Safety, Pharmacokinetics and Efficacy of Artemisinins in Pregnancy

Veronica Ades

doi:10.4081/idr.2011.2412

Abstract

Malaria in pregnancy can lead to serious maternal and fetal morbidity and mortality. Access to the most effective antimalarials in pregnancy is essential. Resistance to current therapies is high for all antimalarial therapies except artemisinins. Artemisinin-based combination therapy is current the first line of malaria treatment recommended by the WHO for children, adults and pregnant women in second or third trimester. Due to potential embryotoxicity of artemisinins identified in animal studies, artemisinins are not considered safe for use in first trimester of pregnancy. Artemisinins are more rapidly metabolized in pregnant women, but this does not seem to reduce efficacy. Most studies show very high cure rates for pregnant women. Areas for further research include the safety profile in first trimester of pregnancy, the effect of HIV infection on artemisinin use in pregnancy, the relationship between the pharmacokinetic profile and efficacy, and the use of artemisinin-based combination therapy for intermittent preventive treatment in pregnancy.

Highlights

Malaria in pregnancy has been associated with poor pregnancy outcomes, including intrauterine growth restriction, low birth weight, spontaneous abortion, neonatal death, preeclampsia, maternal anemia, and maternal death.[1,2,3] Diagnosis of malaria in pregnancy is compromised by low parasitemia burdens associated with sequelae
There is a growing body of evidence in favor of the use of artemisinins in pregnancy; there are a number of unanswered questions that would benefit from further research
Artemisinins do appear to be safe in second and third trimester, but data from animal studies indicates that there is a teratogenic and embryolethal effect in rats, guinea pigs and rabbits. It is not clear whether this effect is reflected in humans, and there are some significant differences in human organogenesis as compared with rodent organogenesis that could have a protective effect for human fetuses

Summary

Introduction

Malaria in pregnancy has been associated with poor pregnancy outcomes, including intrauterine growth restriction, low birth weight, spontaneous abortion, neonatal death, preeclampsia, maternal anemia, and maternal death.[1,2,3] Diagnosis of malaria in pregnancy is compromised by low parasitemia burdens associated with sequelae. The WHO-recommended first-line treatment for malaria in first trimester of pregnancy is quinine plus clindamycin.[11] Data are limited on the effects of artemisinin-derived compounds in pregnancy. They are considered to be safe in second and third trimesters, but still requires further evaluation to determine if they are is safe in first trimester. Artemether Artemether was the first artemisinin derivative to be evaluated on a large scale.[12] It is most commonly administered in an oral co-formulation of artemether-lumefantrine and is a highly effective treatment for children and adults with uncomplicated malaria.[11] Because it is a fat-soluble compound, artemether is not ideal for intramuscular or intravenous administration, limiting its utility for severe malaria, which requires parenteral treatment.[12]. Four animal studies involving artesunate show similar patterns of anomalies and embryotoxicity seen with all artemisinin derivatives.[23,24,25,26]

50 Thailand Dihydroartemisinin-piperaquine

Findings

Discussion