Rizatriptan (brand name Maxalt) has several serious drug interactions, most notably with MAO inhibitors, other migraine medications, and drugs that raise serotonin levels. Some of these combinations are strictly contraindicated, meaning they should never be used together, while others require dose adjustments or careful monitoring.
MAO Inhibitors
This is the most dangerous interaction. You cannot take rizatriptan if you currently use or have recently used an MAO inhibitor, a type of medication prescribed for depression and sometimes Parkinson’s disease. Common examples include isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl), and tranylcypromine (Parnate). MAO inhibitors slow the breakdown of rizatriptan in your body, which can cause dangerously high levels of the drug to build up.
The required gap is at least two weeks. Even after you stop taking an MAO inhibitor, you need to wait a full 14 days before using rizatriptan. This waiting period exists because MAO inhibitors have long-lasting effects on your body’s enzyme systems that don’t resolve immediately after your last dose.
SSRIs, SNRIs, and Serotonin Syndrome
Rizatriptan works partly by activating serotonin receptors. When combined with other medications that also increase serotonin, the result can be a potentially life-threatening condition called serotonin syndrome. The medications most commonly involved are SSRIs (like fluoxetine, sertraline, and escitalopram) and SNRIs (like venlafaxine and duloxetine), which are widely prescribed for depression and anxiety.
Serotonin syndrome symptoms typically appear within minutes to hours of taking the interacting drugs. Warning signs include agitation, confusion, rapid heartbeat, high blood pressure, heavy sweating, fever, muscle spasms, tremor, and loss of coordination. A diagnosis generally requires at least three of these symptoms in someone taking a serotonin-affecting drug. The risk is highest when you first start combining the medications or when a dose is increased.
This doesn’t necessarily mean you can never use rizatriptan if you take an antidepressant. Many people do use both, but it requires close monitoring, especially in the early period after starting or adjusting doses. Do not stop your antidepressant on your own because of this interaction.
Other Migraine Medications
You should not take rizatriptan within 24 hours of using ergot-type migraine medications, such as ergotamine or dihydroergotamine. Both rizatriptan and ergot drugs cause blood vessel constriction, and combining them can lead to dangerous, prolonged vasospasm (sustained tightening of blood vessels).
The same spacing rule applies to other triptans. If you’ve taken sumatriptan, naratriptan, zolmitriptan, or any other triptan, you need to wait before switching to rizatriptan. Stacking triptans increases the risk of cardiovascular side effects without improving migraine relief.
Propranolol Requires a Lower Dose
Propranolol, a beta-blocker often prescribed to prevent migraines, significantly increases rizatriptan levels in the bloodstream. If you take propranolol, your rizatriptan dose needs to be cut. The recommended limit is 5 mg per dose, with a maximum of 15 mg in any 24-hour period. For comparison, the standard maximum for adults not on propranolol is 30 mg in 24 hours. Other beta-blockers like nadolol and metoprolol don’t appear to have the same effect, but propranolol specifically alters how your body processes rizatriptan.
St. John’s Wort and Herbal Supplements
St. John’s Wort, a popular herbal supplement used for mood support, raises serotonin levels in the brain. Combining it with rizatriptan increases the chance of serotonin-related side effects, including mental status changes, sweating, elevated blood pressure, and muscle-related symptoms. Because St. John’s Wort is sold over the counter, people often don’t think of it as a “real” medication, but it has clinically meaningful interactions with triptans. If you use St. John’s Wort regularly, make sure your prescriber knows before you start rizatriptan.
Health Conditions That Rule Out Rizatriptan
Beyond drug interactions, certain medical conditions make rizatriptan unsafe regardless of what else you’re taking. Rizatriptan constricts blood vessels, which is how it relieves migraine pain but also why it poses risks for people with cardiovascular problems.
- Ischemic heart disease: This includes a history of heart attack, angina (chest pain from reduced blood flow), or documented silent ischemia (reduced heart blood flow without symptoms).
- Coronary artery vasospasm: Including Prinzmetal’s angina, a condition where heart arteries temporarily spasm and narrow.
- Uncontrolled high blood pressure: Rizatriptan can raise blood pressure further, making it dangerous if your blood pressure is already poorly managed.
- Other significant cardiovascular disease: Any underlying heart or blood vessel condition that could worsen with vessel constriction.
Dosing Limits to Keep in Mind
Even without any of these interactions, rizatriptan has strict dosing boundaries. The maximum is 30 mg in any 24-hour period for most adults, or 15 mg if you take propranolol. If your first dose doesn’t fully relieve the migraine and the headache returns, you can take a second dose, but you need to wait at least two hours after the first one. Taking more than the recommended amount increases the risk of serious cardiovascular side effects and medication-overuse headache over time.