2631 Primaquine

Pharmacology and toxicology

Primaquine, an 8-aminochinoline derivative, acts against vivax and ovale malaria by destroying the exoerythrocytic forms of the malaria parasite. It is used after suppressive therapy with chloroquine to eliminate the pathogen completely to prevent a relapse of vivax and ovale malaria. Primaquine should not be used in pregnancy because of the potential risk of hemolytic effects in the fetus. As yet, there arc no studies that permit a well-grounded risk assessment. However, there is no substantial evidence for a teratogenic potential in humans (Philips-Howard 1996).

Recommendation. Primaquine should not be used in pregnancy. Instead, it is recommended that weekly prophylaxis be continued in these cases, with 300mg chloroquine base, until delivery. After delivery, therapy with primaquine can be started. Inadvertent pregnancy exposure during the first trimester requires neither termination of pregnancy nor invasive diagnostic procedures.

2.6.32 Artemisinin derivatives

Pharmacology and toxicology

Artemisinin derivatives like artesunate, artemether, artemether dihy-droartemisinin, and artemotil are the most potent antimalarials available. These compounds combine rapid blood schizonticide activity with a wide therapeutic index. Artemisinin derivatives are used nowadays as artimisin-based-combination therapy (ACT) or as monotherapy for the treatment of inultidrug-resistant falciparum malaria. Recommended artimisin-based combinations are artemether plus lumefantrine, artesunate plus sulphadoxine/pyrimethamine, artesunate plus amodiaquine, and artesunate plus mefloquine.

Very limited experience with artemisinin use in the second and third trimesters did not demonstrate any adverse effects on the children (Philips-Howard 1996). In a prospective treatment study, artesunate (it = 528) or artemether (n = 11) was used to treat 539 episodes of acute P, falciparum malaria (44 episodes occurred during the first trimester). Birth outcomes were not significantly different from community rates for abortion, stillbirth, congenital abnormality, or mean duration of gestation. An earlier report from the same group on 83 women treated with artemisinin derivatives appears to be a subset of the more recent publication (McGready 200IB, 1998). In Gambia, a total of 287 pregnant women were exposed to artesunate plus sulphadoxine/pyrimethamine during a mass drug administration, and no increased risk of adverse pregnancy outcome was noted, comparing the exposed to the non-exposed pregnancies; 35 women were exposed in the first trimester (Deen 2001). In a small study (n = 28), no increased risk of adverse pregnancy outcome was found after the use of artemether for the treatment of falciparum malaria in the second or third trimester of pregnancy (Adam 2004A).

These reassuring data have led the WHO to sanction the use of artemisinin derivatives in the second and third trimesters of pregnancy for treatment of multidrug-resistant falciparum malaria (WHO 2002). However, first-trimester experience is still too limited for a well-grounded risk assessment.

Recommendation. The artemisinin derivatives can be used as monotherapy or as ACT (e.g. artesunate plus sulphadoxine/pyrimethamine, artesunate plus mefloquine) in the second and third trimesters of pregnancy for treatment of multidrug-resistant falciparum malaria. During first trimester, artemisinin derivatives should only be used if there is no safe and effective alternative. Inadvertent use of these antimalarials during the first trimester does not require termination of pregnancy. To evaluate fetal morphologic development, a detailed ultrasound examination can be considered after first-trimester exposure to artemisinin derivatives.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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