fluralaner
{{Short description|Chemical compound}}
{{Use dmy dates|date=June 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image = Fluralaner.svg
| width = 275
| alt =
| chirality = Racemic mixture
| pronounce = {{IPAc-en|ˌ|f|l|ʊər|ə|ˈ|l|æ|n|ər}} {{respell|FLOOR|ə|LAN|ər}}
| tradename = Bravecto, Exzolt
| Drugs.com =
| MedlinePlus =
| DailyMedID = Fluralaner
| routes_of_administration = By mouth
| ATCvet = yes
| ATC_prefix = P53
| ATC_suffix = BE02
| ATC_supplemental =
| legal_AU = S5
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE =
| legal_UK =
| legal_US = Rx-only
| legal_US_comment = {{cite web | title=Bravecto- fluralaner solution | website=DailyMed | date=16 November 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4181fa7-e45f-4beb-a3f5-49c987d584ac | access-date=29 June 2024}}{{cite web | title=Bravecto 1-Month- fluralaner tablet, chewable | website=DailyMed | date=19 May 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8fced6df-02cf-46b5-b794-c1512913e6d4 | access-date=29 June 2024}}{{cite web | title=Bravecto- fluralaner solution | website=DailyMed | date=13 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fed84d87-049a-4e22-8091-451cde091815 | access-date=29 June 2024}}{{cite web | title=Bravecto- fluralaner tablet, chewable | website=DailyMed | date=22 May 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1fcbf232-cfd4-481e-ba9b-6251b7b468d7 | access-date=29 June 2024}}
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | title=Bravecto EPAR | website=European Medicines Agency | date=26 March 2014 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/bravecto | access-date=29 June 2024}}{{cite web | title=Bravecto PI | website=Union Register of medicinal products | date=13 February 2014 | url=https://ec.europa.eu/health/documents/community-register/html/v158.htm | access-date=29 June 2024}}{{cite web | title=Exzolt EPAR | website=European Medicines Agency | date=20 October 2017 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/exzolt | access-date=26 June 2024}}{{cite web | title=Exzolt PI | website=Union Register of medicinal products | date=22 August 2017 | url=https://ec.europa.eu/health/documents/community-register/html/v212.htm | access-date=29 June 2024}}
| legal_status = RU: Rx-only; OTC{{cite web | title = Bravecto (fluralaner) for the Treatment and Prophylaxis of Arachnoenthomoses in Dogs. Full Prescribing Information | url = http://www.msd-animal-health.ru/Binaries/bravecto0316_tcm53-179097.pdf | publisher = Intervet GesmbH | access-date = 14 November 2016 | language = Russian | archive-url = https://web.archive.org/web/20180517004228/http://www.msd-animal-health.ru/Binaries/bravecto0316_tcm53-179097.pdf | archive-date = 17 May 2018 | url-status = dead }}
| bioavailability = 20–27%; reduced in the fasted state{{cite journal | vauthors = Walther FM, Allan MJ, Roepke RK, Nuernberger MC | title = The effect of food on the pharmacokinetics of oral fluralaner in dogs | journal = Parasites & Vectors | volume = 7 | issue = 1 | pages = 84 | date = March 2014 | pmid = 24598049 | pmc = 3975707 | doi = 10.1186/1756-3305-7-84 | doi-access = free }}
| protein_bound =
| metabolism =
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| CAS_number = 864731-61-3
| CAS_supplemental =
| PubChem = 25144319
| PubChemSubstance =
| IUPHAR_ligand =
| DrugBank =
| ChemSpiderID = 29398949
| UNII = WSH8393RM5
| KEGG = D10402
| ChEBI =
| ChEMBL = 2364610
| synonyms = {{ubl|A1443, AH252723
|4-[(5RS)-5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-1,2-oxazol-3-yl]-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]-o-toluamide
}}
| IUPAC_name = (±)-4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide
| C = 22
| H = 17
| Cl = 2
| F = 6
| N = 3
| O = 3
| SMILES = Cc1cc(ccc1C(=O)NCC(=O)NCC(F)(F)F)C2=NOC(C2)(c3cc(cc(c3)Cl)Cl)C(F)(F)F
| StdInChI = 1S/C22H17Cl2F6N3O3/c1-11-4-12(2-3-16(11)19(35)31-9-18(34)32-10-21(25,26)27)17-8-20(36-33-17,22(28,29)30)13-5-14(23)7-15(24)6-13/h2-7H,8-10H2,1H3,(H,31,35)(H,32,34)
| StdInChIKey = MLBZKOGAMRTSKP-UHFFFAOYSA-N
| density =
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}}
