Overview:

Clopidogrel is an antiplatelet drug indicated for the secondary prevention of atherothrombotic events and the prevention of atherothrombotic/thromboembolic events in atrial fibrillation.

Background:

NPRA has received information from the European Medicines Agency (EMA) regarding the risk of interaction between clopidogrel and boosted antiviral human immunodeficiency virus (HIV) therapy, leading to insufficient inhibition of platelet aggregation.

In a safety review conducted by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), it was found that HIV-infected patients treated with ritonavir- or cobicistat-boosted antiretroviral therapies (ART) had significantly lower exposure to the clopidogrel active metabolite and reduced platelet inhibition. .  The clinical relevance of these findings is not clear. However, there have been spontaneous reports of HIV-infected patients treated with boosted ART, who have experienced reocclusive events after de-obstruction or have suffered thrombotic events under a clopidogrel loading treatment schedule. Concomitant use of ritonavir may decrease exposure of clopidogrel and average platelet inhibition. For these reasons, it is recommended that clopidogrel should not be used concomitantly with boosted ART¹.

Based on all available evidence found in EudraVigilance and the literature, EMA has concluded that all product registration holders of clopidogrel-containing products should update the product information to include the risk of interaction with boosted ART.

Adverse Drug Reaction Reports:

NPRA has received a total of 369 reports with 591 adverse events suspected to be related to clopidogrel. To date, no adverse event related to the ineffectiveness of the drug due to interaction with ritonavir or cobicistat has been reported to the NPRA².

Advice for Healthcare Professionals:

• When prescribing clopidogrel, please be mindful on the risk of interaction between clopidogrel and boosted antiviral human immunodeficiency virus (HIV) therapy which may lead to insufficient inhibition of platelet aggregation.
• Please report all adverse events suspected to be related to the use of clopidogrel to NPRA.

References:

1. European Medicines Agency (2019). PRAC recommendations on signals (adopted at the 13-16 May 2019 PRAC meeting). EMA/PRAC/265212/2019.
2. The Malaysian Adverse Drug Reactions database, NPRA [Accessed: July 2019]

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, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.