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Drug Interaction Report

2 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

treosulfan zanubrutinib

Applies to: treosulfan, zanubrutinib

MONITOR: Coadministration with treosulfan may increase the plasma concentrations of drugs that are substrates of CYP450 3A4, 2C19, and/or the efflux transporter P-glycoprotein (P-gp). The proposed mechanism is decreased clearance due to inhibition of these routes of elimination due to treosulfan. According to physiologically-based pharmacokinetic modeling, treosulfan is predicted to be a weak to moderate CYP450 3A4 inhibitor and weak inhibitor of CYP450 2C19, with negligible inhibitory effects on P-gp. However, according to the manufacturer, in vitro studies were unable to exclude potential drug-drug interactions with high plasma concentrations of treosulfan and CYP450 3A4, 2C19, and/or P-gp substrates.

MANAGEMENT: Caution is recommended if treosulfan is coadministered with substrates of CYP450 3A4, 2C19, and/or P-gp, particularly those with a narrow therapeutic range. Some authorities advise that if concomitant use is required, the dosage of these substrates should be administered either 2 hours before or 8 hours after administration of the treosulfan infusion. The prescribing information of the substrates may be consulted for potential dose reductions.

References (4)
  1. (2021) "Product Information. Trecondyv (treosulfan)." Medexus Pharmaceuticals Inc.
  2. (2022) "Product Information. Trecondi (treosulfan)." Link Medical Products Pty Ltd T/A Link Pharmaceuticals, 1
  3. (2021) "Product Information. Trecondi (treosulfan)." medac UK
  4. (2025) "Product Information. Grafapex (treosulfan)." Medexus pharma Inc

Drug and food interactions

Major

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)
  1. (2023) "Product Information. Brukinsa (zanubrutinib)." BeiGene USA, Inc, SUPPL-7
  2. (2022) "Product Information. Brukinsa (zanubrutinib)." Innomar Strategies Inc.
  3. (2022) "Product Information. Brukinsa (zanubrutinib)." Beigene Aus Pty Ltd

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.


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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.

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Further information

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