Published: May 2003
Publications
Clozapine and Cardiac Safety: Updated Advice for Prescribers
Information on this subject has been updated. Read the most recent information.
Prescriber Update 24(1): 13
May 2003
Committee on Safety of Medicines, and Medicines Control Agency, United Kingdom
Reprinted from Current Problems in Pharmacovigilance 2002;28:8 with permission from the Medicines Control Agency, London, United Kingdom.
Patients who develop clozapine-induced myocarditis
or cardiomyopathy should not be re-exposed to clozapine.
Key information for prescribers
Patients who develop clozapine-induced myocarditis or cardiomyopathy should not be re-exposed to clozapine.
Clozapine is an atypical antipsychotic agent contraindicated in patients with severe cardiac disorders. An increased incidence of myocardial disease in clozapine users has been recognised for some years and information for prescribers has been updated accordingly. A recent re-evaluation of serious adverse cardiac events in association with use of clozapine has resulted in a strengthening of these warnings.
Before starting clozapine therapy, patients are required undergo a history and physical examination. Patients with a history of cardiac illness or abnormal cardiac findings on physical examination should be referred to a specialist for other examinations that might include an ECG and echocardiogram, and clozapine should only be initiated if severe heart disease is excluded and the benefits of treatment are considered to clearly outweigh the risks. The prescribing doctor should consider performing a pre-treatment ECG to allow comparisons if symptoms develop later.
Rare cases of myocarditis have been reported, some of which have been fatal. Post-marketing experience suggests that the increased risk of myocarditis occurs most commonly in the first two months of treatment. Very rare cases of cardiomyopathy have also been reported; these cases generally occurred later in treatment and some were fatal. Pericarditis and pericardial effusion have also been associated with clozapine treatment.
Tachycardia is a common side effect of clozapine treatment that occurs in about 25% of users, especially during dose titration in early treatment. However, it is also a key symptom of myocardial disease. It is therefore essential that patients who have persistent tachycardia at rest, especially in the first two months of treatment, are closely observed for other signs and symptoms of myocarditis/cardiomyopathy. These include palpitations, arrhythmias, symptoms mimicking myocardial infarction, chest pain and other unexplained symptoms of heart failure.
A minority of clozapine-treated patients experience ECG changes similar to those seen with other antipsychotic drugs, including S-T segment depression and flattening or inversion of T-waves, which normalise after discontinuation of clozapine. The clinical significance of these changes is unclear. However, such abnormalities have been observed in patients with myocarditis, which should therefore be considered. If clozapine-induced myocarditis or cardiomyopathy is suspected, clozapine treatment should be discontinued promptly and the patient referred urgently to a cardiologist for diagnostic evaluation.
Patients who have developed clozapine-induced myocarditis or cardiomyopathy should not be re-exposed to clozapine.
Key information for prescribers:
- Patients must have a history and physical examination prior to starting therapy. The treating physician should consider performing a pre-treatment ECG.
- Patients who have persistent tachycardia at rest, especially during the first two months of treatment, should be closely observed for other signs or symptoms of myocarditis or cardiomyopathy. These include palpitations, arrhythmias, symptoms mimicking myocardial infarction, chest pain and other unexplained symptoms of heart failure.
- Patients in whom myocarditis or cardiomyopathy is suspected should stop clozapine and undergo urgent diagnostic evaluation by a cardiologist.
- Patients with clozapine-induced myocarditis or cardiomyopathy must not be re-exposed to clozapine.
Copies of this article can be obtained from: http://www.mca.gov.uk/ourwork/monitorsafequalmed/currentproblems/cpoct2002.pdf
