|Year : 2016 | Volume
| Issue : 1 | Page : 54-56
Artesunate-, sulfadoxine-, and pyrimethamine-induced cardiotoxicity
Divya Goel, Shafiqa Aslam, Rani Walia, Akshay Sadhotra
Department of Pharmacology, MMIMSR, Mullana, Ambala, Haryana, India
|Date of Submission||20-Apr-2016|
|Date of Acceptance||04-May-2016|
|Date of Web Publication||2-Jun-2016|
Department of Pharmacology, MMIMSR, Mullana, Ambala, Haryana
Source of Support: None, Conflict of Interest: None
Here, we report oral artesunate, sulphadoxine and pyrimethamine (sp) induced cardio toxicity case in a female patient. Artesunate is a highly efficacious and relatively safe antimalarial drug. Common adverse reactions to artemisinin derivatives are mild i.e. nausea, vomiting, anorexia and dizziness which are seen in majority of the patients. While serious toxic effects of artesunate are less frequent i.e., neutropenia, anemia, hemolysis, elevated liver enzymes, allergic reactions and cardiac effects. Cardiac effects due to artesunate are very rare. This case recalls the artesunate potential to cause myocardial injury.
Keywords: Artesunate, cardiotoxicity, malaria, sulfadoxine and pyrimethamine
|How to cite this article:|
Goel D, Aslam S, Walia R, Sadhotra A. Artesunate-, sulfadoxine-, and pyrimethamine-induced cardiotoxicity. BLDE Univ J Health Sci 2016;1:54-6
Malaria is one of the major public health problems of the country. Around 1.5 million laboratory-confirmed cases of malaria are annually reported in India.  The primary objective of treatment is to ensure the rapid and complete elimination of the Plasmodium parasite from the patient's blood to prevent the progression of uncomplicated malaria to chronic infection or severe disease/death.  Around 50% of the total malaria cases reported are due to Plasmodium falciparum.  P. falciparum infections are known to lead to severe malaria, if timely treatment with effective drugs is not administered. 
Successful malaria control depends greatly on treatment with efficacious antimalarial drugs. The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the P. falciparum and Plasmodium vivax parasite by combining the two active ingredients with different mechanisms of action and different biochemical targets in the parasite.  ACTs are the most effective antimalarial medicines available today. When two drugs are used with different modes of action and therefore different resistance mechanisms, then the per-parasite probability of developing resistance to both drugs at the same cell division is the product of their individual per-parasite probabilities. Hence, the chance of parasites simultaneously developing resistance as a result of genetic mutations to two drugs with different modes of action is much lower than the chance of parasites developing resistance to single drug. 
Studies have shown that Gambian children treated with sulfadoxine-pyrimethamine (SP) + artesunate (three doses) were five times less likely to produce infectious gametocytes as children treated with SP alone.  Adverse effects observed with artemisinins are mild and mainly consist of gastrointestinal symptoms (vomiting, diarrhea, abdominal pain, and anorexia), fatigue, and dizziness.  Cardiovascular effects of artesunate are extremely rare; here, we report a case of cardiac effects to oral intake of artesunate and SP.
| Case Report|| |
A 27-year-old female patient had low-grade fever associated with chills and occipital headache at night and malaise and body ache during the day for 8 days. As she was a medical graduate, she thought it is a viral flu infection and took paracetamol 500 mg SOS for this. After 8 days, when she did not get relief, she took tablet cefixime 200 mg BD herself. After 2 days of treatment with cefixime and paracetamol, she continued with fever, chills, and malaise. Then, she visited medical outpatient department and was prescribed paracetamol 500 mg BD and was advised PBF to rule out malaria. At the same time, she was advised to take larinate 200 for malaria if microscopy examination comes out to be positive. Larinate 200 kit contains 3 tablets of artesunate 200 mg, 3 tablets of sulfadoxine 500 mg and pyrimethamine 25 mg. She was advised to take four tablets at stat - one tablet of artesunate 200 mg and 3 tablets of sulfadoxine and pyrimethamine at stat on the 1 st day. She was suffering from fever with malaise for the past many days, so she took the tablets as written on larinate packing without waiting for the microscopy result. Next day in the morning, she was feeling dizzy, tingling sensation, and dry mouth. She was feeling dehydrated and had palpitations. She was rushed to emergency, her heart beat at that time was 150. She was given intravenous fluid, but still she had body aches, malaise, and chills. She was discharged in the evening. She stopped taking larinate, and her PBF also came out to be negative for malaria, but she continued to have palpitations. She was again rushed to hospital. Holter monitoring was done which showed tachycardia [Figure 1], heart rate - 150, and ectopic beats [Figure 2]. She had tachycardia for 1 week. After 10 days, Holter electrocardiogram (ECG) was done again which she was normal [Figure 3].
She was without any complaints after 4 weeks of therapy. However, as her wording, she gets nightmares about tachycardia as thumping heart will come out of her.
She also had a past history of adverse drug reaction to chloroquine. Few years ago, she took chloroquine 500 mg 2 tablets stat dose; after few hours, she felt dizzy and had diplopia.
| Discussion|| |
Artesunate is a derivative of the "quing hao," which has been used worldwide for more than 20 years for the treatment of malaria.
Antimalarial drugs produce many toxic effects, but artemisinins are well tolerated, with a low percentage of adverse effects. Adverse effects observed with artemisinins are mild and serious toxic effects such as neutropenia, anemia, hemolysis, and elevated levels of liver enzymes have been noted rarely. 
The signs and symptoms of cardiotoxicity are produced after the acute overdosage of artesunate. There is a paucity of reports of serious adverse effects with artesunate-based therapies.
In the present case, the patient was admitted to emergency department with tachycardia and hypotension after taking the combination of artesunate, sulfadoxin, and pyrimethamine.
Till date, there is no direct evidence for significant cardiovascular effects of artesunate, although a case of limited myocardial necrosis occurring just after the completion of antimalarial treatment with artemether/lumefantrine had been recently reported in an experimentally induced malaria in a 20-year-old healthy female volunteer, although its pathophysiological explanation was not clear.  In vitro studies have shown that artemisinin inhibits depolarizing as well as repolarizing action potentials by interacting with Na+ and K+ ion channels.  Administration of artesunate in dogs exhibited decreased heart rate and blood pressure and changes in the ECG. 
Although there is a lack of direct evidence of cardiotoxicity due to artemisinins, it has the potential to cause it. This patient also had a past history of intolerance to chloroquine. This cardiotoxicity could be a kind of intolerance to artesunate as the physician was unable to find any other cause of tachycardia.
| Conclusion|| |
Artesunate is a highly effective antimalarial and safe drug. However, the possibility of cardio-vascular effects of artesunate should always be kept in mind prior to its administration, especially in malaria-endemic regions.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]