Evaluation of the potential for pharmacodynamic and pharmacokinetic drug interactions between selegiline transdermal system and two sympathomimetic agents (pseudoephedrine and phenylpropanolamine) in healthy volunteers

Selegiline transdermal system is a recently approved monoamine oxidase inhibitor antidepressant. Medications that inhibit monoamine oxidase type A can augment the pressor effects of sympathomimetic amines, increasing the potential for hypertensive crisis. This study examined the potential for drug-drug interactions during treatment with selegiline transdermal system and pseudoephedrine or phenylpropanolamine. Two studies were conducted with 25 healthy volunteers to assess changes in blood pressure and heart Fate during administration of pseudoephedrine or phenylpropanolamine alone or together with selegiline transdermal system. No significant differences in mean maximum changes in vital signs occurred with pseudoephedrine. No significant differences were found in mean maximum changes in systolic heart rate with phenylpropanolamine; however, 4 of 12 subjects each experienced 1 isolated protocol-defined minimal pressor response without concurrent adverse effects (1 with phenylpropanolamine alone; 3 with phenylpropanolamine + selegiline transdermal system). Pharmacokinetic parameters obtained following selegiline transdermal system and pseu-: doephedrine or phenylpropanolamine were unremarkable. The results suggest that selegiline transdermal system 6 mg/24 h does not significantly alter the pharmacodynamics or pharmacokinetics of either pseudoephedrine or phenylpropanolamine when administered to healthy volunteers; however, it is prudent to avoid coadministration of selegiline transdermal system and sympathomimetics.