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Mebendazole
12 PA R T
DRUGS USED IN TROPICAL MEDICINE
Mebendazole Allyson K Bloom, Edward T Ryan DESCRIPTION
DOSE
Methyl 5-benzoylbenzimidazole-2-carbamate.
For adults and children >2 years of age unless otherwise indicated.
AVAILABLE PRODUCTS
l
1. Mebendazole chewable tablets (generic mebendazole, Teva Pharmaceuticals) are available in 100 mg. 2. Mebendazole oral tablets can also be found under other names in other countries, including Anelmin®, Pantelmin® and Wormin®. 3. The manufacturer has discontinued production of mebendazole in the US.
INDICATIONS 1. Treatment of infections caused by nematodes, including Ascaris spp., hookworm, Enterobius spp., Trichuris spp., Trichinella spp., visceral and cutaneous larva migrans and Capillaria spp. 2. Mebendazole has also been reported to shorten the course of Angiostrongylus infection (unlabeled). 3. Mebendazole has been used for treatment of echinococcal disease as second-line therapy behind albendazole (unlabeled).
MODE OF ACTION Benzimidazoles bind to, and inhibit the polymerization of, betatubulin. This inhibits cytoplasmic microtubule formation and glucose uptake within the parasite. This leads to immobilization and death of adult worms.
PHARMACOKINETICS Bioavailability of mebendazole is poor, but is increased when ingested with food. As a result of poor absorption it can be used to target luminal-dwelling adult worms. Higher doses and longer courses are required for treatment of systemic disease. Absorbed drug undergoes rapid, first pass hepatic metabolism into inactive metabolites and excretion of absorbed drug is half renal and half biliary. There is significant intra- and inter-individual variability.
DOSE ADJUSTMENTS IN RENAL FAILURE Adjustments for short courses are likely unnecessary. Close monitoring of long-term therapy is recommended.
DOSE ADJUSTMENTS IN LIVER FAILURE Close monitoring of long-term therapy is recommended if biliary obstruction is present.
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Treatment of ascariasis and trichuriasis: 100 mg twice daily for three days or 500 mg once (drug of choice, but some studies report low cure rates for triuchuriasis). Treatment of capillariasis: 200 mg twice daily for 21 days (second-line therapy behind albendazole). Treatment of enterobiasis: 100 mg once, repeat at two weeks. Treatment of hookworm: 100 mg twice daily for three days (less effective than albendazole for Necator spp.). Treatment of trichinellosis: 200–400 mg three times daily for three days then 400–500 mg three times daily for 10 days (with steroids; second-line therapy behind albendazole). Treatment of visceral larva migrans: 100–200 mg twice daily for five days. Treatment of strongyloidiasis: 100 mg twice daily for three days (longer therapy may be required for cure; second-line therapy behind ivermectin). Treatment of mansonellosis: 100 mg twice daily for 21 days (second-line therapy, but may be alternate to diethylcarbamazine [DEC] in onchocerca-endemic areas). Treatment of echinococcal hydatid disease: 20–50 mg/kg daily for 3–6 months (second-line therapy behind albendazole). Treatment of alveolar echinococcosis: 20–50 mg/kg daily for prolonged course (second-line therapy behind albendazole).
ROUTE OF ADMINISTRATION Oral.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS Generally very well tolerated, especially for courses of three days or less. Abdominal pain, diarrhea and elevated liver function tests have been reported. With prolonged therapy and higher-thanrecommended doses, neutropenia and hepatitis have rarely occurred. Rare hypersensitivity reactions include rash, urticaria and angioedema.
KEY DRUG INTERACTIONS Decreased mebendazole levels have been reported when mebendazole has been co-administered with phenytoin or carbamazepine,
M ebendazole
and dose increases may be warranted in treatment of systemic infections.
CONTRAINDICATIONS Avoid if previous serious adverse effect or hypersensitivity.
USE IN SPECIAL POPULATIONS PREGNANCY Category C. Mebendazole is teratogenic in animals, but has not been well studied in humans. No increased morbidity reported in case reports of women inadvertently treated during pregnancy. However, there was a trend towards increased congenital defects with exposure in the first trimester.
LACTATION Mebendazole is excreted in animal milk; not well studied in humans.
PEDIATRICS Studies in children <2 years old are limited, but the few available suggest that it is well tolerated.
ELDERLY (AGE > 60 YEARS) No recommendations for dose adjustments are available for patients >60 years of age.
RESISTANCE In livestock, decreased binding to tubulin has led to resistance to benzimidazoles; this has not yet been demonstrated in humans, although some studies suggest decreasing efficacy.
STORAGE Store at room temperature.
FURTHER READING Dayan AD. Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropica 2003;86:141–59. Drugs for Parasitic Infections. Med Lett Drugs Ther 2004;46:e1–12. Horton J. Mebendazole. In: Grayson ML, ed. Kucer’s Antibiotics, 6th ed. London: Hodder; 2010;2240–4. Lexi-Comp Online. Available at: http://online.lexi.com (last accessed 1st March 2012). Liu LX, Weller PF. Antiparasitic Drugs. New Engl J Med 1996;334:1178–84. Luder PJ, Siffert B, Witassek F, et al. Treatment of hydatid disease with high oral doses of mebendazole: Long term follow up of plasma mebendazole levels and drug interactions. Eur J Clin Pharm 1986;31:443–8.
