WHO Acute Hazard classification: Not listed.

Mechanism of action of Rafoxanide

The molecular mode of action of salicylanilides, including rafoxanide, 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

Acute Toxicity and Tolerance of Rafoxanide

• LD50 acute, rats, p.o. 980 to >2000 mg/kg (depending on the studies)
• LD50 acute, mice, p.o. 232 to 300 mg/kg (depending on the studies)
• LD50 acute, rabbits, p.o. 3200 mg/kg
• The safety margin after oral administration is ~6 and the therapeutic index >5. Usual therapeutic doses are: 3 mg/kg s.c., 7.5 - 15 mg/kg p.o.
• In cattle, doses ≥80 mg/kg can caused loss of appetite and diarrhea; doses ≥100 mg/kg caused neurotoxic symptoms and blindness; at doses >200 mg/kg fatalities were recorded.
• Sheep are more sensitive to rafoxanide. Cases of blindness were reported at doses ≥40 mg/kg.
• Sick or otherwise weak animals are more sensitive.

Toxic Symptoms caused by Rafoxanide Poisoning

• Most frequent symptoms of rafoxanide intoxication are:
• Loss of appetite
  
• Diarrhea
  
• Mydriasis (dilatation of the pupil)
• Blindness

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

• At therapeutic doses rafoxanide usually does not cause ADRs, excepting those previously described, but in a mild and transient form. 
• Rafoxanide is sometimes used in combination with benzimidazoles and/or ivermectin. Such combinations do not affect the pharmacological behavior of rafoxanide.

Antidote and Treatment of Rafoxanide Intoxication

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

Pharmacokinetics of Rafoxanide

• After oral administration rafoxanide is slowly absorbed into the bloodstream. Maximum blood concentrations are reached 2 to 3 days after treatment. Rafoxanide binds to >99% to plasma proteins. It is well distributed throughout the whole body but has a particular affinity for the thyroid gland.
• Excretion is rather slow, mainly through bile and feces, mostly as unchanged parent molecule. Less than 1% of the administered dose was found in urine. Excretion half-life is about 10 days. Rafoxanide remains detectable in blood for more than 100 days after treatment.

Environmental Toxicity of Rafoxanide

• 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 livestock, rafoxanide 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.

• Rafoxanide belongs to the chemical class of the salicylanilides.
• Rafoxanide is not used in human medicines.
  
• Rafoxanide is not used in crop pesticides.
• Rafoxanide 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 rafoxanide.