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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 |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | 74% (Tmax = 2–4 hours) [1] |
Elimination half-life | 14 hours [1] |
Excretion | Bile duct (major route) |
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ECHA InfoCard | 100.267.822 |
Chemical and physical data | |
Formula | C26H17ClF9N3O3 |
Molar mass | 625.88 g·mol−1 |
3D model (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 GABA-receptors (those gated by the neurotransmitter gamma-aminobutyric acid) and other ligand-gated chloride channels. Isoxazolines, among the chloride channel modulators, bind to a distinct and unique target site within the insect GABA-gated chloride channels, thereby blocking pre-and post-synaptic transfer of chloride ions across cell membranes. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. [3]
According to clinical studies performed prior to marketing:
According to post-marketing safety experience:
In vivo studies (repeat-dose toxicology in laboratory animals, target animal safety, field studies) provided by MERIAL, the company that produces afoxolaner-derivative medicines, did not show evidence of neurological or behavioural effects suggestive of GABA-mediated perturbations in mammals. The Committee for Medicinal Products for Veterinary Use (CVMP) therefore concluded that binding to dog, rat or human GABA receptors is expected to be low for afoxolaner. [4]
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]
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.
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.
Mange is a type of skin disease caused by parasitic mites. Because various species of mites also infect plants, birds and reptiles, the term "mange", or colloquially "the mange", suggesting poor condition of the skin and fur due to the infection, is sometimes reserved for pathological mite-infestation of nonhuman mammals. Thus, mange includes mite-associated skin disease in domestic mammals, in livestock, and in wild mammals (for example, foxes, coyotes, cougars and wombats. Severe mange caused by mites has been observed in wild bears. Since mites belong to the arachnid subclass Acari, another term for mite infestation is acariasis.
Chlorfenvinphos is an organophosphorus compound that was widely used as an insecticide and an acaricide. The molecule itself can be described as an enol ester derived from dichloroacetophenone and diethylphosphonic acid. Chlorfenvinphos has been included in many products since its first use in 1963. However, because of its toxic effect as a cholinesterase inhibitor it has been banned in several countries, including the United States and the European Union. Its use in the United States was cancelled in 1991.
Acepromazine, acetopromazine, or acetylpromazine is a phenothiazine derivative antipsychotic drug. It was used in humans during the 1950s as an antipsychotic, but is now almost exclusively used on animals as a sedative and antiemetic. A closely related analogue, chlorpromazine, is still used in humans.
Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family. Fipronil disrupts the insect central nervous system by blocking the ligand-gated ion channel of the GABAA receptor and glutamate-gated chloride (GluCl) channels. This causes hyperexcitation of contaminated insects' nerves and muscles. Fipronil's specificity towards insects is believed to be due to its greater binding affinity for the GABAA receptors of insects than to those of mammals, and for its action on GluCl channels, which do not exist in mammals. As of 2017, there does not appear to be significant resistance among fleas to fipronil.
Selamectin is a topical parasiticide and anthelminthic used on dogs and cats. It treats and prevents infections of heartworms, fleas, ear mites, sarcoptic mange (scabies), and certain types of ticks in dogs, and prevents heartworms, fleas, ear mites, hookworms, and roundworms in cats. It is structurally related to ivermectin and milbemycin. Selamectin is not approved for human use.
Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle and sheep. Moxidectin kills some of the most common internal and external parasites by selectively binding to a parasite's glutamate-gated chloride ion channels. These channels are vital to the function of invertebrate nerve and muscle cells; when moxidectin binds to the channels, it disrupts neurotransmission, resulting in paralysis and death of the parasite.
Carprofen is a nonsteroidal anti-inflammatory drug (NSAID) of the carbazole and propionic acid class that was previously for use in humans and animals but is now only available to veterinarians for prescribing as a supportive treatment for various conditions in animals. Carprofen reduces inflammation by inhibition of COX-1 and COX-2; its specificity for COX-2 varies from species to species. Marketed under many brand names worldwide, carprofen is used as a treatment for inflammation and pain, including joint pain and postoperative pain.
Tepoxalin, sold under the brand name Zubrin among others, is a non-steroidal anti-flammatory drug (NSAIDs) generally used in veterinary medicine to reduce swelling in animals with osteoarthritis. In rare circumstances, tepoxalin can also be used in human pharmacology to relieve pain caused by musculoskeletal conditions such as arthritis and hip dysplasia.
