Alprostadil adverse effects

The usual dose of intracavernosal alprostadil is 10 to 20 meg up to a maximum of 60 meg. Patients should start with 1.25 meg, which should be increased by 1.25 to 2.50 meg at 30-minute intervals to the lowest dose that produces a firm erection for 1 hour and does not produce adverse effects. In clinical practice, however, most patients start with 10 meg and titrate quickly. 

Intracavernosal alprostadil is most commonly associated with local adverse effects, usually during the first year of therapy. Adverse events include... 

Alprostadil is PGEi available for exogenous administration. Alprostadil is widely used in neonates with cyanotic congenital heart disease to maintain the patency of the ductus arteriosus. Reported adverse effects include fever, apnea, flushing, bradycardia, and hyperostosis. Continuous chronic infusion of alprostadil via a portable pump and neuromuscular electrical stimulation help to improve the quality of life in patients with severe chronic heart failure waiting for a donor heart, as both treatments can be performed at home. 

Investigators from the Department of Pediatrics in Johns Hopkins Hospital, after seeing a neonate who had marked leukocytosis temporally related to alprostadil, conducted a retrospective study of neonatal leukocytosis induced by alprostadil in 45 neonates (5). They concluded that alprostadil infusion is a predictable cause of leukocytosis in neonates with congenital heart disease. Alprostadil-induced leukocytosis was especially prominent in three patients with splenic disorders associated with the hetero-taxy syndrome. Many of the other adverse effects of alprostadil, including respiratory depression, hypotension, fever, and lethargy, were also associated with sepsis. The authors considered that it is reasonable to look for sepsis in infants receiving alprostadil, but that it is equally reasonable to withdraw empirical therapy once infection has been ruled out. Leukocytosis associated with alprostadil infusion has not been previously reported and is not listed in the alprostadil package insert. 

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. 

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. 

---