Mebendazole

Mebendazole exerts its effect on helminths by causing degenerative changes in their tegument and intestinal cells. It achieves this by binding to the colchicine-sensitive site of tubulin, which inhibits the polymerization or assembly of microtubules. As a consequence, the susceptible parasites' larval and adult stages experience impaired uptake of glucose and depletion of glycogen stores. Additionally, the endoplasmic reticulum and the mitochondria in the germinal layer undergo degenerative alterations, leading to the release of lysosomes. This disruption ultimately results in a decreased production of adenosine triphosphate (ATP), which is vital for the helminth's survival. With diminished energy production, the parasite becomes immobilized and eventually perishes.

• Ancylostoma duodenale or Necator americanus - Hookworm
• Ascariasis - Roundworm
• Capillariasis
• Echinococcus, cystic
• Enterobiasis - Pinworm
• Toxocariasis
• Trichinellosis
• Trichostrongyliasis
• Trichuriasis - Whipworm

Ancylostoma duodenale or Necator americanus (Hookworm):

Oral: 100 mg twice daily for 3 days (manufacturer's labeling; CDC 2018b) or 500 mg as a single dose .

Repeat in 3 weeks if not cured with initial treatment.

Ascariasis (Roundworm):

Oral: 100 mg twice daily for 3 days or 500 mg as a single dose.

Repeat in 3 weeks if not cured with initial treatment.

Capillariasis (Off-Label Use):

Oral: 200 mg twice daily for 20 days .

Echinococcus, Cystic (Alternative Agent) (Off-Label Use):

Oral: 40 to 50 mg/kg/day in 3 divided doses for 3 to 6 months .

Enterobiasis (Pinworm):

Oral: 100 mg as a single dose (manufacturer's labeling).

Repeat in 2 weeks .

Toxocariasis (Off-Label Use):

Oral: 100 to 200 mg twice daily for 5 days.

Trichinellosis (Trichinella spiralis) (Off-Label Use):

Oral: 200 to 400 mg 3 times daily for 3 days, followed by 400 to 500 mg 3 times daily for 10 days .

Trichostrongyliasis (Off-Label Use):

Oral: 100 mg twice daily for 3 days .

Trichuriasis (Whipworm):

Oral: 100 mg twice daily for 3 days or 500 mg as a single dose.

Repeat in 3 weeks if not cured with initial treatment.

• Tablets: 100mg, 500mg

• Hookworm (Ancylostoma duodenale or Necator americanus):
• Limited data available in children <2 years: Oral: 100 mg twice daily for 3 days or 500 mg as a single dose; repeat in 3 weeks if not cured with initial treatment.
• Ascariasis (Ascaris lumbricoides; roundworm):
• Oral: 100 mg twice daily for 3 days or 500 mg as a single dose. Treatment can be repeated in 3 weeks if not cured with initial treatment; the 3-day regimen may be preferred in patients who remain infected after initial treatment.
• Capillariasis (Capillaria hepatica or Capillaria philippinensis):
• Limited data available: Oral: 200 mg twice daily for 20 days.
• Pinworm (Enterobius vermicularis):
• Limited data available in children <2 years: Oral: 100 mg as a single dose; repeat in 2 weeks.
• Toxocariasis (roundworm; ocular or visceral larva migrans):
• Limited data available: Oral: 100 to 200 mg twice daily for 5 days; however, longer duration may be necessary; optimal treatment duration is unknown.
• Trichinellosis (Trichinella species):
• Limited data available: Oral: 200 to 400 mg three times daily for 3 days, then 400 to 500 mg three times daily for 10 days; longer duration or repeat courses may be needed if treatment is not initiated promptly.
• Trichuriasis (Trichuris trichiura; whipworm):
• Limited data available in children <2 years: Oral: 100 mg twice daily for 3 days; repeat in 3 weeks if not cured with initial treatment.

• There are no specific dietary restrictions associated with the use of mebendazole. However, it is generally recommended to take mebendazole with water and not with grapefruit juice or milk, as these substances may interfere with the drug's absorption or metabolism.
• Additionally, it's a good practice to maintain a balanced and healthy diet while taking mebendazole, as proper nutrition can support your overall health and immune system, which may be essential in combating parasitic infections.

• Hypersensitivity to the active substance Mebendazole or to any of the excipients.

