Albendazole

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Albendazole
Albendazole2DACS.svg
Albendazole-from-xtal-2007-3D-balls.png
Systematic (IUPAC) name
Methyl [5-(propylthio)-1H-benzoimidazol-2-yl]carbamate
Clinical data
Trade names Albenza
AHFS/Drugs.com monograph
MedlinePlus a610019
Pregnancy cat. D (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability <5%[1]
Protein binding 70%[1]
Metabolism Hepatic[1]
Half-life 8-12 hours[1]
Excretion Urine, faeces[1]
Identifiers
CAS number 54965-21-8 YesY
ATC code P02CA03 QP52AC11
PubChem CID 2082
DrugBank DB00518
ChemSpider 1998 YesY
UNII F4216019LN YesY
KEGG D00134 YesY
ChEBI CHEBI:16664 YesY
ChEMBL CHEMBL1483 YesY
NIAID ChemDB 007895
Chemical data
Formula C12H15N3O2S 
Mol. mass 265.333 g/mol
 YesY (what is this?)  (verify)

Albendazole, marketed as Albenza (United States), Eskazole, Zentel, Andazol, and Alworm, is a benzimidazole drug used for the treatment of a variety of parasitic worm infestations. It is marketed in the U.S. by Amedra Pharmaceuticals, and by GlaxoSmithKline in international markets.[2] Albendazole was first discovered at the SmithKline Animal Health Laboratories in 1972. It is a broad-spectrum anthelmintic, effective against roundworms, tapeworms, and flukes of domestic animals and humans.[3]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[4]

Medical uses[edit]

It is effective first-line of treatment against:

Other uses[edit]

Discarded bottles of albendazole distributed in Africa

In Africa, albendazole is being used to treat lymphatic filariasis as part of efforts to stop transmission of the disease.[6] In sub-Saharan Africa, albendazole is used in conjunction with ivermectin, and elsewhere in the world, the medicine is used in combination with diethylcarbamazine.[6]

In Brazil and other countries, it is used against giardiasis.[7]

 
 

Side effects[edit]

Albendazole may cause abdominal pain, dizziness, headache, fever, nausea, vomiting, or temporary hair loss.

In rare cases, it may cause persistent sore throat, severe headache, seizures, vision problems, yellowing eyes or skin, dark urine, stomach pain, easy bruising, mental/mood changes, very stiff neck, or changes in amount of urine. Elevation of liver enzymes during treatment is a common side effect, but in rare cases, acute liver failure has been reported. Allergic reactions are also possible.

Rarely, albendazole has been reported to cause marrow suppression, agranulocytosis, or aplastic anemia, which may be permanent.[8] The risk of developing this side effect seems to be increased in patients with liver disease, including echinococcal cysts. Because of this dangerous side effect, it is important to regularly monitor complete blood counts.

Drug interactions[edit]

Antiepileptics[edit]

The drugs carbamazepine, phenytoin, and phenobarbital lower the plasmatic concentration and the half life of albendazole.[9]

Antacids/histamine H2 antagonists[edit]

The drug cimetidine heightens serum albendazole concentrations, and increases the half life of albendazole.[10] This might be a helpful interaction on more severe cases, because it boosts the potency of albendazole.[11]

Contraindications[edit]

Hypersensitivity to the benzimidazole class of compounds contraindicates its use.

Pregnancy class[edit]

Do not take when pregnant, and do not become pregnant for one month after taking this drug; in Australia it is assigned class D. Pharmacokinetic studies have shown that trace amounts of albendazole appears in semen. Given this potential for teratogenicity, the manufacturers advise that the male sexual partner should also use adequate protections.

Mechanism of action[edit]

As a vermicidal, albendazole causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes occur in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosome.

Other animals[edit]

Albendazole has been used as an anthelmintic and for control of flukes in a variety of animal species, including cattle, sheep, goats, swine, camels, dogs, cats, elephants, poultry, and others. In many countries, it is very commonly used for ruminant livestock. For use in livestock, albendazole is marketed by Zoetis (formerly Pfizer Animal Health) in numerous countries (including the United States and Canada) as Valbazen in oral suspension and paste formulations; by Interchemie in the Netherlands and elsewhere as Albenol-100; by Channelle Animal Health Ltd. in the United Kingdom as Albex; by Ravensdown in New Zealand as Albendazole; etc. Although most formulations are administered orally, Ricomax (ricobendazole, or albendazole sulfoxide) is administered by subcutaneous injection.

