Review confirms small increased cardiovascular risk with daily doses at or above 2,400 mg

European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) has completed a review confirming a small increase in the risk of cardiovascular problems, such as heart attacks and strokes, in patients taking high doses of ibuprofen (at or above 2,400 mg per day). The review clarifies that the risk with high-dose ibuprofen is similar to the risk seen with some other non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors and diclofenac.

No increase in cardiovascular risk is seen with ibuprofen at doses up to 1,200 mg per day, which is the highest dose generally used for over-the-counter (OTC) preparations taken by mouth in the European Union (EU).

The PRAC concluded that the benefits of ibuprofen outweigh the risks but recommended updating advice on the use of high-dose ibuprofen to minimise the cardiovascular risk. High doses of ibuprofen (2,400 mg per day or higher) should be avoided in patients with serious underlying heart or circulatory conditions, such as heart failure, heart disease and circulatory problems or in those who have previously had a heart attack or stroke.

In addition, doctors should carefully assess a patient’s risk factors for heart or circulatory conditions, before initiating long-term treatment with ibuprofen, particularly if high doses are required. Risk factors for these conditions include smoking, high blood pressure, diabetes and high blood cholesterol.

These recommendations follow PRAC’s review of data on ibuprofen from several publications, including combined analyses of numerous clinical trials (known as meta-analyses) and data from population-based studies.

The PRAC also reviewed data on the interaction between ibuprofen and low-dose aspirin when the latter is taken to reduce the risk of heart attacks and strokes. The PRAC noted that ibuprofen has been shown in laboratory studies to reduce the anti-clotting effects of aspirin. However it remains uncertain whether long-term use of ibuprofen in clinical practice reduces the benefits of low-dose aspirin in preventing heart attacks and strokes. Occasional use of ibuprofen should not affect the benefits of low-dose aspirin.

The PRAC recommended that updated advice on the cardiovascular risk of high-dose ibuprofen be included in the product information of ibuprofen medicines, along with information on the available evidence on the interaction between ibuprofen and aspirin.

The recommendations for ibuprofen also apply to dexibuprofen, a medicine similar to ibuprofen. A high dose of dexibuprofen is a dose at or above 1,200 mg per day.

The PRAC recommendations for ibuprofen and dexibuprofen will now be sent the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a final position. The CMDh is a body representing EU Member States and Iceland, Liechtenstein and Norway.


Posted on the EMA website on 13 April 2015