Risk of Convulsions:

During post-marketing experience with mebendazole, convulsions have been reported in infants below the age of 1 year .

Hematologic Effects:

Agranulocytosis and neutropenia have been reported with mebendazole use at doses higher and for longer durations than recommended for the treatment of soil-transmitted helminth infections. If Mebendazole is used at higher doses or for an extended period, it is essential to monitor blood counts.

Metronidazole Drug Interaction and Serious Skin Reactions:

Concomitant use of mebendazole and metronidazole has been associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To avoid potential risks, it is recommended to refrain from using mebendazole and metronidazole together.

Limited case reports indicate that a small quantity of mebendazole can be detected in human milk after oral administration. There is currently no evidence of any adverse effects on breastfed infants, and the reports on its impact on milk production are inconclusive. Due to the scarcity of clinical data during lactation, it is challenging to definitively assess the risk of Mebendazole to a breastfed infant. Therefore, when considering the use of Mebendazole, it is essential to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication and any potential adverse effects on the breastfed infant, either from Mebendazole itself or the underlying maternal condition.

Pregnancy Category C.

Risk Summary:

Available published literature on mebendazole use in pregnant women has not indicated a clear association between mebendazole and an increased risk of major birth defects or miscarriages. However, untreated helminthic infection during pregnancy poses risks to both the mother and fetus.

Animal reproduction studies have shown adverse developmental effects when mebendazole was administered to pregnant rats during the organogenesis period, even at single oral doses as low as 10 mg/kg (approximately 0.2-fold the maximum recommended human dose [MRHD]). Maternal toxicity was observed at the highest doses .

The estimated background risk of major birth defects and miscarriage in the indicated populations is unknown. All pregnancies carry a background risk of birth defects, 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 approximately 2-4% and 15-20%, respectively.

Clinical Considerations:

Untreated soil-transmitted helminth infections during pregnancy can lead to adverse outcomes, including maternal iron deficiency anemia, low birth weight, and neonatal and maternal death.

Data:

Human Data:

Numerous published studies, including prospective pregnancy registries, case-control, retrospective cohort, and randomized controlled studies, have not found an association between mebendazole use and a significant risk of major birth defects or miscarriages. While these studies did not identify a specific pattern or frequency of major birth defects associated with mebendazole use, the findings are limited by methodological constraints, such as recall bias, confounding factors, and, in some cases, small sample sizes or exclusion of first-trimester mebendazole exposures.

Animal Data:

In embryo-fetal developmental toxicity studies conducted on rats, mebendazole doses up to 2.5 mg/kg/day on gestation days 6-15 showed no adverse effects on dams or their progeny. However, dosing at ≥10 mg/kg/day resulted in reduced body weight gain and decreased pregnancy rate. Maternal toxicity, including body weight loss and maternal death, was observed at 40 mg/kg/day. At 10 mg/kg/day, increased embryo-fetal resorption, decreased pup weight, and an elevated incidence of malformations (primarily skeletal) were observed. Mebendazole was also found to be 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 and higher (approximately 0.1-fold the MRHD, based on mg/m2), there was an increased embryo-fetal resorption (100% at 40 mg/kg) and the presence of fetal malformations, including skeletal, cranial, and soft tissue anomalies. However, dosing of hamsters and rabbits did not lead to 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. However, at 40 mg/kg (0.8-fold the MRHD, based on mg/m2), a reduction in the number of live pups was observed, and there was no survival at weaning. No abnormalities were found upon gross and radiographic examination of pups at birth.

• High-Fat Meals: Taking mebendazole with a high-fat meal may lead to a modest increase in the drug's bioavailability. It is recommended to follow the dosing instructions and take the medication as directed, regardless of food intake.
• Grapefruit Juice: Avoid consuming grapefruit juice while taking mebendazole, as it may interfere with the drug's metabolism and lead to higher levels of the medication in the bloodstream.
• Alcohol: It is advisable to avoid consuming alcohol during mebendazole treatment, as alcohol may interact with the drug and increase the risk of adverse effects or impact liver function.
• Milk or Dairy Products: Some sources suggest that taking mebendazole with milk or dairy products may enhance its absorption. However, it is generally recommended to take mebendazole with water or as directed by your healthcare provider.

