, Volume 72, Issue 7, pp 937-961
Date: 15 Dec 2012

Dihydroartemisinin/Piperaquine

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Abstract

Artemisinin-based combination regimens are recommended by WHO for the treatment of uncomplicated Plasmodium falciparum malaria. One such combination comprises the artemisinin derivative dihydroartemisinin and the bisquinolone piperaquine. Eurartesim® is the only dihydroartemisinin/piperaquine formulation that meets international good manufacturing practice standards. This article reviews the pharmacological properties of dihydroartemisinin and piperaquine, and the therapeutic efficacy and tolerability of dihydroartemisinin/piperaquine in the treatment of uncomplicated P. falciparum malaria.

A number of trials have shown dihydroartemisinin/piperaquine to be highly effective in the treatment of uncomplicated P. falciparum malaria. Two pivotal, randomized, open-label, multicentre trials demonstrated the Eurartesim® formulation of dihydroartemisinin/piperaquine to be noninferior to artesunate plus mefloquine in children and adults in Asia and noninferior to artemether/lumefantrine in children in Africa, in terms of polymerase chain reaction-corrected cure rates. In both trials, dihydroartemisinin/piperaquine recipients were significantly less likely than artesunate plus mefloquine recipients or artemether/lumefantrine recipients to experience reinfection. Gametocyte carriage was greater in patients receiving dihydroartemisinin/piperaquine than in those receiving comparator antimalarial regimens.

The Eurartesim® formulation of dihydroartemisinin/piperaquine was generally well tolerated in the treatment of uncomplicated P. falciparum malaria, and was associated with significantly less nausea, vomiting and dizziness than artesunate plus mefloquine. Although prolongation of the corrected QT interval has been reported in patients receiving dihydroartemisinin/piperaquine, there are currently no clinical data signalling that it is associated with clinically significant arrhythmias.

In conclusion, dihydroartemisinin/piperaquine is a valuable option for use in the first-line treatment of uncomplicated P. falciparum malaria.

Various sections of the manuscript reviewed by: M. Mayxay, University of Health Sciences and Wellcome Trust-Mahosot Hospital-Oxford University Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Laos; P. Piola, Epicentre, Paris, France; J. Tarning, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; N. Valecha, National Institute of Malaria Research, Delhi, India.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘dihydroartemisinin-piperaquine’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE and EMBASE search terms were ‘dihydroartemisinin-piperaquine’ or ‘piperaquine-dihydroartemisinin’ or ‘dihydroartemisinin plus piperaquine’. Searches were last updated 10 April 2012.
Selection: Studies in patients with uncomplicated Plasmodium falciparum malaria who received dihydroartemisinin/piperaquine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Dihydroartemisinin/piperaquine, uncomplicated Plasmodium falciparum malaria, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.