Clinical and non-clinical safety of artemisinin derivatives in pregnancy.

Malaria in pregnancy is a clinically wasting infectious disease, where drug therapy has to be promptly initiated. Currently, the treatment of this infection depends on the use of artemisinin derivatives. The World Health Organization does not recommend the use of these drugs in the first trimester of pregnancy due to non-clinical findings that have shown embryolethality and teratogenic effects. Nevertheless, until now, this toxicity has not been proved in humans. Artemisinin derivatives mechanisms of embryotoxicity are related to depletion of circulating embryonic primitive erythroblasts. Species differences in this sensitive period for toxicity and the presence of malaria infection, which could reduce drug distribution to the fetus, are significant to the risk assessment of artemisinin derivatives treatment to pregnant women. In this review we aimed to assess the results of non-clinical and clinical studies with artemisinin derivatives, their mechanisms of embryotoxicity and discuss the safety of their use during pregnancy.