Disease Prevention and Control / Communicable Diseases / Malaria
Assessment of the Safety of Artemisinin Compounds in Pregnancy:Report of Two Informal Consultations Convened by WHO in 2002 | ||
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PAHO Malaria Page |
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Background and Executive SummaryVarious artemisinin compounds have been used as treatment for different forms of malaria since the early 1980s, initially in China, where they were first developed, and subsequently in many other countries. The literature on their use in pregnancy has been limited and animal studies have suggested that their use in pregnancy be restricted. With the increasing amount of interest in artemisinin combinations and artemisinin compounds in general, more studies—preclinical and clinical—are being envisaged and undertaken. In 2001, a WHO report concluded:1 "Preclinical studies have consistently shown that artemisinin and its derivatives do not exhibit mutagenic or teratogenic activity, but all of these drugs caused fetal resorption in rodents at relatively low doses of 1/200-1/400 of the LD50, i.e. > 10 mg/kg, when given after the sixth day of gestation. Reports on the use of these drugs during pregnancy are limited. However, malaria can be particularly hazardous during pregnancy. Artemisinin and its derivatives are therefore the drugs of choice for severe malaria and can be used for treatment of uncomplicated malaria during the second and third trimester of pregnancy in areas of multiple drug resistance. Owing to lack of data, their use in the first trimester is not recommended. The inadequacy of current knowledge on the use of these drugs during pregnancy should be understood by prescribers and all such use should, in principle, be monitored. Clinical outcomes of both a successful and adverse nature should be reported to regulatory authorities." With more data becoming available, it was time to re-evaluate existing data and policies on the use of artemisinin compounds in pregnancy. The 2000 WHO recommendations were reviewed in two consultations held in WHO in May and July of 2002. These reviews concluded with the following WHO recommendations for the use of artemisinin compounds in pregnancy. WHO Position Statement on the Current Use of Artemisinin Derivatives in Pregnancy Infection with Plasmodium falciparum malaria in pregnancy is dangerous to both the mother and her child, so efficacious treatment is important. There are limited data on the clinical safety of antimalarial therapies in pregnancy. Artemisinin compounds, alone or in combination with other antimalarials, represent a relatively new and highly efficacious treatment for malaria, and it is important to determine their safety and efficacy in pregnancy. Published data on 607 pregnancies in which artemisinin compounds were given during the second or third trimesters no evidence of treatment-related, adverse pregnancy outcomes. Similar data show normal outcomes in 124 pregnancies exposed to artemisinin compounds in the first trimester. These numbers are too small to provide an adequate profile of the safety of these compounds when used to treat malaria in pregnancy. In animal studies with artemisinin compounds, there is clear evidence of death of embryos and some evidence for morphological abnormalities in early pregnancy. There is also some evidence for adverse effects on fetal body weight and survival when the drug is given later in pregnancy. Further work is required to better understand the relevance of the animal data for humans. Presently, artemisinin compounds cannot be recommended for treatment of malaria in the first trimester. However, they should not be withheld if treatment is considered to be lifesaving for the mother and other antimalarials are considered to be unsuitable. Because the safety data are limited, artemisinin compounds should only be used in the second and third trimesters when other treatments are considered unsuitable. There is a need for further evidence of the safety of artemisinin compounds in pregnancy. All pregnant women treated with artemisinin compounds should be carefully followed up to document the pregnancy outcomes and subsequent development of the child and reported to the appropriate authorities. To guide the further development of policies on use of artemisinin derivatives, alone or in combination, during pregnancy, additional research and documentation of the efficacy and safety of the compounds as therapy for malaria, and as intermittent preventive treatment for malaria, is planned. WHO is monitoring the accumulating evidence on safety and efficacy of artemisinin compounds used in pregnancy. This position statement is under continuous review and will be updated as needed. 1 Antimalarial drug combination therapy. Report of a WHO Technical Consultation, Geneva, 4-5 April 2001 (document WHO/CDS/RBM/2001.35, available on request from CDS, World Health Organization, 1211 Geneva 27, Switzerland. Also available at http://www.rbm.who.int/).
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