Risks associated with CAMZYOS

Risk of heart failure due to systolic dysfunction

A reduction in LVEF is an expected on-target effect of CAMZYOS. This LVEF effect is generally small (mean reduction of 4% in a pivotal Phase 3 trial of CAMZYOS [N=251]) and contributes to the efficacy of treatment with CAMZYOS. Some patients may see a decrease in their LVEF to <50% due to an excess medicinal effect of CAMZYOS, which may lead to heart failure.

Risk factors and groups

Patients with a serious intercurrent illness such as serious infection or arrhythmia (including atrial fibrillation or other uncontrolled tachyarrhythmia) or those undergoing major cardiac surgery may be at greater risk of developing systolic dysfunction and heart failure.

Risk mitigation

Assess patients presenting with signs and symptoms of systolic dysfunction, including new or worsening dyspnoea, chest pain, fatigue, palpitations, leg oedema or elevations in N-terminal pro hormone B-type natriuretic peptide (NT proBNP), and promptly evaluate cardiac function. Advise patients to report any signs or symptoms of heart failure (described above) immediately to their HCP or seek medical attention. Regular echocardiograms must be performed, as described in the Treatment and Dosing section of this website, in order to mitigate the risk of heart failure. Please see the Approved Summary of Product Characteristics for additional information. In the presence of intercurrent illnesses, such as infections or arrhythmias that may impair systolic function, dose increases are not recommended.

Risk of heart failure due to drug interactions with CYP2C19 inhibitors and moderate or strong CYP3A4 inhibitors

CAMZYOS is primarily metabolized by CYP2C19 and (to a lesser extent) CYP3A4. Coadministration or discontinuation of CYP2C19 inhibitors or moderate or strong CYP3A4 inhibitors may alter the plasma concentration of CAMZYOS. Starting or increasing the dose of any CYP2C19 inhibitor or a moderate or strong CYP3A4 inhibitor may increase the risk of heart failure due to systolic dysfunction; conversely, discontinuation or decreasing the dose of these inhibitor types may lead to loss of response to CAMZYOS.

Risk factors and groups

Patients treated with CYP2C19 inhibitors or moderate or strong CYP3A4 inhibitors.

Risk mitigation

HCPs should consider, prior to and throughout treatment, the potential for drug interactions involving CAMZYOS, including those arising from coadministration with over-the-counter medications (such as omeprazole or esomeprazole) and herbal supplements. Refer to Table 1 for guidance on CAMZYOS dose adjustment and LVEF monitoring recommendations when initiating or changing the dose of a CYP2C19 inhibitor or a moderate or strong CYP3A4 inhibitor.

Examples of CYP2C19 inhibitors and moderate/strong CYP3A4 inhibitors are shown in Table 2. Please be aware that this is not an exhaustive list of CYP2C19 inhibitors or moderate/strong CYP3A4 inhibitors nor their indications. Intermittent use of products that might interact with CAMZYOS, including prescription and over-the-counter medications, herbal supplements and grapefruit juice, is not recommended

Table 2: Examples of CYP2C19 inhibitors and moderate/strong CYP3A4 inhibitors

CYP=cytochrome P450; HIV=human immunodeficiency virus; OCD=obsessive compulsive disorder. Information adapted from the Food and Drug Administration, 2020; Park, 2003; Orlando, 2003; and the SmPC Section 4.5.

Inform the patient that they must consult their prescribing HCP and pharmacist prior to taking any new medications or herbal supplements, changing the dose or stopping any medications or herbal supplements they may currently be taking.

Embryo-foetal toxicity

CAMZYOS may cause embryo-foetal harm when administered to a pregnant patient based on pregnancy data from animal studies. There are no data on the use of CAMZYOS in pregnant patients. CAMZYOS should not be used during pregnancy.

Risk factors and groups

Pregnant patients and patients of childbearing potential not using effective contraception.

Risk mitigation

Prior to treatment initiation, confirm a negative pregnancy test in patients of childbearing potential. Inform the patient about the risk of embryo-foetal toxicity associated with CAMZYOS and counsel the patient on the need to avoid pregnancy. Recommend use of effective form of contraception during treatment and for 6 months after the last dose is administered. Please instruct the patient to inform you if they are pregnant or suspect they are pregnant immediately. If, at any point, a patient becomes pregnant while receiving CAMZYOS, inform the patient of the potential risk to the fetus.