WHO Acute Hazard classification: Not listed.

Mechanism of action of Monepantel

The molecular mode of action of monepantel is different to the one of all other anthelmintics. Monepantel acts on a particular nicotinic acetylcholine receptor subunit (Hco-MPTL-1) that occurs only in nematodes and not in other organisms, e.g. in mammals. As all other acetylcholine receptors, this particular one is also present in the membrane of certain neurons and neuromuscular junctions and is responsible for the correct transmission of the nerve signals. Monepantel blocks these receptors and the affected worms are paralyzed and die or are expelled.

Acute Toxicity and Tolerance of Monepantel

• LD50 acute, rats, p.o. >2000 mg/kg
• LD50 acute, rats, dermal >2000 mg/kg
• Sheep and goats tolerate monepantel very well.
• Adult sheep tolerate single oral doses of up to 125 mg/kg (~33x the therapeutic dose) without toxic symptoms.
• Lambs 2 to 4 weeks old tolerated doses of up to 37.5 mg/kg (10x the therapeutic dose) without toxic symptoms. Lambs 12 to 15 weeks old tolerated repeated treatment at 18.5 mg/kg (5x the recommended dose) every 3 weeks, during 24 weeks (8 treatments) without toxic symptoms.

Toxic Symptoms caused by Monepantel Poisoning

• As a general rule, poisoning with monepantel is quite unusual, due to its low toxicity, the high safety margins and the fact that most sheep and goats tolerate monepantel very well.
• In safety studies in dogs and rats the most affected organ after heavy overdosing was the liver. Increased weights of the thymus, thyroid and adrenal glands were also recorded.
• In most tolerance studies no external symptoms of toxicity were observed. Following treatment at 125 mg/kg (33x the recommended dose) transient decrease of appetite, slight increases in several plasma values (fluoride oxalate glucose, serum glucose, urea, alanine aminotransferase) and slight decrease of hemoglobin.
  

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

• No adverse drug reactions have been recorded after treatment at the recommended dose.
  

Antidote and Treatment of Monepantel Intoxication

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

Pharmacokinetics of Monepantel

• After oral administration monepantel is quickly absorbed into the bloodstream and rapidly metabolized to monepantel's sulfone derivative that has a similar efficacy as the parent molecule. Four hours after administration, the sulfone derivative predominates over the parent molecule. Mean residence time in blood for monepantel and monepantel sulfone are about 5 and 110 hours, respectively.
• About 95% of the administered dose is metabolized to the sulfone derivative. The maximum blood concentration of the sulfone derivative is reached about 2 hours after administration.
• Only about 4% of the administered dose is excreted unchanged through the feces. About 27% of the administered dose is excreted through the feces in the form of the sulfone derivative. The remaining amount is further metabolized and partly excreted through urine (up to 30% of the administered dose).

Environmental Toxicity of Monepantel

• Monepantel is slightly toxic to fish and aquatic invertebrates (>100 mcg/l).
• 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 sheep and goats, monepantel 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.

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