What medications cannot be taken with Rizatriptan (a serotonin receptor agonist)?

Medications That Cannot Be Taken with Rizatriptan

Rizatriptan is absolutely contraindicated with MAO inhibitors (within 2 weeks of use), ergot-containing medications (within 24 hours), and other triptans (within 24 hours), while propranolol requires dose adjustment of rizatriptan. 1

Absolute Contraindications

MAO Inhibitors

• Do not take rizatriptan if you have taken a MAO inhibitor within the last 2 weeks, as this combination is strictly contraindicated by the FDA. 1
• This restriction applies to all MAO inhibitors regardless of type or indication. 1

Ergot-Containing Medications

• Rizatriptan must not be taken within 24 hours of ergot-containing medicines including ergotamine and dihydroergotamine (DHE). 1
• The Mayo Clinic consensus recommends holding ergotamine at least 2 days prior to procedures, reflecting concerns about prolonged vasoconstriction that outlasts pharmacological duration. 2
• Combining these agents creates risk of severe hypertensive response and prolonged vasospasm. 2

Other Triptans

• Do not take any other triptan medication within 24 hours of rizatriptan, including sumatriptan, naratriptan, zolmitriptan, almotriptan, eletriptan, or frovatriptan. 1
• This contraindication exists across all triptan formulations (oral, nasal, subcutaneous). 2

Required Dose Adjustment

Propranolol

• If taking propranolol, rizatriptan dose must be reduced to 5 mg (rather than the standard 10 mg dose). 1
• Propranolol significantly affects rizatriptan metabolism, necessitating this mandatory dose reduction. 2
• This applies to all propranolol-containing products including Inderal, Inderal LA, and Innopran XL. 1

Medications Requiring Caution (Not Absolute Contraindications)

SSRIs and SNRIs

• The theoretical risk of serotonin syndrome with SSRIs/SNRIs combined with triptans is low, and these medications are commonly co-prescribed. 2
• The American Headache Society position paper concluded that available evidence does not support limiting triptan use with SSRIs/SNRIs, though vigilance is warranted. 3
• Of 29 FDA cases reviewed, only 10 met Sternbach criteria for serotonin syndrome, and none met Hunter criteria. 4
• The Mayo Clinic consensus notes "the risk of serotonin syndrome with combining triptans and SSRIs or SNRIs is low." 2

Common pitfall: Despite the 2006 FDA alert, the evidence does not support prohibiting this combination—only increased awareness and monitoring are needed. 4, 3

Other Serotonergic Agents

• Exercise caution when combining rizatriptan with other serotonergic medications including:
  • Opioids (particularly tramadol, meperidine, methadone, fentanyl) 5
  • Over-the-counter dextromethorphan 5
  • St. John's Wort 5
  • L-tryptophan supplements 5

Cardiovascular Contraindications

Rizatriptan should not be given to patients with:

• Ischemic heart disease or coronary artery vasospasm 1
• History of myocardial infarction 1
• Prinzmetal's angina 1
• Uncontrolled hypertension 1
• History of stroke or transient ischemic attack 1
• Peripheral vascular disease or ischemic bowel disease 1

Clinical Monitoring Recommendations

• Start with low doses when adding a second serotonergic medication and monitor closely in the first 24-48 hours. 5
• For triptan-naive patients with multiple cardiovascular risk factors (age, diabetes, hypertension, smoking, obesity, strong family history of CAD), perform cardiovascular evaluation before prescribing. 1
• Consider administering first dose in medically-supervised setting with ECG monitoring for high-risk patients. 1

Important caveat: The long half-life of some serotonergic medications (particularly fluoxetine) means drug interactions can persist for weeks after discontinuation, requiring adequate washout periods. 6