Amodiaquine-Associated Asthenia: A Case Based Review and Gaps in Literature

Document Type : Review Article

Authors

1 Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Nigeria

2 Department of Pediatrics, Faculty of Clinical Sciences, College of Medicine, University of Ibadan, Nigeria

Abstract

Introduction: Amodiaquine is a partner drug in the artemisinin-based combination therapy artesunate-amodiaquine. Reports of the adverse drug reaction known as amodiaquine-associated asthenia are scarce, and this adverse reaction needs to be investigated in detail. This article presents and reviews a case of amodiaquine-associated asthenia. A literature search for the characteristics of this adverse reaction highlighted gaps in the literature.

Methods: A case of probable amodiaquine asthenia was described and discussed under the sub-headings of epidemiology, clinical features, laboratory features, aetiopathogenesis, and management. A literature search limited to Medline Health Databases (Medline and PubMed Central, PMC) using the search terms and was conducted on 10 March 2015. Retrieved literature on the subject was closely scrutinized for relevant details of adverse drug reactions to amodiaquine when used in the management or prophylaxis of malaria. Cited literature within retrieved manuscripts was examined manually for other relevant literature. Papers retrieved from the search were used to describe the existing knowledge and gaps in it of the adverse drug reaction under sub-categories of incidence, clinical features, laboratory features, aetiopathogenesis, and management. 

Results: Thirty-nine manuscripts were retrieved; 20 had content relevant to the objectives of this review. The frequency of amodiaquine-associated asthenia in different populations ranged from 12–36%. There is a paucity of reports, and no detailed study of this adverse reaction has been published in popular English medical literature.

Conclusion: With the use of amodiaquine as a partner drug in antimalarial combination therapies being scaled up, well-structured studies are needed on adverse reactions to amodiaquine and to investigate amodiaquine-associated asthenia. In addition, approaches to elucidating this adverse reaction more effectively in children need to be developed. 

