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
- Mydriasis (dilatation of the pupil)
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.
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- 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.
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.
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