Migraine treatment with Ubrelvy (ubrogepant) requires careful consideration of potential drug interactions, as its metabolism is affected by various medications, supplements, and even foods. The primary pathways involved are the cytochrome P450 3A4 (CYP3A4) enzyme and the drug efflux transporters, P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). By understanding how these pathways influence Ubrelvy levels in the body, patients can work with their healthcare providers to manage and avoid potentially dangerous combinations.
The Absolute "Do Not Take" List: Strong Inhibitors and Inducers
The most critical drug interactions with Ubrelvy involve medications that are either strong inhibitors or strong inducers of the CYP3A4 enzyme. For patient safety, these combinations are strictly prohibited or must be avoided entirely.
Strong CYP3A4 Inhibitors
Strong CYP3A4 inhibitors block the enzyme that breaks down Ubrelvy. This can cause Ubrelvy levels to build up to potentially harmful concentrations in the bloodstream, increasing the risk of adverse side effects such as fatigue, nausea, and more serious reactions.
- Antifungal Medications: Including ketoconazole, itraconazole, and posaconazole.
- Antibiotics: Specifically clarithromycin.
- HIV Protease Inhibitors: Such as ritonavir (also found in the COVID-19 treatment Paxlovid), atazanavir, and lopinavir.
- Other Medications: Idelalisib, cobicistat, and certain antidepressants like nefazodone are also strong inhibitors.
Strong CYP3A4 Inducers
On the other end of the spectrum, strong CYP3A4 inducers accelerate the metabolism of Ubrelvy. This causes the drug to be cleared from the body too quickly, potentially leading to a loss of effectiveness.
- Antibiotics: The most notable is rifampin.
- Antiseizure Medications: Including phenytoin, carbamazepine, and phenobarbital.
- Herbal Supplements: St. John's wort is a potent inducer and should be avoided.
Interactions Requiring Caution and Management
Not all interactions require complete avoidance. Other drugs that moderately inhibit or induce the CYP3A4 pathway, or affect drug transporters like P-gp and BCRP, can alter Ubrelvy's effectiveness or safety. In these cases, careful monitoring or modifications to treatment may be necessary.
Moderate and Weak CYP3A4 Modulators
These drugs can influence the levels of Ubrelvy. For moderate inhibitors like verapamil or grapefruit juice, adjustments to the Ubrelvy regimen may be required.
- Calcium Channel Blockers: Examples include verapamil and diltiazem.
- Antibiotics: Moderate inhibitors include ciprofloxacin and erythromycin.
- Immunosuppressants: Cyclosporine is a notable example.
- Antidepressants: Fluvoxamine is a moderate inhibitor.
- Food: Grapefruit and grapefruit juice are moderate CYP3A4 inhibitors and should be avoided or consumed with caution.
BCRP and P-gp Inhibitors
Ubrelvy is also a substrate for BCRP and P-gp efflux transporters. Inhibitors of these proteins can increase Ubrelvy exposure and the risk of side effects.
- Heart Medications: Including quinidine and carvedilol.
- Herbal Supplements: Curcumin (found in turmeric) is a known inhibitor.
- Blood Medications: Eltrombopag is an example.
Important Drug Interaction Information at a Glance
To help visualize the range of interactions, the following table provides a summary of major drug classes and their effect on Ubrelvy.
| Drug Class or Substance | Examples | Interaction with Ubrelvy | Clinical Recommendation |
|---|---|---|---|
| Strong CYP3A4 Inhibitors | Ketoconazole, clarithromycin, ritonavir, itraconazole | Significantly increases Ubrelvy levels, potentially risking toxicity | CONTRAINDICATED; DO NOT TAKE |
| Strong CYP3A4 Inducers | Rifampin, phenytoin, St. John's Wort | Significantly decreases Ubrelvy levels, potentially reducing effectiveness | AVOID CONCOMITANT USE |
| Moderate CYP3A4 Inhibitors | Verapamil, cyclosporine, grapefruit juice | Increases Ubrelvy levels, potentially increasing side effect risk | Regimen adjustment may be necessary, consult healthcare provider |
| P-gp or BCRP Inhibitors | Carvedilol, quinidine, curcumin supplements | Increases Ubrelvy levels, potentially increasing side effect risk | Regimen adjustment may be necessary, consult healthcare provider |
| Other Medications | Mild CYP3A4 modulators | Variable effect on Ubrelvy levels | Regimen adjustment may be necessary |
What to Discuss with Your Healthcare Provider
Before you start taking Ubrelvy, a thorough discussion with your doctor is essential. Inform them of every medication and supplement you take, including:
- Prescription drugs, especially any for heart conditions, infections, or seizures.
- Over-the-counter (OTC) medicines like vitamins and herbal remedies.
- Dietary supplements, including curcumin and St. John's wort.
- Pre-existing medical conditions, particularly liver or kidney problems, as these can affect how your body processes Ubrelvy.
Conclusion
The safe and effective use of Ubrelvy depends on a clear understanding of its potential drug interactions. The most critical interactions involve the CYP3A4 enzyme and the P-gp/BCRP drug transporters, which can lead to dangerously high or ineffective drug levels in the body. Patients must strictly avoid strong CYP3A4 inhibitors and inducers, while other medications or substances like grapefruit require careful management. Always provide your healthcare provider with a complete list of all medications and supplements to ensure proper guidance and prevent adverse reactions. The information presented here is for educational purposes and should not replace professional medical advice.
For more detailed information, consult the official FDA prescribing information for Ubrelvy.
