Rasagilineinteractions

Meperidine: Risk of serotonin syndrome Dextromethorphan: Risk of psychosis or bizarre behavior MAO inhibitors: Risk of non-selective MAO inhibition and hypertensive crisis

7.1 Meperidine

Serious, sometimes fatal reactions have been precipitated with concomitant use of meperidine (e.g., Demerol and other tradenames) and MAO inhibitors including selective MAO-B inhibitors.

7.2 Dextromethorphan

The concomitant use of rasagiline tablets and dextromethorphan was not allowed in clinical studies. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Therefore, in view of rasagiline's MAO inhibitory activity, dextromethorphan is contraindicated for use with rasagiline tablets.

7.3 MAO Inhibitors

Rasagiline tablets are contraindicated for use with other MAO inhibitors because of the increased risk of nonselective MAO inhibition that may lead to a hypertensive crisis.

7.4 Sympathomimetic

Medications The concomitant use of rasagiline tablets and sympathomimetic medications was not allowed in clinical studies. Severe hypertensive reactions have followed the administration of sympathomimetics and nonselective MAO inhibitors. Hypertensive crisis has been reported in patients taking the recommended dose of rasagiline tablets and sympathomimetic medications. Severe hypertension has been reported in patients taking the recommended dose of rasagiline tablets and ophthalmic drops containing sympathomimetic medications. Because rasagiline is a selective MAOI, hypertensive reactions are not ordinarily expected with the concomitant use of sympathomimetic medications. Nevertheless, caution should be exercised when concomitantly using recommended doses of rasagiline tablets with any sympathomimetic medications including nasal, oral, and ophthalmic decongestants and cold remedies.

7.5 Antidepressants

Concomitant use of rasagiline tablets with one of many classes of antidepressants (e.g., SSRIs, SNRIs, triazolopyridine, tricyclic, or tetracyclic antidepressants) is not recommended. Concomitant use of rasagiline and MAO inhibitors is contraindicated.

7.6 Ciprofloxacin or

Other CYP1A2 Inhibitors Rasagiline plasma concentrations may increase up to 2 fold in patients using concomitant ciprofloxacin and other CYP1A2 inhibitors. This could result in increased adverse events. Patients taking concomitant ciprofloxacin or other CYP1A2 inhibitors should not exceed a dose of rasagiline tablets 0.5 mg once daily.

7.7 Tyramine/Rasagiline

Interaction MAO in the gastrointestinal tract and liver (primarily type A) provides protection from exogenous amines (e.g., tyramine) that have the capacity, if absorbed intact, to cause a tyramine reaction with hypertension including clinical syndromes referred to as hypertensive urgency, crisis, or emergency. Foods and medications containing large amounts of exogenous amines (e.g., from fermented cheese, herring, over-the-counter cough/cold medications) may cause release of norepinephrine resulting in a rise in systemic blood pressure. Results of a special tyramine challenge study indicate that rasagiline is selective for MAO-B at recommended doses and can be used without dietary tyramine restriction. However, certain foods may contain very high amounts (i.e., 150 mg or greater) of tyramine and could potentially cause a hypertensive reaction in individual patients taking rasagiline tablets due to increased sensitivity to tyramine. Selectivity for inhibiting MAO-B diminishes in a dose-related manner as the dose is progressively increased above the recommended daily doses. There were no cases of hypertensive crisis in the clinical development program associated with 1mg daily rasagiline tablet treatment, in which most patients did not follow dietary tyramine restriction. There have been postmarketing reports of patients who experienced significantly elevated blood pressure (including rare cases of hypertensive crisis) after ingestion of unknown amounts of tyramine-rich foods while taking recommended doses of rasagiline tablets. Patients should be advised to avoid foods containing a very large amount of tyramine while taking recommended doses of rasagiline tablets.

7.8 Dopaminergic

Antagonists It is possible that dopamine antagonists, such as antipsychotics or metoclopramide, could diminish the effectiveness of rasagiline.