Halofantrine Side Effects
Applies to halofantrine: oral tablet
Higher risk may be associated with larger than recommended doses, previous or concurrent mefloquine treatment, preexisting QT interval prolongation, or concurrent administration of other QT interval-prolonging drugs. Prolonged QTc interval has been reported in up to 81% of adults treated with standard halofantrine doses and in 100% of patients treated with high doses (72 mg/kg). Prolonged QTc interval has been reported in 50% of children and prolonged PR interval has been reported in 38% of children (n=21). Females may have a higher risk of adverse cardiovascular effects.
It has been proposed that halofantrine prolongs repolarization by blocking HERG potassium channels.[Ref]
Cardiovascular side effects have included QT interval prolongation, torsades de pointes, ventricular arrhythmias, and death. Chest pain and palpitations have been reported less than 1% of patients in clinical trials, and orthostatic hypotension has been reported in less than 1% to 33% of patients. Hypertensive crisis (1/933) and cerebrovascular accident (1/933) have been reported, although causality was not clearly established. Quinidine-like electrocardiographic changes have also been reported.[Ref]
Gastrointestinal (GI) side effects have included abdominal pain (8.5%), diarrhea (6%), vomiting (4.3%), and nausea (3.4%), although these symptoms may also occur with a malarial infection. Abdominal distention, anorexia, constipation, dyspepsia, and stomatitis have been reported in less than 1% of patients. GI upset has also been reported.[Ref]
Hematologic side effects have included decreased hematocrit, decreased or increased white blood cells, decreased platelet counts, hemolysis, and hemolytic anemia. These reactions may also occur with a malaria infection.[Ref]
Nervous system side effects have included dizziness (4.5%) and headache (3%). Asthenia, confusion, convulsions, depression, paresthesia, and sleep disorder have been reported in less than 1% of patients.[Ref]
Ocular side effects have included abnormal vision (less than 1%).[Ref]
Hepatic side effects have included increased hepatic transaminases, which returned to normal within 2 to 3 weeks.[Ref]
Renal side effects have included blackwater fever (acute intravascular hemolysis with acute renal failure and hemoglobinuria) requiring hemodialysis patients taking halofantrine for Plasmodium falciparum infections (n=2). Causality was not clearly established. One patient had a positive Coombs test.[Ref]
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3. "From the Centers for Disease Control and Prevention. Sudden death in a traveler following halofantrine administration--Togo, 2000." JAMA 285 (2001): 1836
4. Nosten F, ter Kuile FO, Luxemburger C, et al "Cardiac effects of antimalarial treatment with halofantrine." Lancet 341 (1993): 1054-6
5. Touze JE, Heno P, Fourcade L, et al. "The effects of antimalarial drugs on ventricular repolarization." Am J Trop Med Hyg 67 (2002): 54-60
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7. Mbai M, Rajamani S, January CT "The anti-malarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels." Cardiovasc Res 55 (2002): 799-805
8. White NJ, Pukrittayakamee S "Clinical malaria in the tropics." Med J Aust 159 (1993): 197-203
9. Sahr F, Willoughby VR, Gbakima AA, Bockarie MJ "Apparent drug failure following artesunate treatment of Plasmodium falciparum malaria in Freetown, Sierra Leone: four case reports." Ann Trop Med Parasitol 95 (2001): 445-9
10. Piippo K, Holmstrom S, Swan H, et al. "Effect of the antimalarial drug halofantrine in the long QT syndrome due to a mutation of the cardiac sodium channel gene SCN5A." Am J Cardiol 87 (2001): 909-11
11. "Sudden death in a traveler following halofantrine administration--Togo, 2000." MMWR Morb Mortal Wkly Rep 50 (2001): 169-70, 179
12. "Product Information. Halfan (halofantrine)." GlaxoSmithKline, Philadelphia, PA.
13. Karbwang J, Na Bangchang K "Clinical pharmacokinetics of halofantrine." Clin Pharmacokinet 27 (1994): 104-19
14. Sowunmi A, Fehintola FA, Ogundahunsi OA, Ofi AB, Happi TC, Oduola AM "Comparative cardiac effects of halofantrine and chloroquine plus chlorpheniramine in children with acute uncomplicated falciparum malaria." Trans R Soc Trop Med Hyg 93 (1999): 78-83
15. Winstanley P "Malaria: treatment." J R Coll Physicians Lond 32 (1998): 203-7
16. Ezeamuzie IC, Igbigbi PS, Ambakederemo AW, Abila B, Nwaejike IN "Halofantrine-induced pruritus amongst subjects who itch to chloroquine." J Trop Med Hyg 94 (1991): 184-8
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More about halofantrine
- During Pregnancy or Breastfeeding
- Dosage Information
- Drug Interactions
- 1 Review
- Drug class: miscellaneous antimalarials
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Some side effects may not be reported. You may report them to the FDA.