How to manage rizatriptan and propranolol interaction?

Managing Rizatriptan-Propranolol Interaction

When prescribing rizatriptan to patients taking propranolol, reduce the rizatriptan dose to 5 mg with a maximum of 15 mg (three 5 mg doses) in any 24-hour period for adults, and use only a single 5 mg dose (maximum 5 mg per 24 hours) for pediatric patients weighing ≥40 kg. 1

Mechanism of Interaction

Propranolol significantly increases rizatriptan exposure through inhibition of monoamine oxidase-A (MAO-A), the primary metabolic pathway for rizatriptan. 2

• Propranolol 120 mg twice daily increases rizatriptan AUC by approximately 67-70% and Cmax by approximately 75%. 1, 2
• This interaction is specific to propranolol and does not occur with other beta-blockers such as nadolol or metoprolol, which do not inhibit MAO-A. 2
• In vitro studies confirm that propranolol, but not other beta-adrenoceptor blockers, significantly inhibits the production of rizatriptan's indole-acetic acid metabolite. 2

Specific Dosing Adjustments

Adult Patients on Propranolol

• Use only the 5 mg dose of rizatriptan. 1
• Maximum of 3 doses in any 24-hour period (total 15 mg daily). 1
• Do not use the standard 10 mg dose. 1

Pediatric Patients (6-17 years) on Propranolol

• For patients weighing ≥40 kg (88 lb): use only a single 5 mg dose with a maximum of 5 mg in 24 hours. 1
• For patients weighing <40 kg (88 lb): rizatriptan should not be prescribed to propranolol-treated patients in this weight category. 1

Alternative Beta-Blocker Considerations

If migraine prophylaxis with a beta-blocker is needed and the patient requires rizatriptan for acute treatment, consider switching from propranolol to an alternative beta-blocker that does not interact:

• Nadolol (80 mg twice daily) does not significantly alter rizatriptan pharmacokinetics and requires no dose adjustment. 2
• Metoprolol (100 mg twice daily) does not significantly alter rizatriptan pharmacokinetics and requires no dose adjustment. 2
• Other beta-1 selective agents like atenolol, bisoprolol, or nebivolol are reasonable alternatives, though they lack specific interaction data with rizatriptan. 3

Safety Profile of the Interaction

Despite the significant pharmacokinetic interaction, clinical safety data are reassuring:

• No serious adverse events attributable to the propranolol-rizatriptan interaction were observed in controlled studies. 2
• No subjects developed serious clinical, laboratory, or other significant adverse experiences during coadministration. 2
• The dose reduction strategy effectively mitigates the increased exposure while maintaining therapeutic efficacy. 1

Additional Contraindications to Monitor

When managing patients on rizatriptan, regardless of propranolol use, ensure the following medications are avoided:

• Ergot-containing drugs (ergotamine, dihydroergotamine, methysergide) must not be used within 24 hours of rizatriptan due to additive vasospastic effects. 3, 1
• Other triptans must not be used within 24 hours of rizatriptan. 1
• MAO-A inhibitors are absolutely contraindicated with rizatriptan. 1

Clinical Pitfalls to Avoid

• Do not attempt to circumvent the interaction by timing doses differently—studies show that incorporating a 1-2 hour delay between propranolol and rizatriptan administration does not eliminate the pharmacokinetic effect. 2
• Do not reduce the propranolol dose to 60 mg twice daily as a strategy to allow standard rizatriptan dosing—this does not produce a statistically significant change in the interaction. 2
• Remember that this interaction is unique to propranolol among beta-blockers; switching to metoprolol or nadolol eliminates the need for rizatriptan dose adjustment. 2