Camzyos Drug Interactions

Pharmacodynamic interactions: If treatment with a new negative inotrope is initiated or if the dose of a negative inotrope is increased in a patient receiving mavacamten, close medical supervision with monitoring of LVEF should be provided until stable doses and clinical response have been achieved (see Dosage & Administration and Precautions).
Pharmacokinetic interactions: Effect of other medicinal products on mavacamten: In CYP2C19 intermediate, normal, rapid and ultra-rapid metabolisers, mavacamten is primarily metabolised by CYP2C19 and to a lesser extent by CYP3A4. In CYP2C19 poor metabolisers, metabolism is mostly by CYP3A4 (see Pharmacology: Pharmacokinetics under Actions). CYP2C19 inhibitors/inducers and CYP3A4 inhibitors/inducers may thus affect the clearance of mavacamten and increase/decrease mavacamten plasma concentration, and this will depend on the CYP2C19 phenotype.
All clinical drug-drug interaction studies mainly enrolled CYP2C19 normal metabolisers and no CYP2C19 poor metabolisers were included in the assessment of the drug-drug interaction and therefore the effect of co-administration of CYP2C19 and CYP3A4 inhibitors with mavacamten in CYP2C19 poor metabolisers is not completely certain.
Recommendations for dose modification and/or additional monitoring of patients initiating or discontinuing treatment with, or changing the dose of, concomitant medicinal products that are inhibitors of CYP2C19 or CYP3A4 or inducers of CYP2C19 or CYP3A4 are provided in Table 6. (See Table 6.)
Strong CYP2C19 plus strong CYP3A4 inhibitors: Co-administration of mavacamten with the combination of a strong CYP2C19 and a strong CYP3A4 inhibitor is contra-indicated (see Contraindications).
CYP2C19 inhibitors: The effect of a moderate and strong CYP2C19 inhibitor on the PK of mavacamten was not investigated in a clinical drug-drug interaction study. The effect of a strong CYP2C19 inhibitor (e.g., ticlopidine) will be similar to the effect of the CYP2C19 poor metabolising status (see Table 4).
Co-administration of mavacamten with a weak CYP2C19 inhibitor (omeprazole) resulted in a 48% increase in mavacamten AUC_inf with no effect on C_max in CYP2C19 normal metabolisers.
Intermittent administration of a CYP2C19 inhibitor (such as omeprazole or esomeprazole) is not recommended (see Precautions).
CYP3A4 inhibitors: Co-administration of mavacamten with a strong CYP3A4 inhibitor (itraconazole) in CYP2C19 normal metabolisers resulted in an increase in mavacamten plasma concentration of up to 59% and 40% in AUC_0-24 and C_max, respectively.
Co-administration of mavacamten with a moderate CYP3A4 inhibitor (verapamil) in CYP2C19 normal metabolisers resulted in an increase in mavacamten plasma concentration of 16% and 52% in AUC_inf and C_max, respectively. This change was not considered clinically significant.
CYP2C19 and CYP3A4 inducers: No clinical interaction studies were conducted to investigate the effect of concomitant administration with a strong CYP3A4 and CYP2C19 inducer. Co-administration of mavacamten with a strong inducer of both CYP2C19 and CYP3A4 (e.g., rifampicin) is expected to significantly affect the pharmacokinetics (PK) of mavacamten and leads to reduced efficacy and therefore co-administration with strong inducers of both CYP2C19 and CYP3A4 is not recommended. If discontinuing concomitant treatment with a strong inducer of CYP2C19 or CYP3A4 increase clinical assessments and mavacamten dose should be reduced (see Dosage & Administration).

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Effect of mavacamten on other medicinal products: Mavacamten in vitro data suggest a potential induction of CYP3A4 substrates. Co-administration of a 17-day course of mavacamten at clinical relevant exposures in CYP2C19 normal, rapid and ultra-rapid metabolisers did not decrease the exposure to ethinyl oestradiol and norethindrone, which are the components of typical oral contraceptives and substrates for CYP3A4. Furthermore, co-administration of a 16-day course of mavacamten in CYP2C19 normal metabolisers, at clinical relevant exposures, resulted in a 13% decrease in midazolam plasma concentration. This change was not considered clinically significant.