Cardiovascular safety of sublingual apomorphine in patients on stable doses of oral antihypertensive agents and nitrates.

Sublingual (SL) apomorphine (2 to 6 mg) has been shown to be effective for treatment of male erectile dysfunction. Many patients with erectile dysfunction are also being treated for systemic hypertension and/or cardiovascular disease. In a double-blind, randomized, placebo-controlled, crossover trial, SL apomorphine 5 mg and placebo were administered on alternate days to 162 men who were on long-term therapy (> or =4 weeks) with angiotensin-converting enzyme inhibitors, beta blockers, diuretics, calcium channel blockers, alpha(1) blockers, or short- or long-acting nitrates. Blood pressure and heart rate were measured before and after dosing; cardiac rhythm was recorded by 4-hour Holter monitoring. The only potentially clinically significant interactions between SL apomorphine and the antihypertensive agents or short-acting nitrates were greater orthostatic decreases in systolic blood pressure in the alpha-blocker and calcium channel blocker groups (-10 and -6 mm Hg vs placebo, respectively). Administration of SL apomorphine after dosing with long-acting nitrates resulted in significant decreases in blood pressure when patients were standing (mean systolic change, -5 to -9 mm Hg 30 to 60 minutes postdose, p <0.05; mean diastolic change, -3 to -4 mm Hg 50 to 60 minutes postdose, p <0.05). The most common adverse events with SL apomorphine were dizziness, nausea, and headache. Syncope occurred in 1 patient in the beta-blocker group; symptomatic hypotension occurred in 2 patients each in the short- and long-acting nitrate groups. Thus, in patients receiving common antihypertensive agents and short-acting nitrates, as well as in most patients receiving long-acting nitrates, SL apomorphine at higher than recommended doses produced no clinically significant changes in heart rate or blood pressure greater than changes seen with SL apomorphine alone.

Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. The Apomorphine Study Group.

OBJECTIVES: A sublingual (SL) formulation of apomorphine has been developed and found effective in penile erectile dysfunction (ED). This study assessed the efficacy and safety of several doses of apomorphine SL in a dose-optimization schedule compared with placebo. METHODS: In this 8-week, multicenter, double-blind clinical trial, 569 patients were randomized to four groups: a dose-optimization group in which patients began with 2 mg, increased or decreased the dosage as needed for 4 weeks, and thereafter maintained an optimal dose for 4 weeks; two fixed-dose groups of either 5 or 6 mg; and a placebo group. Efficacy was assessed by patient and partner responses to home-use questionnaires about sexual function and activity and by responses to the International Index of Erectile Function and the Brief Sexual Function Inventory. RESULTS: In all apomorphine SL groups, a significantly higher percentage of patients compared with the placebo group achieved and maintained an erection firm enough for intercourse (48% to 53% versus 35% for placebo, P < or =0.001) and a significantly higher percentage of attempts resulted in intercourse (45% to 51% versus 33%, P < or =0.001). The responses to the questionnaires completed by the patients and partners were similar. Apomorphine SL was well tolerated; nausea, the most common side effect, was dose related and diminished substantially during the second 4-week period at all doses. The dose-optimization schedule resulted in fewer adverse events without impacting efficacy. CONCLUSIONS: Apomorphine SL is an effective and safe treatment for ED, with 2 and 4 mg providing the most acceptable therapeutic index.