ANALYTIC STUDY IN PATIENTS PRESENTING TO A TERTIARY CARE HOSPITAL REGARDING THE ARTEMETHER-LUMEFANTRINE INDUCED QTc INTERVAL CHANGES IN ECG
Abstract
Background: Malaria is one of the most common causes of morbidity and mortality in our part of the world. Artemether-Lumefantrine (AL) Combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. Some of the previous anti-malarial were associated with prolongation of QTc interval. Similar query was raised about AL therapy. This study was conducted to determine the risk of QTc interval prolongation in ECG of patients with Falciparum malaria using oral Artemether-Lumefantrine (AL) combination therapy. Methods: The venue of this analytical, quasi-experimental study was Medical Unit A, Khyber Teaching Hospital Peshawar, spanning 1st August 2015 to 31st July 2016. The study sample included male and female patients, having Plasmodium falciparum rings in their peripheral smear. These patients were treated with oral Artemether- Lumefantrine (AL) combination for 3 consecutive days in recommended doses. Electrocardiography (ECG) profile before and after 72 hours’ treatment with AL was noted for discernable QTc interval changes. The calculated prolongation of the QTc interval between these two study points was analyzed using Paired samples t-test. The statistically significant P value for this study was 0.05. SPSS version 23 was used for statistical analysis. Results: Amongst 200 cases, the QTc interval was noted to be normal before the start of the treatment in all. There was no significant prolongation of QTc interval following the treatment (p-value= 0.119) in the treated patients. It appears that cardiotoxicity is a remote adverse effect of AL combination therapy and that its use is safe in patients with Falciparum malaria. Conclusion: It can thus be concluded thatAL is a safe drug combination for the treatment of falciparum malaria with negligible cardiotoxic adverse effects.Keywords: Artemether- Lumefantrine (AL) combination Therapy; QTc interval; Arrhythmia; CardiotoxicityReferences
WHO. World Malaria Report 2008. [Internet]. [cited 2016 Sep 15]. Available from: http://apps.who.int/iris/bitstream/10665/43939/1/9789241563697_eng.pdf
WHO, editor. Guidelines for the treatment of malaria. Geneva: World Health Organization; 2006. p.253.
Prequalification Team - Medicines [Internet]. [cited 2016 Sep 15]. Available from: http://apps.who.int/prequal/default.htm
Novartis Drug Regulatory Affairs. Coartem®/Riamet® Dispersible (artemether/lumefantrine) Basic Prescribing Information. 2009.
Makanga M, Krudsood S. The clinical efficacy of artemether/lumefantrine (Coartem). Malar J 2009;8(Suppl 1):S5.
White NJ, Looareesuwan S, Warrell DA. Quinine and quinidine: a comparison of EKG effects during the treatment of malaria. J Cardiovasc Pharmacol 1983;5(2):173–5.
Nosten F, ter Kuile FO, Luxemburger C, Woodrow C, Kyle DE, Chongsuphajaisiddhi T, et al. Cardiac effects of antimalarial treatment with halofantrine. Lancet 1993;341(8852):1054–6.
Gundersen SG, Rostrup M, von der Lippe E, Platou ES, Myrvang B, Edwards G. Halofantrine-associated ventricular fibrillation in a young woman with no predisposing QTc prolongation. Scand J Infect Dis 1997;29(2):207–8.
Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS, et al. Fatal neurotoxicity of arteether and artemether. Am J Trop Med Hyg 1994;51(3):251–9.
Hien TH, Day NP, Nguyen HP, Nguyen TH, Tran TH, Pham PL, et al. A Controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med 1996;335(2):76–83.
Price R, van Vugt M, Phaipun L, Luxemburger C, Simpson J, McGready R, et al. Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives. Am J Trop Med Hyg 1999;60(4):547–55.
Vugt MV, Wilairatana P, Gemperli B, Gathmann I, Phaipun L, Brockman A, et al. Efficacy of six doses of artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 1999;60(6):936–42.
van Vugt M, Gathmann I, Looareesuwan S, Wilairatana P, McGready R, Villegas L, et al. Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg 2000;94(5):545–8.
Bazzet HC. An analysis of the time-relations of electrocardiograms. Heart 1920;7:353–70.
van Vugt M, Ezzet F, Nosten F, Gathmann I, Wilairatana P, Looareesuwan S, et al. No evidence of cardiotoxicity during antimalarial treatment with artemether-lumefantrine. Am J Trop Med Hyg 1999;61(6):964–7.
Matson PA, Luby SP, Redd SC, Rolka HR, Meriwether RA. Cardiac effects of standard-dose halofantrine therapy. Am J Trop Med Hyg 1996;54(3):229–31.
Traebert M, Dumotier B. Antimalarial drugs: QT prolongation and cardiac arrhythmias. Expert Opin Drug Saf 2005;4(3):421–31.
Touze JE, Bernard J, Keundjian A, Imbert P, Viguier A, Chaudet H, et al. Electrocardiographic changes and halofantrine plasma level during acute falciparum malaria. Am J Trop Med Hyg 1996;54(3):225–8.
Palmer KJ, Holliday SM, Brogden RN. Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1993;45(3):430–75.
Khandave SS, Joshi SS, Sawant SV, Onkar SV. Evaluation of bioequivalence and cardio-hepatic safety of a single dose of fixed dose combination of Artemether and Lumefantrine. J Bioequiv Availab 2010;2(4):81–5.
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