Included as part of the PRECAUTIONS section.
Risk Of Convulsions
Convulsions have been reported in infants below the age
of 1 year during post-marketing experience with mebendazole [see ADVERSE
Agranulocytosis and neutropenia have been reported with
mebendazole use at higher doses and for more prolonged durations than is
recommended for the treatment of soil-transmitted helminth infections. Monitor
blood counts if VERMOX™ CHEWABLE is used at higher doses or for prolonged
Metronidazole Drug Interaction And Serious Skin Reactions
Stevens-Johnson syndrome/toxic epidermal necrolysis
(SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole.
Avoid concomitant use of mebendazole and metronidazole.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In carcinogenicity tests of mebendazole in mice and rats,
no carcinogenic effects were seen at doses as high as 40 mg/kg (0.4 to 0.8-fold
the MRHD, based on mg/m²) given daily over two years. No mutagenic activity was
observed with mebendazole in a bacterial reverse gene mutation test.
Mebendazole was mutagenic in the absence of S-9 when tested using a continuous
(24 hour) treatment incubation period in the mouse lymphoma thymidine kinase
assay. Mebendazole was aneugenic in vitro in mammalian somatic cells. In the in
vivo mouse micronucleus assay, orally administered mebendazole induced an
increased frequency of micronucleated polychromatic erythrocytes with evidence
suggestive of aneugenicity. Doses up to 40 mg/kg in rats (0.8-fold the MRHD,
based on mg/m²), given to males for 60 days and to females for 14 days prior to
gestation, had no effect upon fetuses and offspring.
Use In Specific Populations
The available published
literature on mebendazole use in pregnant women has not reported a clear
association between mebendazole and a potential risk of major birth defects or
miscarriages [see Data]. There are risks to the mother and fetus
associated with untreated helminthic infection during pregnancy [see
In animal reproduction studies,
adverse developmental effects (i.e., skeletal malformations, soft tissue
malformations, decreased pup weight, embryolethality) were observed when
mebendazole was administered to pregnant rats during the period of
organogenesis at single oral doses as low as 10 mg/kg (approximately 0.2-fold
the maximum recommended human dose (MRHD)). Maternal toxicity was present at
the highest of these doses [see Data].
The estimated background risk
of major birth defects and miscarriage for the indicated populations is
unknown. All pregnancies have a background risk of birth defect, loss, or other
adverse outcomes. In the U.S. general population, the estimated background risk
of major birth defects and miscarriage in clinically recognized pregnancies is
2-4% and 15-20%, respectively.
Disease-Associated Maternal And/Or
helminth infections in pregnancy are associated with adverse outcomes including
maternal iron deficiency anemia, low birth weight, neonatal and maternal death.
Several published studies, including prospective
pregnancy registries, case-control, retrospective cohort, and randomized
controlled studies, have reported no association between mebendazole use and a
potential risk of major birth defects or miscarriage. Overall, these studies
did not identify a specific pattern or frequency of major birth defects with
mebendazole use. However, these studies cannot definitely establish the absence
of any mebendazole-associated risk because of methodological limitations, including
recall bias, confounding factors and, in some cases, small sample size or
exclusion of first trimester mebendazole exposures.
Embryo-fetal developmental toxicity studies in rats
revealed no adverse effects on dams or their progeny at doses up to 2.5
mg/kg/day on gestation days 6-15 (the period of organogenesis). Dosing at
≥ 10 mg/kg/day resulted in a lowered body weight gain and a decreased
pregnancy rate. Maternal toxicity, including body weight loss in one animal and
maternal death in 11 of 20 animals, was seen at 40 mg/kg/day. At 10 mg/kg/day,
increased embryo-fetal resorption (100% were resorbed at 40 mg/kg/day),
decreased pup weight and increased incidence of malformations (primarily
skeletal) were observed. Mebendazole was also embryotoxic and teratogenic in
pregnant rats at single oral doses during organogenesis as low as 10 mg/kg
(approximately 0.2-fold the MRHD, based on mg/m²).
In embryo-fetal developmental toxicity studies in mice
dosed on gestation days 6-15, doses of 10 mg/kg/day and higher resulted in
decreased body weight gain at 10 and 40 mg/kg/day and a higher mortality rate
at 40 mg/kg/day. At doses of 10 mg/kg/day (approximately 0.1-fold the MRHD,
based on mg/m²) and higher, embryo-fetal resorption increased (100% at 40
mg/kg) and fetal malformations, including skeletal, cranial, and soft tissue
anomalies, were present. Dosing of hamsters and rabbits did not result in
embryotoxicity or teratogenicity at doses up to 40 mg/kg/day (0.6 to 1.6-fold
the MRHD, based on mg/m²).
In a peri-and post-natal toxicity study in rats,
mebendazole did not adversely affect dams or their progeny at 20 mg/kg/day. At
40 mg/kg (0.8-fold the MRHD, based on mg/m²), a reduction of the number of live
pups was observed and there was no survival at weaning. No abnormalities were
found on gross and radiographic examination of pups at birth.
Limited data from case reports demonstrate that a small
amount of mebendazole is present in human milk following oral administration.
There are no reports of effects on the breastfed infant, and the limited
reports on the effects on milk production are inconsistent. The limited clinical
data during lactation precludes a clear determination of the risk of VERMOX™
CHEWABLE to a breastfed infant; therefore, developmental and health benefits of
breastfeeding should be considered along with the mother's clinical need for
VERMOX™ CHEWABLE and any potential adverse effects on the breastfed infant from
VERMOX™ CHEWABLE or from the underlying maternal condition.
The safety and effectiveness of VERMOX™ CHEWABLE 500 mg
tablets have been established in pediatric patients 1 to 16 years of age. Use
of VERMOX™ CHEWABLE 500 mg tablets in children is supported by evidence from
adequate and well-controlled studies of VERMOX™ CHEWABLE 500 mg tablets [see Clinical
The safety and effectiveness of mebendazole, including
VERMOX™ CHEWABLE have not been established in pediatric patients less than one
year of age. Convulsions have been reported with mebendazole use in this age
group [see WARNINGS AND PRECAUTIONS and
Clinical studies of mebendazole did not include
sufficient numbers of subjects aged 65 and older to determine whether they
respond differently from younger subjects.
The safety and effectiveness of VERMOX™ CHEWABLE 500 mg
tablets have been established in adults for the treatment of gastrointestinal
infections by T. trichiura and A. lumbricoides. Use of VERMOX™
CHEWABLE 500 mg tablets in adults for these indications is supported by
evidence from an adequate and well-controlled trial in pediatric patients ages
1 to 16 years [see Clinical Studies], safety data in adults [see ADVERSE
REACTIONS], pharmacokinetic data in adults [see CLINICAL PHARMACOLOGY],
and the evidence from published literature.