Fluralaner, (INN){{cite journal | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 69 | journal = WHO Drug Information | date = 2013 | volume = 27 | issue = 1 | page = 59 | url = http://apps.who.int/medicinedocs/documents/s20154en/s20154en.pdf | archive-url = https://web.archive.org/web/20161114234623/http://apps.who.int/medicinedocs/documents/s20154en/s20154en.pdf | url-status = dead | archive-date = 14 November 2016 | access-date = 14 November 2016}} sold under the brand name Bravecto among others, is a systemic insecticide and acaricide that is administered orally{{cite journal | vauthors = Walther FM, Allan MJ, Roepke RK, Nuernberger MC | title = Safety of fluralaner chewable tablets (Bravecto), a novel systemic antiparasitic drug, in dogs after oral administration | journal = Parasites & Vectors | volume = 7 | issue = 1 | pages = 87 | date = March 2014 | pmid = 24606886 | pmc = 3975339 | doi = 10.1186/1756-3305-7-87 | doi-access = free }} or topically.{{cite journal | vauthors = Ranjan S, Young D, Sun F | title = A single topical fluralaner application to cats and to dogs controls fleas for 12 weeks in a simulated home environment | journal = Parasites & Vectors | volume = 11 | issue = 1 | pages = 385 | date = July 2018 | pmid = 29970135 | pmc = 6029119 | doi = 10.1186/s13071-018-2927-0 | doi-access = free }}
Mode of action
Fluralaner inhibits γ-aminobutyric acid (GABA)-gated chloride channels (GABAA receptors) and L-glutamate-gated chloride channels (GluCls).{{cite journal | vauthors = Gassel M, Wolf C, Noack S, Williams H, Ilg T | title = The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity | journal = Insect Biochemistry and Molecular Biology | volume = 45 | pages = 111–124 | date = February 2014 | pmid = 24365472 | doi = 10.1016/j.ibmb.2013.11.009 | doi-access = free | bibcode = 2014IBMB...45..111G }} Potency of fluralaner is comparable to fipronil (a related GABA-antagonist insecticide and acaricide).{{cite journal | vauthors = Asahi M, Kobayashi M, Matsui H, Nakahira K | title = Differential mechanisms of action of the novel γ-aminobutyric acid receptor antagonist ectoparasiticides fluralaner (A1443) and fipronil | journal = Pest Management Science | volume = 71 | issue = 1 | pages = 91–95 | date = January 2015 | pmid = 24591229 | doi = 10.1002/ps.3768 }}
Society and culture
= Legal status =
The US Food and Drug Administration (FDA) approved it for flea treatment in dogs in May 2014,{{cite web | url = http://drjustinelee.com/new-fleatick-medication-bravecto-just-approved/ | title = New Flea/Tick Medication by Merck Just Approved: Bravecto | date = 21 May 2014 | access-date = 3 November 2014 | vauthors = Lee J | archive-date = 15 June 2018 | archive-url = https://web.archive.org/web/20180615010504/https://drjustinelee.com/new-fleatick-medication-bravecto-just-approved/ | url-status = live }} and approved the combination fluralaner/moxidectin (Bravecto Plus) as a topical treatment for cats in November 2019.{{cite web |title=Bravecto Plus (fluralaner and moxidectin topical solution) for Cats Receives Approval from US Food and Drug Administration |url=https://www.merck-animal-health.com/blog/2019/11/15/bravecto-plus-fluralaner-and-moxidectin-topical-solution-for-cats-receives-approval-from-us-food-and-drug-administration/ |website=Merck Animal Health |access-date=22 May 2021 |date=15 November 2019 |archive-date=19 September 2022 |archive-url=https://web.archive.org/web/20220919055339/https://www.merck-animal-health.com/blog/2019/11/15/bravecto-plus-fluralaner-and-moxidectin-topical-solution-for-cats-receives-approval-from-us-food-and-drug-administration/ |url-status=live }}{{cite web |author=Center for Veterinary Medicine |title=Fact Sheet for Pet Owners and Veterinarians about Potential Adverse Events Associated with Isoxazoline Flea and Tick Products |url=https://www.fda.gov/animal-veterinary/animal-health-literacy/fact-sheet-pet-owners-and-veterinarians-about-potential-adverse-events-associated-isoxazoline-flea |website=U.S. Food and Drug Administration (FDA) |access-date=22 May 2021 |date=31 July 2020 |archive-date=22 May 2021 |archive-url=https://web.archive.org/web/20210522014444/https://www.fda.gov/animal-veterinary/animal-health-literacy/fact-sheet-pet-owners-and-veterinarians-about-potential-adverse-events-associated-isoxazoline-flea |url-status=dead }}{{cite web | title=Bravecto Plus EPAR | website=European Medicines Agency | date=7 June 2018 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/bravecto-plus | access-date=29 June 2024}}{{cite web | title=Bravecto Plus PI | website=Union Register of medicinal products | date=16 May 2018 | url=https://ec.europa.eu/health/documents/community-register/html/v224.htm | access-date=29 June 2024}} The EU approved fluralaner in March 2014.