Dihydroartemisinin-piperaquine-primaquine

The combination of dihydroartemisinin, piperaquine, and primaquine is used for the treatment of malaria, particularly for Plasmodium falciparum and Plasmodium vivax infections. This combination leverages the fast-acting properties of dihydroartemisinin (an artemisinin derivative), the long-lasting antimalarial effects of piperaquine, and primaquine's ability to eliminate liver stages and block transmission. ## Pharmacological Properties Dihydroartemisinin acts rapidly to clear asexual blood-stage parasites, while piperaquine provides a prolonged protective effect due to its long half-life. Primaquine is added to eliminate hypnozoites (dormant liver stages) in P. vivax infections and to reduce transmission by killing gametocytes. When administered together, these drugs show interesting pharmacokinetic interactions. Studies have shown that dihydroartemisinin-piperaquine significantly increases plasma primaquine levels, with geometric mean ratios of primaquine combined versus primaquine alone for maximum concentration (Cmax) at 148%, and area under the concentration-time curve at approximately 129%[1]. This interaction is similar to that observed between primaquine and chloroquine, and may enhance the radical curative effect of the combination. ## Clinical Efficacy The combination has demonstrated excellent efficacy in treating malaria infections. Dihydroartemisinin-piperaquine clears asexual P. vivax parasites faster than chloroquine and is more effective in blocking human-to-mosquito transmission[4]. The addition of primaquine to this combination provides radical cure by eliminating hypnozoites that could cause relapse. Dihydroartemisinin-piperaquine also provides excellent post-exposure prophylaxis against potential recurrences for more than two months due to piperaquine's long terminal elimination half-life[4]. ## Safety Profile The combination is generally well-tolerated. Like chloroquine, piperaquine can prolong the QT interval, though large randomized clinical trials have not revealed evidence of cardiotoxicity[5]. However, the World Health Organization recommends caution in patients with congenital QT prolongation or those taking other medications that prolong the QT interval. ## Resistance Concerns Resistance to piperaquine has been increasingly reported since 2010, particularly in Southeast Asia, with western Cambodia being the epicenter where over 40% of dihydroartemisinin-piperaquine treatments failed to eliminate parasites from patients' blood by 2014[5]. The mechanism of piperaquine resistance appears to involve amplification of parasite proteases plasmepsin 2 and plasmepsin 3, as well as mutations in the PfCRT gene[5]. ## Recommendations This triple combination aligns with the World Health Organization's recommendation to add a single dose of primaquine to artemisinin-based combination therapies (ACTs) to reduce P. falciparum transmission in low-transmission settings. Dihydroartemisinin-piperaquine is one of six ACTs recommended for uncomplicated malaria treatment[5].

Brand names

EurartesimDuoCotecxinArtekin

Other names

dihydroartemisinin/piperaquine + primaquineDHA/PPQ + PQDHA-PQP plus PQ