Alprostadil intracavernosal

Intracavernosal alprostadil is still the most effective treatment, although its use is limited by the side effects and the inconvenience of self-injection and rapid onset of action, which results in an unnatural erection. More than 90% of alprostadil intracavernosal injections result in successful sexual intercourse (126). Transurethral alprostadil is a micro-suppository that is inserted into the stem of the urethra using an applicator. Although it is a more convenient route of administration, its overall efficacy is about 50% (126,127). 

Intracavernosal Alprostadil Caverject, Caverject Impulse, Edex 1.25-60 meg 5-20 minutes prior to intercourse0 Three times weekly, 24 hours between injections... 

Intracavernosal Alprostadil (Caverject) 5-mcg 10-mcg 20-mcg injection 2.5-60 meg 5-10 minutes before intercourse... 

Intracavernosal alprostadil is effective in 70% to 90% ofpatients. However, a high proportion of patients discontinue its use because of perceived ineffectiveness inconvenience of administration unnatural, nonspontane-ous erection needle phobia loss of interest and cost of therapy. 

Intracavernosal alprostadil has been used successfully in combination with VEDs or vasoactive agents (e.g., papaverine, phentolamine, atropine) that act by different mechanisms. Phosphodiesterase inhibitors should not be added to intracavernosal alprostadil because the combination can cause prolonged erections and priapism. 

Intracavernosal alprostadil acts rapidly with an onset of 5 to 15 minutes. The duration of action is dose related and, within the usual dosage range, lasts less than 1 hour. 

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 should be injected 5 to 10 minutes before intercourse using a 0.5-inch, 27- or 30-gauge needle or an autoinjector. The maximum number of injections is one per day and three per week. 

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

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 Following intracavernosal injection of 20 meg, mean peripheral plasma concentrations at 30 to 60 minutes after injection (89 to 102 peg/mL, respectively) were not significantly greater than baseline levels of endogenous alprostadil (96 peg/mL). 

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. 

Alprostadil is rapidly metabolized locally within the corpus cavernosum and in the urethra by enzymatic oxidation of the 15-hy-droxyl group to 15-keto-PGE,. 15-Keto-PGE, has only 1-2% of the biological activity of PGE,. 15-Keto-PGE, is rapidly reduced to the inactive metabolite 13,14-dihydro, 15-keto-PGE, which is the most abundant metabolite in plasma. DHK-PGE, is further metabolized to other inactive metabolites. The half-life of alprostadil after intracavernosal administration is 5-10 min (135).Only a small fraction of the dose reaches the systemic circulation after intracavernosal or intraure-... 

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. 

Alprostadil is commercially available as an intracavernosal injection (Caverject and Edex) and as an intraurethral insert (medicated urethral system for erection MUSE). 

Both commercially available formulations of alprostadil are FDA-approved as monotherapy for the management of erectile dysfnnc-tion. Alprostadil is more effective by the intracavernosal than by the intraurethral route. ... 

The enhanced efficacy of the intracavernosal inj ection may be related to the excellent bioavailability of the drug when injected directly into the corpora cavernosum. In contrast, intraurethral alprostadil doses generally are several hundred times larger than intracavernosal doses. Intraurethral alprostadil must be absorbed from the urethra. 

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. 

Both formulations of alprostadil are considered more invasive than VEDs or phosphodiesterase inhibitors. For this reason, intracavernosal alprostadil is generally prescribed after patients fail to respond to or cannot use the less invasive interventions. Intracavernosal alprostadil is preferred over intraurethral alprostadil because the former is more effective than the latter. Also, intracavernosal alprostadil may be preferred in patients with diabetes mellitus, who are accustomed to injectable drug therapy and may suffer from peripheral neuropathies, which decreases the patient s perception of pain upon injection. Intraurethral alprostadil is generally reserved as a treatment of last resort for patients who fail other less invasive and more effective forms of therapy and also refuse surgery. 

In various controlled and uncontrolled studies, the overall efficacy of intracavernosal alprostadil is 70% to 90%. In a large parallel design, double-blind, multicenter study, Linet and associates documented three relevant characteristics of intracavernosal alprostadil ... 

Tolerance does not appear to develop with continued use of intracavernosal alprostadil at home. 

Intracavernosal injection should be made into one corpus cavernosum only. From this injection site, the drug will reach the other corpus cavernosum through vascular communications between the two corpora. Alprostadil acts rapidly, with an onset in 5 to 15 minutes. The duration is directly related to the dose, and within the usual dosage range of 2.5 to 20 meg, the duration of the erection lasts no more than 1 hour. Local enzymes in the corpora cavernosum quickly metabolize alprostadil. Any alprostadil that escapes into the systemic circulation is deactivated on first passage through the lungs. Hence the plasma half-life of alprostadil is approximately 1 minute. Also, dose modification is not necessary in patients with renal or hepatic diseases. 

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. 

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