The European Medicines Agency has published a communication to healthcare professionals (DHPC)
Dear healthcare professional!
[
Registration certificate holder/Applicant], in agreement with the European Medicines Agency (EMA) and the [
National Competent Authority], hereby informs you of the following:
Summary
- Cases of drug-induced liver injury (DILI) have been reported with the use of metamizole.
- Inform patients:
- on how to recognize early symptoms indicating drug-induced liver injury;
- about the need to stop using metamizole if such symptoms occur and to seek medical attention for an assessment of the condition and monitoring of liver function.
- The medicinal product should not be re-administered to patients who experienced an episode of liver injury during treatment with metamizole, unless no other cause of the liver injury has been established.
The instructions for medical use must be updated accordingly in the sections “Special warnings and precautions for use” and “Adverse reactions”.
Information on safety issues
Metamizole is a non-opioid pyrazolone derivative with potent analgesic, antipyretic and weak anti-inflammatory properties, <indicated from 3 months of age in patients weighing at least 5 kg for the treatment of severe or persistent pain and fever.> [As indications may differ at the local level, adjust at the national level if necessary].
<Metamizole is also available in fixed combinations, such as <active substances of the combination> for use in <approved indications>. [Adjust at the national level if necessary].
New safety information has recently been identified, prompting a review of data regarding the potential risk of drug-induced liver injury with the use of metamizole. PRAC considered information from all available sources, including adverse reaction reports and scientific literature data.
It has been established that liver injury is predominantly hepatocellular in nature and occurs from several days to months after the start of treatment. Signs and symptoms include elevated serum liver enzymes with or without jaundice, often in the context of hypersensitivity reactions (for example, skin rash, blood dyscrasias, fever and eosinophilia) or features of autoimmune hepatitis. In some patients, liver injury resolved upon re-administration of the medicinal product.
The mechanism of liver injury caused by metamizole has not been clarified, but the available data point to an immunoallergic nature.
As a rule, drug-induced liver injury can progress to potentially serious outcomes, such as acute liver failure requiring a liver transplant.
Cases of liver injury with the use of metamizole are considered to be very rare, but the exact frequency cannot be calculated.
Early recognition of potential liver injury resulting from the use of metamizole is important. Patients should be taught to watch closely for symptoms of liver injury and, if they occur, to stop using metamizole and see a doctor. Healthcare professionals are advised to assess and monitor liver function in patients with signs and symptoms suggestive of any liver injury.
Re-administration of metamizole is not recommended in the event of an episode of liver injury that occurred during treatment with metamizole and for which no other cause of liver injury has been established.
Full text of this communication to healthcare professionals regarding safety of usewww.ema.europa.eu/en/documents/dhpc/direct-healthcare-professional-communication-dhpc-metamizole-risk-drug-induced-liver-injury_en.pdf
