Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders

Abstract

In a prospective, placebo-controlled, one group crossover design study, we tested whether adding programmed intracavernous PGE1 injections (IC-PGE1) can improve the effectiveness of sildenafil in erectile dysfunction (ED) patients unresponsive to monotherapy with this drug. In all, 40 ED patients who had experienced unsatisfactory erections with both the 50 and 100 mg sildenafil doses were treated with four bi-weekly 20 lg IC-PGE1 injections given in the clinic and provided with either placebo or 50 mg sildenafil capsules for the next 4 weeks. Thereafter, they were crossed over to the other oral treatment for an additional 4-week period. The IIEF-Erectile Function domain score (IIEF-EFS), the main outcome measure, was found considerably higher (Po0.001) with the combined IC-PGE1-50 mg sildenafil treatment than with IC-PGE1-placebo or sildenafil alone (50 or 100 mg) in a subset of 26 subjects (65%). They thus shifted from the 'severe' or 'moderate' to the 'mild' grading of ED classification.

Intracavernous administration of bone marrow mononuclear cells: a new method of treating erectile dysfunction?

“…Major factors associated with this include atherosclerosis, nerve damage and smooth muscle atrophy [16]. Several approaches have demonstrated some promise in the improvement of responsiveness to PDE5 inhibitors including propionyl-L-carnitine [17,18], intracavernous PGE1 [19], and testosterone gel [20,21]. However these studies are early and do not address the underlying biological cause in many of the situations of ED.…”

Combination Pharmacotherapy in the Management of Patients with Hard-to-Treat Erectile Dysfunction

“…Alprostadil, combined with phentolamine and/or papaverine (Double Mix and Trimix), has in fact been part of the protocol in ICI therapy when response to alprostadil alone remains inadequate. Combination pharmacotherapy had been studied by using research animal models [3,4] and in various clinical settings [5–20], generally with favorable treatment outcome.…”

Contemporary Intracavernous Pharmacotherapy for Erectile Dysfunction in the Aging Male

“…Shabsigh and colleagues reported results from a large, multicenter randomized trial demonstrating 85-90% improvements in the ability to achieve and maintain an erection (international index of erectile function [IIEF]-5 questions 3 and 4) for men using intracavernous alprostadil alfadex treatment, having previously failed sildenafil 100 mg therapy [55]. Another novel regimen showing initial promise consists of on-demand sildenafil and scheduled ICI (20 µg bi-weekly); two-thirds of men demonstrated a substantial improvement in their erectile function, but further evaluation of such schedules is required [56].…”

“…Combining intracavernous therapy and oral PDE-5 inhibitor treatment for patients not responding to either monotherapy is a promising, recently reported approach for difficult-to-treat ED [56,76]. Although there remains a lack of rand- omized comparative drug trials, using multiple agents with different mechanisms of action and potential synergies has resulted in salvage rates of 30-100% where monotherapy has previously failed [76,77].…”