Alprostadil dosing

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. 

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. 

Intraurethral alprostadil, 125 to 1,000 meg, should be administered 5 to 10 minutes before intercourse. Before administration, the patient should empty his bladder and void completely. No more than two doses per day are recommended. 

The dose of alprostadil that is selected for self-injection treatment should provide the patient with an erection that is satisfactory for sexual intercourse and that is maintained for no longer than 1 hour. If the duration of erection is more than 1 hour, reduce the dose. 

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. 

Maintenance therapy-The first injections of alprostadil must be done at the physician s office by medically trained personnel. The recommended frequency of injection is 3 times/week or less, with at least 24 hours between each dose. 

Initiation of therapy - T trate dose under the supervision of a physician to test a patient s response to alprostadil, to demonstrate proper administration technique and to monitor for evidence of hypotension. Individually titrate patients to the lowest dose that is sufficient for sexual intercourse. If necessary, increase the dose (or decrease) on separate occasions in a stepwise manner until the patient achieves an erection that is sufficient for sexual intercourse. 

Excretion - The metabolites of alprostadil are excreted primarily by the kidney, with almost 90% of an administered IV dose excreted in urine within 24 hours postdose. The remainder of the dose is excreted in the feces. 

Priapism Prolonged erection (lasting more than 4 to 6 or fewer hours) and priapism (erection lasting more than 6 hours) have occurred in patients using alprostadil. To minimize the chances of prolonged erection or priapism, titrate slowly to the lowest effective dose. 

Alprostadil JProstaglandin E ] (Prostin VR) [Vasodilator/ Prostaglandin] WARNING Apnea in up to 12% of neonates esp <2 kg at birth Uses Conditions ductus arteriosus blood flow must be maintained sustain puhn/systemic circulation until OR (eg, pulm atresia/stenosis and transposition) Action Vasodilator (ductus arteriosus very sensitive), pit inhibitor Dose 0.05 mcg/kg/min IV to lowest that maintains response Caution [X, -] Contra Neonatal resp distress synd Disp Inj meg SE Cutaneous vasodilation, Sz like activity, jitteriness, T temp, thrombocytopenia, BP may cause apnea Interactions T Effects OF anticoagulants antihypertensives, effects OF cyclosporine EMS Given to newborns in hospital OD May cause apnea, bradycardia, hypotension, and flushing symptomatic and supportive... 

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. 

A 57-year-old man with erectile impotence, who had previously been treated with intracorporeal injections of papaverine and alprostadil, resulting in recurrent episodes of priapism necessitating aspiration, decided to try intraurethral alprostadil (MUSE). The dose needed to achieve a full erection in the clinic was titrated to 1 ig, but after 5 months this was found to be inadequate unless supplemented by a hot bath before MUSE administration. The patient stated that with MUSE alone the erection lasted for 5-10 minutes but on the two previous occasions when he had had a hot bath for 20 minutes and then used MUSE, the erection had lasted 3-4 hours. However, on the third occasion, priapism lasted 20 hours and necessitated corporeal aspiration for detumescence. 

Cervical laceration associated with misoprostol has been reported in a 33-year-old woman who received four doses of vaginal misoprostol (total dose 100 micrograms) for labor induction. Uterine rupture has occurred during induction of labor with misoprostol, usually in women who have had a previous cesarean section (22,23). Uterine dehiscence occurred in one and uterine rupture in three of 48 women with prior cesarean sections treated with intravaginal misoprostol 50 micrograms for cervical ripening (24). In comparison, uterine rupture occurred in one of 89 women who had an oxytocin infusion and none of 24 patients who received intravaginal alprostadil. 

Alprostadil. IntraurethralPGE, (al-prostadil) is absorbed from the urethra and distributes to the erectile tissue (cavemosal smooth muscles) by communicating blood vessels between the corpus spongiosum and the corpora cavernosa. The transurethral absorption is biphasic with an initial rapid phase followed by slower absorption. Approximately 80% of the administered dose is absorbed within 10 min and about 20%of the total dose reaches the cavemosal tissue. 

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-... 

The effectiveness of alprostadil is dose related over the range of 2.5 to 20 meg. The mean duration of erection is directly related to the dose of alprostadil administered and ranges from 12 to 44 minutes. 

A higher percentage of patients with psychogenic and neurogenic erectile dysfunction responded to alprostadil and at a lower dose when compared to patients with vasculogenic erectile dysfunction. 

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. 

Intracavernosal injections should be performed using a 0.5-inch, 27- or 30-gauge needle. Also, a tuberculin syringe or a syringe prefilled with diluent as supplied by the manufacturer should be used to ensure precise measurement of doses. Patients with needle phobia, poor vision, or poor manual dexterity can use commercially available autoinjectors (e.g., Peninject) to facilitate the administration of 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. ... 

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