Drug Interactions between Focinvez and zanubrutinib
This report displays the potential drug interactions for the following 2 drugs:
- Focinvez (fosaprepitant)
- zanubrutinib
Interactions between your drugs
fosaprepitant zanubrutinib
Applies to: Focinvez (fosaprepitant) and zanubrutinib
ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of zanubrutinib, which is primarily metabolized by the isoenzyme. Based on pharmacokinetic modeling, the moderate CYP450 3A4 inhibitor diltiazem (60 mg three times daily) is predicted to increase zanubrutinib peak plasma concentration (Cmax) and systemic exposure (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. 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. 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).
MANAGEMENT: The manufacturer recommends reducing the dosage of zanubrutinib to 80 mg twice daily when coadministered with moderate CYP450 3A4 inhibitors. Patients should be closely monitored for development of zanubrutinib-related toxicities, and further dosage adjustments made or treatment withheld as needed in accordance with the product labeling. Following discontinuation of the CYP450 3A4 inhibitor, the previous dosage of zanubrutinib should be resumed.
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
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
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.
See also
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. |
Further information
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