Safety profile of artemether: Analysis based on 15-year data retrived from FDA adverse event reporting system (FAERS)

Abstract

Objective: Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium (P.) falciparum malaria. This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system (FAERS).

Methods: This is a retrospective analysis on 15-year data of artemether-related adverse effects (AEs) retrieved from the FAERS. AEs were classified according to System Organ Class (SOC) and Preferred Terms (PT). Signal detection was performed using Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), and Empirical Bayes Geometric Mean (EBGM). Stratified analyses examined the impact of demographic factors such as sex, age, and time-to-onset. Temporal patterns and associated risk factors were also investigated.

Results: Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs, exhibiting significantly elevated RORs (males: ROR 381.36, 95% CI 247.06-588.60; females: ROR 455.11, 95% CI 286.43-723.12). Sex-specific differences were evident, with females showing a higher incidence of reproductive-related AEs, including spontaneous abortion and premature labour. Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration, indicating a rapid onset. The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.

Conclusions: Artemether is associated with a notable frequency of early-onset AEs, particularly hematological and hepatobiliary disorders. The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches. Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.

Keywords

Artemether / Adverse events / FDA adverse event reporting system / Signal detection / Hematological toxicity / Hepatotoxicity

Conflict of interest statement

The authors declare no conflicts of interest related to this work.

Funding

This research received no extramural funding.

Authors’ contributions

BJ extracted FAERS data, conducted the primary statistical analyses, and contributed to the initial drafting of the manuscript. JXW participated in data collection, data cleaning, and visualization, and assisted in interpreting the pharmacovigilance findings. XCL contributed to literature review, methodological refinement, and verification of analytical procedures. LLH supported data validation, helped refine the study design, and provided critical revisions to improve the intellectual content of the manuscript. TTH assisted with figure preparation, data quality assessment, and technical support throughout the study. BN conceived and designed the overall study, supervised all stages of data analysis and interpretation, critically revised the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript.

Publisher’s note

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Edited by Lei Y, Pan Y, Zhang Q

Acknowledgments

The authors thank the FDA for providing open access to the FAERS database.

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