CAMZYOS (mavacamten) important safety information¹

• Hypersensitivity to the active substance or to any of its excipients listed in section 6.1 of the SmPC
• During pregnancy and in women of childbearing potential not using effective contraception*
• Concomitant treatment with strong CYP3A4 inhibitors in patients with CYP2C19 poor metaboliser phenotype and undetermined CYP2C19 phenotype^†
• Concomitant treatment with the combination of a strong CYP2C19 inhibitor and a strong CYP3A4 inhibitor^†

*Please refer to Sections 4.4 and 4.6 in the CAMZYOS Summary of Product Characteristics for further information on the use of CAMZYOS during pregnancy and in women of childbearing potential.^1
†Please refer to Sections 4.2, 4.4 and 4.5 in the CAMZYOS Summary of Product Characteristics for further information on drug interactions with CAMZYOS.¹

CAMZYOS reduces LVEF and may cause heart failure due to systolic dysfunction. Patients with a serious intercurrent illness such as infection or arrhythmia (including atrial fibrillation or other uncontrolled tachyarrhythmia) or those undergoing major cardiac surgery may be at greater risk of systolic dysfunction and progress to heart failure. New or worsening dyspnoea, chest pain, fatigue, palpitations, leg oedema or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of systolic dysfunction and should prompt an evaluation of cardiac function. LVEF should be measured prior to initiating treatment and closely monitored thereafter. Treatment interruption may be necessary to ensure that LVEF remains ≥50%.

CAMZYOS is primarily metabolised by CYP2C19 and to a lesser extent by CYP3A4 and mostly by CYP3A4 in CYP2C19 poor metabolisers, which may lead to the following interactions:

• Starting or increasing the dose of a strong or moderate CYP3A4 inhibitor or any CYP2C19 inhibitor may increase risk of heart failure due to systolic dysfunction
• Stopping or decreasing dose of any inhibitor of CYP3A4 or CYP2C19 may lead to a loss of  therapeutic response to CAMZYOS
• Starting a strong CYP3A4 or strong CYP2C19 inducer may lead to a loss of therapeutic response to CAMZYOS
• Stopping a strong CYP3A4 or strong CYP2C19 inducer may increase risk of heart failure due to systolic dysfunction

Prior to and during CAMZYOS treatment, the potential for interactions, including over the counter medicinal products (such as omeprazole or esomeprazole), should be considered. Dose adjustment of CAMZYOS and/or close monitoring may be required in patients initiating or discontinuing treatment with, or changing the dose of concomitant medicinal products that are inhibitors or inducers of CYP2C19 or CYP3A4. Intermittent administration of these medicinal products is not recommended.

The safety of concomitant use of CAMZYOS with disopyramide, or use of CAMZYOS in patients taking beta blockers in combination with verapamil or diltiazem has not been established. Therefore, patients should be closely monitored when taking these concomitant medicinal products.

CAMZYOS is suspected to cause embryo-foetal toxicity when administered to a pregnant woman based on animal studies. Due to risk to the foetus, CAMZYOS is contraindicated during pregnancy and in women of childbearing potential not using effective contraception. Before initiation of treatment, women of childbearing potential must be informed of this risk to the foetus, must have a negative pregnancy test and must use effective contraception during treatment and for 6 months after treatment discontinuation.