Anthelmintic
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Albendazole is a broad-spectrum anthelmintic that is used both in humans and in mass treatments of farm animals (1,2). The human use of albendazole is apparently widespread (1). The animal data suggest risk, but the poor oral bioavailability in humans suggests low risk. One source stated that the developmental toxicity of albendazole observed in animals was attributable to the active metabolite, albendazole sulfoxide (1). Moreover, in rats, the bioavailability is much higher than in humans (20%–30% vs. 1%). There is a potential, though, for much higher plasma concentrations of the metabolite if the drug is consumed with a fatty meal. If albendazole is required during pregnancy, avoiding the 1st trimester should be considered (2).
FETAL RISK SUMMARY
Albendazole is an orally administered, benzimidazole class, broad-spectrum anthelmintic used in the treatment of parenchymal neurocysticercosis 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. However, administration of albendazole with a fatty meal will markedly increase the levels of the metabolite in human plasma (up to fivefold on average) (3).
Reproduction studies have been conducted in mice, rats, and rabbits. In rats, albendazole did not adversely affect male or female fertility at oral doses 0.32 times the recommended human dose based on BSA (RHD). The drug was embryotoxic and teratogenic (skeletal malformations) in pregnant rats given oral doses during organogenesis that were 0.10 and 0.32 times the RHD, respectively. Similar toxicity was observed in pregnant rabbits at 0.60 times the RHD, but the dose was maternally toxic (33% mortality). No teratogenicity was observed in mice given oral doses up to 0.16 times the RHD during organogenesis (3).
A reproductive study in rats examined the effect of oral albendazole (0, 10, or 20 mg/kg/day) administered on gestational days 9–11. Compared with 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 restriction, 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 (4).
In another report by the above researchers, pregnant rats were administered albendazole 0, 10, 20, or 30 mg/kg/day on gestational days 10–12 (1). Dose-related resorptions and growth restriction were observed in the three groups receiving albendazole. At 10 mg/kg/day, increased development delay of limb buds was observed, but <5% of the embryos had abnormal heads or shapes. At the two higher doses, however, >20% of the embryos had morphologic alterations in head shapes and in the development of forelimb buds, branchial bars, eyes, and telencephalon. As in their initial communication, the researchers concluded that differences in maternal metabolism might have accounted for the observed interlitter differences in adverse fetal outcomes (1).
It is not known if albendazole or its active metabolite, albendazole sulfoxide, cross 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 (3).
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 (5). The women were followed up to term, and all delivered normal infants. Moreover, some of the offspring have been followed up for up to 1 year without noting any adverse effects from the exposure (5).
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 (6). 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 (6).
Several reports have described the use of albendazole during human pregnancy as either single dose or multiple doses. No adverse effects of the drug were observed in the offspring (7–13).
BREASTFEEDING SUMMARY
Consistent with its molecular weight (about 265) and negligible bioavailability, very low amounts of albendazole and its active metabolite are excreted into breast milk. In a 2009 report, 33 women who were breastfeeding healthy full-term infants between 2 weeks and 6 months after birth received a single 400-mg dose of albendazole (14). Milk samples were collected at 6, 12, 24, and 36 hours after the dose and maternal blood samples were obtained at 6 hours. The mean peak milk concentrations of the parent drug and active metabolite, occurred at 6 hours, 31.9 and 312.8 ng/mL, respectively. At 36 hours, the parent drug was not detected in milk. The milk:maternal serum ratios (range) for the parent drug and active metabolite were 0.9 (0.2–6.5) and 0.6 (0.1–1.5), respectively. The authors concluded that the low concentrations in milk were unlikely to cause harm in a nursing infant (14).
A 2002 reference concluded that a single oral dose could be given to pregnant and lactating women (15).
References
1.Mantovani A, Ricciardi C, Stazi AV, Macri C. Effects observed on gestational day 13 in rat embryos exposed to albendazole. Reprod Toxicol 1995;9:265–73.
2.de Silva N, Guyatt H, Bundy D. Anthelmintics. A comparative review of their clinical pharmacology. Drugs 1997;53:769–88.
3.Product information. Albenza. SmithKline Beecham Pharmaceuticals, 2001.
4.Mantovani A, Macri C, Stazi AV, Ricciardi C. Effects of albendazole on the early phases of rat organogenesis in vivo: preliminary results (abstract). Teratology 1992;46:25A.
5.Horton J. The use of antiprotozoan and anthelmintic drugs during pregnancy and contraindications. J Infect 1993;26:104–5.
6.Torlesse H, Hodges M. Anthelmintic treatment and haemoglobin concentrations during pregnancy. Lancet 2000;356:1083.
7.Auer H, Kollaritsch H, Juptner J, Aspock H. Albendazole and pregnancy. Appl Parasitol 1994;35:146–7.
8.Cowden J, Hotez P. Mebendazole and albendazole treatment of geohelminth infections in children and pregnant women. Pediatr Infect Dis J 2000;19:659–60.
9.Torlesse H, Hodges. Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone). Trans R Soc Trop Med Hyg 2001;95:195–201.
10.Montes H, Soetkino R, Carr-Locke DL. Hydatid disease in pregnancy. Am J Gastroenterol 2002;97:1553–5.
11.Can D, Oztekin O, Oztekin O, Tinar S, Sanci M. Hepatic and splenic hydatid cyst during pregnancy: a case report. Acta Gynecol Obstet 2003;268:239–40.
12.Elliott AM, Quigley MA, Nampijja M, Muwanga M, Ndibazza J, Whitworth JAG. Helminth infection during pregnancy and development of infantile eczema. JAMA 2005;294:2032–4.
13.Yilmaz N, Kiymaz N, Etlik O, Yazici T. Primary hydatid cyst of the brain during pregnancy—case report. Neurol Med Chir (Tokyo) 2006;46:415–7.
14.Abdel-Tawab AM, Bradley M, Ghazaly EA, Horton J, El-Setouhy M. Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole. Br Clin Pharmacol 2009;68:737–42.
15.Allen HE, Crompton DWT, de Silva N, LoVerde PT, Olds GR. New policies for using anthelmintics in high risk groups. Trends Parasitol 2002;18:381–2.