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Drug Interactions between deferasirox and mavacamten

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

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Interactions between your drugs

Moderate

deferasirox mavacamten

Applies to: deferasirox and mavacamten

MONITOR: Coadministration with inducers of CYP450 2C19 and/or CYP450 3A4 may decrease the plasma concentrations of mavacamten. According to the prescribing information, mavacamten is primarily metabolized by CYP450 2C19 (74%) and to a lesser extent by CYP450 3A4 (18%) and 2C9 (8%). Concomitant use of a single dose of mavacamten (15 mg) with the potent CYP450 2C19 and 3A4 inducer rifampin (600 mg once daily) is predicted to decrease mavacamten peak plasma concentration (Cmax) and systemic exposure (AUC) by 22% and 87%, respectively, in CYP450 2C19 normal metabolizers, and by 4% and 69%, respectively, in CYP450 2C19 poor metabolizers. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of mavacamten should be considered during coadministration with CYP450 2C19 and/or 3A4 inducers. Alternative treatments may be required if an interaction is suspected. Because mavacamten reduces systolic contraction and left ventricular ejection fraction, the risk of heart failure due to systolic dysfunction may increase following discontinuation of CYP450 inducers as the levels of induced enzymes normalize. It may be advisable to follow up with clinical and echocardiographic assessments.

References

  1. (2022) "Product Information. Camzyos (mavacamten)." MyoKardia Inc
  2. (2023) "Product Information. Camzyos (mavacamten)." Bristol-Myers Squibb Australia Pty Ltd, 2

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Drug and food interactions

Major

mavacamten food

Applies to: mavacamten

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mavacamten. 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. According to the prescribing information, mavacamten is primarily metabolized by CYP450 2C19 (74%) and to a lesser extent by CYP450 3A4 (18%) and 2C9 (8%). When mavacamten (25 mg) was coadministered with the moderate CYP450 3A4 inhibitor verapamil (sustained-release 240 mg) in intermediate and normal metabolizers of CYP450 2C19, mavacamten systemic exposure (AUC) increased by 15% and peak plasma concentration (Cmax) increased by 52%. Concomitant use of mavacamten with diltiazem, another moderate CYP450 3A4 inhibitor, in CYP450 2C19 poor metabolizers is predicted to increase mavacamten AUC and Cmax by up to 55% and 42%, respectively. Concomitant use of mavacamten (15 mg) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily) is predicted to increase mavacamten AUC and Cmax by up to 130% and 90%, respectively. Because mavacamten reduces systolic contraction and left ventricular ejection fraction, increased exposure may potentiate the risk of heart failure. 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.

Food does not affect the extent of absorption of mavacamten. No clinically significant difference in mavacamten exposure was observed following administration with a high-fat meal. However, the time to reach peak plasma concentration (Tmax) was increased by 4 hours.

MANAGEMENT: Mavacamten may be administered with or without food. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with mavacamten.

References

  1. (2022) "Product Information. Camzyos (mavacamten)." MyoKardia Inc
  2. (2023) "Product Information. Camzyos (mavacamten)." Bristol-Myers Squibb Australia Pty Ltd, 2

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Moderate

deferasirox food

Applies to: deferasirox

ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.

References

  1. (2005) "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals

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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.