CLOSANTEL: Safety Summary for Veterinary Use

WHO Acute Hazard classification: Not listed.


Mechanism of action of Closantel

The molecular mode of action of salicylanilides, including closantel, is not completely elucidated. They all are uncouplers of the oxidative phosphorylation in the cell mitochondria, which disturbs the production of ATP, the cellular "fuel". This seems to occur through suppression of the activity of succinate dehydrogenase and fumarate reductase, two enzymes involved in this process. This impairs the parasites motility and probably other processes as well. It seems that closantel also disturbs the liquid and ion transport mechanisms in the parasites membranes.

Recently it has been discovered that closantel also inhibits chitinase in Onchocerca volvulus, a filarial nematode causing river blindness in humans. Chitinase is an enzyme involved in larval molting. Its inhibition interrupts their development to adult worms.


Acute Toxicity and Tolerance of Closantel

  • LD50 acute, rats, p.o. 262 to 342 mg/kg (depending on the studies)
  • LD50 acute, rats, s.c. 67 mg/kg
  • LD50 acute, mice, p.o. 331 mg/kg
  • LD50 acute, mice, i.m. 56.8 mg/kg
  • Safety margins after oral administration (lower after parenteral administration):
    • Cattle ~6
    • Sheep ~4
  • In cattle fatalities can occur already after single doses of 82.5 mg/kg (usual therapeutic doses: 10 mg/kg p.o., 3 mg/kg s.c.)
  • In sheep single oral doses of ~100 mg/kg can cause heavy intoxication symptoms

Toxic Symptoms caused by Closantel Poisoning

  • Most frequent symptoms of closantel intoxication are:
    • Loss of appetite
    • Ataxia (uncoordinated movements)
    • Weakness
    • Visual disturbance
    • Blindness
  • Other symptoms reported in sheep: depression, prostration, colic, reduced skin sensitivity, opistothonus (severe hyperextension of head, neck and spinal column building a kind of a bridge or arche), nystagmus (uncontrolled eye movements), mydriasis (dilatation of the pupil), loss of pupillary reflex and blindness. Fatalities can also happen.
  • Once blindness appears it is usually irreversible.
  • Histopathological changes after heavy intoxications affect mainly the CNS (Central Nervous System), which shows intramyelinic vacuolization in the white substance of brain and cerebellum. The ocular nerve is also affected by vacuolization and edema, and becomes fibrotic and atrophic, usually irreversibly. Retinal damage can also be severe. In case of heavy intoxications the liver can be also severely damaged (necrosis).

Closantel Side Effects, Adverse Drug Reactions (ADRs) and Warnings

  • In goats, subcutaneous injection of closantel can cause brief but strong pain at the injection site.
  • At therapeutic doses closantel usually does con cause ADRs, excepting those previously described but in a mild and transient form. 
  • The combination of closantel and ivermectin does not affect the pharmacological behavior of closantel.

Antidote and Treatment of Closantel Intoxication

  • There is no specific antidote for closantel.
  • Treatment consists in supportive and symptomatic measures.

Pharmacokinetics of Closantel

  • After oral administration closantel is readily absorbed into the bloodstream. Four days after treatment up to 60% of the injected and 30% of the drenched closantel is absorbed to blood. In the blood, unchanged closantel binds strongly and almost completely (>99%) to plasma albumins. Peak plasma levels are reached 10 to 48 hours after administration, both after oral or intramuscular administration. Half-life in plasma is 3 to 4 weeks.
  • Due to the strong binding to plasma albumins, closantel residues in the tissues are rather low; the highest ones were found in the lungs and the kidneys. Closantel is poorly metabolized. About 80% of the administered dose is excreted through the feces, >98% in the form of the parent molecule. Excretion 48 hours after oral administration reached ~45% of the administered dose, but only ~10% after intramuscular injection. Excretion half-life in the organism is 2 to 3 weeks.
  • In dairy cows about 1% of the administered dose is excreted unchanged through the milk.
  • Influence of the diet. In ruminants, fasting slows the passage of food through the stomach and the gut, which increases the time for absorption of closantel into blood and hence its plasma concentration and bioavailability. Consequently it is recommended to keep healthy animals off food for up to 24 hours before treatment with closantel. This should not be done with heavy pregnant, stressed, or weak animals. Fasting animals should have access to drinking water.

Environmental Toxicity of Closantel

  • Closantel is toxic to many aquatic organisms.
  • Not being used in crop pesticides or in public hygiene, knowledge on its environmental fate and impact is very scarce.
  • Nevertheless, it can be assumed that correctly used in cattle, sheep and goats, closantel is unlikely to be detrimental for the environment, including coprophagous insects.

Additional information

Click here for a list and overview of all safety summaries of antiparasitic active ingredients in this site.

  • Closantel belongs to the chemical class of the salicylanilides.
  • Closantel is not used in human medicines.
  • Closantel is not used in crop pesticides.
  • Closantel is not used in public or domestic hygiene as a biocide.
  • Click here for General safety of antiparasitics for for domestic animals.
  • Click here for General safety of antiparasitics for for humans.
  • Click here for General safety of antiparasitics for for the environment.
  • Click here for technical and commercial information on closantel.

WARNING

If you intend to use a veterinary drug containing this active ingredient you must carefully read and follow the safety instructions in the product label.  Always ask your veterinary doctor, or pharmacist, or contact the manufacturer. Be aware that the safety instructions for the same veterinary medicine may vary from country to country.

The information in this page must not be confused with the Materials and Safety Datasheets (MSDS) officially issued by manufacturers for active ingredients and many other chemicals. MSDSs target safety during manufacturing, transport, storage and handling of such materials. This safety summary is a complement to the information on product labels and MSDS.

The toxicity of an active ingredient must not be confused with the toxicity of finished products, in this case parasiticidal drugs or pesticides. Finished products contain one or more active ingredients, but also other ingredients that can be relevant from the safety point of view.

All information in this site is made available in good faith and following a reasonable effort to ensure its correctness and actuality. Nevertheless, no this regarding guarantee is given, and any liability on its accuracy, integrity, sufficiency, actuality and opportunity is denied. Liability is also denied for any possible damage or harm to persons, animals or any other goods that could follow the transmission or use of the information, data or recommendations in this site by any site visitor or third parties.

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