Drug Interaction Report
3 potential interactions and/or warnings found for the following 2 drugs:
- zanubrutinib
- suzetrigine
Interactions between your drugs
zanubrutinib suzetrigine
Applies to: zanubrutinib, suzetrigine
MONITOR: Coadministration with inducers of CYP450 3A4 may decrease 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. Both suzetrigine and M6-SUZ are primarily metabolized by CYP450 3A4. When a single dose of suzetrigine was administered with the potent CYP450 3A4 inducer rifampin at steady state, mean suzetrigine peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 80% and 93%, respectively, while mean Cmax of M6-SUZ increased by 30% and AUC decreased by 85%. Coadministration with efavirenz, a moderate CYP450 3A4 inducer, is predicted to decrease the mean Cmax and AUC of suzetrigine by 29% and 63%, respectively, while the mean Cmax of M6-SUZ is predicted to increase by 30% and AUC to decrease by 60%. The interaction has not been studied with other, less potent CYP450 3A4 inducers.
MANAGEMENT: The potential for diminished pharmacologic effects of suzetrigine should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.
References (1)
- (2025) "Product Information. Journavx (suzetrigine)." Vertex Pharmaceuticals
Drug and food interactions
zanubrutinib food
Applies to: zanubrutinib
GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations of zanubrutinib. The proposed mechanism 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 zanubrutinib was administered with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) in clinical study subjects, zanubrutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 157% and 278%, respectively. Data derived from pharmacokinetic modeling have also been reported for several additional CYP450 3A4 inhibitors. For example, the potent CYP450 3A4 inhibitor clarithromycin (250 mg twice daily) is predicted to increase zanubrutinib Cmax and AUC by 175% and 183%, respectively. The moderate CYP450 3A4 inhibitor diltiazem (60 mg three times daily) is predicted to increase zanubrutinib Cmax and AUC by 151% and 157%, respectively. Another moderate CYP450 3A4 inhibitor, erythromycin (500 mg four times daily), is predicted to increase zanubrutinib Cmax and AUC by 284% and 317%, respectively. Likewise, fluconazole 200 mg once daily is predicted to increase zanubrutinib Cmax and AUC by 179% and 177%, respectively; while fluconazole 400 mg once daily is predicted to increase zanubrutinib Cmax and AUC by 270% and 284%, respectively. 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. Increased zanubrutinib exposure may potentiate the risk of toxicities such as hemorrhage, infection, cytopenias, malignancies, and serious cardiac arrhythmias (primarily atrial fibrillation and atrial flutter).
Food does not affect the oral bioavailability of zanubrutinib. No clinically significant differences in zanubrutinib Cmax or AUC were observed following administration of a high-fat meal (approximately 1000 calories; 50% from fat) in healthy subjects.
MANAGEMENT: Zanubrutinib may be administered with or without food. Patients should avoid consumption of grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during treatment with zanubrutinib.
References (3)
- (2023) "Product Information. Brukinsa (zanubrutinib)." BeiGene USA, Inc, SUPPL-7
- (2022) "Product Information. Brukinsa (zanubrutinib)." Innomar Strategies Inc.
- (2022) "Product Information. Brukinsa (zanubrutinib)." Beigene Aus Pty Ltd
suzetrigine food
Applies to: suzetrigine
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.
References (1)
- (2025) "Product Information. Journavx (suzetrigine)." Vertex Pharmaceuticals
Therapeutic duplication warnings
No duplication 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.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
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