Afoxolaner
Clinical Particulars
Afoxolaner is an isoxazoline insecticide, and acaracide. Afoxolaner kills parasites by overstimulating their nervous systems. It also kills fleas before they can lay eggs and helps reduce environmental contamination (PubChem, 2024).
Pharmacokinetics
Mechanism of Action
Afoxolaner blocks the normal movement of charged chloride particles (ions) in and out of nerve cells, especially those associated with gamma-aminobutyric acid (GABA). This substance conveys messages between nerves (neurotransmitters). Uncontrolled nervous system activity results in the paralysis and death of fleas, ticks, and mites (PubChem, 2024).
Veterinary Applications
Authorised Species (Dogs): Insecticide and acaracide. Afoxolaner is active against adult fleas and ticks:
Treatment of flea infestation in dogs (Ctenocephalides felis and C. canis) for at least five weeks. The product can be used as a treatment strategy to control Flea Allergy Dermatitis (FAD).
Treatment of tick infestation in dogs (Dermacentor reticulatus, Ixodes ricinis, Ixodes hexagonus, Rhipicephalus sanguineus, Hyalomma marginatum). One treatment kills ticks for up to one month.
Fleas and ticks must attach to the host and commence feeding to be exposed to the active substance.
Treatment of demodicosis (caused by Demodex canis).
Treatment of sarcoptic mange (caused by Sarcoptes scabiei var. canis).
Treatment of ear mite infestations (caused by Otodectes cynotis).
Unauthorised Species (rabbits, hedgehogs): Insecticide and acaracide (Refs).
Pharmacodynamics
Metabolism
Hepatic: Some limited hepatically biotransformed metabolites REF.
Elimination
Mixed Routes: Protein binding is high (more than 99%). Elimination is via biliary excretion of free afoxolaner and renal excretion of hepatically biotransformed metabolites. The terminal elimination half-life in the dog is ≈15 days REF.
Precautions
Adverse Effects
Dogs
Very rarely, mild, short-duration self-limiting gastrointestinal effects and transient neurological signs have been reported (SPC Data).
Neurological: Hyperactivity, panting, ataxia, muscle tremors, and seizures have been reported (Palmieri 2020; SPC Data).
Gastrointestinal: Mild gastrointestinal effects (vomiting, diarrhoea) are reported rarely (Palmieri 2020; SPC Data).
Rabbits
No adverse reactions or clinically relevant physiological changes are expected (food intake, body weight or physical examination parameters, e.g., heart percentage, respiratory percentage, and body temperature)
Contraindications
Hypersensitivity: Do not use in animals with known or suspected hypersensitivity to the agent or any excipient (SPC Data).
Advisory: Use with caution in dogs with a history of seizures or epilepsy, as isoxazolines are associated with increased seizure frequency and severity (Palmieri 2020; SPC Data).
Reproductive Safety
Pregnancy: Can be used in breeding, pregnant and lactating dogs (SPC Data).
Lactation: Can be used in breeding, pregnant and lactating dogs (SPC Data).
Male Fertility: Can be used in breeding, pregnant and lactating dogs (SPC Data).
Female Fertility: Can be used in breeding, pregnant and lactating dogs (SPC Data).
Potentially Significant Interactions
None Reported: In dogs, Afoxolaner has been safely used alongside vaccines, anthelmintics, antibiotics (including topicals), steroids, NSAIDS, anaesthetics, and antihistamines (SPC Data).
Overdose
Prevalence: None Known; No data. Unlikely to occur.
Mechanism: None Known; No data
Presenting Signs: None Known; No data
Clinical Response: None Known; No data
Species Specific Toxicity Information: None Known; No data
Reversal: None Known; No data
Availability
UK Formulations
Nexguard Spectra® Chewable tablets for dogs
1.35–3.5 kg: Afoxolaner (mg) 9.375 + Milbemycin oxime (mg)1.875
>3.5–7.5 kg: Afoxolaner (mg) 18.75 + Milbemycin oxime (mg) 3.75
>7.5–15 kg: Afoxolaner (mg) 37.50 + Milbemycin oxime (mg) 7.5
>15–30 kg: Afoxolaner (mg) 75.00 + Milbemycin oxime (mg) 15.00
>30–60 kg: Afoxolaner (mg) 150.00mg + Milbemycin oxime (mg) 30.00
Nexguard Chewable Tablets®
Afoxolaner: 11.3, 28.3, 68.0, 136.0 mg tablets
Identifiers
Systematic Name: IUPAC Name - 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol (PubChem, 2024).
Systematic Name: 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]naphthalene-1-carboxamide
Formula: C26-H17-Cl-F9-N3-O3
Pharmacotherapeutic Group: Ectoparasiticides for systemic use; Isoxazolines
ATC vet code: QP53BE01
Evidence Base
Sojka, P.A., 2018. ISOXAZOLINES. Journal of Exotic Pet Medicine 27, 118–122. https://doi.org/10.1053/j.jepm.2018.02.038
UK SPC, n.d. Nexgard Spectra 19 mg / 4 mg Chewable Tablets for Dogs >3.5–7.5 kg Product Information Database [WWW Document]. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A011070 (accessed 11.30.22).
Wismer, T., Means, C., 2018. Toxicology of Newer Insecticides in Small Animals. Veterinary Clinics of North America: Small Animal Practice, Common Toxicologic Issues in Small Animals: An Update 48, 1013–1026. https://doi.org/10.1016/j.cvsm.2018.06.005
Monograph Details
Criteria
Active Substance: Afoxolaner
Resources
Reference Management: Zotero Database
Development Team
Monograph Author(s): S McArthur B Vet Med MRCVS (last updated 20/03/2024)
Monograph Editor(s): TBA (last updated 20/03/2024)
Monograph Contact
Information & Permissions: stuart.mcarthur717@gmail.com