EMA/PRAC recommends removal of modified release paracetamol from the market.

European Union Regulator agency European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that modified- or prolonged-release form of popular painkiller paracetamol should be removed from market.

The recommendation was based on results of a literature review that found out that these medicines behave in a complex way in cases of overdosing, and the amount of drug release cannot be predicted. The complex pharmacokinetics in cases of overdosing might result in severe liver damage or death. 

The review was conducted following a request by Swedish medicines authority, the Medical Products Agency, which had noted problems in managing overdose with such a product since marketing approval.

"Experience has shown that in overdose (particularly at high doses), because of the way the paracetamol in modified-release products is released in the body, the usual treatment procedures developed for immediate-release products are not appropriate," the EMA said in the news release.

The matter is much more complicated if the product also contains Tramadol, because of the additional effect of overdosing with Tramadol too.

This is of particular concern in cases when the physician is unaware that modified release paracetamol has been taken, which affects decisions such as when and for how long to give an antidote.

The PRAC committee could not identify means to reduce the harm to patients or design a standard and feasible protocol to manage overdoing, that could be easily adapted across whole of European Union. The committee finally concluded that the risk involved with overdosing outweighs the benefits offered by modified or extended release preparations.

The Committee therefore recommended that, “The marketing of modified-release paracetamol medicines should be suspended. Immediate-release paracetamol products, which are not affected by this review, will continue to be available as before.”

The PRAC recommendations will be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures–Human (CMDh), which will review the matter and release a position statement on the issue.

Full text of EMA statement.