Patients using a self-injection program of therapy should receive proper instruction in both intracavernosal injection and aseptic technique. Physicians should ensure that patients are able to demonstrate competence and skill with the injection procedure prior to initiating self-injection.
The initial treatment dose is established in the physicians office. The lowest effective dose sufficient to induce an erection lasting up to 1 hour should be used. The patient may expect an erection to occur within 5 to 20 minutes. Patients who require dosage adjustments and are self-injecting alprostadil, should not increase or decrease their dose without the advice of their physician. Generally, patients should not use alprostadil more than once a day and not more than 3 times a week, with at least 24 hours between each use.
Alprostadil is labelled for “single use only”. Patients should discard any unused solution after withdrawing the proper volume for their dose. The vial should not be shaken once reconstituted.
Reconstituted vials of alprostadil which on visual inspection appear cloudy, colored or contain particulate matter, should be discarded.
Patients who experience an erection lasting longer than 2 hours should attempt to detumesce using methods prescribed by their physician.
Patients should be advised on the possible adverse effects associated with the use of alprostadil; the most frequent being mild to moderate penile pain after injection. A patient should report to his physician if he complains of: any penile pain not previously present, an increased intensity of pain, nodules or hard tissue appearing in the penis, or curvature of the erect penis. There is the potential for infection with any type of injection, therefore patients should also report any occurrences of penile redness, swelling, or tenderness. The importance of regular physician visits to assess the continued safety and efficacy of alprostadil treatment should be stressed to the patient.
A potentially serious adverse reaction with intracavernosal therapy is priapism. Accordingly, the patient should be instructed to contact the physician's office immediately or, if unavailable, to seek immediate medical assistance if an erection persists for longer than 3 hours.
In clinical trials, the use of concomitant medicines such as antihypertensives, diuretics, antidiabetic agents (including insulin) or NSAIDs, did not affect the safety or efficacy of alprostadil.
The use of alprostadil intracavernosally does not offer any protection from the spread of sexually transmitted diseases. Individuals using alprostadil should be properly counselled with regards to protective measures to safeguard against the spread of sexually transmitted diseases, including human immunodeficiency virus (HIV) infection.
Patients should be instructed not to reuse or share needles or syringes. The patient should not allow anyone else to use this medicine. Patients should dispose of used needles, syringes, and vials, safely and properly .
A patient administration guide, found in every package, provides a step-by-step method for the proper preparation and administration of alprostadil. Patients should be instructed to carefully follow this guide for self-injection.
Long-term carcinogenicity studies have not been conducted. Reproductive studies in the rat with alprostadil at doses of up to 0.2 mg/kg/day did not adversely affect or alter spermatogenesis, conferring a 200-fold margin of safety at usual human doses. A battery of mutagenicity assays including, bacterial mutation (Ames), alkaline elution, rat micronucleus, sister chromatid exchange, CHO/HGPRT mammalian cell forward gene mutation and unscheduled DNA synthesis (UDS), revealed no potential for mutagenesis.
A one-year irritancy study was conducted in male Cynomolgus monkeys. Three groups of 5 animals received twice weekly intracavernosal injections of either 3 or 8.25 µg alprostadil or vehicle. A further 2 groups of 6 animals were given 8.25 µg alprostadil or vehicle twice weekly, as above, and in addition, multiple doses during weeks 44, 48 and 52. Three monkeys receiving vehicle and 3 monkeys receiving 8.25 µg alprostadil were held for evaluation following a 4-week recovery period. No evidence of alprostadil-related penile or systemic tissue lesions were found. Local irritation noted in control and treated monkeys was considered to be related to the injection procedure itself and any penile lesions found were reversible. After the 4-week recovery period, a regression in histological changes in the penis was observed.
