Advice for healthcare professionals:
- cases of cardiac arrest, cardiac failure, and myocardial infarction, including fatal cases, have been reported in patients receiving anti-cancer therapy with carfilzomib – not all cases occurred in patients with a pre-existing cardiac disorder
- monitor patients for signs and symptoms of cardiac disorders before and during treatment with carfilzomib
- stop carfilzomib if severe or life-threatening cardiac events occur; restarting treatment may be considered at a lower dose once the condition is controlled and the patient is functionally stable
- report any suspected adverse drug reactions (ADR) associated with carfilzomib via the Yellow Card Scheme
Reminder of risk of cardiac events with carfilzomib
Carfilzomib is indicated in combination with either lenalidomide and dexamethasone or dexamethasone alone for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy.
Carfilzomib has been associated with new or worsening cardiac failure, decreased ejection fraction, pericarditis, atrial fibrillation, tachycardia, myocardial ischaemia, and myocardial infarction – see section 4.4 of the Summary of Product Characteristics. Death due to cardiac arrest has occurred within a day of carfilzomib administration and fatal outcomes have also been reported following cardiac failure and myocardial infarction.
MHRA recently received a report from a Coroner following death by cardiac arrest of a man given carfilzomib, cyclophosphamide, and dexamethasone in a clinical trial. The Pharmacovigilance Expert Advisory Committee of the Commission on Human Medicines considered the safety profile for carfilzomib and risks of cardiac reactions. The Committee advised that warnings about risks in the product information of carfilzomib are clear but emphasised the need for prescribers to be reminded of the risk.
UK suspected adverse drug reactions
In 2018, approximately 22,000 vials of carfilzomib were dispensed in the UK, making the estimated UK exposure since launch about 84,000 vials.
Since 2013 and up to July 2019, 5 cases of cardiac failure, 5 of arrhythmia, 3 of cardiac arrest, 2 of pericarditis, 2 of left ventricular failure, and 5 of myocardial infarction, of which 6 were fatal (including the Coroner’s case), have been reported in the UK in post-marketing settings and in clinical trials in patients administered carfilzomib. Some of the patients in these cases did not report pre-existing cardiac disorders.
Reminder of advice to minimise risk
The risk of cardiac failure with carfilzomib is increased in elderly patients (those aged 75 years and older) and in Asian patients.
Although adequate hydration is required before starting treatment (see Summary of Product Characteristics), all patients should be monitored for evidence of volume overload, especially patients at risk of cardiac failure.
Patients with marked or severe cardiac failure (New York Heart Association [NYHA] Class III and IV), recent history of myocardial infarction (in the last 4 months), and patients with uncontrolled angina or arrhythmias should have a comprehensive medical assessment before starting treatment with carfilzomib. Particular attention should be given to the control of blood pressure and fluid management and patients should remain under close follow-up during treatment.
Stop carfilzomib if severe or life-threatening cardiac events occur. Restarting of treatment may be considered at a lower dose once the condition is controlled and the patient is functionally stable.
Pulmonary hypertension has also been reported in patients treated with carfilzomib and patients should be evaluated as appropriate.
Report adverse drug reactions on a Yellow Card
Carfilzomib is subject to additional monitoring. Healthcare professionals are asked to report any suspected adverse drug reactions (ADRs) to drugs under additional monitoring to the Yellow Card Scheme.
It is easiest and quickest to report ADRs online via the Yellow Cards website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.
Article citation: Drug Safety Update volume 13, issue 1: August 2019: 3.