Key takeaways

Medications that impact the pathways that play a role in the metabolism of Nurtec can be dangerous, resulting in increased or decreased exposure to the active ingredient.
Adverse effects that can result from Nurtec interactions involve the change in exposure to the active ingredient; interactions that increase metabolism can result in individuals not experiencing the therapeutic benefit of the medication, whereas those that decrease metabolism can result in increased exposure and possible side effects.
While a major substrate of CYP3A4 and P-glycoprotein, Nurtec is a minor substrate of CYP2C9, which may result in less severe impacts on its metabolism when given with other medications that impact that metabolic pathway.
In the event of a Nurtec interaction, if it is identified that the interaction is resulting in increased exposure to the medication, individuals should monitor for new onset of side effects and hold off on re-dosing Nurtec for a minimum of 48 hours. In the setting of concomitant administration, which results in decreased exposure and potentially a reduction in therapeutic efficacy, individuals should not exceed the recommended dose without the advice of a healthcare professional.

In this article:

Drug interactions
Foods interactions
Other interactions
Avoiding interactions
When to see a doctor

In this article

Drug interactions
Foods interactions
Other interactions
Avoiding interactions
When to see a doctor

Nurtec (rimegepant) is an orally disintegrating tablet prescription drug and a member of the calcitonin gene-related peptide (CGRP) receptor antagonists, sometimes called gepants. It is manufactured by Pfizer and is approved by the Food and Drug Administration (FDA) for both the prevention and acute treatment of migraines with or without aura. Nurtec and other gepants are substrates of CYP enzymes and drug transporters, which translates to a high potential for drug interactions. Nurtec specifically is a major substrate of the isoenzyme CYP3A4 and drug transporter P-glycoprotein, so use with other medications and certain foods that inhibit or induce this specific enzyme or drug transporter can particularly impact the metabolism of Nurtec. Such medications include those for migraines, antimicrobials, and over-the-counter products like St. John’s wort and grapefruit juice. It’s important to be aware of Nurtec interactions, as concomitant use with certain drugs and foods can affect Nurtec’s effectiveness or cause adverse effects.

Nurtec drug interactions

The most concerning drug interactions that can occur with Nurtec are when it is taken with strong CYP3A4 or P-glycoprotein inhibitors or inducers.

CYP3A4 inhibitors

Strong CYP3A4 inhibitors encompass a broad grouping of medications. CYP3A4 inhibitors interact with Nurtec by preventing the metabolism of the active ingredient, rimegepant. The prescribing information for Nurtec ODT recommends avoiding co-administration of these medications as it is expected the CYP3A4 inhibitors will decrease the metabolic elimination of rimegepant and increase the risk of toxicity.

One study of 22 healthy volunteers demonstrated that coadministration of rimegepant as a single 75 mg dose with itraconazole 200 mg daily, a well-known strong CYP3A4 inhibitor, increased the serum concentrations of rimegepant significantly. Therefore, coadministration of Nurtec ODT with strong CYP3A4 inhibitors is considered contraindicated.

Concomitant consumption could result in an increased risk of adverse effects of the medication, including severe headache, confusion, slurred speech, loss of coordination, stiff muscles, and high fever. If an individual takes Nurtec and a strong CYP3A4 inhibitor concomitantly and begins to experience any unexpected or unusual side effects, it is recommended to call a poison control center or get immediate medical attention.

The maximum daily dose of Nurtec ODT is 75mg, the only dosage form available, so this interaction cannot be counteracted by trialing alternative doses. Zavzpret (zavegepant) is another member of the gepant medication class that still relies on the CYP3A4 metabolic pathway but to a lesser degree than Nurtec ODT; therefore, individuals on a strong CYP3A4 inhibitor needing a member of the CGRP inhibitor drug class may be better off with this medication, at least while the CYP3A4 inhibitor is warranted.

Examples of CYP3A4 inhibitors include:

CYP3A4 inducers

The opposite to CYP3A4 inhibitors, CYP3A4 inducers are also generally contraindicated to be coadministered with Nurtec as they may decrease the serum concentration of the active ingredient, rimegepant, resulting in a loss of clinical efficacy and possible migraine attacks.

Common CYP3A4 inhibitors include certain anticonvulsants and antimicrobials. While not studied directly in clinical trials, the pharmacokinetic study of 21 healthy volunteers showed that a single 75mg dose of rimegepant with rifampin, a strong CYP3A4 inducer, decreased the exposure of rimegepant by up to 80%.

The prescribing information for rimegepant states that coadministration with moderate to strong CYP3A4 inhibitors should be avoided. Patients on treatment with CYP3A4 inhibitors may best be managed with medications outside of the CGRP inhibitor drug class, such as with NSAIDs like ibuprofen, acetaminophen or some Triptans, like sumatriptan; if necessary to receive a medication in the same drug class, an individual may be better managed with Zavzpret (zavegepant) given a decreased dependence on the CYP3A4 metabolic pathway.

