Sublingual Agents - Apomorphine

Apomorphine Versus Placebo

Efficacy. Overall, results from the five placebo-controlled trials indicated statistically significant improvements with respect to measures of erectile function (e.g. mean percentage of successful intercourse attempts, percentage of attempts resulting in erections firm enough for intercourse, rigidity ≥40 percent, and the mean IIEF “Erectile Function” domain score) in patients treated with apomorphine compared with those who received placebo. Clinically significant differences were seen in the mean percentage of improved erectile function with apomorphine compared with placebo arms.

Harms. There was insufficient information on the occurrence of any adverse events in these trials to allow comparison of incidence of harms across apomorphine and placebo groups. Adverse events such as nausea, headache, dizziness, and yawning occurred more frequently among patients who received apomorphine than among those who received placebo. The results from two trials suggested that the use of apomorphine was not associated with an increased incidence of any serious adverse events compared with the use of placebo.^{248, 250}

Dose-response Effect of Apomorphine

Efficacy. Limited evidence from two trials indicated that the mean percentage of successful intercourse attempts did not differ across groups who received various doses of apomorphine treatment (e.g. 3mg, 4 mg, 5 mg, 6 mg, 2–6 mg). This observation suggests that the efficacy of apomorphine may not be dose-related.

Harms. In multiple-dose trials, the occurrence of nausea, yawning, dizziness, vomiting, and glossitis was numerically greater in patients who received higher doses of apomorphine.^{248, 252, 253}

Intracavernosal Injections

Prostaglandin E1 (PGE1)

Efficacy. The administration of PGE₁ was shown to have improved erections more frequently relative to no treatment, placebo,papaverine, moxisylate, linsidomine, sodium nitroprusside, or the combination of linsidomine and urapidil. The rates of improvement in erection for patients receiving PGE₁, sexual therapy, or the combination of papaverine plus phentolamine were found to be similar. Patients who received PGE₁ alone experienced rates of improved erection similar to those among patients who received papaverine combined with phentolamine, while improved erection was less frequent after treatment with PGE₁ plus papaverine. Limited detailed evidence suggests that trimix was at least as effective as PGE₁ alone. Compared with trimix alone, the combination of trimix and sodium bicarbonate improved erections, while trimix combined with atropine did not produce such benefit. The interpretation of results from trials using trimix is complicated, because concentrations of the three constituents varied from study to study.³⁹²

Harms. Penile pain occurred more frequently in patients treated with PGE₁ than among those treated with placebo, moxisylate, or the combination of papaverine and phentolamine. The pain associated with the treatment was significantly less frequent when the PGE₁ was injected slowly, or in combination with either lidocaine or procaine, but not when injected in combination with sodium bicarbonate. The combination of papaverine and phentolamine was less frequently associated with pain in comparison with either PGE₁ alone or PGE₁ plus papaverine. The treatment with trimix was associated with priapism more frequently relative to treatment with PGE₁. The variation in rates of priapism may additionally depend on proper testing of the agent in the office setting, dose adjustment process for use at home, teaching sessions during which the patient administers his own injection under supervision, patient compliance, instruction handouts, and/or missed injections.

Subcutaneous Injections

Melanotan II, PT-141 (cyclic heptapeptide melanocortin analog), Apomorphine

Efficacy. The trial results indicated greater improvements on RigiScan in patients who received either melanotan II²⁹⁵ or PT-141²⁹⁸compared with those who received placebo.

Harms. Although adverse events were generally mild, subcutaneous treatments were associated with an increased risk of nausea and headache in comparison with placebo.

Intraurethral Suppositories

Alprostadil

Efficacy. The use of IU alprostadil was shown to be associated with a higher sexual intercourse success rate compared with placebo.

Harms. Patients receiving IU alprostadil had an increased risk of local pain compared with those who received placebo. The followup period of the trials did not exceed 3 months, so the relative benefits and harms of long-term treatment with IU suppositories remain unclear.

Topical Treatments