General Information

Caverject (alprostadil) is a prostaglandin E1 agonist.

Caverject is specifically indicated for the treatment of erectile dysfunction.

Caverject is supplied as an intracavernosal injection. The recommended dosing/administration is as follows:

Erectile Dysfunction of Vasculogenic, Psychogenic, or Mixed Etiology

• Initiate dosing with 2.5 mcg of alprostadil.
• If there is a partial response at 2.5 mcg, the dose may be increased to 5 mcg within 1 hour. Use a new vial for each dose of Caverject.
• During titration, no more than 2 doses should be given within a 24-hour period.
• The optimal dose should produce an erection suitable for intercourse that does not exceed a duration of 1 hour.
• The patient must stay in the physician's office until complete detumescence occurs.

If additional titration is required, doses in increments of 5 to 10 mcg may be given at least 24 hours apart. Repeat the titration as necessary until the optimal dose is achieved. Doses greater than 60 mcg are not recommended.

Erectile Dysfunction of Pure Neurogenic Etiology (e.g., Spinal Cord Injury)

• Initiate dosing with 1.25 mcg of alprostadil.
• If there is a partial response, the dose may be increased to 2.5 mcg within 1 hour. Use a new vial for each dose of Caverject.
• During titration, no more than 2 doses should be given within a 24-hour period.
• The optimal dose should produce an erection suitable for intercourse that does not exceed a duration of 1 hour.
• The patient must stay in the physician's office until complete detumescence occurs.

If additional titration is required, a dose of 5 mcg may be given during the next 24 hours. Thereafter, doses in increments of 5 mcg may be given at least 24 hours apart until the optimal dose is reached. Doses greater than 60 mcg are not recommended.

Maintenance Dosage for Patient Home Use

• Once the dose of Caverject has been determined in the physician's office, additional dose adjustment may be required after consultation with the physician. Adjust the dose in accordance with the titration guidelines described above.
• The recommended frequency of injection is no more than 3 times weekly, with at least 24 hours between each dose.
• Re-evaluate patients regularly (every 3 months or as clinically appropriate) and determine if dosage adjustments are needed.

Mechanism of Action

Caverject (alprostadil) is a prostaglandin with a wide variety of pharmacological actions including vasodilation and inhibition of platelet aggregation. Alprostadil induces erection by relaxation of trabecular smooth muscle and by dilation of cavernosal arteries by binding to its receptors and increasing intracellular cyclic adenosine monophosphate (cAMP) levels via modulation of adenylate cyclase. This leads to expansion of lacunar spaces and entrapment of blood by compressing the venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism. Alprostadil also attenuates presynaptic noradrenaline release in the corpus cavernosum.

Side Effects

The drug's most common side effect is penile pain. Other side effects include bleeding at the injection site and an unhealthy, prolonged erection of four to six hours.

Clinical Trial Results

The efficacy of Caverject was investigated in men with a diagnosis of erectile dysfunction due to psychogenic, vasculogenic, neurogenic, and/or mixed etiology in two double-blind placebo controlled studies (Study 1 and Study 2) and in one 6-month open-label study (Study 3). In clinical studies (Study 1 and Study 3), over 80% of patients experienced an erection sufficient for sexual intercourse after intracavernosal injection of Caverject.

Study 1: A total of 153 men with ED with a mean age of 53 years (range 23–69 years) were enrolled. The study had three phases: a 2.5 week, randomized, double-blind, placebo-controlled crossover phase in which each man received in-office injections of placebo or 2.5 mcg, 5 mcg, 7.5 mcg, or 10 mcg of Caverject; a 2 week, open-label, in-office dose-titration phase to identify the optimum home-use dose (the latter dose was defined as a dose inducing an erection sufficient for intercourse and lasting ≤ 60 minutes); and a 4-week open-label, at-home phase. In the double-blind placebo-controlled, crossover phase, each dose of Caverject was significantly more effective than placebo by clinical evaluation ("full penile rigidity") and by RigiScan criteria (≥ 70% rigidity for at least 10 minutes); there was no response to placebo. The percentage of responders increased with increasing doses of Caverject. The overall response rates in the crossover and dose-titration phases were 76% (117/153) by clinical evaluation and 51% (78/152) by RigiScan criteria. Seventy-three percent of the injections in 102 men who used Caverject in the at-home phase resulted in satisfactory intercourse. Seventy-five percent of the men who used Caverject in the at-home phase remained on the dose identified as optimum for them during the dose-titration phase; 17% and 8% of the men decreased or increased their dose, respectively. The mean duration of erection per injection was 70.8 minutes.

Study 2: A total of 296 men with ED with a mean age of 54 years (range 21–74 years) were enrolled in this double-blind, placebo controlled, parallel-arm design study. The men were randomly assigned to one of five groups and received either a single dose of placebo, 2.5 mcg, 5 mcg, 10 mcg, or 20 mcg of Caverject. No patient responded to placebo. The differences in the response rates in both the clinical and the RigiScan evaluations between each of the doses of Caverject and placebo were statistically significant. There was also a statistically significant dose-response relationship with higher clinical response rates and higher RigiScan response rates with increasing doses of Caverject (with exception of the 10-mcg dose). The mean duration of erection after injection ranged from 12 minutes after the 2.5-mcg dose to 44 minutes after the 20-mcg dose and the relationship was linear.

Study 3: The efficacy of Caverject was further evaluated in a 6-month, open-label, at-home study in 683 men with ED with a mean age of 58 years (range 20–79 years). The optimum dose of Caverject was established by titration in 89% of men (606/683). A total of 471/683 men (69%) completed the 6-month study. Eighty-seven percent of the 13,762 injections of Caverject administered resulted in satisfactory sexual activity. The mean duration of erection was 67.5 minutes.