Closantel

BRAND NAMES

• Flukiver (closantel; widely associated with liver fluke treatment, historically Bayer/Elanco in different markets) 

• Closamectin (closantel + ivermectin combination; commonly marketed by Zoetis in many regions) 

• Razar (in some regional veterinary markets; closantel-based formulations)

MECHANISM OF ACTION

Closantel is a salicylanilide anthelmintic that acts by uncoupling oxidative phosphorylation in the mitochondria of susceptible parasites. This disrupts ATP synthesis, causing severe energy depletion and ultimately leading to parasite death. It is particularly effective against liver flukes and blood-feeding nematodes.

PHARMACOKINETICS

Absorption

Closantel is poorly absorbed from the gastrointestinal tract after oral administration, but the fraction that is absorbed is highly protein-bound (mainly to plasma albumin), which results in a long persistence in the bloodstream. This strong binding also contributes to its long half-life and sustained anthelmintic activity in animals.

Distribution

Closantel shows very high plasma protein binding (~99%), mainly to albumin, which is why it remains largely within the bloodstream. Because of this strong binding, its free (unbound) fraction is very low (~1%), and it has a low volume of distribution, indicating minimal tissue penetration.

Metabolism

Closantel undergoes minimal metabolism in the host, with most of the drug remaining unchanged in the body. It is only slightly biotransformed in the liver, and the parent compound is mainly responsible for its anthelmintic effect.

Elimination

Closantel is eliminated mainly via the bile into feces as unchanged drug, with minimal renal excretion. Its slow elimination is due to high plasma protein binding, resulting in a long half-life and prolonged action.

PHARMACODYNAMICS

Closantel is a salicylanilide anthelmintic that acts by uncoupling oxidative phosphorylation in parasite mitochondria, preventing ATP production. This leads to rapid energy depletion and death of susceptible parasites. It is most effective against blood-feeding nematodes andliver flukes, with prolonged activity due to high plasma protein binding and slow elimination.

ADMINISTRATION

Closantel is administered mainly by oral or subcutaneous routes in veterinary practice, depending on the formulation and species. It is commonly given as a drench (oral solution) for sheep and cattle, or as an injectable preparation in some formulations. The drug is usually administered as a single dose or at long dosing intervals due to its long half-life and persistent activity against parasites.

DOSAGE AND STRENGTH

Closantel dosage in veterinary practice depends on species and formulation, but it is commonly administered at about 10 mg/kg body weight in sheep and cattle (oral or injectable forms). Available strengths vary by product, typically including 5%, 10%, and 12.5% solutions (50–125 mg/mL). The exact dose and formulation should always follow veterinary guidelines and product labeling to avoid toxicity.

DRUG INTERACTIONS

1. High protein binding competition – Drugs that are also highly protein-bound may compete with closantel for albumin binding sites.

2. Increased free drug fraction – Competition can increase the unbound (active) closantel level in blood.

3. Higher toxicity risk – Elevated free drug may increase risk of adverse effects (especially neurotoxicity/ocular toxicity in overdose).

4. Additive effects with other anthelmintics – Combining with similar antiparasitic drugs may increase pharmacologic or toxic effects.

5. Slower clearance impact – Any drug affecting liver or biliary function may potentially alter closantel elimination.

FOOD INTERACTIONS

1. Administration with feed – Closantel may be given orally, sometimes alongside or shortly after feeding in livestock.

2. Minimal effect of food – Food has little to no significant impact on its absorption due to its low and slow uptake.

3. Possible slight reduction in absorption – Heavy or fatty feeding may slightly reduce oral absorption in some cases.

4. Residue persistence – Because closantel is long-acting, residues may remain in animal tissues.

5. Withdrawal period requirement – Treated animals must observe withdrawal times before milk or meat is used for human consumption.

CONTRAINDICATIONS

1. Check hypersensitivity – Do not use in animals with known allergy to closantel.

2. Confirm species suitability – Avoid use in non-target or sensitive species.

3. Assess animal health status – Do not administer to severely weak or debilitated animals.

4. Avoid overdose risk – Ensure correct dosing to prevent toxicity (eye and nervous system damage).

5. Ensure food safety compliance – Do not use if withdrawal periods for meat or milk cannot be followed.

SIDE EFFECTS

1. Check hypersensitivity – Do not use in animals with known allergy to closantel.

2. Confirm species suitability – Avoid use in non-target or sensitive species.

3. Assess animal health status – Do not administer to severely weak or debilitated animals.

4. Avoid overdose risk – Ensure correct dosing to prevent toxicity (eye and nervous system damage).

5. Ensure food safety compliance – Do not use if withdrawal periods for meat or milk cannot be followed.

OVER DOSE

Closantel overdose causes toxicity due to high drug levels, leading to neurological signs like ataxia, weakness, and depression, along with possible eye damage and blindness. Severe cases may cause irreversible injury, and treatment is only supportive.

TOXICITY

Closantel toxicity occurs mainly due to overdose or accidental exposure, leading to neurotoxicity and ocular toxicity. Affected animals may show signs such as ataxia, weakness, depression, and loss of coordination, along with retinal damage that can resultin blindness. In severe cases, the damage may be irreversible, and there is no specific antidote, so treatment is supportive and symptomatic.