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Artesunate/Amodiaquine-Induced Acute Extrapyramidal Reactions in Children and Younger Adults: Case Series Assessment

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Abstract

Introduction

Several studies conducted in African countries reported the artesunate and amodiaquine (AS/AQ) tablet as a safe and well-tolerated anti-malarial drug in children and younger adults. The aim of this case series assessment was to assess the causal relationship between the AS/AQ tablet and extrapyramidal reactions in children and younger adults and to investigate the factor(s) predisposing to the adverse drug reactions.

Methods

The causal relationship of all the cases was first assessed individually using the Naranjo Probability Scale and then subjected to a case series assessment using Austin Bradford–Hill criteria.

Results

A total of 43 acute extrapyramidal reactions associated with the AS/AQ tablet were reported between 2012 and 16 November, 2015 to the Eritrean Pharmacovigilance Centre. The causality was found to be probable or highly probable for 33 (76.7 %) of the cases and the rest (10; 23.3 %) of the cases had a possible causal association. The extrapyramidal reactions had more or less similar clinical features in most of the cases and were characterized by abnormal involuntary contractions of muscles. The median age and body weight of the cases were 15 years and 40 kg, respectively, and 70 % of them were males. 90.7% of the reactions manifested in children and younger adults (aged <26 years). In most of the cases, reactions manifested in the third day from the start of treatment and 88.3 % of cases were hospitalized.

Conclusion

The causal relationship between the AS/AQ tablet and extrapyramidal reactions in children and younger adults was found to be apparent and possibly owing to dose accumulation or an overdose of amodiaquine.

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Acknowledgments

We thank our colleagues in the Uppsala Monitoring Centre, Sweden, Dr. Kristina Star, Prof. Ralph Edwards, Dr. Pia Caduff, and Alem Zekarias, for their review and valuable comments.

We also acknowledge the reporters namely Dr. Eyob Beyene, Dr. Ghide Gebreweld, Dr. Tsegazeab Kflizghi, Dr. Henok Tekie, Dr. Estifanos Haile, Dr. Lemlem Mengs, Kibrom Teame, Adiam Amanuel, Abraham Thomas, Fithawit Semere, Dr. Seltene Tewelde, Dr. Hailemichael Gheberemariam, Dr. Foto Ghide, Dr. Simon Hidru, Dr. Abdu Osman, Tesfagebriel Araya, Solomon Dair, Dr. Yacob Hassen, and Dr. Tsegai Tesfagabr for their vigilance.

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Authors and Affiliations

  1. Eritrean Pharmacovigilance Centre, Ministry of Health, P.O. Box: 212, Asmara, Eritrea

    Mulugeta Russom, Elsa Mekonnen & Selamawit Ghebrehiwet

  2. School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea

    Dawit Tesfai

  3. World Health Organization Country Office, Asmara, Eritrea

    Semere Gebregiorgis & Abdulmumini Usman

  4. National Malaria Control Program, Ministry of Health, Asmara, Eritrea

    Selam Mihreteab

  5. National Medicines and Food Administration, Ministry of Health, Asmara, Eritrea

    Iyassu Bahta

  6. Tesseney Hospital, Tesseney, Eritrea

    Gelila Abrham

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  1. Mulugeta Russom
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  2. Dawit Tesfai
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Corresponding author

Correspondence to Mulugeta Russom.

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Funding

No sources of funding were used to assist in the preparation of this study.

Conflict of interest

The authors Mulugeta Russom, Dawit Tesfai, Semere Gebregiorgis, Abdulmumini Usman, Selam Mihreteab, Iyassu Bahta, Elsa Mekonnen, Selamawit Ghebrehiwet, and Gelila Abrham declare that they have no conflicts of interest that are directly relevant to the content of this study.

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Russom, M., Tesfai, D., Gebregiorgis, S. et al. Artesunate/Amodiaquine-Induced Acute Extrapyramidal Reactions in Children and Younger Adults: Case Series Assessment. Drug Saf 39, 763–768 (2016). https://doi.org/10.1007/s40264-016-0429-6

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  • DOI: https://doi.org/10.1007/s40264-016-0429-6

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