CAMZYOS (mavacamten) interactions with other
medicinal products1
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 CAMZYOS, close medical supervision with monitoring of LVEF should be provided until stable doses and clinical response have been achieved.
Pharmacokinetic interactions
Effect of other medicinal products on CAMZYOS
In CYP2C19 intermediate, normal, rapid and ultra-rapid metabolisers, CAMZYOS is primarily metabolised by CYP2C19 and to a lesser extent by CYP3A4. In CYP2C19 poor metabolisers, metabolism is mostly by CYP3A4. CYP2C19 inhibitors/inducers and CYP3A4 inhibitors/inducers may thus affect the clearance of CAMZYOS and increase/decrease CAMZYOS 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 CAMZYOS in CYP2C19 poor metabolisers is not completely certain.
Strong CYP2C19 plus strong CYP3A4 inhibitors
Co-administration of CAMZYOS with the combination of a strong CYP2C19 and a strong CYP3A4 inhibitor is contraindicated.
CYP2C19 inhibitors
The effect of a moderate and strong CYP2C19 inhibitor on the PK of CAMZYOS 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.
Co-administration of CAMZYOS with a weak CYP2C19 inhibitor (omeprazole) resulted in a 48% increase in CAMZYOS AUCinf with no effect on Cmax in CYP2C19 normal metabolisers.
Intermittent administration of a CYP2C19 inhibitor (such as omeprazole or esomeprazole) is not recommended.
CYP3A4 inhibitors
Co-administration of CAMZYOS with a strong CYP3A4 inhibitor (itraconazole) in CYP2C19 normal metabolisers resulted in an increase in CAMZYOS plasma concentration of up to 59% and 40% in AUC0-24 and Cmax, respectively.
Co-administration of CAMZYOS with a moderate CYP3A4 inhibitor (verapamil) in CYP2C19 normal metabolisers resulted in an increase in CAMZYOS plasma concentration of 16% and 52% in AUCinf and Cmax, 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 CAMZYOS with a strong inducer of both CYP2C19 and CYP3A4 (e.g., rifampicin) is expected to significantly affect the PK of CAMZYOS 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 CAMZYOS dose should be reduced.
Effect of CAMZYOS on other medicinal products
CAMZYOS in vitro data suggest a potential induction of CYP3A4 substrates. Co-administration of a 17-day course of CAMZYOS 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 CAMZYOS in CYP2C19 normal metabolisers, at clinical relevant exposures, resulted in a 13% decrease in midazolam plasma concentration. This change was not considered clinically significant.
Please refer to Sections 4.2 and 4.5 of the CAMZYOS Summary of Product Characteristics for further information
on dose modification/monitoring of CAMZYOS with concomitant medicinal products
Please refer to the CAMZYOS Summary of Product Characteristics for further information on dosing, initiation and safety.
LVEF, left ventricular ejection fraction; PK, pharmacokinetics.
