Ubrelvy (ubrogepant) cannot be taken with a category of drugs called strong CYP3A4 inhibitors. This is the only absolute contraindication on the FDA label, but several other medications and supplements require dose changes or should be avoided because they interfere with how your body processes the drug. Here’s what falls into each category and why it matters.
Medications That Are Strictly Off-Limits
Ubrelvy is broken down in your body by a liver enzyme called CYP3A4. Certain medications block that enzyme so effectively that Ubrelvy builds up to potentially unsafe levels in your bloodstream. These are called strong CYP3A4 inhibitors, and the FDA label lists them as a hard contraindication, meaning you should not take Ubrelvy at all while using them.
Common examples include:
- Ketoconazole and itraconazole: antifungal medications often prescribed for serious fungal infections
- Clarithromycin: an antibiotic used for respiratory and skin infections (sometimes sold as Biaxin)
Other strong CYP3A4 inhibitors you may encounter include certain HIV medications (ritonavir, cobicistat-containing regimens) and the antibiotic telithromycin. If you’re prescribed any of these, you need a different migraine treatment for as long as you’re taking them.
Medications That Require a Lower Dose
Moderate CYP3A4 inhibitors don’t block the enzyme as completely, but they still raise Ubrelvy levels enough to require a dose adjustment. Common drugs in this group include verapamil (a blood pressure and heart rhythm medication), fluconazole (a widely prescribed antifungal), and certain other medications your pharmacist can identify. When you’re taking one of these, your prescriber will typically lower your Ubrelvy dose to keep blood levels in a safe range.
Drugs That Make Ubrelvy Less Effective
The opposite problem happens with strong CYP3A4 inducers. These medications speed up the enzyme that breaks down Ubrelvy, clearing the drug from your system so quickly that it may not work at all. The FDA label specifically says to avoid taking Ubrelvy with:
- Rifampin: an antibiotic used for tuberculosis and certain other infections
- Phenytoin: a seizure medication
- Barbiturates: older sedatives sometimes used for seizures or anxiety
- St. John’s Wort: an herbal supplement commonly taken for mood support
St. John’s Wort catches many people off guard because it’s sold over the counter and seems harmless, but it is one of the most potent enzyme inducers found in supplements. If you take it regularly, Ubrelvy is expected to lose its effectiveness.
Moderate and weak CYP3A4 inducers don’t require you to stop Ubrelvy entirely, but they do call for a dose adjustment. In those cases, the recommended approach is to use the higher 100 mg dose for both the initial and second doses.
Grapefruit Juice
Grapefruit and grapefruit juice are natural CYP3A4 inhibitors. While the FDA label groups them with the broader enzyme inhibitor warning rather than calling them out with a specific blood-level study, the standard guidance for any drug processed through this pathway is to be cautious with grapefruit. A small glass is unlikely to cause a major problem, but drinking large quantities regularly could raise Ubrelvy levels in the same way a moderate inhibitor would.
Kidney and Liver Concerns
While not a drug interaction in the traditional sense, the health of your liver and kidneys changes how much Ubrelvy stays in your system, effectively mimicking the effect of taking it with an inhibitor.
Severe liver impairment increases Ubrelvy exposure by about 115%, more than doubling the amount of active drug in your blood. In that case, the maximum dose is capped at 50 mg. Mild or moderate liver impairment doesn’t require a change.
The pattern is similar for kidney function. Severe kidney impairment calls for a reduced 50 mg dose. End-stage renal disease, where kidney function is near zero, is the one condition where Ubrelvy use should be avoided entirely. Mild or moderate kidney impairment requires no adjustment.
What About Other Migraine Medications?
Ubrelvy works by blocking CGRP receptors, a different mechanism than triptans (like sumatriptan) or NSAIDs (like ibuprofen). The FDA label does not list triptans, NSAIDs, or acetaminophen as contraindicated with Ubrelvy. However, if you’re taking another CGRP-targeting medication, such as a monthly injectable like erenumab or fremanezumab for migraine prevention, it’s worth discussing with your prescriber since both drugs act on the same pathway.
There is no specific warning about alcohol on the Ubrelvy label, though alcohol is a common migraine trigger on its own and can worsen the nausea and drowsiness that some people experience with the medication.