1087
DRUGS USED IN TROPICAL MEDICINE
Mebendazole Allyson K Bloom, Edward T Ryan DESCRIPTION
DOSE
Methyl 5-benzoylbenzimidazole-2-carbamate.
For adults and children >2 years of age unless otherwise indicated.
AVAILABLE PRODUCTS
l
1. Mebendazole chewable tablets (generic mebendazole, Teva Pharmaceuticals) are available in 100 mg. 2. Mebendazole oral tablets can also be found under other names in other countries, including Anelmin®, Pantelmin® and Wormin®. 3. The manufacturer has discontinued production of mebendazole in the US.
INDICATIONS 1. Treatment of infections caused by nematodes, including Ascaris spp., hookworm, Enterobius spp., Trichuris spp., Trichinella spp., visceral and cutaneous larva migrans and Capillaria spp. 2. Mebendazole has also been reported to shorten the course of Angiostrongylus infection (unlabeled). 3. Mebendazole has been used for treatment of echinococcal disease as second-line therapy behind albendazole (unlabeled).
MODE OF ACTION Benzimidazoles bind to, and inhibit the polymerization of, betatubulin. This inhibits cytoplasmic microtubule formation and glucose uptake within the parasite. This leads to immobilization and death of adult worms.
PHARMACOKINETICS Bioavailability of mebendazole is poor, but is increased when ingested with food. As a result of poor absorption it can be used to target luminal-dwelling adult worms. Higher doses and longer courses are required for treatment of systemic disease. Absorbed drug undergoes rapid, first pass hepatic metabolism into inactive metabolites and excretion of absorbed drug is half renal and half biliary. There is significant intra- and inter-individual variability.
DOSE ADJUSTMENTS IN RENAL FAILURE Adjustments for short courses are likely unnecessary. Close monitoring of long-term therapy is recommended.
DOSE ADJUSTMENTS IN LIVER FAILURE Close monitoring of long-term therapy is recommended if biliary obstruction is present.
1086
l
l l
l
l l
l
l
l
Treatment of ascariasis and trichuriasis: 100 mg twice daily for three days or 500 mg once (drug of choice, but some studies report low cure rates for triuchuriasis). Treatment of capillariasis: 200 mg twice daily for 21 days (second-line therapy behind albendazole). Treatment of enterobiasis: 100 mg once, repeat at two weeks. Treatment of hookworm: 100 mg twice daily for three days (less effective than albendazole for Necator spp.). Treatment of trichinellosis: 200–400 mg three times daily for three days then 400–500 mg three times daily for 10 days (with steroids; second-line therapy behind albendazole). Treatment of visceral larva migrans: 100–200 mg twice daily for five days. Treatment of strongyloidiasis: 100 mg twice daily for three days (longer therapy may be required for cure; second-line therapy behind ivermectin). Treatment of mansonellosis: 100 mg twice daily for 21 days (second-line therapy, but may be alternate to diethylcarbamazine [DEC] in onchocerca-endemic areas). Treatment of echinococcal hydatid disease: 20–50 mg/kg daily for 3–6 months (second-line therapy behind albendazole). Treatment of alveolar echinococcosis: 20–50 mg/kg daily for prolonged course (second-line therapy behind albendazole).
ROUTE OF ADMINISTRATION Oral.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS Generally very well tolerated, especially for courses of three days or less. Abdominal pain, diarrhea and elevated liver function tests have been reported. With prolonged therapy and higher-thanrecommended doses, neutropenia and hepatitis have rarely occurred. Rare hypersensitivity reactions include rash, urticaria and angioedema.
KEY DRUG INTERACTIONS Decreased mebendazole levels have been reported when mebendazole has been co-administered with phenytoin or carbamazepine,
M ebendazole
and dose increases may be warranted in treatment of systemic infections.
CONTRAINDICATIONS Avoid if previous serious adverse effect or hypersensitivity.
USE IN SPECIAL POPULATIONS PREGNANCY Category C. Mebendazole is teratogenic in animals, but has not been well studied in humans. No increased morbidity reported in case reports of women inadvertently treated during pregnancy. However, there was a trend towards increased congenital defects with exposure in the first trimester.
LACTATION Mebendazole is excreted in animal milk; not well studied in humans.
PEDIATRICS Studies in children <2 years old are limited, but the few available suggest that it is well tolerated.
ELDERLY (AGE > 60 YEARS) No recommendations for dose adjustments are available for patients >60 years of age.
RESISTANCE In livestock, decreased binding to tubulin has led to resistance to benzimidazoles; this has not yet been demonstrated in humans, although some studies suggest decreasing efficacy.
STORAGE Store at room temperature.
FURTHER READING Dayan AD. Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropica 2003;86:141–59. Drugs for Parasitic Infections. Med Lett Drugs Ther 2004;46:e1–12. Horton J. Mebendazole. In: Grayson ML, ed. Kucer’s Antibiotics, 6th ed. London: Hodder; 2010;2240–4. Lexi-Comp Online. Available at: http://online.lexi.com (last accessed 1st March 2012). Liu LX, Weller PF. Antiparasitic Drugs. New Engl J Med 1996;334:1178–84. Luder PJ, Siffert B, Witassek F, et al. Treatment of hydatid disease with high oral doses of mebendazole: Long term follow up of plasma mebendazole levels and drug interactions. Eur J Clin Pharm 1986;31:443–8.
1087