Examples of CYP3A4 inducers include:

P-glycoprotein (P-gp) inhibitors

P-glycoprotein (P-gp) is a protein embedded in cell membranes that transports substances, including drugs and toxins, out of cells. It is critical in protecting cells from harmful substances and is found in many tissues throughout the body. P-gp inhibitors can result in drug interactions when coadministered with other medications that depend on P-gp as part of their drug absorption and disposition, such as rimegepant.

Lasmiditan is a strong P-gp inhibitor that should not be taken concurrently with Nurtec as this will result in increased rimegepant blood levels and side effects of Nurtec ODT. A pharmacokinetic study described an increased exposure of rimegepant when administered with P-gp inhibitor cyclosporine or quinidine.

Prescribing information for rimegepant states to avoid taking a repeat dose of Nurtec ODT within 48 hours if given concomitantly with P-gp inhibitors. As all members of the gepant drug class are at least minor substrates of P-gp, the best management approach in those on medications considered P-go inhibitors requiring migraine therapy is to select a medication from an entirely different drug class.

Examples of P-gp inhibitors:

P-glycoprotein inducers

Many P-gp inducers are also CYP3A4 inducers and can similarly interact with Nurtec ODT by decreasing serum concentrations of the active ingredient, rimegepant. This may negate taking Nurtec ODT as a preventative medication and result in episodic migraines. Exceeding the daily dose to overcome this interaction is not recommended.

Examples of P-gp inducers:

Nurtec food interactions

Nurtec ODT administration under fed conditions delayed achieving a maximal serum concentration by 1 to 1.5 hours. A high-fat meal reduced the maximal concentration by 53%, while a low-fat meal only reduced it by 36%. In clinical trials, Nurtec ODT was administered without regard to food, so the clinical impact of the reduction in rimegepant concentrations and exposure due to administration with food is unknown.

Some supplements may play a beneficial role in migraine prophylaxis. Magnesium supplements have some evidence supporting the prevention of migraines by increasing mitochondrial function. Vitamin B2 (riboflavin) may also possibly be effective in migraine prevention based on several small clinical trials that have demonstrated that riboflavin reduces migraine frequency. Like magnesium, the mechanism of riboflavin’s benefit is assumed to be related to improved mitochondrial function. Coenzyme Q10 is another supplement deemed possibly effective in preventing migraines, again due to improved mitochondrial function.

Nurtec and grapefruit

Grapefruit juice is a known CYP3A4 inhibitor, so the guidance to avoid coadministration of Nurtec and CYP3A4 inhibitors should also apply to grapefruit juice consumption. As prescribing information for rimegepant recommends avoiding a second dose within 48 hours when used concomitantly with moderate to strong CYP3A4 inhibitors when managing an acute migraine, the same should hold true if the individual has consumed grapefruit juice. If grapefruit juice is regularly consumed, second doses of rimegepant within 48 hours should be avoided.

Other Nurtec interactions

Healthcare providers should consider special considerations for those with certain medical conditions, as described below.

Nurtec and concomitant medical conditions

Nurtec labeling outlines medical conditions in which it should be taken cautiously. Nurtec hasn’t been studied in patients with kidney problems like end-stage renal disease or in patients on dialysis. Therefore, the medication should be avoided in those with severe renal impairment. In individuals with severe liver problems, such as Child-Pugh C, rimegepant should be avoided as blood concentrations will be significantly higher than those without hepatic impairment or a lesser degree of impairment.

A pregnancy registry exists to monitor pregnancy outcomes in women exposed to Nurtec during pregnancy. There is not sufficient data on the developmental risk associated with the use of Nurtec in pregnant women to fully understand the impact on fetal development outside of limited animal data. Labeling for Nurtec also summarizes the risk of continuing Nurtec in those breastfeeding, stating a relative infant dose of less than 1% of the maternal weight-adjusted dose in breast milk. Therefore, the development and health benefits of breastfeeding should be weighed with the female’s clinical indication for Nurtec.

How to minimize Nurtec interactions

Always carry a complete list of medications, including supplements, on your person. Any time you’re inquiring about medical advice, provide this list so that a thorough review and drug information assessment can be performed to minimize the risk of drug interactions. Anytime you start a new medication, and new signs or symptoms arise, however mild they might be, it is best to review them with your healthcare professional. Also, be mindful of the possibility of allergic reactions, which may present as swelling of the face and require immediate medical intervention.

When to talk to a healthcare provider about Nurtec interactions

This article does not provide a complete list of Nurtec interactions. Be mindful of the risk of Nurtec when used in combination with prescription and over-the-counter medications. Communicate with a healthcare professional anytime you use Nurtec so that a comprehensive review of interactions can occur, including interference with known medication conditions, to ensure proper management and monitoring.