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 dyspnea, chest pain, fatigue, palpitations, leg edema 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 TFDA-approved package insert 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 or decreased response due to drug interactions

CAMZYOS is primarily metabolized by CYP2C19 and secondarily by CYP3A4 and mostly by CYP3A4 in CYP2C19 poor metabolizers, 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.

• Concomitant treatment with strong CYP3A4 inhibitors in patients with CYP2C19 poor metabolizer phenotype and undetermined CYP2C19 phenotype is contraindicated.
• Concomitant treatment with the combination of a strong CYP2C19 inhibitor and a strong CYP3A4 inhibitor is contraindicated.
• 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.

Risk factors and groups

Patients treated with CYP2C19 or CYP3A4 inhibitors, or CYP2C19 or CYP3A4 inducers.

Risk mitigation

Prior to and throughout treatment, the potential for drug interactions involving CAMZYOS should be considered, 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 or CYP3A4 inhibitor or a CYP2C19 or CYP3A4 inducer.

Examples of CYP2C19 and CYP3A4 inhibitors and CYP2C19 and CYP3A4 inducers are shown in Table 2. Please be aware that this is not an exhaustive list of CYP2C19 or CYP3A4 inhibitors or CYP2C19 or CYP3A4 inducers nor their indications, and please refer to the sections on drug interactions, dosing and administration in the packaging insert for more information. 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

Omeprazole is considered a weak CYP2C19 inhibitor at a dose of 20 mg once daily and a moderate CYP2C19 inhibitor at a total daily dose of 40 mg

CYP=cytochrome P450; HIV=human immunodeficiency virus; OCD=obsessive compulsive disorder. Information adapted from the Food and Drug Administration, 2020; Park, 2003; and Orlando, 2003. Please refer to the relevant sections on interactions, and dosing and administration in the package insert for complete information.

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-fetal toxicity

CAMZYOS may cause embryo-fetal 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 highly 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-fetal toxicity associated with CAMZYOS and counsel the patient on the need to avoid pregnancy. Recommend use of a highly effective form of contraception during treatment and for at least 4 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.