Spinosad is an insecticide based on chemical compounds found in the bacterial species Saccharopolyspora spinosa. The genus Saccharopolyspora was discovered in 1985 in isolates from crushed sugarcane. The bacteria produce yellowish-pink aerial hyphae, with bead-like chains of spores enclosed in a characteristic hairy sheath. This genus is defined as aerobic, Gram-positive, nonacid-fast actinomycetes with fragmenting substrate mycelium. S. spinosa was isolated from soil collected inside a nonoperational sugar mill rum still in the Virgin Islands. Spinosad is a mixture of chemical compounds in the spinosyn family that has a generalized structure consisting of a unique tetracyclic ring system attached to an amino sugar (D-forosamine) and a neutral sugar (tri-Ο-methyl-L-rhamnose). Spinosad is relatively nonpolar and not easily dissolved in water.
Nitenpyram is a chemical frequently used as an insecticide in agriculture and veterinary medicine. The compound is an insect neurotoxin belonging to the class of neonicotinoids which works by blocking neural signaling of the central nervous system. It does so by binding irreversibly to the nicotinic acetylcholine receptor (nACHr) causing a stop of the flow of ions in the postsynaptic membrane of neurons leading to paralysis and death. Nitenpyram is highly selective towards the variation of the nACHr which insects possess, and has seen extensive use in targeted, insecticide applications.
The combination milbemycin oxime/lufenuron is a parasite control drug in which the active ingredient, milbemycin oxime, eliminates worms, while a second active ingredient, lufenuron, arrests the development of eggs and larvae, preventing them from maturing and continuing the infestation of an animal. This combination is registered for animal use only. To achieve efficacy, the treatment is administered once monthly, together with food, in a dosage suitable for the weight of the affected animal. The usual ratio is 500 μg milbemycin oxime and 10 mg lufenuron/kg body weight. Novartis indicates the proper dosage by color-coding the packages.
Thelazia callipaeda is a parasitic nematode, and the most common cause of thelaziasis in humans, dogs and cats. It was first discovered in the eyes of a dog in China in 1910. By 2000, over 250 human cases had been reported in the medical literature.
Thelaziasis is the term for infestation with parasitic nematodes of the genus Thelazia. The adults of all Thelazia species discovered so far inhabit the eyes and associated tissues of various mammal and bird hosts, including humans. Thelazia nematodes are often referred to as "eyeworms".
Milbemycin oxime, sold under the brand name Interceptor among others, is a veterinary medication from the group of milbemycins, used as a broad spectrum antiparasitic. It is active against worms (anthelmintic) and mites (miticide).
Pyriprole is for veterinary use on dogs against external parasites such as fleas and ticks.
Fluralaner (INN) is a systemic insecticide and acaricide that is administered orally or topically. The U.S. Food and Drug Administration (FDA) approved it under the trade name Bravecto for flea treatment in dogs in May 2014 and Bravecto Plus as a topical treatment for cats in November 2019, with warnings about possible side effects in both species. The EU approved the drug in February 2014. Australia approved it for the treatment and prevention of ticks and fleas on dogs in January 2015. For treating mites in chickens, a solution for use in drinking water is available under the name Exzolt; it was introduced by the EU in 2017.
Grapiprant is a small molecule drug that belongs in the piprant class. This analgesic and anti-inflammatory drug is primarily used as a pain relief for mild to moderate inflammation related to osteoarthritis in dogs. Grapiprant has been approved by the FDA's Center for Veterinary Medicine and was categorized as a non-cyclooxygenase inhibiting non-steroidal anti-inflammatory drug (NSAID) in March 2016.
Isoxazolines are a class of five-membered heterocyclic chemical compounds, containing one atom each of oxygen and nitrogen which are located adjacent to one another. The ring was named in-line with the Hantzsch–Widman nomenclature. They are structural isomers of the more common oxazolines and exist in three different isomers depending on the location of the double bond. The relatively weak N-O bond makes isoxazolines prone to ring-opening and rearrangement reactions.
Lotilaner, sold under the brand name Xdemvy, is an ectoparasiticide (anti-parasitic) medication used for the treatment of blepharitis caused by infestation by Demodex. It is used as an eye drop.
Sarolaner, sold under the brand name Simparica, is an ectoparasiticide veterinary medication for the treatment of flea and tick infestations in dogs. It is also used off-label to control sarcoptic mange and demodectic mange.