Basic Information
ID DDInter2009 and DDInter1347
Interaction Coadministration with inhibitors of CYP450 2C19 or CYP450 3A4 may increase the plasma concentrations of mavacamten.
Management The prescribing information suggests initiating mavacamten at the recommended starting dosage of 5 mg orally once daily in patients who are on stable therapy with a weak CYP450 2C19 inhibitor or a moderate CYP450 3A4 inhibitor. Conversely, when initiating the inhibitor in patients already receiving mavacamten, the prescribing information recommends reducing the dosage of mavacamten by one level (i.e., 15 to 10 mg; 10 to 5 mg; or 5 to 2.5 mg) and scheduling a clinical and echocardiographic assessment 4 weeks after inhibitor initiation. The dosage of mavacamten should not be titrated upwards until 12 weeks after inhibitor initiation. In patients who are on stable treatment with mavacamten 2.5 mg once daily, initiation of concomitant weak CYP450 2C19 or moderate CYP450 3A4 inhibitors should be avoided because a lower dose of mavacamten is not available.
References [1] "Product Information. Camzyos (mavacamten)." MyoKardia Inc (2022):
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.