Drug Interactions between propranolol and rizatriptan

ADJUST DOSE: Coadministration with propranolol may increase the plasma concentrations of rizatriptan. The exact mechanism is unknown but may involve propranolol inhibition of rizatriptan metabolism via monoamine oxidase, subtype A. In 11 healthy subjects, propranolol (120 mg orally every 12 hours for 7 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of rizatriptan (10 mg single dose) by 75% and 67%, respectively, compared to placebo. A 4-fold increase in rizatriptan AUC was observed in one case. In 20 healthy subjects, reducing the dosage of propranolol (60 mg twice daily for 7 days) and/or staggering the time of administration (1 to 2 hours) lessened somewhat but did not eliminate the effect on rizatriptan pharmacokinetics. In contrast, 25 healthy subjects given a single 10 mg dose of rizatriptan following nadolol (80 mg every 12 hours) or metoprolol (100 mg every 12 hours) for 7 days demonstrated no evidence of a significant pharmacokinetic interaction. No adverse effects were attributed to any of the drug combinations in the studies, and no effect on the active N-monodesmethyl metabolite of rizatriptan was reported.

MANAGEMENT: Caution is advised if rizatriptan must be used with propranolol. Patients treated with propranolol should not receive greater than 5 mg of rizatriptan as a single dose, nor more than a maximum of 3 doses in any 24-hour period. It is important to note that some combination products (e.g., meloxicam-rizatriptan) are considered contraindicated with propranolol if they contain greater than 5 mg of rizatriptan in a single dose. Patients should be monitored for rizatriptan-related adverse effects which include arrhythmias, cerebrovascular events, chest tightness or pressure, vasospasm reactions, fatigue, and dizziness. It appears that the full range of rizatriptan dose may be used during coadministration with atenolol, metoprolol, nadolol, or timolol.