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Albendazole
Albendazole Allyson K Bloom, Edward T Ryan DESCRIPTION Methyl 5-(propylthio)-2-benzimidazole carbamate.
DOSE ADJUSTMENTS IN RENAL FAILURE
AVAILABLE PRODUCTS
Dose adjustments are likely unnecessary, as urinary excretion of albendazole and its metabolites are negligible.
1. Albendazole tablets (Albenza®, GlaxoSmithKline) are available in 200 mg. 2. Albendazole oral tablets can also be found under other names in other countries including Albex®, Alzental®, Eskazole®, Helmidazole®, Parhel® and Zentel®. 3. Albendazole suspension (Zentel®, GlaxoSmithKline) is available in some countries in 100 mg per 5 ml.
INDICATIONS 1. Treatment of neurocysticercosis caused by Taenia solium. 2. Treatment of hydatid disease caused by Echinococcus spp. 3. Treatment of nematode infection, including those caused by Ascaris spp., hookworm, Enterobius spp., Trichuris spp., Strongyloides spp., cutaneous and visceral larva migrans, trichinella, Gnathostoma spp., Capillaria spp. and Gongylonema spp. (unlabeled). 4. Treatment of giardiasis (unlabeled). 5. Treatment of AIDS-related microsporidiosis (unlabeled). 6. Treatment of infection caused by Clonorchis sinensis (unlabeled). 7. Albendazole has also been used for treatment of anisakiasis, prevention of clinical disease in patients who may have been exposed to Baylisascaris procyonis and as second-line or adjunctive therapy in filariasis (unlabeled).
DOSE ADJUSTMENTS IN LIVER FAILURE Close monitoring is recommended if biliary obstruction is present.
DOSE All doses are for adults. For children: 15 mg/kg/day up to maximum daily dose of 800mg. l
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MODE OF ACTION The active metabolite of albendazole – albendazole sulfoxide – binds to, and inhibits, the polymerization of beta-tubulin. This inhibits cytoplasmic microtubule formation and glucose uptake within the parasite. This leads to immobilization and death of adult worms and prevents hatching of eggs.
PHARMACOKINETICS Bioavailability of albendazole is poor, but is increased when ingested with food. Absorption can be increased five-fold when albendazole is ingested with high-fat foods. Albendazole is rapidly converted to albendazole sulfoxide via first pass hepatic metabolism, reaching peak levels 2–5 hours after ingestion. Albendazole sulfoxide is 70% protein bound in plasma and is distributed throughout tissue, including cerebrospinal fluid. Concentrations in hydatid cyst fluid are higher than those seen for mebendazole. The mean half-life is 8–12 hours, with excretion probably through the biliary system. Conversion to albendazole sulfoxide also occurs in the gut epithelium, where the metabolite is then excreted directly into the lumen. There is significant intra- and inter-individual variability.
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Treatment of echinococcal hydatid disease: 400 mg twice daily with fatty food (often in conjunction with surgical resection/aspiration, as clinically indicated). Duration of therapy ranging from few weeks to prolonged, depending on clinical course and indication. Treatment of alveolar echinococcosis: 400 mg twice daily with fatty food over prolonged course. Treatment of neurocysticercosis caused by Taenia solium: 400 mg twice daily for 8–28 days, repeated as necessary (in setting of viable cysts, with steroids and anti-seizure therapy). Treatment of ascariasis and hookworm infection: 400 mg once children <2 years: 200 mg once (more effective for Ancylostoma than Necator; increased duration to three days may improve efficacy). Treatment of enterobiasis: 400 mg once, repeated at two weeks. Treatment of chronic strongyloidiasis: 400 mg twice daily for three days (second-line therapy behind ivermectin). Treatment of trichuriasis: 400 mg daily for three days. Treatment of trichinellosis: 400 mg twice daily for 8–14 days (with steroids). Treatment of capillariasis: 400 mg daily for ten days. Treatment of cutaneous larva migrans: 400 mg daily for three days. Treatment of visceral larva migrans: 400 mg daily for five days. Treatment of giardiasis: 400 mg daily for five days. Treatment of AIDS-related microsporidiosis: 400 mg twice daily for ≥2–3 weeks.
