Rizatriptan Drug Interactions: What to Avoid and What to Tell Your Doctor

Why Drug Interactions With Rizatriptan Matter

Rizatriptan (Maxalt) is generally a well-tolerated medication, but it has several serious drug interactions that must be respected. Two are outright contraindications — meaning you should never take rizatriptan if these apply. Others require dose adjustments or careful monitoring. Always give your doctor and pharmacist a complete list of every medication, supplement, and herbal product you take before using rizatriptan.

CONTRAINDICATED: MAO Inhibitors (MAOIs)

Do not take rizatriptan if you have used an MAO inhibitor (MAOI) in the past 14 days. This is an absolute contraindication.

MAOIs are a class of antidepressants and Parkinson's medications. They include:

Phenelzine (Nardil)

Tranylcypromine (Parnate)

Isocarboxazid (Marplan)

Selegiline (Eldepryl, Emsam) — particularly in higher doses

Linezolid (Zyvox) — an antibiotic with MAOI activity

Methylene blue injection — used in some surgical procedures; has MAOI activity

Why is this dangerous? MAO-A inhibitors block the enzyme that metabolizes rizatriptan (and its active metabolite). In one study, the MAO-A inhibitor moclobemide increased rizatriptan blood levels by 119% and increased its active metabolite by over 400%. Irreversible MAOIs would be expected to have an even greater effect, leading to potentially toxic drug levels.

CONTRAINDICATED: Other Triptans and Ergot Drugs (Within 24 Hours)

Do not take rizatriptan within 24 hours of:

Any other triptan (sumatriptan, eletriptan, zolmitriptan, frovatriptan, naratriptan, almotriptan) — risk of additive vasospasm

Ergot-containing medications: ergotamine, dihydroergotamine (DHE), ergotamine-containing combination products — also risk of additive vasospasm

Both triptans and ergot drugs cause vasoconstriction. Taking them together can cause dangerously prolonged or severe vasospasm affecting blood flow to the heart or extremities.

MAJOR INTERACTION: Propranolol (Requires Dose Reduction)

Propranolol is a beta-blocker commonly used for both high blood pressure and migraine prevention. When taken together with rizatriptan, propranolol increases rizatriptan blood levels by approximately 70% by inhibiting the MAO-A enzyme that metabolizes rizatriptan.

If you take propranolol, your doctor will prescribe a lower dose of rizatriptan:

Adults on propranolol: Maximum 5 mg per dose; max 15 mg (three 5 mg doses) per 24 hours

Pediatric patients ≥40 kg on propranolol: Single 5 mg dose only per 24 hours (maximum 5 mg/day)

Rizatriptan should NOT be prescribed to propranolol-treated pediatric patients weighing less than 40 kg

Note: Other beta-blockers (nadolol, metoprolol) do NOT appear to have this interaction and do not require a rizatriptan dose adjustment.

MODERATE INTERACTION: SSRIs and SNRIs (Risk of Serotonin Syndrome)

Combining rizatriptan with serotonin-enhancing antidepressants increases the risk of serotonin syndrome — a potentially life-threatening condition. The risk is considered low but real, particularly when doses are high.

Common SSRIs: fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), paroxetine (Paxil), citalopram (Celexa)

Common SNRIs: venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq)

Signs of serotonin syndrome: agitation, confusion, rapid heart rate, high fever, tremor, muscle rigidity, sweating, diarrhea. Seek emergency care immediately if these occur.

What About Food and Alcohol?

Food does not affect the bioavailability of rizatriptan, though it can delay the time to peak effect by about one hour. You can take rizatriptan with or without food.

Alcohol: Avoid drinking alcohol after taking rizatriptan. Alcohol can worsen dizziness, drowsiness, and the overall side effect profile. There are also potential vascular interactions.

Complete List of What to Tell Your Doctor Before Taking Rizatriptan

Any MAO inhibitors (or if you stopped one in the past 2 weeks)

Propranolol (Inderal) specifically — different from other beta-blockers

Any other triptan migraine medications

Ergotamine or ergot-containing medications

Any SSRIs or SNRIs (antidepressants)

Any heart medications, blood pressure medications, or cholesterol drugs

Any herbal supplements — especially St. John's Wort (which affects serotonin levels)

For a full guide to side effects, see Rizatriptan Side Effects: What to Expect and When to Call Your Doctor. And if you need help finding rizatriptan at a pharmacy near you, medfinder can help.