Keywords

References

Margraff F, Bertram D. Adverse drug reaction reporting by patients: an overview of fifty countries. Drug Saf. 2015;37(6):409-19. doi: 10.1007/s40264-014-0162-y
Carleton B, Poole R, Smith M, Leeder J, Ghannadan R, Ross C, et al. Adverse drug reaction active surveillance: developing a national network in Canada's children's hospitals. Pharmacoepidemiol Drug Saf. 2009;18(8):713-21. doi: 10.1002/pds.1772
Carleton BC, Smith MA, Gelin MN, Heathcote SC. Paediatric adverse drug reaction reporting: understanding and future directions. Can J Clin Pharmacol. 2007;14(1):e45-57.
Munoz MJ, Ayani I, Rodriguez-Sasiain JM, Gutierrez G, Aguirre C. [Adverse drug reaction surveillance in pediatric and adult patients in an emergency room]. Med Clin (Barc). 1998;111(3):92-8.
Oshikoya KA, Awobusuyi JO. Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria. BMC Clin Pharmacol. 2009;9:14. doi: 10.1186/1472-6904-9-14
Mokuolu OA, Okoro EO, Ayetoro SO, Adewara AA. Effect of artemisinin-based treatment policy on consumption pattern of antimalarials. Am J Trop Med Hyg. 2007;76(1):7-11.
FMOH. Federal Ministry of Health, Nigeria National Antimalarial Treatment Policy [PDF]. Abuja, Nigeria: National Malaria and Vector Control Division; 2005 [2016 May 31]. Available from: http://apps.who.int/medicinedocs/documents/s18401en/s18401en.pdf.
Graupner J, Gobels K, Grobusch MP, Lund A, Richter J, Haussinger D. Efficacy of amodiaquine in uncomplicated falciparum malaria in Nigeria in an area with high-level resistance to chloroquine and sulphadoxine/pyrimethamine. Parasitol Res. 2005;96(3):162-5. doi: 10.1007/s00436-005-1325-7
Woodtli W, Vonmoos P, Siegrist P, Zollikofer H. [Amodiaquine-induced hepatitis with leukopenia]. Schweiz Med Wochenschr. 1986;116(29):966-8.
Olliaro P, Mussano P. Amodiaquine for treating malaria. Cochrane Database Syst Rev. 2003;2000(2):CD000016.
Sinclair D, Zani B, Donegan S, Olliaro P, Garner P. Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database Syst Rev. 2009(3):CD007483. doi: 10.1002/14651858.cd007483.pub2
Bassi PU, Osakwe AI, Isah A, Suku C, Kalat M, Jalo I, et al. Safety of artemisinin-based combination therapies in Nigeria: a cohort event monitoring study. Drug Saf. 2013;36(9):747-56. doi: 10.1007/s40264-013-0044-8
Brasseur P, Vaillant MT, Olliaro PL. Anti-malarial drug safety information obtained through routine monitoring in a rural district of South-Western Senegal. Malar J. 2012;11:402. doi: 10.1186/1475-2875-11-402
Adisa R, Fakeye TO, Dike D. Evaluation of adverse drug reactions to artemisinin-based combination therapy in a Nigerian University Community. Trop J Pharm Res. 2008;7(2):937-44. doi: 10.4314/tjpr.v7i2.14680
Neftel KA, Woodtly W, Schmid M, Frick PG, Fehr J. Amodiaquine induced agranulocytosis and liver damage. Br Med J (Clin Res Ed). 1986;292(6522):721-3. doi: 10.1136/bmj.292.6522.721
Wittes R. Adverse reactions to chloroquine and amodiaquine as used for malaria prophylaxis: a review of the literature. Can Fam Physician. 1987;33:2644-9.
Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, et al. Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J. 2008;7:127. doi: 10.1186/1475-2875-7-127
Zwang J, Dorsey G, Djimde A, Karema C, Martensson A, Ndiaye JL, et al. Clinical tolerability of artesunate-amodiaquine versus comparator treatments for uncomplicated falciparum malaria: an individual-patient analysis of eight randomized controlled trials in Sub-Saharan Africa. Malar J. 2012;11:260. doi: 10.1186/1475-2875-11-260
Metushi IG, Cai P, Dervovic D, Liu F, Lobach A, Nakagawa T, et al. Development of a novel mouse model of amodiaquine-induced liver injury with a delayed onset. J Immunotoxicol. 2015:12(3):247-60. doi: 10.3109/1547691X.2014.934977
Lind DE, Levi JA, Vincent PC. Amodiaquine-induced agranulocytosis: toxic effect of amodiaquine in bone marrow cultures in vitro. Br Med J. 1973;1(5851):458-60. doi: 10.1136/bmj.1.5851.458
Akindele MO, Odejide AO. Amodiaquine-induced involuntary movements. BMJ. 1976;2(6029):214-5. doi:10.1136/bmj.2.6029.214
Adjei GO, Goka BQ, Rodrigues OP, Hoegberg LC, Alifrangis M, Kurtzhals J. Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose. Ghana Med J. 2009;43(3):135-8.
McIntosh HM, Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database Syst Rev. 2000(2):CD000256.
Okoli CO, Ugwu CE, Ubaka MC, Ezike CA, Akah AP. Efficacy of artesunate-amodiaquine combination therapy for uncomplicated malaria in patients in south-eastern Nigeria. J Appl Res. 2010;10(1):17-23.
Maiteki-Sebuguzi C, Jagannathan P, Yau VM, Clark TD, Njama-Meya D, Nzarubara B, et al. Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children. Malar J. 2008;7:106. doi: 10.1186/1475-2875-7-106
Falade C, Manyando C. Safety profile of Coartem: the evidence base. Malar J. 2009;8 Suppl 1:S6. doi: 10.1186/1475-2875-8-S1-S6
Falade CO, Ogundele AO, Yusuf BO, Ademowo OG, Ladipo SM. High efficacy of two artemisinin-based combinations (artemether-lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria. Trop Med Int Health. 2008;13(5):635-43. doi: 10.1111/j.1365-3156.2008.02043.x
Egunsola O, Oshikoya KA. Comparative safety of artemether-lumefantrine and other artemisinin-based combinations in children: a systematic review. Malar J. 2013;12:385. doi: 10.1186/1475-2875-12-385
Osorio L, Gonzalez I, Olliaro P, Taylor WR. Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Colombia. Malar J. 2007;6:25. doi: 10.1186/1475-2875-6-25
White NJ. Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia. 1999;41(1-3):301-8.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-45. doi:10.1038/clpt.1981.154
Choonara I, Rieder MJ. Drug Toxicity and adverse drug reactions in children, a brief historical review. Paediatr Perinat Drug Ther. 2002;5(1):12-6.
Oshikoya KA. Adverse drug reactions in children: types, incidence, and risk factors. Niger J Paediatr. 2006;33(2):29-35.
Lepeu G, Codine P, Janbon F, Bertrand A. [Amodiaquine-induced agranulocytosis]. Nouv Presse Med. 1981;10(34):2827-8.
Douer D, Schwartz E, Shaked N, Ramot B. Amodiaquine-induced agranulocytosis: drug inhibition of myeloid colonies in the presence of patient's serum. Isr J Med Sci. 1985;21(4):331-4.
Rhodes EG, Ball J, Franklin IM. Amodiaquine induced agranulocytosis: inhibition of colony growth in bone marrow by antimalarial agents. Br Med J (Clin Res Ed). 1986;292(6522):717-8. doi: 10.1136/bmj.292.6522.717
Aymard JP, Rouveix B, Ferry R, Janot C, May T, Legras B, et al. Amodiaquine-induced agranulocytosis: report of a case with in vitro studies of granulocyte-macrophage progenitor cells. Acta Haematol. 1989;82(1):40-2. doi: 10.1159/000205276
Clarke JB, Neftel K, Kitteringham NR, Park BK. Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine. Int Arch Allergy Appl Immunol. 1991;95(4):369-75. doi: 10.1159/000235475
Uetrecht J. Role of animal models in the study of drug-induced hypersensitivity reactions. Aaps J. 2005;7(4):E914-21. doi: 10.1208/aapsj070489
Park BK, Pirmohamed M, Kitteringham NR. Idiosyncratic drug reactions: a mechanistic evaluation of risk factors. Br J Clin Pharmacol. 1992;34(5):377-95. doi: 10.1111/j.1365-2125.1992.tb05647.x
International Journal of Travel Medicine and Global Health
Volume 4, Issue 2
Spring 2016
Pages 41-46

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History

  • Receive Date: 31 March 2016
  • Revise Date: 04 April 2016
  • Accept Date: 28 April 2016

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