Afoxolaner
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| Clinical data | |
|---|---|
| Pronunciation | /eɪˌfɒksoʊˈlænər/ ay-FOK-soh-LAN-ər |
| Trade names | Nexgard, Frontpro |
| Other names | 4-[(5RS)-5-(5-Chloro-α,α,α-trifluoro-m-tolyl)-4,5-dihydro-5-(trifluoromethyl)-1,2-oxazol-3-yl]-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]naphthalene-1-carboxamide |
| License data |
|
QP53BE01 (WHO) | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 74% (Tmax = 2–4 hours)[1] |
| Elimination half-life | 14 hours[1] |
| Excretion | Bile duct (major route) |
| Identifiers | |
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JSmol) | |
| Chirality | Racemic mixture |
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Afoxolaner (INN[2]) is an insecticide and acaricide that belongs to the isoxazoline chemical compound group.
It acts as an antagonist at
Safety
Toxicity for mammals
According to clinical studies performed prior to marketing:
- The oral toxicity profile of afoxolaner consists of a diuretic effect (rats only), effects secondary to a reduction in food consumption (rats and rabbits only) and occasional vomiting and/or diarrhea (dogs, 120 and 200 mg/kg bodyweight (bw)) following high oral doses. No treatment-related effects on vomiting or diarrhea were noted following oral doses of up to 31.5 mg/kg bw in the pivotal target animal safety study, nor in the EU field trial.[4]
- mild gastrointestinal effects (vomiting, diarrhea), pruritus, lethargy, anorexia, and neurological signs (convulsions, ataxia and muscle tremors) have been reported in less than 0.1% of 10,000 animals treated, including isolated reports, most reported adverse reactions being self-limiting and of short duration,[5]
- (in combination with milbemycin oxime): vomiting, diarrhea, lethargy, anorexia, and pruritus were observed in 0.2 to 1% of 10,000 animals treated and were generally self-limiting and of short duration,[3]
- In vitro studies reported that afoxolaner can bind to
According to post-marketing safety experience:
- (in combination with milbemycin oxime): erythema and neurological signs (convulsions, ataxia and muscle tremors) have been reported in less than 0.1% of 10,000 animals treated, including isolated reports,[3]
- The US Food and Drug Administration FDA reports[6] that some drugs in this class (isoxazolines), including afoxolaner, can have adverse neurologic effects on some dogs, such as muscle tremors, ataxia, and convulsions.
- Extralabel use of afoxolaner in a pet pig has been described without any adverse effects.[7] Experimental use in commercial pigs also did not result in any adverse effects.[8]
Selectivity in insects over mammalians
In vivo studies (repeat-dose
Selectivity for insect over mammalian GABA-receptors has been demonstrated for other isoxazolines.[9] The selectivity might be explained by the number of pharmacological differences that exist between GABA-gated chloride channels of insects and vertebrates.[10]
Legal status
The marketing authorization was granted by the European Medicines Agency in February 2014, for Nexgard and January 2015, for Nexgard Spectra, after only 14[11] and 12[4] months of quality, safety and efficacy assessment performed by the Committee for Medicinal Products for Veterinary Use (CVMP).[12] Therefore, long-term effects are not known.
Brand names
Afoxolaner is the active ingredient of the veterinary medicinal products Nexgard, Frontpro, and Nexgard Spectra (in combination with milbemycin oxime).[13][14][15] They are indicated for the treatment and prevention of flea infestations, and the treatment and control of tick infestations in dogs and puppies (8 weeks of age and older, weighing 4 pounds (~1.8 kilograms) of body weight or greater) for one month.[16] These products are administered orally and poisons fleas once they start feeding.
References
- ^ a b c "Frontline NexGard (afoxolaner) for the Treatment and Prophylaxis of Ectoparasitic Diseases in Dogs. Full Prescribing Information" (PDF) (in Russian). Sanofi Russia. Archived from the original (PDF) on 13 July 2018. Retrieved 14 November 2016.
- ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 70" (PDF). World Health Organization. pp. 276–7. Retrieved 14 November 2016.
- ^ a b c "NexGard Spectra product information - Annex I "Summary of product characteristics"" (PDF). European Medicines Agency. Retrieved 13 November 2019.
- ^ a b c d "CVMP assessment report for NexGard (EMEA/V/C/002729/0000)" (PDF). European Medicines Agency. Retrieved 14 November 2019.
- ^ "NexGard product information - Annex I "Summary of product characteristics"" (PDF). European Medicines Angency. Retrieved 14 November 2019.
- ^ "CVM Updates - Animal Drug Safety Communication: FDA Alerts Pet Owners and Veterinarians About Potential for Neurologic Adverse Events Associated with Certain Flea and Tick Products". Center for Veterinary Medicine. U.S. Food and Drug Administration. Retrieved 2018-09-22.
- PMID 33102538.
- PMID 29914951.
- PMID 25688713.
- S2CID 5028039.
- ^ "CVMP Assessment Report for NEXGARD SPECTRA(EMEA/V/C/003842/0000)" (PDF). European Medicines Agency. Retrieved 14 November 2019.
- ^ "Committee for Medicinal Products for Veterinary Use (CVMP) - Section "Role of the CVMP"". European Medicines Agency. 17 September 2018. Retrieved 14 November 2019.
- PMID 24631502.
- PMID 25148564.
- PMID 27514901.
- ^ "Boehringer-Ingelheim companion-animals-product NexGard (afoxolaner)". Boehringer Ingelheim International GmbH. Retrieved 13 November 2019.