Mebendazole - BioPharma Notes

Mebendazole is benzimidazole derivative and is used as broad spectrum anthelminthic. It was introduced in year 1972. It became very popular after its introduction as it retained only broad-spectrum anthelminthic activity but not toxicity of its predecessor thiabendazole.

Therapeutic uses of mebendazole

Mebendazole is used to treat infection caused by roundworms (Ascaris lumbricoides), pinworms (Enterobius vermicularis), whipworms (Trichuris trichiura) and in hookworm infestation (Necator americanus and Ancylostoma duodenale). It is drug of choice in enterobiasis and trichuriasis.
It has some activity against S. stercoralis.
Its efficacy may differ in different condition depending on severity of infection and helminth strains.

Table 1- Efficacy rats of mebendazole observed in different studies

It binds to β-tubulin with high affinity and inhibit microtubule polymerization in parasites. Affected parasites are expelled in the feces. It also blocks glucose uptake in parasites and depletes its glycogen store.
It inhibits hatching of nematode eggs and larvae. Ascaris ova are killed.
Its lethal action on worms is slow and may takes 2-3 days to develop.

Its absorption is poor and erratic. Only 10% is absorbed after oral administration. Its absorption can be enhanced by fatty meal. Its systemic bioavailability is less (22%) due to poor absorption and rapid first-pass hepatic metabolism.
It binds extensively to plasma proteins (around 95%). It undergoes extensive metabolism. Its major metabolites are inactive and have less clearance rate than mebendazole.
The metabolites are excreted in urine and bile within 24- 48 hours.

It is mostly well tolerated. It doesn’t cause systemic toxicity even in the presence of anemia and malnutrition.
GI effects are common. Abdominal discomfort and diarrhea are common in massive infestation and expulsion of GI worms. In high doses, effects like hair loss, allergic reaction, reversible neutropenia and granulocytopenia have been reported. It may cause reversible elevation of serum transaminases.

Available as 100 mg tablets and liquid suspension.
The recommended dose is 100 mg bid for 3 days for hookworm and roundworm infestation. For enterobiasis single dose of 100 mg which is repeated after a week.
300 mg tid for 3 days in taenia infestation.

Its safety during pregnancy is unknown. However, based on animal data, it is contraindicated during pregnancy. It can be used in 2^nd and 3^rd trimester if absolutely necessary.
There are no data on its excretion in human milk. Animal data suggest that little is excreted in animal milk. It is used with caution, but breastfeeding women can be treated if required.
According to WHO, they should be used in children only after their first year.
Contraindicated in persons who are hypersensitive to it.