Ubrelvy (ubrogepant) is a valuable medication for the acute treatment of migraine attacks, but its safety and efficacy depend heavily on avoiding certain drug and substance combinations. The primary concern involves the cytochrome P450 (CYP) enzyme system, specifically CYP3A4, which plays a major role in metabolizing Ubrelvy in the liver. Substances that inhibit or induce this enzyme can cause Ubrelvy levels to rise to toxic concentrations or drop so low that the medication becomes ineffective. Before starting Ubrelvy, it is crucial to discuss all medications, vitamins, and supplements with your healthcare provider to prevent potentially dangerous interactions.
Strong CYP3A4 Inhibitors: A Contraindication
The most serious interactions involve strong CYP3A4 inhibitors, which dramatically increase the concentration of Ubrelvy in the bloodstream. This can raise the risk of severe side effects, including hypersensitivity reactions like anaphylaxis, as well as high blood pressure and Raynaud's phenomenon. The FDA strictly contraindicates the co-administration of Ubrelvy with these substances.
Common strong CYP3A4 inhibitors to avoid:
- Antifungals: Ketoconazole, itraconazole.
- Antibiotics: Clarithromycin.
- Antivirals: Ritonavir (including Paxlovid), nelfinavir, indinavir.
- Certain other medications: Nefazodone.
Moderate and Weak CYP3A4 Inhibitors
While not strictly contraindicated, taking Ubrelvy with moderate CYP3A4 inhibitors requires a dose adjustment and caution. For example, if you are on a moderate inhibitor, you should not take a second dose of Ubrelvy within 24 hours of the first. This is because the inhibitor slows down the breakdown of Ubrelvy, causing it to linger in your system longer.
Examples of moderate and weak CYP3A4 inhibitors that require caution:
- Antibiotics: Ciprofloxacin, erythromycin.
- Antifungals: Fluconazole.
- Heart Medications: Verapamil, diltiazem.
- Other Medications: Cyclosporine, fluvoxamine.
CYP3A4 Inducers: Reducing Ubrelvy's Effectiveness
In contrast to inhibitors, CYP3A4 inducers increase the activity of the enzyme responsible for breaking down Ubrelvy. This can cause the medication to be cleared from your system too quickly, reducing its overall effectiveness. Concomitant use with strong inducers should be avoided.
Examples of CYP3A4 inducers that can decrease Ubrelvy's efficacy:
- Anticonvulsants: Phenytoin, carbamazepine, barbiturates.
- Antibiotics: Rifampin.
- Herbal Supplements: St. John's wort.
Other Medication and Lifestyle Interactions
Ubrelvy's interactions are not limited to the CYP3A4 enzyme. Other transport proteins like BCRP and P-gp also affect its clearance. Inhibitors of these proteins can also increase Ubrelvy levels, necessitating dosage adjustments. Lifestyle factors like food and alcohol consumption are also important considerations.
Substances affecting BCRP/P-gp transporters:
- Heart Medications: Quinidine, carvedilol.
- Other Medications: Eltrombopag.
- Supplements: Curcumin (in high doses, often found in supplements).
Lifestyle considerations:
- Grapefruit Juice: This is a moderate CYP3A4 inhibitor and should be avoided or limited. Do not take a second dose of Ubrelvy within 24 hours if you have consumed grapefruit products.
- Alcohol: While not a direct drug interaction, alcohol can increase side effects like dizziness and drowsiness, and it is a common migraine trigger for many individuals.
Drug Interaction Comparison Table
| Interaction Category | Examples of Substances to Avoid | Effect on Ubrelvy | Required Action |
|---|---|---|---|
| Strong CYP3A4 Inhibitors | Ketoconazole, itraconazole, clarithromycin, ritonavir | Significantly increases Ubrelvy exposure, high risk of side effects | Avoid use completely |
| Strong CYP3A4 Inducers | Rifampin, phenytoin, St. John's wort | Significantly decreases Ubrelvy effectiveness | Avoid use completely |
| Moderate CYP3A4 Inhibitors | Grapefruit juice, verapamil, fluconazole, ciprofloxacin | Increases Ubrelvy exposure, risk of side effects | Dose adjustment required; limit to one dose per 24 hours |
| BCRP or P-gp Inhibitors | Quinidine, carvedilol, eltrombopag, curcumin supplements | Increases Ubrelvy exposure, risk of side effects | Dose adjustment required |
| Alcohol | Alcoholic beverages | Increases side effects (nausea, drowsiness); potential migraine trigger | Avoid or use with caution; consult provider |
Important Warnings for Specific Patient Groups
Certain patient populations must be particularly cautious or avoid Ubrelvy altogether:
- Pregnancy and Breastfeeding: Ubrelvy is not generally recommended for use during pregnancy due to limited data and animal studies suggesting potential fetal harm. For women who are pregnant or planning to be, safer alternative treatments should be considered after consulting a healthcare provider. Ubrelvy is also not recommended while breastfeeding, as it is unknown if it is safe for the infant.
- Liver Problems: Since Ubrelvy is metabolized by the liver, patients with severe hepatic impairment (Child-Pugh Class C) should not take Ubrelvy. Dose adjustments are needed for those with less severe liver issues.
- Kidney Problems: For patients with severe renal impairment (creatinine clearance 15-29 mL/min), a dose adjustment is necessary. Patients with end-stage renal disease (creatinine clearance < 15 mL/min) should avoid Ubrelvy entirely.
- Hypersensitivity: If you have a history of serious allergic reactions to ubrogepant or any of the product's ingredients, Ubrelvy is contraindicated.
Conclusion
To ensure the safe and effective use of Ubrelvy, understanding its potential interactions is essential. Patients must avoid combining it with strong CYP3A4 inhibitors and inducers, and exercise significant caution with moderate inhibitors, grapefruit products, and certain supplements. Individuals who are pregnant, breastfeeding, or have pre-existing liver or kidney conditions also require specific medical advice before use. By closely adhering to these warnings and maintaining open communication with healthcare professionals, patients can minimize risks and manage their migraine attacks safely. For detailed clinical information, please consult the official UBRELVY prescribing information.
