, 250 mu g for 27 %, 500 mu g for 32%. 1000 mu g for 6%, and finally 1000 mu g plus a pubic b and for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients ( > 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 mu g). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least on ce in course of the study. More patients reported penile pain while treated with 500 mu g than with 250 mu g (P < 0.05) during the first 4 weeks, Howe ver, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the cl inic or at home. Conclusion Recommending 500 mu g as a starting dose increased the percentag e of patients reporting at least one EAS of 4-5, with or without sexual int ercourse, from 28% to 60%. No serious dose-related systemic effects were se en. When starting on 500 mu g, patients were more likely to find directly t he dose that gave sufficient response and treatment satisfaction. We sugges t that the appropriate starting dose of MUSE should be 500 mu g.