Albendazole l l
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l
l
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l
Treatment of clonorchiasis: 10 mg/kg daily for seven days. Treatment of gnathostomiasis: 400 mg twice daily for 21 days (with surgical resection if possible). Treatment of gongylonemiasis: 10 mg/kg daily for three days (with surgical resection). Treatment of mansonellosis: 400 mg twice daily for 7–10 days (not effective against microfilariae). Treatment of onchocerciasis: 400 mg daily for 3–7 days (second-line therapy, may be synergistic with ivermectin). Treatment of loiasis: 400 mg twice daily for 3–7 days (second line therapy). Treatment of lymphatic filariasis: 400 mg once in combination with antifilarial agents.
ROUTE OF ADMINISTRATION Oral.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS Generally very well tolerated. Adverse events are rarely reported with courses less than seven days and when they do occur tend to be mild and transient. Symptoms from dying parasites may also contribute to the incidence of adverse effects. l
Gastrointestinal: elevations in liver enzymes can occur, usually mild, with rarer cases of hepatitis and liver failure. Abdominal pain, nausea and vomiting have been reported. l Hematologic: bone marrow suppression can rarely occur and is more common in patients with underlying hepatic dysfunction. Usually resolves with discontinuation of treatment. l Neurologic: headaches and dizziness. Use with caution in individuals with retinal cysticercosis owing to inflammation and risk of detachment. l Dermatologic: alopecia and more rarely hypersensitivity reactions, erythema multiforme and Stevens-Johnson syndrome.
KEY DRUG INTERACTIONS Albendazole is a minor substrate of the CYP1A2 and CYP3A4 isoenzymes and a weak inhibitor of the CYP1A2 isoenzyme. Steroids and praziquantel have been reported to increase plasma levels of albendazole sulfoxide, which may be clinically desirable. Chloroquine and other anti-malarials may decrease the level of anthelminthics, but this has not been demonstrated specifically for albendazole. Ritonavir use may decrease plasma levels of albendazole. Conivaptan strongly inhibits CYP3A4 and should be discontinued at least seven days prior to initiation of CYP3A4 substrates.
CONTRAINDICATIONS Avoid if previous serious adverse effect or hypersensitivity.
USE IN SPECIAL POPULATIONS PREGNANCY Category C. Albendazole 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. The World Health Organization (WHO) endorses treatment of pregnant women in the second and third trimesters (but not the first) for intestinal helminthiasis/anemia, if clinically indicated.
LACTATION Albendazole is excreted in animal milk; not well studied in humans.
PEDIATRICS Studies in children younger than 6 years are limited, but several studies have shown albendazole to be safe in children as young as 1 year of age. For children 1–2 years old, a dose of 200 mg is re commended. Use of albendazole in children <1 year old is not recommended.
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. Shield suspension form from light.
FURTHER READING Abba K, Ramaratnam S, Ranganathan LN. Anthelmintics for people with neurocysticercosis (Review). Cochrane Database System Rev 2010;3:CD000215. Bethony J, Brooker S, Albonico M, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 2006;367:1521–32. Corti N, Heck A, Rentsch K, et al. Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers. Eur J Clin Pharm 2009;65:999–1006. Drugs for Parasitic Infections. Med Lett Drugs Ther 2004;46:e1–12. 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. Horton J. Mebendazole. In: Grayson ML, ed. Kucer’s Antibiotics, 6th edn. London: Hodder; 2010:2227–39. Ndyomugyenyi R, Kabatereine N, Olsen A, Magnussen P. Efficacy of Ivermectin and Albendazole alone and in combination for treatment of soil-transmitted helminths in pregnancy and adverse effects: A randomized open label controlled intervention in Masindi District, Western Uganda. Am J Trop Med Hyg 2008;79:856–63. Solaymani-Mohammadi S, Genkinger JM, Loffredo CA, Singer SM. A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infection with Giardia duodenalis. PLOS Neg Trop Dis 2010;3:e682.
