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The European Medicines Agency (EMA) has confirmed that high doses of ibuprofen and related molecule dexibuprofen carry a small increased risk of cardiovascular diseases, such as heart attack and stroke.
A high dose of ibuprofen is defined as 2,400mg or more per day. No increased risk was found at up to 1,200mg, which is generally the highest dose for over-the-counter oral preparations in the EU. For dexibuprofen (the active enantiomer of ibuprofen), which is used alone or in combination with ibuprofen, a high dose is defined as 1,200mg or above.
As a result — and in line with the class warning already in place for non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors and diclofenac — the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that product information and dosing guidelines be updated to reflect the risks.
The PRAC’s position, announced on 13 April 2015, follows a comprehensive safety review begun in June 2014 at the request of the UK’s Medicines and Healthcare products Regulatory Agency. It considered systemic (oral and intravenous) dosing, but not topical applications (gels and sprays).
In general, the benefits of ibuprofen were found to outweigh the risks, but prescribers should carefully assess the patient’s cardiovascular and circulatory risk before starting long-term treatment with ibuprofen, particularly at high doses, the committee concluded.
Inam Haq, associate medical director for Arthritis Research UK, describes NSAIDs as a “lifeline” for many people with arthritis but says the charity agrees that advice around high-dose ibuprofen should be updated to minimise cardiovascular risk.
“GPs are fully aware of the risks of prescribing high-dose ibuprofen, and there has been a marked reduction in the use of other NSAIDs, such as diclofenac, and a switch to naproxen in recent years,” says Haq. “Therefore, we would advise that individuals take the smallest dose for the shortest length of time possible, although this isn’t always practical for people with a long-term condition such as arthritis.”
Haq adds that the charity would advise people with arthritis to seek an annual review of their painkillers with their GP. This will ensure their cardiovascular risk is regularly checked and will allow them to seek advice about alternatives to NSAIDs.
A UK community pharmacist says it is “extremely rare” to see a prescription for more than 1,200mg of ibuprofen per day, and that it is common practice to double-check prescriptions that exceed this dose.
The PRAC also reviewed data relating to the effect of ibuprofen on the anticoagulant effects of low-dose aspirin: while data on the impact of long-term ibuprofen were inconclusive, occasional use should not affect the benefits of low-dose aspirin, the committee concluded.
Its recommendations will now go to the EU’s Co-ordination Group for Mutual Recognition and Decentralised Procedures — Human, who will adopt a final position on the measures. If approved, they will be implemented in all EU member states, plus Iceland, Lichtenstein and Norway.
