Mebendazole

Name: MEBENDAZOLE
Class: Anthelminthic
Risk Factor: CM

Fetal Risk Summary

Mebendazole is a synthetic anthelminthic agent. Although embryotoxic and teratogenic in rats at single oral doses as low as 10 mg/kg (approximately equal to the human dose based on mg/m2) (1), this effect has not been observed in multiple other animal species (2).
No reports of human teratogenicity caused by mebendazole have been located. One manufacturer has reports of 1st trimester mebendazole exposure in 170 pregnancies going to term without an identifiable teratogenic risk (1). There was also no increased risk of spontaneous abortion following 1st trimester exposure (1). An earlier manufacturer knew of only one malformation, a digital reduction of one hand, in 112 infants exposed in utero to the drug (3).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 64 newborns had been exposed to mebendazole during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Four (6.3%) major birth defects were observed (three expected), one of which was a limb reduction defect (none expected). No anomalies were observed in five other defect categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, and hypospadias) for which specific data were available.
During a 1984 outbreak of trichinosis (Trichinella spiralis) in Lebanon, four pregnant patients were treated with mebendazole and corticosteroids (4). Two women, both in the 1st trimester, had miscarriages. The authors did not mention if this was caused by the disease or the drug. Neither fetus was examined. The remaining two patients, both in the 3rd trimester, delivered healthy infants. In a separate case, a pregnant patient, also with trichinosis, was treated with mebendazole and delivered a normal infant (5). The period of pregnancy when the infection and treatment occurred was not specified.
In Sri Lanka, Necator americanus, one of the two known causes of hookworm, is endemic and it is an important contributor to iron-deficiency anemia in pregnancy (6). Consequently, the routine use of mebendazole is recommended in the 2nd trimester of pregnancy. A study published in 1999 compared the pregnancy outcomes of women treated with mebendazole (N=5,275) to a control group (N=1,737) that was not treated (6). There was no significant difference in the rate of major congenital malformations for exposures anytime during pregnancy, 1.8% (97 of 5,275) vs. 1.5% (26 of 1,737), odds ratio (OR) 1.24, 95% confidence interval (CI) 0.8–1.91. For 1st trimester exposure, the incidence was 2.5% (10 of 407), OR 1.66 95%, CI 0.81–3.56, p=0.23 (6). In other comparisons between the two groups, significant decreases occurred in the exposed group in the incidence of stillbirths and perinatal deaths (1.9% vs. 3.3%, p=0.0004), and low (Ј1500 g) birthweights (1.1% vs. 2.3%, p=0.0003) (6). The researchers concluded that, although there was no significant increase in the number of major defects associated with mebendazole, the agent should not be used during the 1st trimester, and a small increased risk of defects could not be excluded (6).
A 1985 review of intestinal parasites and pregnancy concluded that treatment of the pregnant patient should only be considered if the “parasite is causing clinical disease or may cause public health problems” (7). When indicated, mebendazole was recommended for the treatment of Trichuris trichiura (whipworm) occurring during pregnancy (7). A 1986 review recommended mebendazole therapy, when indicated, for the treatment of Ascaris lumbricoides (roundworm) and Enterobius vermicularis (threadworm, seatworm, or pinworm) (8), although another review recommended piperazine for this purpose, in spite of the known poor absorption of mebendazole (9).

Breast Feeding Summary

One nursing woman, in her 10th week of lactation, was treated with mebendazole (100 mg twice daily for 3 days) for a roundworm infection (10). Immediately before this she had been treated for 7 days with metronidazole for genital Trichomonas vaginalis. Milk production decreased markedly on the 2nd day of mebendazole therapy and stopped completely within 1 week. Although no mechanism was suggested, the author concluded that the halt in lactation was mebendazole-induced.
In contrast to the above report, a 1994 Reference described no effect on lactation or breast feeding in four postpartum women treated with mebendazole, 100 mg twice daily for 3 days, for various intestinal parasites (11). In one of the patients, the maternal plasma concentration of mebendazole at the end of therapy was below 20 ng/mL, and milk levels were undetectable. The authors attributed the decreased milk production in the case above to maternal anxiety from having passed a roundworm per rectum (11).
Based on the more recent data, breast feeding should not be withheld during mebendazole therapy. Only about 2%–10% of an oral dose is absorbed (12) and, as expected, the amounts of the drug excreted into milk are below the level of detection and appear to be clinically insignificant.

References

1. Product information. Vermox. McNeil Consumer, 2000.
2. Beard TC, Rickard MD, Goodman HT. Medical treatment for hydatids. Med J Aust 1978;1:633–5.
3. Shepard TH. Catalog of Teratogenic Agents, 8th ed. Baltimore, MD: Johns Hopkins University Press, 1995:261.
4. Blondheim DS, Klein R, Ben-Dror G, Schick G. Trichinosis in southern Lebanon. Isr J Med Sci 1984;20:141–4.
5. Draghici O, Vasadi T, Draghici G, Codrea A, Mihuta A, Dragan S, Biro S, Mocuja D, Mihuja S. Comments with Reference to a trichinellosis focus. Rev Ig (Bacteriol) 1976;21:99–104.
6. de Silva NR, Sirisena JLGJ, Gunasekera DPS, Ismail MM, de Silva HJ. Effect of mebendazole therapy during pregnancy on birth outcome. Lancet 1999;353:1145–9.
7. D'Alauro F, Lee RV, Pao-In K, Khairallah M. Intestinal parasites and pregnancy. Obstet Gynecol 1985;66:639–43.
8. Ellis CJ. Antiparasitic agents in pregnancy. Clin Obstet Gynecol 1986;13:269–75.
9. Leach FN. Management of threadworm infestation during pregnancy. Arch Dis Child 1990;65:399–400.
10. Rao TS. Does mebendazole inhibit lactation? NZ Med J 1983;96:589–90.
11. Kurzel RB, Toot PJ, Lambert LV, Mihelcic AS. Mebendazole and postpartum lactation. N Z Med J 1994;107:439.
12. American Hospital Formulary Service. Drug Information 1997. Bethesda, MD: American Society of Health-System Pharmacists, 1997:44–6.

Continue reading here: Vaccine, Varicella Virus

Was this article helpful?

0 0