Viability and Safety of Combination Drug Therapies for Erectile Dysfunction

Abstract

In some patients with erectile dysfunction (ED) oral, topical or intracavernous drug therapy fails. However, several classes of drugs demonstrate efficacy for ED, creating the potential for pharmacological combinations preferable to implantation of a penile prosthesis. Preliminary reports suggest that combining oral, topical or intracavernous drugs may salvage patients in whom monotherapy fails. Agents that lead to activation or increases in cyclic nucleotides (cyclic adenosine monophosphate and guanosine monophosphate) with or without nitric oxide donors or nitrates, or alpha-adrenergic antagonists have been used to treat ED. The phosphodiesterase-5 inhibitor sildenafil has been combined with alprostadil (prostaglandin E1) and administered by either the intraurethral or intracavernous route. Successful intercourse following this combination varies from 47% to 100% when monotherapy with each has failed. The introduction of apomorphine has led to its unapproved use in combination with sildenafil in Europe. Combination strategies may allow lower drug doses and reduced adverse effects. The encouraging preliminary observations combined with the potential for adverse events provide a scientific rationale for prospective, randomized clinical trials with adequate numbers of subjects.