Introduction

Name

• Fluralaner, Bravecto®.

Class of drug

• Ectoparasiticides for systemic use.
• Isoxazoline.
• Systemic insecticide and acaricide.

Description

Chemical name

• 4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide.

Molecular formula

• C22H17Cl2F6N3O3

Molecular weight

• 556.28

Physical properties

• Chewable tablet:
  • Light to dark brown tablet with a smooth or slightly rough surface and circular shape. Some marbling, speckles or both may be visible.
• Spot-on solution:
  • Clear, colorless to yellow solution.

Storage requirements

• Shelf life as packaged for sale: 2 years.
• Do not store above 86°F (30°C).
• Pipettes should be kept in the outer packaging to prevent solvent loss or moisture uptake. The sachets should only be opened immediately prior to use.

Uses

Indications

• Treatment and prevention of flea infestations for 12 weeks.
• Immediate and persistent flea (Ctenocephalides felis) killing activity for 12 weeks:
  • Onset of effect is within 8 hours for fleas.
  • Part of treatment strategy for the control of flea allergy dermatitis (FAD) Skin: flea bite hypersensitivity.
  • Contributes to control of the environmental flea populations in areas to which treated dogs have access Flea: control.
• Treatment and control of tick infestations Tick control:
  • Onset of effect is within 12 hours for ticks (I. ricinus Ixodes ricinus).
• Immediate and persistent tick killing activity for 12 weeks:
  • EU: Ixodes ricinus, Dermacentor reticulatus Dermacentor reticulatus, D. variabilis, Rhipicephalus sanguineus Rhipicephalus sanguineus.
  • US: Ixodes scapularis Ixodes scapularis, Dermacentor variabilis Dermacentor variabilis, Rhipicephalus sanguineus.
• Immediate and persistent tick killing activity for 8 weeks:
  • EU: Rhipicephalus sanguineus Rhipicephalus sanguineus (chewable tablet).
  • US: Amblyomma americanum Amblyomma americanum.

Efficacy against other ectoparasites

• Sarcoptes scabiei Sarcoptes scabiei mites were eliminated 4 weeks post treatment in infested dogs and clinical signs improved.
• Demodectic mange Skin: demodectic mange miticidal efficacy, based on mite numbers found via skin scrapings in demodectic mange cases, was 99.8%  at 4 weeks post treatment, >99.9% at 8 weeks and 100% 12 weeks post treatment.
• Linognathus setosus Linognathus setosus (sucking lice, natural infection) were eliminated within 4 weeks after a single oral treatment and this led to complete dermatological recovery that was maintained at the end of the study (12 weeks). Efficacy against sucking lice, based on reduction in louse counts in comparison to pre-treatment counts, was 85.7% (day 1), 96.8% (day 7) and 100% (days 28 and 84). No lice were seen on treated dogs 4 and 12 weeks after treatment.

Break transmission of dog/flea tapeworm

• Prevents transmission of Dipyldium caninum Dipyldium caninum from infected fleas to dogs (laboratory study) for up to 12 weeks following single oral or topical administration.

Administration

Precautions

Interactions

with other drugs

• None known.
• Theoretical competition with other highly bound drugs (eg non-steroidal anti-inflammatory drugs (NSAIDs). However, protein binding of fluralaner, carprofen or warfarin was not reduced in an in vitro study in dog plasma using the maximum expected plasma concentrations.
• No interactions with routinely used veterinary medicinal products in dogs during clinical field trials.

