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Drug Interactions between larotrectinib and quizartinib

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

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Interactions between your drugs

Minor

larotrectinib quizartinib

Applies to: larotrectinib and quizartinib

Coadministration with mild or moderate inhibitors of CYP450 3A4 is not expected to have clinically significant effects on the pharmacokinetics of quizartinib or its major circulating active metabolite, AC886. According to the prescribing information, quizartinib is primarily metabolized via oxidation by CYP450 3A4/5 in vitro, and AC886 is formed and metabolized by CYP450 3A4/5. Following coadministration of a single 53 mg dose of quizartinib with ketoconazole, a potent CYP450 3A4 inhibitor, quizartinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 17% and 94%, respectively, while the Cmax and AUC of AC886 decreased by 60% and 94%, respectively. By contrast, clinically significant changes in the Cmax and AUC of quizartinib and AC886 were not observed following coadministration of single-dose quizartinib with fluconazole, a moderate CYP450 3A4 inhibitor. Therefore, no dosage adjustments are recommended when quizartinib is coadministered with mild and moderate CYP450 3A4 inhibitors.

References (1)
  1. (2023) "Product Information. Vanflyta (quizartinib)." Daiichi Sankyo, Inc.

Drug and food interactions

Moderate

larotrectinib food

Applies to: larotrectinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of larotrectinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of larotrectinib by certain compounds present in grapefruit. When a single 100 mg dose of larotrectinib was coadministered with itraconazole, a potent CYP450 3A4 inhibitor, larotrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 4.3-fold, respectively, compared to administration of larotrectinib alone. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (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 exposure to larotrectinib may increase the risk of adverse effects such as neurotoxicity (delirium, dysarthria, dizziness, gait disturbance, paraesthesia, encephalopathy, memory impairment, tremor) and hepatotoxicity (elevations in liver transaminases).

Food does not alter the pharmacokinetics of larotrectinib to a clinically significant extent. When a single 100 mg dose of larotrectinib was administered with a high-fat meal (approximately 900 calories; 58 g carbohydrate, 56 g fat, 43 g protein) in healthy study subjects, larotrectinib peak plasma concentration (Cmax) was reduced by 35% while systemic exposure (AUC) was similar compared to administration in the fasted state.

MANAGEMENT: Larotrectinib may be taken with or without food. Patients should avoid the consumption of grapefruit and grapefruit juice during treatment.

References (1)
  1. (2018) "Product Information. Vitrakvi (larotrectinib)." Bayer Pharmaceutical Inc

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Multikinase inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

  • larotrectinib
  • quizartinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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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.

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