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DOSE ADJUSTMENTS IN RENAL FAILURE
AVAILABLE PRODUCTS
Dose adjustments are likely unnecessary, as urinary excretion of albendazole and its metabolites are negligible.
1. Albendazole tablets (Albenza®, GlaxoSmithKline) are available in 200 mg. 2. Albendazole oral tablets can also be found under other names in other countries including Albex®, Alzental®, Eskazole®, Helmidazole®, Parhel® and Zentel®. 3. Albendazole suspension (Zentel®, GlaxoSmithKline) is available in some countries in 100 mg per 5 ml.
INDICATIONS 1. Treatment of neurocysticercosis caused by Taenia solium. 2. Treatment of hydatid disease caused by Echinococcus spp. 3. Treatment of nematode infection, including those caused by Ascaris spp., hookworm, Enterobius spp., Trichuris spp., Strongyloides spp., cutaneous and visceral larva migrans, trichinella, Gnathostoma spp., Capillaria spp. and Gongylonema spp. (unlabeled). 4. Treatment of giardiasis (unlabeled). 5. Treatment of AIDS-related microsporidiosis (unlabeled). 6. Treatment of infection caused by Clonorchis sinensis (unlabeled). 7. Albendazole has also been used for treatment of anisakiasis, prevention of clinical disease in patients who may have been exposed to Baylisascaris procyonis and as second-line or adjunctive therapy in filariasis (unlabeled).
DOSE ADJUSTMENTS IN LIVER FAILURE Close monitoring is recommended if biliary obstruction is present.
DOSE All doses are for adults. For children: 15 mg/kg/day up to maximum daily dose of 800mg. l
l l
l
MODE OF ACTION The active metabolite of albendazole – albendazole sulfoxide – binds to, and inhibits, the polymerization of beta-tubulin. This inhibits cytoplasmic microtubule formation and glucose uptake within the parasite. This leads to immobilization and death of adult worms and prevents hatching of eggs.
PHARMACOKINETICS Bioavailability of albendazole is poor, but is increased when ingested with food. Absorption can be increased five-fold when albendazole is ingested with high-fat foods. Albendazole is rapidly converted to albendazole sulfoxide via first pass hepatic metabolism, reaching peak levels 2–5 hours after ingestion. Albendazole sulfoxide is 70% protein bound in plasma and is distributed throughout tissue, including cerebrospinal fluid. Concentrations in hydatid cyst fluid are higher than those seen for mebendazole. The mean half-life is 8–12 hours, with excretion probably through the biliary system. Conversion to albendazole sulfoxide also occurs in the gut epithelium, where the metabolite is then excreted directly into the lumen. There is significant intra- and inter-individual variability.
1088
l l
l l
l l l l l
Treatment of echinococcal hydatid disease: 400 mg twice daily with fatty food (often in conjunction with surgical resection/aspiration, as clinically indicated). Duration of therapy ranging from few weeks to prolonged, depending on clinical course and indication. Treatment of alveolar echinococcosis: 400 mg twice daily with fatty food over prolonged course. Treatment of neurocysticercosis caused by Taenia solium: 400 mg twice daily for 8–28 days, repeated as necessary (in setting of viable cysts, with steroids and anti-seizure therapy). Treatment of ascariasis and hookworm infection: 400 mg once children <2 years: 200 mg once (more effective for Ancylostoma than Necator; increased duration to three days may improve efficacy). Treatment of enterobiasis: 400 mg once, repeated at two weeks. Treatment of chronic strongyloidiasis: 400 mg twice daily for three days (second-line therapy behind ivermectin). Treatment of trichuriasis: 400 mg daily for three days. Treatment of trichinellosis: 400 mg twice daily for 8–14 days (with steroids). Treatment of capillariasis: 400 mg daily for ten days. Treatment of cutaneous larva migrans: 400 mg daily for three days. Treatment of visceral larva migrans: 400 mg daily for five days. Treatment of giardiasis: 400 mg daily for five days. Treatment of AIDS-related microsporidiosis: 400 mg twice daily for ≥2–3 weeks.
