Name ALBENDAZOLE
Class: Anthelmintic Risk Factor: CM
FeM..Risk..Summary
BreasiFeeding.Summary
References
H3>Fetal Risk Summary
Albendazole is an orally administered, benzimidazole class, broad-spectrum anthelmintic used in the treatment of parenchymal neurocysticerosis caused by larval forms of the pork tapeworm, Taenia solium. It is also active against the larval forms of Echinococcus granulosus. Plasma concentrations of albendazole are negligible or undetectable because of poor systemic absorption attributable to low water solubility and its rapid hepatic metabolism to the active metabolite, albendazole sulfoxide (1). However, administration of albendazole with a fatty meal will markedly increase the levels of the metabolite in human plasma (up to 5-fold on average) (1).
Reproduction studies have been conducted in mice, rats, and rabbits (1). In rats, albendazole did not adversely affect male or female fertility at oral doses 0.32 times the recommended human dose (RHD) based on body surface area. The drug was embyrotoxic and teratogenic (skeletal malformations) in pregnant rats at oral doses of 10 mg/kg/day and 30 mg/kg/day (0.10 and 0.32 times the RHD, respectively) administered during organogenesis. Similar toxicity was observed in pregnant rabbits at 30 mg/kg/day (0.60 times the RHD) during organogenesis. However, the dose in rabbits was maternally toxic (33% mortality). No teratogenicity was observed in mice given oral doses up to 0.16 times the RHD (30 mg/kg/day) during organogenesis (1).
A reproductive study in rats examined the effect of oral albendazole (0, 10, or 20 mg/kg/day) administered on gestational days 9 to 11 (2). Compared to controls, the 10 mg/kg dose resulted in a decrease in crown-rump length, a small increase in resorptions, but no teratogenicity. The high dose, however, caused marked fetal growth retardation, an increase in the number of resorptions, and craniofacial and skeletal malformations. Because the severity of the toxic effects differed significantly among the litters, the results suggested that differences in maternal metabolism of albendazole might be involved (2).
In another report by the above researchers, pregnant rats were administered albendazole 0, 10, 20, or 30 mg/kg/day on gestational days 10 to 12 (3). Dose-related resorptions and growth retardation were observed in the three groups receiving albendazole. At 10 mg/kg/day, increased development delay of limb buds was observed, but less than 5% of the embryos had abnormal heads or shapes. At the two higher doses, however, more than 20% of the embryos had morphologic alterations in head shapes and in the development of forelimb buds, branchial bars, eyes, and telencephalon (3). As in their initial communication, the researchers concluded that differences in maternal metabolism may have accounted for the observed interlitter differences in adverse fetal outcomes (3).
It is not known if albendazole or its active metabolite, albendazole sulfoxide, crosses the placenta. The molecular weight of the parent compound (about 265) is low enough for transfer, but the poor oral bioavailability suggests that little, if any, of this agent reaches the plasma. No information is available on the metabolite other than that portions of it undergo further oxidative metabolism before elimination (1).
A brief 1993 publication reported the "accidental" exposure to "high doses" (specific doses not given) of albendazole for systemic infections during the 1st trimester in 10 women (4). The women were followed to term, and all delivered normal infants. Moreover, some of the offspring have been followed for up to 1 year without noting any adverse effects from the exposure (4).
In a randomized, placebo-controlled field trial in western Sierra Leone, anthelmintic treatment was studied as part of a strategy to control maternal anemia caused by parasitic infections (5). A single oral dose of albendazole (400 mg) was given to 61 pregnant women in the 2nd trimester. No adverse pregnancy outcomes attributable to the drug were observed.
In summary, albendazole is a broad-spectrum anthelmintic that is used both in humans and in mass treatments of farm animals (3,6). Although the human use of albendazole is apparently widespread (3), the published human pregnancy data are too limited to assess its fetal risk. The drug is embryo toxic and teratogenic in rats and rabbits, but not in mice at the dose tested. One source stated that the developmental toxicity of albendazole observed in animals was attributable to the active metabolite, albendazole sulfoxide (3). At least in rats, the oral bioavailability of albendazole is much higher than in humans: 1% in humans vs. 20% to 30% in rats (3). Because of the limb reduction defects observed at all doses in one animal study, the potential for much higher plasma concentrations of the metabolite if the drug is consumed with a fatty meal, and the very limited human pregnancy data, the use of albendazole during pregnancy is not recommended. If albendazole is required during pregnancy, avoiding the 1st trimester is strongly advised. A 1997 review also concluded that 1st trimester exposure to albendazole should be avoided (5).
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