{{cite web | url = https://www.zenopa.com/news/801695271/msd-animal-health-receives-eu-approval-for-bravecto | title = MSD Animal Health receives EU approval for Bravecto | date = 19 February 2014 | access-date = 3 November 2014 | archive-date = 27 March 2019 | archive-url = https://web.archive.org/web/20190327122933/https://www.zenopa.com/news/801695271/msd-animal-health-receives-eu-approval-for-bravecto | url-status = live }} Australia approved it for the treatment and prevention of ticks and fleas on dogs in January 2015.{{cite web | url = https://apvma.gov.au/sites/default/files/gazette_10022015.pdf | access-date = 14 February 2019 | title = Agricultural and Veterinary Chemicals | publisher = Australian Pesticides and Veterinary Medicines Authority | date = 10 February 2015 | archive-date = 19 September 2022 | archive-url = https://web.archive.org/web/20220919055340/https://apvma.gov.au/sites/default/files/gazette_10022015.pdf | url-status = live }} For treating mites in chickens, a solution for use in drinking water is available under the brand name Exzolt{{Cite web | vauthors = Imrie P |date=24 June 2020 |title=Backyard poultry red mite treatment launches |url=https://www.vettimes.co.uk/news/backyard-poultry-red-mite-treatment-launches/ |access-date=1 December 2023 |website=Vet Times}} and was approved for use in the EU in 2017.{{cite journal | vauthors = Brauneis MD, Zoller H, Williams H, Zschiesche E, Heckeroth AR | title = The acaricidal speed of kill of orally administered fluralaner against poultry red mites (Dermanyssus gallinae) on laying hens and its impact on mite reproduction | journal = Parasites & Vectors | volume = 10 | issue = 1 | pages = 594 | date = December 2017 | pmid = 29197422 | pmc = 5712167 | doi = 10.1186/s13071-017-2534-5 | doi-access = free }}
Bravecto 1-Month was approved by the FDA in November 2024 for the addition of the indication for the treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for one month in dogs and puppies eight weeks of age and older, and weighing {{convert|4.4|lbs|kg}} or greater.{{cite web | title=Recent Animal Drug Approvals | website=U.S. Food and Drug Administration (FDA) | date=2 December 2024 | url=https://www.fda.gov/animal-veterinary/approved-animal-drug-products-green-book/recent-animal-drug-approvals | access-date=21 December 2024 }} {{PD-notice}}[https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/16308 fda.gov]
Research
Fluralaner is being investigated to determine its ability to reduce the incidence of mosquito-borne diseases,{{cite journal | vauthors = Miglianico M, Eldering M, Slater H, Ferguson N, Ambrose P, Lees RS, Koolen KM, Pruzinova K, Jancarova M, Volf P, Koenraadt CJ, Duerr HP, Trevitt G, Yang B, Chatterjee AK, Wisler J, Sturm A, Bousema T, Sauerwein RW, Schultz PG, Tremblay MS, Dechering KJ | title = Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 29 | pages = E6920–E6926 | date = July 2018 | pmid = 29967151 | pmc = 6055183 | doi = 10.1073/pnas.1801338115 | bibcode = 2018PNAS..115E6920M | doi-access = free }} as well as bed bugs.{{cite news | vauthors = Murez C |title=Two veterinary drugs may help eliminate bedbugs |url=https://www.upi.com/Health_News/2022/12/01/veterinary-medicine-bedbugs/6091669903318/ |access-date=3 December 2022 |publisher=United Press International, Inc. |date=1 December 2022}}{{cite journal | vauthors = Sheele JM |title=A Preliminary Report Showing Spinosad and Fluralaner Are Able to Incapacitate Cimex lectularius L., the Common Bed Bug |journal=Cureus |year=2020 |volume=12 |issue=4 |pages=e7529 |doi=10.7759/cureus.7529 |doi-access=free |pmid=32377477 |pmc=7198093 |s2cid=216501793 }}
References
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Category:Drugs developed by Merck & Co.
Category:Trifluoromethyl compounds