Common:

● Abdominal pain or discomfort

● Diarrhea

● Nausea

● Vomiting

● Dizziness

● Headache

● Rash or itching

Less common:

● Fatigue or weakness

● Fever

● Loss of appetite

● Stomach cramps

● Excessive gas or bloating

Rare:

● Allergic reactions, such as hives or difficulty breathing

● Jaundice (yellowing of the skin or eyes)

● Unusual bleeding or bruising

● Dark urine

● Persistent sore throat or fever

● Severe skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis

• Concurrent administration of cimetidine may hinder the liver's metabolism of mebendazole, leading to higher levels of the drug in the bloodstream, especially during prolonged treatment. In such cases, it is advisable to monitor plasma concentrations and make necessary dose adjustments.
• Findings from a case-control study investigating an outbreak of Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/ TEN) indicated a potential link between SJS/ TEN and the simultaneous use of mebendazole and metronidazole. However, additional data supporting this drug-drug interaction are currently unavailable. Hence, it is recommended to avoid the concomitant use of mebendazole and metronidazole.

● Sudden weakness

● Red or swollen gums

● Difficulty swallowing

● Easy bruising or bleeding

● Feeling unwell

● Fever

● Chills

● Sore throat

● Mouth sores

● Swelling in your face or tongue

● Sores around your eyes, nose, mouth, or genitals

● Hives

● Skin rash that spreads and leads to blistering or peeling

Pregnancy Category C

Risk Summary:

Available published literature on mebendazole use in pregnant women has not indicated a clear association between mebendazole and an increased risk of major birth defects or miscarriages. However, untreated helminthic infection during pregnancy poses risks to both the mother and fetus.

Animal reproduction studies have shown adverse developmental effects when mebendazole was administered to pregnant rats during the organogenesis period, even at single oral doses as low as 10 mg/kg (approximately 0.2-fold the maximum recommended human dose [MRHD]). Maternal toxicity was observed at the highest doses [see Data].

The estimated background risk of major birth defects and miscarriage in the indicated populations is unknown. All pregnancies carry a background risk of birth defects, 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 approximately 2-4% and 15-20%, respectively.

Clinical Considerations:

Untreated soil-transmitted helminth infections during pregnancy can lead to adverse outcomes, including maternal iron deficiency anemia, low birth weight, and neonatal and maternal death.

Data:

Human Data:

Numerous published studies, including prospective pregnancy registries, case-control, retrospective cohort, and randomized controlled studies, have not found an association between mebendazole use and a significant risk of major birth defects or miscarriages. While these studies did not identify a specific pattern or frequency of major birth defects associated with mebendazole use, the findings are limited by methodological constraints, such as recall bias, confounding factors, and, in some cases, small sample sizes or exclusion of first-trimester mebendazole exposures.

Animal Data:

In embryo-fetal developmental toxicity studies conducted on rats, mebendazole doses up to 2.5 mg/kg/day on gestation days 6-15 showed no adverse effects on dams or their progeny. However, dosing at ≥10 mg/kg/day resulted in reduced body weight gain and decreased pregnancy rate. Maternal toxicity, including body weight loss and maternal death, was observed at 40 mg/kg/day. At 10 mg/kg/day, increased embryo-fetal resorption, decreased pup weight, and an elevated incidence of malformations (primarily skeletal) were observed. Mebendazole was also found to be 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 and higher (approximately 0.1-fold the MRHD, based on mg/m2), there was an increased embryo-fetal resorption (100% at 40 mg/kg) and the presence of fetal malformations, including skeletal, cranial, and soft tissue anomalies. However, dosing of hamsters and rabbits did not lead to 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. However, at 40 mg/kg (0.8-fold the MRHD, based on mg/m2), a reduction in the number of live pups was observed, and there was no survival at weaning. No abnormalities were found upon gross and radiographic examination of pups at birth.

Lactation

Limited case reports indicate that a small quantity of mebendazole can be detected in human milk after oral administration. There is currently no evidence of any adverse effects on breastfed infants, and the reports on its impact on milk production are inconclusive. Due to the scarcity of clinical data during lactation, it is challenging to definitively assess the risk of Mebendazole to a breastfed infant. Therefore, when considering the use of Mebendazole, it is essential to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication and any potential adverse effects on the breastfed infant, either from Mebendazole itself or the underlying maternal condition.

