oHCM Regional Summit

• This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

CAMZYOS 2,5 mg hard capsules, CAMZYOS 5 mg hard capsules, CAMZYOS 10 mg hard capsules, CAMZYOS 15 mg hard capsules (mavacamten)
Refer to the Summary of Product Characteristics (SmPC) before prescribing.
COMPOSITION: Each capsule contains 2,5 mg, 5 mg, 10 mg or 15 mg of mavacamten. INDICATIONS: CAMZYOS is indicated for the treatment of symptomatic (NYHA, class II‑III) obstructive hypertrophic cardiomyopathy (oHCM) in adult patients. POSOLOGY AND METHOD OF ADMINISTRATION: Treatment should be initiated under the supervision of a physician experienced in the management of patients with cardiomyopathy. Before treatment initiation, patients’ left ventricular ejection fraction (LVEF) should be assessed by echocardiography. If LVEF is < 55%, treatment should not be initiated. Before initiation of treatment, women of childbearing potential must have a negative pregnancy test. Patients should be genotyped for Cytochrome P450 (CYP) 2C19 (CYP2C19) in order to determine appropriate mavacamten dose. Patients with CYP2C19 poor metaboliser phenotype may have increased mavacamten exposures (up to 3 times) that can lead to increased risk of systolic dysfunction compared to normal metabolisers. If treatment initiation occurs prior to determination of CYP2C19 phenotype, patients should follow dosing instructions for poor metabolisers until CYP2C19 phenotype is determined. Posology: The dose range is 2,5−15 mg. CYP2C19 poor metaboliser phenotype: The recommended starting dose is 2.5 mg orally once daily. The maximum dose is 5 mg once daily. The patient should be assessed for early clinical response by left ventricular outflow tract (LVOT) gradient with Valsalva manoeuvre 4 and 8 weeks after treatment initiation. CYP2C19 intermediate, normal, rapid and ultra‑rapid metaboliser phenotype: The recommended starting dose is 5 mg orally once daily. The maximum dose is 15 mg once daily. The patient should be assessed for early clinical response by LVOT gradient with Valsalva manoeuvre 4 and 8 weeks after treatment initiation. Once an individualised maintenance dose is achieved with LVEF ≥ 55%, patients should be assessed every 6 months. For patients with LVEF 50 - < 55% regardless of Valsalva LVOT gradient, patients should be assessed every 3 months. If patient’s LVEF is < 50%, the treatment should be interrupted for 4 weeks and until LVEF returns to ≥ 50%. In patients experiencing an intercurrent illness such as serious infection or arrhythmia, which may impair systolic function, LVEF assessment is recommended, and dose increases are not recommended until intercurrent illness is resolved. Consideration should be given to discontinue treatment in patients who have shown no response after 4‑6 months on the maximum tolerated dose. Dose modification with concomitant medicinal products: For concomitant treatment with inhibitors and inducers of CYP2C19 or CYP3A4, follow the steps listed in SmPC. Missed or delayed doses: If a dose is missed, it should be taken as soon as possible, and the next scheduled dose should be taken at the usual time the following day. 2 doses should not be taken on the same day. Elderly: No dose adjustment is required for patients aged 65 years and older. Renal impairment: No dose adjustment is required for patients with mild to moderate renal impairment. No dose recommendation can be made for patients with severe renal impairment. Hepatic impairment: The mavacamten starting dose should be 2.5 mg in all patients with mild and moderate hepatic impairment. No dose recommendation can be made for patients with severe hepatic impairment. Method of administration: For oral use. Treatment should be taken once daily with or without meals at about the same time each day. The capsule should be swallowed whole with water. CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients. 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. SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Systolic dysfunction defined as symptomatic LVEF < 50%: Mavacamten reduces LVEF and may cause heart failure due to systolic dysfunction defined as symptomatic LVEF < 50%. Patients with a serious intercurrent illness such as infection or arrhythmia, 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 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%. Heart failure risk or loss of response to mavacamten due to interactions: Mavacamten 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/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/CYP2C19 may lead to a loss of therapeutic response to mavacamten; - Starting a strong CYP3A4/strong CYP2C19 inducer may lead to a loss of therapeutic response to mavacamten; - Stopping a strong CYP3A4/strong CYP2C19 inducer may increase risk of heart failure due to systolic dysfunction. Prior to and during mavacamten treatment, the potential for interactions, including over the counter medicinal products, should be considered. Dose adjustment of mavacamten 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/CYP3A4. Intermittent administration of these medicinal products is not recommended. 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. 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. 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. 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 SmPC. For information on dose modifications/monitoring of mavacamten with concomitant medicinal products, refer to the SmPC. Effect of mavacamten on other medicinal products: Mavacamten in vitro data suggest a potential induction of CYP3A4. Pregnancy and lactation: Women of childbearing potential/contraception in females: CAMZYOS is contraindicated in women of childbearing potential not using effective contraception. Therefore, before initiation of treatment in women of childbearing potential, a negative pregnancy test result must be available, and counselling should be provided regarding the serious risk to the foetus. Women of childbearing potential must use effective contraception during treatment and for 6 months after discontinuation of CAMZYOS, since it takes approximately 5 half‑lives to eliminate mavacamten from the body after treatment discontinuation. When stopping mavacamten therapy for planning a pregnancy the possible return of LVOT obstruction and symptom burden should be considered. Pregnancy: CAMZYOS is contraindicated during pregnancy. CAMZYOS should be stopped 6 months before planning a pregnancy. If a patient becomes pregnant, mavacamten must be discontinued. Medical advice should be given regarding the risk of harmful effects to the foetus associated with treatment and ultrasonography examinations should be performed. Breast-feeding: Women must not breast-feed during treatment with mavacamten. Effects on ability to drive and use machines: Mavacamten has minor influence on the ability to drive and use machines. Dizziness may occur during use of mavacamten. Patients should be advised not to drive or use machines if they experience dizziness. UNDESIRABLE EFFECTS: Adverse reactions reported in 2 phase 3 studies (EXPLORER-HCM and VALOR-HCM) are: very common: dizziness, dyspnoea; common: systolic dysfunction, syncope. For a more detailed description of selected adverse reactions, refer to the SmPC.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via
Agency for Medicinal Products and Medical Devices of the Republic of Slovenia, Pharmacovigilance Department, National Centre for Pharmacovigilance, Slovenčeva ulica 22, SI-1000 Ljubljana, Tel: +386 (0)8 2000 500, Fax: +386 (0)8 2000 510, e-mail: h-farmakovigilanca@jazmp.si, web page: www.jazmp.si.
Pack size: box with 28 capsules. MARKETING AUTHORISATION HOLDER: Bristol-Myers Squibb Pharma EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland. Regimen of dispensing: Rp/Spec. Date of preparation: 06-2025

Reference: Camzyos Summary of product characteristics, May 2025