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Drug Interactions between capivasertib and suzetrigine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

capivasertib suzetrigine

Applies to: capivasertib and suzetrigine

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of capivasertib. The proposed mechanism is accelerated clearance of capivasertib due to induction of the CYP450 3A4 isoenzyme, which is the primary route of elimination of capivasertib. Based on clinical studies and model-informed approaches, concomitant use with the potent CYP450 3A4 inducer rifampin is predicted to decrease capivasertib systemic exposure (AUC) by 70% and peak plasma concentration (Cmax) by 60%. Coadministration with the moderate CYP450 3A4 inducer efavirenz, is predicted to decrease capivasertib AUC and Cmax by 60% and 50%, respectively. Data for other, less potent CYP450 3A4 inducers are not available.

MANAGEMENT: Caution and monitoring for reduced therapeutic efficacy are recommended if capivasertib is administered with CYP450 3A4 inducers.

Drug and food interactions

Major

capivasertib food

Applies to: capivasertib

Consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit should be avoided during treatment with capivasertib as they may increase the blood levels of capivasertib. This may increase the risk of side effects such as high blood sugar levels, diarrhea, skin reactions, nausea, vomiting, tiredness, and changes in certain blood tests. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Major

suzetrigine food

Applies to: suzetrigine

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations of suzetrigine and M6-SUZ, a major active metabolite whose systemic exposure (AUC) at steady state is approximately 3 times that of the parent drug but exhibits 3.7-fold less potency in blocking the NaV1.8 voltage-gated sodium channels responsible for transmission of pain signals to the spinal cord and brain. The proposed mechanism for the interaction is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When a single dose of suzetrigine was administered with itraconazole, a potent CYP450 3A4 inhibitor, mean suzetrigine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.5- and 4.8-fold, respectively, while mean Cmax of M6-SUZ decreased by 32% and AUC increased by 4.4-fold. Coadministration of fluconazole, a moderate CYP450 3A4 inhibitor, with suzetrigine dosed according to the manufacturer's recommended dosage modification is predicted to increase the mean Cmax and AUC of suzetrigine by 1.4- and 1.5-fold, respectively, while the mean Cmax and AUC of M6-SUZ are predicted to increase by 1.1- and 1.2-fold, respectively, compared to suzetrigine administered at the regular recommended dosage without fluconazole. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

ADJUST DOSE INTERVAL: Food may delay the absorption of suzetrigine without impacting the overall systemic exposures to parent drug and M6-SUZ. Administration of suzetrigine 100 mg (the first dose) with a high-fat meal (800 to 1000 calories; 50% from fat), a moderate-fat meal (600 calories; 30% from fat), and a low-fat meal (<=500 calories; <=25% from fat) resulted in decreased initial plasma concentrations of suzetrigine and M6-SUZ compared to administration in a fasted state. The median time to reach peak plasma concentration (Tmax) for suzetrigine and M6-SUZ when administered with either a high-fat or moderate-fat meal was 5 hours and 24 hours, respectively, versus 3 hours and 8 to 10 hours, respectively, when administered in the fasted state. The Cmax and AUC of suzetrigine and M6-SUZ were not affected by any of the meal conditions, including a high-fat meal consumed one hour after suzetrigine. Administration of the second suzetrigine dose of 50 mg with or without regard to meals is also predicted to have no effect on the systemic exposures of suzetrigine and M6-SUZ.

MANAGEMENT: Patients should avoid consumption of foods or drinks containing grapefruit during treatment with suzetrigine. The starting dose of 100 mg should be taken on an empty stomach at least 1 hour before or 2 hours after food, although clear liquids (e.g., water, apple juice, vegetable broth, tea, black coffee) may be consumed during this time. Subsequent doses may be taken with or without food.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.