The safety and efficacy of Mebendazole tablets have been proven in pediatric patients aged 1 to 16 years. The use of Mebendazole tablets in children is supported by substantial evidence from well-controlled studies. However, it's important to note that the safety and effectiveness of mebendazole, including Mebendazole, have not been established in pediatric patients younger than one year of age. Convulsions have been reported in this age group with the use of mebendazole.

Rarely, patients treated with significantly higher than recommended dosages and/or for extended periods may experience the following adverse reactions: alopecia, reversible liver function disturbances, hepatitis, agranulocytosis, neutropenia, and glomerulonephritis. It is worth noting that, except for agranulocytosis and glomerulonephritis, these adverse reactions have also been reported in patients treated with standard dosages of Mebendazole.

In the case of accidental overdose, patients may experience symptoms such as abdominal cramps, nausea, vomiting, and diarrhea.

There is no specific antidote for mebendazole overdose. If deemed appropriate, activated charcoal may be administered to aid in the removal of unabsorbed drug. General supportive measures are recommended to manage any potential overdose effects.

Mebendazole is a synthetic anthelmintic with a broad-spectrum activity. Its primary mechanism of action involves inhibiting tubulin polymerization, leading to the disruption and loss of cytoplasmic microtubules.

Absorption:

● Oral Bioavailability: Less than 10% of the administered dose reaches the systemic circulation due to incomplete absorption and significant pre-systemic metabolism (first-pass effect).

● Time to Peak Plasma Concentration: Maximum plasma concentrations are typically observed 2 to 4 hours after oral administration.

● Effect of High-Fat Meal: Dosing with a high-fat meal leads to a slight increase in the bioavailability of mebendazole.

Distribution:

● Plasma Protein Binding: Mebendazole exhibits high plasma protein binding, ranging from 90 to 95%.

● Volume of Distribution: The volume of distribution is 1 to 2 L/kg, indicating that mebendazole can penetrate tissues beyond the vascular space. Data from patients on chronic mebendazole therapy suggests drug distribution in various tissues.

Metabolism:

● Hepatic Metabolism: Mebendazole is extensively metabolized by the liver after oral administration.

● Metabolites: Major metabolites, such as amino and hydroxylated amino forms of mebendazole, are present in significantly higher concentrations in plasma compared to mebendazole itself.

● Influence of Impaired Liver Function: Impaired hepatic function, metabolism, or biliary elimination may result in elevated plasma levels of mebendazole.

Elimination:

● Excretion Pathways: Mebendazole, its conjugated forms, and metabolites likely undergo enterohepatic recirculation and are excreted in both urine and bile.

● Elimination Half-Life: The apparent elimination half-life after oral administration ranges from 3 to 6 hours in most patients.

1. Farahmandian I, Arfaa F, Jalali H, Reza M. Comparative studies on the evaluation of the effect of new anthelminthics on various intestinal helminthiasis in Iran. Effects of anthelminthics on intestinal helminthiasis. Chemotherapy. 1977;23(2):98-105. [PubMed 318981]
Franchi C, Di Vico B, Teggi A. Long-term evaluation of patients with hydatidosis treated with benzimidazole carbamates. Clin Infect Dis. 1999;29(2):304-309. [PubMed 10476732]
Gyorkos TW, Larocque R, Casapia M, et al, "Lack of Risk of Adverse Birth Outcomes After Deworming in Pregnant Women," Pediatr Infect Dis J, 2006, 25(9):791-4. [PubMed 16940835]
Gyorkos TW, St-Denis K. Systematic review of exposure to albendazole or mebendazole during pregnancy and effects on maternal and child outcomes, with particular reference to exposure in the first trimester. Int J Parasitol. 2019;49(7):541-554. [PubMed 31071321]
Horstmann RD, Kern P, Volkmer KJ, Dietrich M. Observations on mebendazole vs. thiabendazole in the treatment of human trichinellosis. Tropenmed Parasitol. 1982;33(3):191-194. [PubMed 7135477]
Hotez PJ, “Hookworm Disease in Children,” Pediatr Infect Dis J, 1989, 8(8):516-20. [PubMed 2671907]
Kahan Y, Lugassy-Akian E, Ovadia A, Dalal I, Somekh E, Tasher D. Safety and tolerability of mebendazole in infants under 1 year of age. J Pediatric Infect Dis Soc. 2021;10(11):1015-1017.