Pharmacology and toxicology
Most infections of adults with common nematodes like ascaris and trichuris will be asymptomatic, and there is rarely an indication for treatment during pregnancy. Severe infections with hookworms may cause anemia, responsible, if during pregnancy, for increased perinatal mortality and morbidity worldwide. The WHO estimates that as many as 44 million pregnant women throughout the world are infected with hookworms (WHO 1996B).
Mebendazole is a highly effective and well-tolerated drug against nematodes in the gastrointestinal tract (such as enterobius, ascaris, trichuris, ankylostoma - pinworms, round-worms, whipworms, and hookworms). The drug is poorly absorbed from the gut. Mebendazole exerts its action through inhibition of glucose uptake by the parasite, causing its starvation and death. Mebendazole had teratogenic effects in some animal studies. Conflicting results of several case reports and (retrospective) studies in hundreds of human pregnancies (including many first-trimester exposures) do not allow a well-founded estimation of human risk. However, an increased risk of congenital malformations was not observed in a study of over 400 pregnant women exposed to mebendazole in the first trimester (de Silva 1999). This was confirmed in a controlled prospective study, where 192 pregnancy outcomes were evaluated and compared with a matched control group (Diav-Citrin 2003). There was no increase in the rate of major malformations. In another prospective study on anthelmintics during pregnancy, where 64 women were exposed to mebendazole in the first trimester (Reuvers-Lodewijks 1999), only one malformation (bilateral clubfoot) was observed, which is below the expected background rate. Although numbers are too small for any definite conclusion, mebendazole does not appear to represent a major teratogenic risk. Improvement of prcgnancy outcomes (regarding stillbirths, peri natal deaths, and birth weight) was observed when mebendazole was used during the second and third trimesters in developing countries, where intestinal helminthiasis is endemic (de Silva 1999).
Flubendazole is structurally related to mebendazole. Teratogenicity has been reported in rats. No significant increase in major malformations was observed in a prospective study of 150 pregnancies after exposure to flubendazole in the first trimester (Reuvers-Lodewijks 1999), and a smaller prospective investigation covering 11 pregnancies (Choi 2005; sec also section 2.6.50).
Recommendation. Mebendazole may be used during pregnancy with helmintic infections that require treatment, but during the first trimester should only be used when strictly indicated and when treatment cannot be delayed. For the treatment of pin worms, pyrvinium, if available, is preferred, Inadvertent use during the first trimester does not require termination of pregnancy or additional diagnostic procedures. The same applies to flubendazole.
Pyrviniumembonate, which is not available in all countries, is effective against enterobius (pinworms) and is very poorly absorbed from the gastrointestinal tract. Embryo- or fetotoxicity has not been observed.
Recommendation. Pyrviniumembonate is the drug of choice for the treatment of enterobiasis/oxyuriasis.
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