Albendazole

 

(GlaxoSmithKline)

Product Description

History and Background

Structure

Mechanism of Action

Indications

Dosage

Adverse Effects

Contraindications and Warnings

Global Elimination of Lymphatic Filariasis

For more information


Product Description

 

(drugs.com)

Trade Name: Albenza, Rx only

Manufacturer: GlaxoSmithKline

Supplied: 200mg, white to off-white,

circular, biconvex, beveled-edged,

film-coated Tiltab® tablets in bottles of 112.

Cost: $210.99 for 112-tablet bottle (Walgreens)

 

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History and Background

Much of the early work on the benzimidazoles as a class was undertaken by Janssen Pharmaceutical in Belgium (now part of J&J), under the direction of Dr Paul Janssen who was an excellent chemist.  Benzimidazoles were originally developed as plant fungicides and later as veterinary anthelminthics.  The first benzimidazole to be developed and licensed for human use was thiabendazole in 1962.  Although thiabendazole was very effective, it was also moderately toxic, which lead to a huge investigation by animal health companies to find better and safer compounds, and the benzimidazole carbamates were discovered.  A number of veterinary anthelminthics were developed and marketed, including parbendazole, fenbendazole, oxfendazole and cambendazole.  The first benzimidazole carbamate to make it into humans was mebendazole, followed by flubendazole (both Janssen products). 

Smith Kline & French Animal Health were working on albendazole, which was first marketed as Valbazen, an animal anthelminth, in the UK in November of 1977.  Albendazole was found to be considerably more active than other benzimidazoles.  This was because it was metabolized to albendazole sulphoxide which was also an active anthelminthic, while almost all the other BZs were metabolized to inactive compounds.  It was eventually approved for human use and marketing in 1987 (Horton, J).

 

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Structure

 

(Dayan, 2003)

The structure of albendazole is (5-(propylthio)-1H-benzimidazol-2-yl)carbamic acid methyl ester (Dayan, 2003). Its molecular formula is C12H15N3O2S and its molecular weight is 265.34 (GlaxoSmithKline). It is relatively insoluble in water and most organic solvents, making it poorly absorbed in the GI tract. After absortion, albendazole is rapidly converted in the liver to the primary metabolite, albendazole sulfoxide, which is generally considered to be the form responsible for the therapeutic activity of albendazole. Albendazole sulfoxide is further metabolized to albendazole sulfone and other primary oxidative metabolites and is excreted from the body (Dayan, 2003).

 

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Mechanism of Action 

Albendazole is found to inhibit the polymerization of  the parasite tubulin into microtubules.  There is a higher affinity of albendazole to the parasite tubulin and so the activity is mediated mainly against the parasite rather than on the host. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the parasites. The worm is then unable to maintain energy production, which leads to immobilization and eventual death (Dayan, 2003). A secondary acton of albendazole may be the be the inhibition of the enzyme fumarate reductase, which is helminth-specific (PharmGKB).

 

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Indications

*It is also used before or after surgical removal of hydatid cysts, to reduce the risk of recurrence due to operative spillage (SkolarMD, 2005).


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Dosage

(GlaxoSmithKline)

The number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are taking albendazole.

(information in tables from MICROMEDEX)

FDA labeled indications

Indication (FDA Labeled) Weight (adults, teenagers, children) Dosage Duration
Hydatid disease weighing 60 kilograms (132 pounds) and over 400 milligrams (mg) two times a day
28- day cycle followed by 14-day abendazole-free intervals, for a total of 3 cycles
Hydatid disease less than 60kg 15 mg/kg/day given in divided doses twice a day with meals; maximum dose 800 mg/day 28- day cycle followed by 14-day abendazole-free intervals, for a total of 3 cycles
Neurocysticercosis weighing 60 kilograms (132 pounds) and over 400mg ORALLY twice daily with meals 8-30 days
Neurocysticercosis less than 60kg 15mg/kg/day ORALLY in two divided doses with meals; maximum dose 800mg/day for 8-30 days,

 

Non-FDA labeled indications

Indication (Non-FDA labeled) Dosage (both adult and pediatric) Duration
Ancylostoma caninum 400mg ORALLY Single dose
Ascariasis 400mg ORALLY Single dose
Chinese liver fluke 10mg/kg ORALLY daily 7 days
Cutaneous larva migrans 400mg ORALLY daily 3 days
Enterobius vermicularis 400mg ORALLY single dose, repeat in 2 weeks
Filariasis (mansonella perstans) 400mg ORALLY twice daily 10 days
Gnathostomiasis 400mg ORALLY twice daily 21 days
Hookworm (Ancylostoma duodenale, Necator americanus) 400mg ORALLY single dose
Microsporidiosis 400mg ORALLY twice daily 21 days
Visceral larva migrans 400mg ORALLY twice daily 5 days

 

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Adverse Effects

COMMON: headache, nausea, vomiting, abdominal pain

RARE: Fever;  skin rash or itching,  sore throat, thining or loss of hair, unusual tiredness and weakness  

SERIOUS: acute renal failure (rare), granulocytopenia, pancytopenia, agranulocytosis, thrombocytopenia (rare), hepatotoxicity (with elevated liver enzymes, leukopenia (Medlineplus and SkolarMD)

 

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Contraindications and Warnings


*Albendazole is contraindicated in patients with known hypersensitivity to the benzimidazole class of compounds.


* Pregnancy: Albendazole has been shown to be teratogenic in animals, however it has not been well studied in pregnant women. Pregnant women should not use albendazole except in clinical circumstances where no alternative management is appropriate. Patients should not become pregnant for at least 1 month following cessation of albendazole therapy. Use if the drug should be discontinued immediately if the patient becomes pregnant during the treatment (SkolarMD).

 

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Global Elimination of Lymphatic Filariasis

Elephantiasis of legs (WHO)

In 1997, the World Health Assembly passed a resolution calling for the global elimination of Lymphatic Filariasis. The strategy for elimnation will be to break transmission of LF over four to six years by treating entire at-risk communities with a simple oral co-administration of two medicines, one of which is albendazole.

Map showing countries with lymphatic filariasis (GlaxoSmithKline)

 

The manuafacturer of this drug, GlaxoSmithKline has formed a collaboration with WHO in this effort and has offered to donate tablets to all countries that require it until LF is eliminated. It is estimated that around one billion people will receive between four and six annual treatments. The company expects to supply about 5 billion treatments over the next 15-20 years, which will make it the single largest drug donation in the history of the pharmaceutical industry (GlaxoSmithKline).

 


Tanzanian community waiting for drug distribution
(GlaxoSmithKline)

 

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References

Websites:

GlaxoSmithKline: http://www.gsk.com/index.htm

Medlineplus: http://www.nlm.nih.gov/medlineplus/druginfo

PharmGKB: http://www.pharmgkb.org/

SkolarMD: http://md.skolar.com/

World Health Organization: http://www.who.int/en/

 

Journal articles:

Dayan, A. D. Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Trop. 2003 May;86(2-3):141-59. Review.

El-On, Joseph. Benzimidazole treatment of cystic echinococcosis. Acta Trop. 2003 Feb;85(2):243-52. Review.

Ottesen EA, Ismail MM, Horton J. The role of albendazole in programmes to eliminate lymphatic filariasis. Parasitol Today. 1999 Sep;15(9):382-6. Review.

 

For more information regarding albendazole, please refer to resources listed in references or you can contact me.

 

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