Alprostadil, for erectile dysfunction

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. 

Fulgham PE, Cochran JS, Denman JL, et al. Disappointing initial results with transurethral alprostadil for erectile dysfunction in a urology practice setting. J Urol 1998 160 2041-2046. 

The newer drug of same category are alprostadil, vardenafil and tadalafil which are recently introduced for erectile dysfunction in man. Apomorphine is... 

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. 

English JC 3rd, King DH, Foley JP. Penile shaft hypopig-mentation lichen sclerosus occurring after the initiation of alprostadil intracavernous injections for erectile dysfunction. J Am Acad Dermatol 1998 39(5 Pt l) 801-3. 

PGE alprostadil (used to maintain the patency of the ductus arteriosus in neonates with congenital heart defects, and for erectile dysfunction by injection into the corpus cavemosum of the penis) misoprostol (used for prophylaxis of peptic ulcer associated with NSAIDs) gemeprost (used as pessaries to soften the uterine cervix and dilate the cervical canal prior to vacuum aspiration for termination of pregnancy). 

Penile shaft lichen sclerosus has been reported in a 63-year-old man in association with alprostadil intraca-vernous injection for erectile dysfunction (5). The authors suggested that the lichen sclerosus had been caused by (1) an isomorphic response to the trauma of repeated needle injection (2) a local cutaneous response to alprostadil-induced collagen synthesis or alprostadil-induced fibroblast production of IL-6, with secondary paracrine/ autocrine-induced collagen synthesis by improper skin exposure by direct injection to the skin or by retrograde flow of alprostadil through the needle puncture tract or (3) a random occurrence of separate events. 

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. 

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. ... 

When treatments for erectile dysfunction are needed, the least invasive forms of treatment should be used first, as they produce the lowest incidence of serions adverse effects. VEDs or phosphodiesterase inhibitors are therefore considered first-line treatments. If these fail, intracavemosal alprostadil injection therapy can be initiated. If this fails, the patient can be tried on a combination of intracavemosal alprostadil pins VED, combination intracavemosal therapy, or intra-nrethral alprostadil. If this fails, the patient may require insertion of a penile prosthesis. 

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). ... 

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. 

Absorption - For treatment of erectile dysfunction, alprostadil is administered by injection into the corpora cavernosa or inserted intraurethrally. 

Colli E, Calabro A, Gentile V, Mirone V, Soli M. Alprostadil sterile powder formulation for intracavernous treatment of erectile dysfunction. Eur Urol 1996 29(1) 59-62. 

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. 

There has been a report of a long-term follow-up program for treatment of erectile dysfunction in 32 patients who used alprostadil for a minimum of 5 years under... 

Erectile dysfunction, that is, the inability to maintain penile erection for the successful performance of sexual activity, has both organic and psychogenic causes, including as a sequelae to prostatic surgery. Erectile dysfunction is estimated to affect up to 30 million men in the United States. Previous therapies have included penile implants, and intrape-nile injections of alprostadil (see p. 420). Sildenafil [sil DEN a HI], the first oral drug approved for the treatment of erectile dysfunction in males, was introduced in early 1998. 

Alprostadil (Cavcijecl) is also available in glass vials for reconstitution to provide 1.0 niL of. solution containing either 10 or 20 /xg/mL for intcrcnvemosal penile injection to diag-no.se or cotreel erectile dysfunction in certain cases of impotence. A urethral suppository is also available this therapeutic use has been all but eliminated, how ever. by the availability of orally administered Viagra. 

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. ... 

FIGURE 81-8. Technique for administration of intraurethral alprostadil with a MUSE appi icator. Reprinted with permission from Kirby R, Carson C, Goldstein I. Erectile Dysfunction, A Clinical Guide. Oxford, England, ISIS Medical Media, 1999 62.)... 

Porst El. Transurethral alprostadil with MUSE (medicated urethral system for erection) vs intracavernous alprostadil—A comparative study in 103 patients with erectile dysfunction. Int J Impot Res 1997 9 187-192. 

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. 

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