The package leaflet and Summary of Product Characteristics (SmPC) of medicinal products containing metamizole will be updated to include the risk of liver injury and pharmacokinetic interactions.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has evaluated the data from the periodic safety update report (PSUR) for metamizole. Following this evaluation, the PRAC recommended an update of the SmPC and package leaflet for medicinal products containing metamizole to include new information on the risk of liver injuries and pharmacokinetic interactions.
Cases of acute hepatitis of predominantly hepatocellular pattern have been reported in patients treated with metamizole with an onset of few days to a few months following treatment initiation. Signs and symptoms include elevated liver enzymes in the serum with or without jaundice, often in the context of hypersensitivity reactions to medicines (e.g. skin rash, blood dyscrasias, fever and eosinophilia) or accompanied by symptoms of autoimmune hepatitis. Most patients recovered upon discontinuation of the metamizole treatment. Nevertheless, in isolated cases, progression to acute liver failure requiring liver transplantation has been reported in isolated cases.
The mechanism of liver injury induced by the use of metamizole is not clear, but data indicate an immuno-allergic mechanism.
Patients should be instructed to contact their physician if they show symptoms suggesting of liver injury.
The metamizole treatment should be stopped by such patients and liver function should be assessed. Metamizole should not be re-introduced in patients with an episode of liver injury during treatment with metamizole for which no other cause of liver injury has been determined.
Pharmacokinetic induction of metabolising enzymes
Metamizole can induce metabolising enzymes including CYP2B6 and CYP3A4.
Co-administration of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus or sertraline, may cause a reduction in plasma concentrations of these drugs with a potential decrease in clinical efficacy. Therefore, caution is advised when metamizole is administered concurrently. Clinical response and/or drug levels should be monitored if necessary.
The SmPCs and package leaflets for the relevant medicinal products are currently being updated.
A DHPC mainly discussing the risk of liver injuries was issued to healthcare professionals.