Erectile dysfunction intracavernosal alprostadil

Papaverine is not FDA approved for erectile dysfunction. Intracavernosal papaverine alone is not commonly used for management of erectile dysfunction because large doses are required, and these produce dose-related adverse effects priapism, corporal fibrosis, hypotension, and hepatotoxicity. Papaverine is more often administered in lower doses combined with phentolamine and/or alprostadil. A variety of formulae have been used, but no one mixture has been proven better than other mixtures (see Table 81-6). Combination formulations are considered to be safer and associated with the potential for fewer serious adverse effects than high doses of any one of these agents. ... 

Intracavernosal alprostadil may be a useful adjunct to other diagnostic tests in the diagnosis of erectile dysfunction (Cave/yecf only). 

Adjunct to the diagnosis of erectile dysfunction (Caverject only) - Patients are monitored for the occurrence of an erection after an intracavernosal injection of alprostadil. Use a single dose of alprostadil that induces a rigid erection. 

Intracavernosal injection or urethral suppository therapy with alprostadil (PGE1) is a second-line treatment for erectile dysfunction. Doses of 2.5-25 meg are used. Penile pain is a frequent side effect, which may be related to the algesic effects of PGE derivatives however, only a few patients discontinue the use because of pain. Prolonged erection and priapism are side effects that occur in less than 4% of patients and are minimized by careful titration to the minimal effective dose. When given by injection, alprostadil may be used as monotherapy or in combination with either papaverine or phentolamine. 

Intracavernosal alprostadil was effective and well tolerated in the treatment of erectile dysfunction, according to the results of a 6-month study (funded by Pharmacia Upjohn) in 848 men (mean age 52 years) with at least a 4-month history of erectile dysfunction (12). This is provided that the individual dose is established by titration and patients receive training in injection techniques and periodic supervision during treatment. An initial dose was established for each patient and the patients then administered the alprostadil themselves at home. Of 727 evaluable patients, 682 (94%) had at least one erectile response after the injection of alprostadil, and 88% of injections lead to a satisfactory sexual response. The most commonly reported adverse event was penile pain, reported by 44% of patients, but only after 8% of injections. In just over half of the patients who had penile pain, the condition was reported as mild. Prolonged erection, penile fibrosis, and priapism occurred in 8,4, and 0.9% of patients respectively. Treatment was withdrawn because of medical events in 4% of patients, and drug-related events accounted for treatment withdrawal in 2% of patients. 

The vasoactive amines phentolamine and papaverine are occasionally used as intracavernosal therapy, usually in combination with alprostadil, although their use for erectile dysfunction is off-label. Moxisylyte is another vasoactive agent used as intracavernosal therapy. The drug is approved in several European countries, but is not approved in the United States. The advantages over alprostadil are that with moxisylyte, sexual stimulation is still required to achieve full erection and that detumescence occurs on ejaculation. 

Although intracavernosal alprostadil injections are effective independent of the etiology for erectile dysfunction, these fail in one-third of patients. Also, they should be used cautiously in patients at risk of priapism, which includes those with sickle cell disease or lymphoproliferative disorders. 

Although many other agents, including papaverine and phen-tolamine, have been used off-label for intracavernosal therapy, al-prostadil is preferentially prescribed. This is because the FDA has approved intracavernosal alprostadil for erectile dysfunction, and because it has a low potential for causing prolonged erections and priapism. 

Once the optimal dosage of intracavernosal alprostadil is established, the patient should return for routine medical follow-up every 3 to 6 months. Some patients may subsequently require dosage adjustment, and this is largely attributed to worsening of the underlying disease that is contributing to the erectile dysfunction. 

Intraurethral alprostadil inserts are marketed as MUSE, which contains a pellet inside a prefllled urethral applicator. Multiple studies show this product to have an overall effectiveness rate of 43% to 60%, " as compared with 70% to 90% for intracavernosal alprostadil. Its decreased effectiveness and inconvenient administration method have resulted in this product being considered a second-line treatment option for patients with erectile dysfunction. However, some patients respond to intraurethral alprostadil even when intracavernosal alprostadil did not work for them. ... 

Linet Ol, Ogring EG for the Alprostadil Study Group. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. N Engl J Med 1996 334 873-877. 

Some manufacturers advise that intracavernosal alprostadil and other drugs used for erectile dysfunction should not be given concurrently. 

There appear to be no published reports of adverse interactions between intracavemous alprostadil (prostaglandin E,) and other drugs used for erectile dysfunction, but some manufacturers say that smooth muscle re-laxants such as papaverine and other drugs used to induce erections such as alpha-blocking drugs [e.g. intracavernosal phentolamine] should not be used concurrently because of the risks of priapism (painful prolonged abnormal erection). ... 

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