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Archived Comments for: Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base

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  1. Halofantrine is too dangerous

    Francois Nosten, Shoklo Malaria Research Unit

    27 December 2009

    Halofantrine was discovered by the Walter Reed Army Institute of Research, developed by SmithKline Beecham (now GlaxoSmithKline), and registered in many countries. Despite this rigorous development, it was discovered after the general release of halofantrine that this effective antimalarial markedly prolongs ventricular repolarisation and thereby predisposes to potentially lethal ventricular tachyarrhythmias. Bouchaud et al (Malaria Journal; 2009, 8:289) review the fatalities associated with halofantrine reported to the manufacturer, and point out that the majority of patients who died had cofactors which would have predisposed them to lethal cardiotoxicity (this is also the case for other drugs with this property which have been withdrawn). They conclude that “in the rare situations in which halofantrine is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females”. We do not believe today that halofantrine is ever the only therapeutic option. Safe and highly effective alternative artemisinin-combination treatments are available. Mefloquine, lumefantrine, piperaquine, atovaquone and the artemisinins are not cardiotoxic. Careful exclusion of cardiac risk factors is unrealistic in most tropical settings. The case series presented here is likely to be an underestimate of the fatalities caused by the drug. Halofantrine should long ago have joined the list of drugs which prolong the QT interval and were withdrawn when their lethal potential became evident: terfenadine (1998), sertindole (1998), astemizole (1999), grepafloxacin (1999), and cisapride (2000). As much safer effective alternatives are available halofantrine is simply too dangerous still to be deployed.

    Francois Nosten (SMRU/MORU)
    Christine Luxemburger (SMRU)
    Feiko ter Kuile (Liverpool School Tropical Medicine)
    Charles Woodrow (MORU)
    Nicholas J White (MORU)

    Competing interests

    No competing interest to declare