EMA has started a review of medicines containing the painkiller metamizole following concerns that the measures in place to minimise the known risk of agranulocytosis may not be effective enough.
Metamizole-containing medicines are authorised in a number of EU countries for treating moderate to severe pain and fever. The authorised uses vary from country to country, ranging from the treatment of pain following surgery or injuries to the treatment of cancer-related pain and fever.
Agranulocytosis is a known side effect of metamizole-containing medicines. It involves a sudden and sharp decrease in the levels of granulocytes, a type of white blood cell. This can lead to serious infections which can be fatal. The product information of the various metamizole-containing medicines currently lists agranulocytosis as either a rare side effect (occurring in up to 1 in 1,000 people) or a very rare side effect (occurring in up to 1 in 10,000 people). Measures in place to minimise this risk vary across countries.
The review was started at the request of the Finnish medicines agency as cases of agranulocytosis are still being reported with metamizole despite the recent strengthening of risk minimisation measures in Finland. Following the most recent reports of cases, the company marketing the only metamizolecontaining medicine authorised in Finland requested that its marketing authorisation be withdrawn for safety reasons.
EMA’s safety committee (PRAC) will now review the risk of agranulocytosis for all metamizolecontaining medicines authorised in the EU in their different authorised uses, and their existing risk minimisation measures. The Committee will assess the impact of agranulocytosis on the benefit-risk balance of the medicines and issue a recommendation on whether their marketing authorisations should be maintained, varied, suspended or revoked across the EU.
As required in this type of procedure (see further information below), EMA invites stakeholders (e.g. healthcare professionals, patients’ organisations, learned societies and the general public) to submit data relevant to this review. Specific questions and a form are available on the EMA website.
Metamizole (also known as dipyrone) is an analgesic medicine (painkiller). It has been used in the EU since the 1920s and is taken by mouth, suppository or injection, to treat moderate to severe pain and fever. The review includes both medicines containing metamizole alone and those containing metamizole in combination with other active substances.
Metamizole-containing medicines are authorised in a number of EU countries: Austria, Belgium, Bulgaria, Croatia, Czech Republic, Germany, Hungary, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia and Spain. In Finland, the only authorised metamizole-containing medicine is being withdrawn.
They are available under a range of names including Afexil, Algifen, Algifen Neo, Algi-Mabo, Algocalmin, Algopyrin, Algozone, Alindor, Alkagin, Alvotor, Analgin, Benlek, Berlosin, Buscapina Compositum, Dialginum, Dolocalma, Flamborin, Gardan, Hexalgin, Locamin, Metagelan, Metalgial, Metamistad, Metamizol, Metapyrin, Natrijev, Nodoryl, Nofebran, Nolotil, Novalgin, Novalgina, Novalgine, Novaminsulfon, Novocalmin, Panalgorin, Piafen, Piralgin, Pyralgin, Pyralgina, Quarelin, Scopolan Compositum, Spasmalgon and Tempalgin.
The review of metamizole-containing medicines has been initiated at the request of the Finnish medicines agency, under Article 107i of Directive 2001/83/EC.
The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. As metamizole-containing medicines are all authorised nationally, the PRAC recommendations will be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.