Alprostadil and Indomethacin: Mechanisms and Clinical Uses

Introduction to Alprostadil

The American Urological Association recommends alprostadil as a synthetic vasodilator identical to prostaglandin E1 that relaxes smooth muscles of the corpus cavernosum and increases cavernous artery diameter to produce erections in patients with erectile dysfunction 1
Alprostadil is FDA-approved as the only single-agent intracavernosal injection therapy for erectile dysfunction in the United States, available in multiple formulations: intracavernosal injection, intraurethral suppository, and topical cream 1, 2

Intraurethral alprostadil achieves successful intercourse in 29.5% to 78.1% of patients with erectile dysfunction, with the largest study showing 64.9% success rate 1

An in-office test must be performed before prescribing either intraurethral or intracavernosal alprostadil to patients with erectile dysfunction, with initial dose requiring healthcare provider supervision due to risk of syncope or prolonged erection 1, 3, 4
Patients need instruction in proper technique and dose titration before home use of alprostadil 1, 3

The American College of Rheumatology notes that indomethacin is an NSAID used for inflammatory conditions, particularly ankylosing spondylitis and other spondyloarthropathies, by inhibiting cyclooxygenase enzymes to reduce prostaglandin synthesis and inflammation 5

No particular NSAID, including indomethacin, is recommended as preferred treatment for ankylosing spondylitis—choice should be based on patient history, risk factors, and comorbidities 5
Multiple head-to-head trials used indomethacin as the comparator NSAID, demonstrating no evidence of superior efficacy over other NSAIDs for pain or stiffness in patients with ankylosing spondylitis 5

Hypertension and depression were more common with continuous NSAID treatment, including indomethacin, in controlled trials 5
Standard NSAID adverse effects, including gastrointestinal complications, cardiovascular risks, and renal toxicity, are associated with indomethacin use 5

The European Society of Cardiology (ESC) and European Society of Anesthesiology (ESA) guidelines do not recommend holding alprostadil or other erectile dysfunction therapies prior to non-cardiac surgery 6
The American College of Cardiology recommends continuation of pulmonary arterial hypertension (PAH)-specific therapies perioperatively, including prostaglandin analogs used for PAH, but makes no mention of holding erectile dysfunction medications 7
The European Society of Cardiology (ESC) and European Society of Anesthesiology (ESA) explicitly recommend that patients receiving PAH-specific treatment, including alprostadil, continue this in the pre-, peri-, and post-operative period without interruption, but this does not apply to erectile dysfunction 6

The American Urological Association (AUA) guidelines note that men treated with alprostadil alone are less prone to progress to ischemic priapism compared to those treated with papaverine and phentolamine 8
The European Society of Cardiology (ESC) and European Society of Anesthesiology (ESA) recommend resuming use of alprostadil when the patient has recovered sufficiently to engage in sexual activity postoperatively 6