Adverse Reactions

Further Reading

Publications

Refereed papers

• Recent references from PubMed and VetMedResource.
• Fourie J J, Meyer L, Thomas E (2019) Efficacy of topically administered fluralaner or imidacloprid/moxidectin on dogs with generalised demodicosis. Parasit Vectors 12 (1), 59 PubMed.
• Gopinath D, Meyer L, Smith J et al (2018) Topical or oral fluralaner efficacy against flea (Ctenocephalides felis) transmission of Dipylidium caninum infection to dogs. Parasit Vectors 11 (1), 557 PubMed.
• Ranjan S, Young D, Sun F (2018) A single topical fluralaner application to cats and to dogs controls fleas for 12 weeks in a simulated home environment. Parasit Vectors 11 (1), 385 PubMed.
• Dongus H, Meyer L, Armstrong R (2017) Water immersion of dogs close to the time of topical fluralaner treatment does not reduce efficacy against a subsequent experimental challenge with Rhipicephalus sanguineus (sensu lato). Parasit Vectors 10 (1), 441 PubMed.
• Kohler-Aanesen H, Saari S, Armstrong R et al (2017) Efficacy of fluralaner (Bravecto™ chewable tablets) for the treatment of naturally acquired Linognathus setosus infestations on dogs. Parasit Vectors 10 (1), 426 PubMed.
• Meadows C, Guerino F, Sun F (2017) A randomized, blinded, controlled USA field study to assess the use of fluralaner topical solution in controlling canine flea infestations. Parasit Vectors 10 (1), 36 PubMed.
• Taenzler J, de Vos C, Roepke R K et al (2017) Efficacy of fluralaner against Otodectes cynotis infestations in dogs and cats. Parasit Vectors 10 (1), 30 PubMed.
• Burgio F, Meyer L, Armstrong R (2016) A comparative laboratory trial evaluating the immediate efficacy of fluralaner, afoxolaner, sarolaner and imidacloprid + permethrin against adult Rhipicephalus sanguineus (sensu lato) ticks attached to dogs. Parasit Vectors 9 (1), 626 PubMed.
• Romero C, Heredia R, Pineda J et al (2016) Efficacy of fluralaner in 17 dogs with sarcoptic mange. Vet Dermatol 27 (5), 353-e88 PubMed.
• Taensler J, Liebenberg J, Roepke R K et al (2016) Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs.​ Parasites and Vectors 9 (1), 392 PubMed.
• Taensler J, Liebenberg J, Mienie M et al (2016) Efficacy of fluralaner spot-on solution against induced infestations with Rhicephalus sanguineus on dogs. Parasites and Vectors 9 (1), 276 PubMed.
• Taensler J, Gale B, Zschiesche E et al (2016) The effect of water and shampooing on the efficacy of fluralaner spot-on solution against Ixodes ricinus and Ctenocephalides felis infestations in dogs. Parasites and Vectors 9 (1), 233 PubMed.
• Fourie J J, Liebenberg J E, Horak I G et al (2015) Efficacy of  orally administered fluralaner (Bravecto™) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs. Parasites and Vectors 8, 187 PubMed.
• Asahi M, Kobayashi M, Matsui H et al (2014) Differential mechanisms of action of the novel γ​-aminobutyric acid receptor antagonist ectoparasiticides fluralaner (A1443) and fipronil. Pest Manag Sci 71 (1), 91-95 PubMed.
• Gassel M, Wolf C, Noack S et al (2014) The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochem Mol Biol 45, 111-124 PubMed.
• Kilp S, Ramirez D, Allan M J et al (2014) Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration. Parasit Vectors 7, 85 PubMed.
• Rohdich N, Roepke R K, Zschiesche E (2014) A randomized, blinded, controlled and multi-centered field study comparing the efficacy and safety of Bravecto (fluralaner) against Frontline (fipronil) in flea- and tick-infested dogs. Parasit Vectors 7, 83 PubMed.
• Walther F M, Allan M J, Roepke R K et al (2014) Safety of fluralaner chewable tablets (Bravecto), a novel systemic antiparasitic drug, in dogs after oral administration. Parasit Vectors 7, 87 PubMed.
• Walther F M, Allan M J, Roepke R K et al (2014) The effect of food on the pharmacokinetics of oral fluralaner in dogs. Parasit Vectors 7, 84 PubMed.
• Walther F M, Fisara P, Allan M J et al (2014) Safety of the concurrent treatment of dogs with Bravecto (fluralaner) and Scalibor protectorband (deltamethrin). Parasit Vectors 7, 105 PubMed.
• Walther F M, Paul A J, Allan M J et al (2014) Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration. Parasit Vectors 7, 86 PubMed.
• Williams H, Young D R, Qureshi T et al (2014) Fluralaner, a novel isoxazoline, prevents flea (Ctenocephalides felis) reproduction in vitro and in a simulated home environment. Parasit Vectors 7, 275 PubMed.
• Zhao C, Casida J E (2014) Insect γ-aminobutyric acid receptors and isoxazoline insecticides: toxicological profiles relative to the binding sites of [³H]fluralaner, [³H]-4'-ethynyl-4-n-propylbicycloorthobenzoate, and [³H]avermectin. J Agric Food Chem 62 (5), 1019-1024 PubMed.

Other sources of information

• European Medicines Agency. European Public Assessment Report. Bravecto. Product Information.
• European Medicines Agency. European Public Assessment Report. Bravecto. Scientific Discussion.
• US Food and Drugs Administration. Bravecto: Freedom of Information Summary.
• Product website: www.bravecto.com (registration required).

Organisation(s)

• ESCCAP: www.esccap.org
• CAPC: www.capcvet.org
• European Veterinary Parasitology College: www.eurovetpar.org
• American Association of Veterinary Parasitologists: www.aavp.org