Albendazole l l
l
l
l
l
l
Treatment of clonorchiasis: 10 mg/kg daily for seven days. Treatment of gnathostomiasis: 400 mg twice daily for 21 days (with surgical resection if possible). Treatment of gongylonemiasis: 10 mg/kg daily for three days (with surgical resection). Treatment of mansonellosis: 400 mg twice daily for 7–10 days (not effective against microfilariae). Treatment of onchocerciasis: 400 mg daily for 3–7 days (second-line therapy, may be synergistic with ivermectin). Treatment of loiasis: 400 mg twice daily for 3–7 days (second line therapy). Treatment of lymphatic filariasis: 400 mg once in combination with antifilarial agents.
ROUTE OF ADMINISTRATION Oral.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS Generally very well tolerated. Adverse events are rarely reported with courses less than seven days and when they do occur tend to be mild and transient. Symptoms from dying parasites may also contribute to the incidence of adverse effects. l
Gastrointestinal: elevations in liver enzymes can occur, usually mild, with rarer cases of hepatitis and liver failure. Abdominal pain, nausea and vomiting have been reported. l Hematologic: bone marrow suppression can rarely occur and is more common in patients with underlying hepatic dysfunction. Usually resolves with discontinuation of treatment. l Neurologic: headaches and dizziness. Use with caution in individuals with retinal cysticercosis owing to inflammation and risk of detachment. l Dermatologic: alopecia and more rarely hypersensitivity reactions, erythema multiforme and Stevens-Johnson syndrome.
KEY DRUG INTERACTIONS Albendazole is a minor substrate of the CYP1A2 and CYP3A4 isoenzymes and a weak inhibitor of the CYP1A2 isoenzyme. Steroids and praziquantel have been reported to increase plasma levels of albendazole sulfoxide, which may be clinically desirable. Chloroquine and other anti-malarials may decrease the level of anthelminthics, but this has not been demonstrated specifically for albendazole. Ritonavir use may decrease plasma levels of albendazole. Conivaptan strongly inhibits CYP3A4 and should be discontinued at least seven days prior to initiation of CYP3A4 substrates.
CONTRAINDICATIONS Avoid if previous serious adverse effect or hypersensitivity.
USE IN SPECIAL POPULATIONS PREGNANCY Category C. Albendazole 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. The World Health Organization (WHO) endorses treatment of pregnant women in the second and third trimesters (but not the first) for intestinal helminthiasis/anemia, if clinically indicated.
LACTATION Albendazole is excreted in animal milk; not well studied in humans.
PEDIATRICS Studies in children younger than 6 years are limited, but several studies have shown albendazole to be safe in children as young as 1 year of age. For children 1–2 years old, a dose of 200 mg is re commended. Use of albendazole in children <1 year old is not recommended.
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. Shield suspension form from light.
FURTHER READING Abba K, Ramaratnam S, Ranganathan LN. Anthelmintics for people with neurocysticercosis (Review). Cochrane Database System Rev 2010;3:CD000215. Bethony J, Brooker S, Albonico M, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 2006;367:1521–32. Corti N, Heck A, Rentsch K, et al. Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers. Eur J Clin Pharm 2009;65:999–1006. Drugs for Parasitic Infections. Med Lett Drugs Ther 2004;46:e1–12. 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. Horton J. Mebendazole. In: Grayson ML, ed. Kucer’s Antibiotics, 6th edn. London: Hodder; 2010:2227–39. Ndyomugyenyi R, Kabatereine N, Olsen A, Magnussen P. Efficacy of Ivermectin and Albendazole alone and in combination for treatment of soil-transmitted helminths in pregnancy and adverse effects: A randomized open label controlled intervention in Masindi District, Western Uganda. Am J Trop Med Hyg 2008;79:856–63. Solaymani-Mohammadi S, Genkinger JM, Loffredo CA, Singer SM. A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infection with Giardia duodenalis. PLOS Neg Trop Dis 2010;3:e682.
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