indication

For adjuvant treatment in combination with fluorouracil after surgical resection in patients with Dukes' stage C colon cancer. Also used to treat malignant melanoma and head/neck cancer. Levamisole was originally used as an antihelminthic to treat worm infestations in both humans and animals.

pharmacology

Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.

mechanism of action

The mechanism of action of levamisole as an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is unknown. The effects of levamisole on the immune system are complex. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. Levamisole can stimulate formation of antibodies to various antigens, enhance T-cell responses by stimulating T-cell activation and proliferation, potentiate monocyte and macrophage functions including phagocytosis and chemotaxis, and increase neutrophil mobility, adherence, and chemotaxis.

toxicity

LD₅₀ = 40 mg/kg (Pigs, subcutaneous); LD₅₀ = 180 mg/kg (rat, oral)

biotransformation

Primarily hepatic (extensive) with both active and inactive metabolites.

absorption

Levamisole is rapidly absorbed (2 hours) from the gastrointestinal tract.

half life

4.4-5.6 hours (biphasic)

drug interactions

Acenocoumarol: Levamisole may increase the anticoagulant effect of acenocoumarol.

Anisindione: Levamisole may increase the anticoagulant effect of anisindione.

Dicumarol: Levamisole may increase the anticoagulant effect of dicumarol.

Warfarin: Levamisole may increase the anticoagulant effect of warfarin.