[Long QTc interval complicating halofantrine therapy in 2 children with Plasmodium falciparum malaria].
Halofantrine has been shown to be very effective against multiple drug resistant falciparum malaria. It is usually administered in children at 24 mg/kg at six-hour intervals for three doses, and a second therapeutic course one week following the initial treatment is recommended. It is usually well tolerated. However, prolongation of the QT interval has been reported in adults receiving this drug for malaria.


METHODS
Two children experienced a prolongation of the QTc interval while receiving halofantrine. The first child, aged two years, had a prolonged QTc interval (490 ms) six hours after the third administration, at the usual therapeutic dose. The second child, aged six years, had a normal QT interval (360 ms) after the first 24 mg/kg dose and had a prolonged QTc (450 ms) during the second course seven days later, 15 h after the last dose. In both cases, the QTc interval returned to normal values (below 440 ms) rapidly after the end of treatment.


CONCLUSIONS
Cardiotoxic effects are felt to be dose-dependant and young children may be particularly at risk due to pharmacological and cardiac immaturity. Therefore, guidelines for drug administration should be followed (administration in a child with an empty stomach, drug not recommended in combination with drugs known to prolong the QTc interval) and monitoring ECG in pediatric patients may be justified. The modalities of the second course in children, which is recommended by the manufacturer to travellers from non-endemic areas, should also be discussed.
Olivier
C
C
Service de pédiatrie, hôpital Louis-Mourier, Colombes, France.
Rizk
C
C
Zhang
D
D
Jacqz-Aigrain
E
E
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D007223:Infant; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000175:diagnosis; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010616:Phenanthrenes / Q000008:administration & dosage / Q000009:adverse effects*
D000962:Antimalarials; D010616:Phenanthrenes; C023768:halofantrine