Evidence map›Paper›PMID 41069600›Full record

SynthesisFrontiers in pharmacology2025

Pharmacogenetics of metamizole-induced agranulocytosis: a systematic review and drug regulation implications.

Giovana Fernanda Santos Fidelis, Carolina Dagli-Hernandez, Romina P Martinelli, Jefman Efendi Marzuki, Baharuddin Baharuddin, Qun-Ying Yue, Brian Edwards, Eder de Carvalho Pincinato, Patricia Moriel

Abstract readSystematic Review
In one paragraph

Synthesis in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Giovana Fernanda Santos Fidelis *School of Medical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.
Carolina Dagli-Hernandez *School of Pharmaceutical Sciences, Universidade de São Paulo, Sao Paulo, Brazil.
Romina P MartinelliDelta PV, Spanish Team, Madrid, Spain.
Jefman Efendi MarzukiFaculty of Medicine, Universitas Surabaya, Surabaya, Indonesia.
Baharuddin BaharuddinFaculty of Medicine, Universitas Surabaya, Surabaya, Indonesia.
Qun-Ying YueUppsala Monitoring Centre, Uppsala, Sweden.
Brian EdwardsInternational Society of Pharmacovigilance, Geneva, Switzerland.
Eder de Carvalho PincinatoSchool of Medical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.
Patricia MorielFaculty of Pharmaceutical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Metamizole (dipyrone) is a widely used analgesic and antipyretic, but its use has been restricted in some countries due to the risk of metamizole-induced agranulocytosis (MIA). This systematic review investigated genetic variants associated with MIA, allele frequencies across ancestry groups, and the drug's legal status. Methods: A literature search was conducted across nine databases for studies published up to 08 April 2025. Study selection and data extraction were performed by two independent reviewers. The Withdrawn 2.0 platform was used to assess the global legal status of metamizole, while allele frequencies were obtained from the gnomAD browser (version v4.1.0) and the Allele Frequency Net Database (AFND). Bibliometric analysis was conducted using the VOS viewer software. Results: In total, four studies were included in the review. Data related to HLA, NAT2, CYP2C9, CYP2C19, and variants located on chromosome nine were reported; however, statistically significant associations were observed only for variants in chromosome nine and HLA-C*04:01. When comparing countries from different continents with varying metamizole status, the analysis of allele frequencies did not reveal sufficient differences in allele frequencies between countries, which does not justify distinct regulatory frameworks. Conclusion: This study highlights the scarcity of data in the literature reporting the association between genetic variants and MIA. Furthermore, there is insufficient evidence to justify the prohibition of metamizole in certain countries based on genetic variants alone. Additional studies are essential to evaluate the prevalence of MIA, better characterize populations, and explore potential genetic associations, particularly concerning the HLA-C*04:01 allele. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024572038, identifier CRD42024572038.

Indexed as

agranulocytosisdipyronemetamizolepharmacogeneticsregulation

Identifiers

PMID41069600
PMCPMC12504837

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.