The Pharmacovigilance Risk Assessment Committee (PRAC), based on the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing metamizole, drew the following conclusions.
Given the available literature data and spontaneous reports on the development of drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), including a close temporal relationship, cases with a positive test on repeated use and repeated withdrawal (de-challenge) and/or with a positive re-challenge test, the PRAC considers the causal relationship between the use of medicinal products containing metamizole and DRESS syndrome to be at least possible.
PRAC concluded that the package inserts of medicinal products containing metamizole should be amended accordingly.
The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the PRAC scientific conclusions.
The CMDh considers that the benefit/risk balance of medicinal products containing metamizole remains unchanged, taking into account the proposed amendments to the package inserts.
Amendments to be included in the relevant sections of the package insert (new text underlined in bold, deleted text struck through).
Section “Special warnings and precautions for use”
Severe skin reactions
Severe life-threatening skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced eosinophilia with systemic symptoms (DRESS syndrome), which can be life-threatening or fatal, have been reported during use of metamizole treatment.
Patients should be informed about the signs and symptoms of skin reactions and monitored closely for them.
If signs appear and symptoms indicating these reactions, or signs of SJS or TEN appear (for example, a progressive skin rash, often with blisters or mucosal lesions), treatment with metamizole should be withdrawn immediately discontinued and must under no circumstances be restarted (see section “Contraindications”).
“Adverse reactions” section
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of metamizole (see the section “Special warnings and precautions for use”).
The following adverse reactions should be added to the section “Skin and subcutaneous tissue disorders” with an unknown frequency:
Drug-induced eosinophilia and systemic symptoms (DRESS)
Перелік лікарських засобів, що містять метамізол (metamizole) і дозволені до медичного застосування в Україні (за даними Державного реєстру лікарських засобів України станом на 06.12.2021).
To analyze the published information, the applicant must use the original text available at the link https://www.ema.europa.eu/en/documents/psusa/metamizole-cmdh-scientific-conclusions-grounds-variation-amendments-product-information-timetable/00001997/202103_en.pdf