Labeled usage (with regard to host species, dosage, withdrawal intervals, reproductive or lactational status, etc.) varies among nations. The US label for Valbazen oral suspension provides examples of some considerations in albendazole use in animals. It specifies dosage of 10 mg of albendazole per kg livemass for cattle and goats; 7.5 mg per kg livemass for sheep. With an albendazole concentration of 113.6 mg/ml in the suspension, these dosages are equivalent to 4 ml and 3 ml of suspension, respectively, per 100 pounds of body weight. Minimum intervals between administration and slaughter for food are 27 days (cattle) and 7 days (sheep and goats). This anthelmintic is not approved for use in female dairy cattle of breeding age or lactating does . The US label indicates that albendazole is not to be administered to female cattle during the first 45 days of pregnancy or for 45 days after removal of bulls; or to ewes or does in the first 30 days of pregnancy or for 30 days after removal of rams or bucks.

The limitations relating to early pregnancy are due to a limited period during which teratogenic effects may occur. Summarized research data relating to the durations of these preslaughter and early pregnancy periods when albendazole should not be administered are found in US FDA NADA 110-048 (cattle) and 140-934 (sheep). Some data and inferences regarding goats are found in US FDA Supplemental NADA 110-048 (approved January 24, 2008).

Maximum residue limits (MRLs) for albendazole in food, adopted by the FAO/WHO Codex Alimentarius in 1993, are 5000, 5000, 100, and 100 micrograms/kg for kidney, liver, fat and muscle, respectively, and 100 micrograms/l for milk. For analysis purposes, MRLs of various nations may pertain to concentration of a marker substance which has been correlated with concentrations of the administered substance and its metabolized products. For example, in Canada, the marker substance specified by Health Canada is albendazole-2-aminosulfone, for which the MRL in liver of cattle is 200 micrograms per kg.

Controversy[edit]

Since 2010, the U.S. price of albendazole has increased by >4000% to over US$100 per 200-mg tablet. Amedra Pharmaceuticals is the U.S. distributor.[2] GlaxoSmithKline retains distribution rights in all markets outside the U.S. The international wholesale price is typically less than US$0.05 per 200-mg tablet. In 2013, GlaxoSmithKline donated 763 million albendazole tablets for the treatment and prevention of parasitic infections in developing countries, bringing the total to over 4 billion tablets donated since 1998.[12]

See also[edit]

References[edit]

  1. ^ a b c d e "Albenza, (albendazole) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 25 February 2014. 
  2. ^ a b "CorePharma and GlaxoSmithKline conclude agreement on US rights for Dexedrine®, Albenza® and Daraprim®". 
  3. ^ Theodorides VJ, Gyurik RJ, Kingsbury WD, Parish RC (1976). "Anthelmintic Activity of Albendazole Against Liver Flukes, Tapeworms, Lung and Gastrointestinal Roundworms". Experientia 32 (8): 702–703. doi:10.1007/BF01919842. PMID 950011. 
  4. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ Horton J (2003). "Albendazole for the Treatment of Echinococcosis". Fundamental and Clinical Pharmacology 17 (2): 205–212. doi:10.1046/j.1472-8206.2003.00171.x. PMID 12667231. 
  6. ^ a b The Carter Center. "Lymphatic Filariasis Elimination Program". Archived from the original on 20 July 2008. Retrieved 2008-07-17. 
  7. ^ Karabay O, Tamer A, Gunduz H, Kayas D, Arinc H, Celebi H (2004). "Albendazole versus Metronidazole Treatment of Adult Giardiasis: An Open Randomized Clinical Study" (pdf). World Journal of Gastroenterology 10 (8): 1215–1217. PMID 15069729. 
  8. ^ "Albenza (Albendazole) – Warnings and Precautions". Retrieved 9 March 2011. 
  9. ^ Lanchote VL, Garcia FS, Dreossi SA, Takayanagui OM (2002). "Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis". Therapeutic Drug Monitoring 24 (3): 338–345. doi:10.1097/00007691-200206000-00003. PMID 12021623. 
  10. ^ Schipper HG, Koopmans RP, Nagy J, Butter JJ, Kager PA, van Boxtel CJ (2000). "Effect of dose increase or cimetidine co-administration on albendazole bioavailability" (pdf). The American Journal of Tropical Medicine and Hygiene 63 (5–6): 270–273. PMID 11421376. 
  11. ^ Wen H, Zhang HW, Muhmut M, Zou PF, New RR, Craig PS (1994). "Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis". Annals of Tropical Medicine and Parasitology 88 (1): 49–52. PMID 8192515. 
  12. ^ Gustavsen, KM; Bradley, MH; Wright, AL (Oct 2009). "GlaxoSmithKline and Merck: private-sector collaboration for the elimination of lymphatic filariasis.". Annals of tropical medicine and parasitology. 103 Suppl 1: S11–5. doi:10.1179/000349809X12502035776478. PMID 19843393. 

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