CLEVASOLE DS SUSPENSION

Indications

• Helminth infections
• Strongyloides infections
• Brugia malayi infections
• Wuchereria bancrofti infections
• Adjunctive therapy in colon cancer with fluorouracil

Dosage

Children: For children aged 1 month to 9 years: Initially 1 mg/kg daily in divided doses on the first day, then increased to 3

Adults: Initially 1 mg/kg daily on the first day, then increased to 6 mg/kg daily in divided doses, with the maximum dose not exceeding 9 mg/kg per day.

Mechanism of action

Levamisole exerts its antiparasitic action by acting as an agonist at L-subtype nicotinic acetylcholine receptors in the muscles of nematodes. This results in paralysis of the worms, preventing their reproductive capabilities. As an immunomodulator, Levamisole restores depressed immune functions, enhances T-cell activation, stimulates antibody formation, and increases macrophage and neutrophil activities.

Pharmacodynamics

Levamisole's pharmacodynamics are characterized by its dual role as an anthelmintic and an immunomodulator. As an anthelmintic, it specifically targets nematodes by agonizing their nicotinic acetylcholine receptors, leading to muscle paralysis. The immunomodulatory effects include activation of natural killer (NK) cells and T-cells, enhancing the host's immune response, and improving macrophage function.

Pharmacokinetics

Levamisole is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver, and its metabolites are excreted in urine. The elimination half-life is approximately 4 to 6 hours. Care should be taken in patients with hepatic impairment, as dose adjustments may be necessary.

Contra-indications

• Blood disorders

Adverse effects

• Arthralgia (long term use)
• Diarrhoea
• Dizziness
• Headache
• Influenza-like illness (long term use)
• Insomnia (long term use)
• Myalgia (long term use)
• Nausea
• Rash (long term use)
• Seizure (long term use)
• Taste altered (long term use)
• Vasculitis (long term use)
• Vomiting

Interactions

• Levamisole moderately decreases exposure to albendazole
• Levamisole increases exposure to ivermectin

Precautions

• Epilepsy
• Sjögren’s syndrome

Pregnancy

Embryotoxic in animal studies, avoid if possible.

Breast-feeding

No information available.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• 50 mg chewable tablets

Indications

• Fascioliasis
• Infection caused by _Fasciola hepatica_
• Infection caused by _Fasciola gigantica_

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Triclabendazole acts on _Fasciola_ species through an unclear mechanism, though it is believed to involve absorption by the outer body covering of the worms. This results in a reduction of the resting membrane potential, inhibition of tubulin function, and disruption of protein and enzyme synthesis necessary for the survival of the parasites. These effects culminate in decreased motility, disruption of the worm's outer surface, and inhibition of spermatogenesis and embryonic cell development. Resistance may develop through alterations in drug uptake and metabolism.

Pharmacodynamics

Triclabendazole and its active metabolites, sulfoxide and sulfone, are effective against both immature and mature stages of _Fasciola hepatica_ and _Fasciola gigantica_. Caution is advised as the drug may prolong the QT interval, necessitating ECG monitoring in patients with a history of QT prolongation or those on other QT-prolonging medications.

Pharmacokinetics

Triclabendazole is absorbed after oral administration and is metabolized in the liver to its active metabolites. The pharmacokinetics profile reveals that these metabolites are responsible for its anthelmintic activity. The exact elimination half-life and excretion details are not provided, but changes in drug metabolism can affect the drug's efficacy and safety.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Headache
• Rash
• Dizziness
• QT interval prolongation

Precautions

• Monitor ECG in patients with a history of QT prolongation or who are taking medications known to prolong the QT interval.
• Use with caution in patients with hepatic impairment.

Pregnancy

Triclabendazole should only be used in pregnancy if the benefits justify the potential risks to the fetus. Animal studies have shown adverse effects.

Breast-feeding

It is not known whether triclabendazole is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral tablet
• Suspension

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.

Pharmacodynamics

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

Triclabendazole is an anthelmintic agent against _Fasciola_ species. The mechanism of action against Fasciola species is not fully understood at this time. In vitro studies and animal studies suggest that triclabendazole and its active metabolites (_sulfoxide_ and _sulfone_) are absorbed by the outer body covering of the immature and mature worms, causing a reduction in the resting membrane potential, the inhibition of tubulin function as well as protein and enzyme synthesis necessary for survival. These metabolic disturbances lead to an inhibition of motility, disruption of the worm outer surface, in addition to the inhibition of spermatogenesis and egg/embryonic cells. **A note on resistance** In vitro studies, in vivo studies, as well as case reports suggest a possibility for the development of resistance to triclabendazole. The mechanism of resistance may be multifactorial and include changes in drug uptake/efflux mechanisms, target molecules, and changes in drug metabolism. The clinical significance of triclabendazole resistance in humans is not yet elucidated.

Pharmacodynamics

Triclabendazole and its metabolites are active against both the immature and mature worms of _Fasciola hepatica_ and _Fasciola gigantica_ helminths. **Effect on QT interval** This drug may prolong the cardiac QT interval. Monitor ECG in patients with a history of QT prolongation or who are taking medications known to prolong the QT interval.