*Artesunate + sulfadoxine-pyrimethamine and artesunate-pyronaridine are not recommended for use in the first trimester of pregnancy. For details of treatment using ACTs in the first trimester of pregnancy, see 5.2.1.4.1 below.

Remarks Artesunate-pyronaridine is now included in the list of options for the treatment of uncomplicated malaria (2022). See the full recommendation and supporting evidence below.

Practical Info The pipeline for new antimalarial drugs is healthier than ever before, and several new compounds are in various stages of development. Some novel antimalarial agents are already registered in some countries. The decision to recommend antimalarial drugs for general use depends on the strength of the evidence for safety and efficacy and the context of use. In general, when there are no satisfactory alternatives, newly registered drugs may be recommended; however, for global or unrestricted recommendations, considerably more evidence than that submitted for registration is usually required, to provide sufficient confidence for their safety, efficacy and relative merits as compared with currently recommended treatments. Several new antimalarial drugs or new combinations have been introduced recently. Some are still in the pre-registration phase and are not discussed here. Arterolane + piperaquine, artemisinin + piperaquine base and artemisinin + napththoquine are new ACTs, which are registered and used in some countries. In addition, there are several new generic formulations of existing drugs. None of these yet has a sufficient evidence base for general recommendation (i.e. unrestricted use). Arterolane + piperaquine is a combination of a synthetic ozonide and piperaquine phosphate that is registered in India. There are currently insufficient data to make general recommendations. Artemisinin + piperaquine base combines two well-established, well-tolerated compounds. It differs from previous treatments in that the piperaquine is in the base form, the artemisinin dose is relatively low, and the current recommendation is for only a 2-day regimen. There are insufficient data from clinical trials for a general recommendation, and there is concern that the artemisinin dose regimen provides insufficient protection against resistance to the piperaquine component. Artemisinin + naphthoquine is also a combination of two relatively old compounds that is currently being promoted as a single-dose regimen, contrary to WHO advice for 3 days of the artemisinin derivative. There are currently insufficient data from rigorously conducted randomized controlled trials to make general recommendations. Many ACTs are generics. The bioavailability of generics of currently recommended drugs must be comparable to that of the established, originally registered product, and the satisfactory pharmaceutical quality of the product must be maintained. Please refer to Good procurement practices for artemisinin-based antimalaria medicines [175].