Overview:

Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy, is an acute condition associated with transient left ventricular dysfunction¹. There are several clinical manifestations of stress cardiomyopathy such as chest pain, sometimes with heart failure, and often with ST-segment changes which may present as acute coronary syndrome. Some possible causes of the disorder include: 1) coronary artery vasospasm; 2) microcirculatory dysfunction; 3) transient obstruction of the left ventricular outflow tract; and 4) excessive release of catecholamine, which seems to have the most important role.

Background:

The National Pharmaceutical Regulatory Agency (NPRA) received information from the European Medicines Agency (EMA) on the risk of stress cardiomyopathy with noradrenaline. A signal of stress cardiomyopathy was initially identified by Ireland during routine signal detection activities. Following a review of the case reports available in EudraVigilance, Ireland confirmed that the signal needed an initial analysis and prioritisation by EMA's Pharmacovigilance Risk Assessment Committee (PRAC).

Having considered the available evidence in EudraVigilance and in the literature, PRAC has agreed that the product information of noradrenaline-containing medicinal products to be updated with the risk of stress cardiomyopathy².

Adverse Drug Reaction Reports:

NPRA has received a total of 157 reports with 194 adverse events suspected to be related to noradrenaline. Majority of the adverse events reported involves vascular disorders (83 events, 42.8%) such as gangrene and peripheral ischaemia. At present, no cases of stress cardiomyopathy following the use of noradrenaline has been reported to NPRA⁴.

Advice for Healthcare Professionals: 

• Patients on noradrenaline should be monitored for stress cardiomyopathy.
• Please report any adverse drug reactions suspected to be associated to noradrenaline use to NPRA.

A directive [Ruj. Kami: (5) dlm. BPFK/PPP/07/25 Jld. 3] has been issued by NPRA for updates to the local product packaging insert related to this safety issue. Please refer to the directive for more information.

References: 

1. Mlinarevic, D. et al. (2017). Pathophysiological Mechanisms of Takotsubo Cardiomyopathy - a Systematic Review. Seemedj 1(1): 27-39.
2. European Medicine Agency (2018). Minutes of the meeting on 5-8 March 2018. EMA/288259/2018.
3. Levophed^® Malaysian Product Package Insert [Last revision date: July 2017].
4. The Malaysian Adverse Drug Reaction Database, NPRA [Accessed: June 2018].

DISCLAIMER:

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.