Study identification


EU PAS number


Study ID


Official title and acronym

Metamizole and risk of agranulocytosis

DARWIN EU® study


Study countries


Study description

Metamizole is an analgesic and antipyretic marketed for more than 50 years in our country. It is a widely used drug in Spain with the indications of analgesic in different situations of moderate or severe acute pain, and antipyretic when other alternatives are not effective1. Agranulocytosis is one of its possible adverse reactions and, although it is rare and has a very low frequency2, it is serious and can lead to the death of the patient. It is characterized by a decrease in peripheral neutrophil count to less than <500 cells/mcl due to immunologic or cytotoxic mechanisms3. Most, but not all, instances of agranulocytosis result from exposure to drugs (idiosyncratic drug-induced agranulocytosis), and either the drug itself or a metabolite may be causative3. Despite agranulocytosis is a well-known adverse reaction for metamizole, there has been an increase recently in the reporting of cases of agranulocytosis to the Spanish pharmacovigilance system. Despite it is a very serious reaction that continues appearing, no study has been performed in years in our country and none with BIFAP. There is a need to carry out a new pharmacoepidemiological study that addresses the issues raised, using secondary sources of information that may be available in health information systems. Research question and objectives: Objective: Estimation of the risk of agranulocytosis associated with the use of metamizole compared to other analgesics / anti-inflammatories with similar use profile (see below), in the BIFAP population. Study design: comparative cohort study. Population: New users of metamizole or other analgesics / anti-inflammatories aged above 2 years, without alterations in bone marrow function (e.g. during or after treatment with cytostatic agents) or diseases of the hematopoietic system. Data analysis:Survival analyses with Cox proportional hazard regression models.

Study status

Research institution and networks


Contact details

Elisa Martín-Merino

Primary lead investigator
Study timelines

Date when funding contract was signed


Data collection


Start date of data analysis


Date of interim report, if expected


Date of final study report

Sources of funding

More details on funding

AEMPS's own resources. No funding has been received.
Study protocol
Initial protocol
English (723.49 KB - PDF)View document
Updated protocol
English (1.05 MB - PDF)View document

Was the study required by a regulatory body?


Is the study required by a Risk Management Plan (RMP)?

Not applicable