BRAVECTO ONE Chewable Tablet 45 mg (Canada)

Fluralaner Chewable Tablet, 45 mg, 100 mg, 200 mg, 400 mg, 560 mg

Veterinary Use Only

DIN 02502216, 02502224, 02502232, 02502240, 02502259

Description

BRAVECTO ONE (Fluralaner Chewable Tablet) for dogs is a light to dark brown flavoured chewable tablet containing 45 mg, 100 mg, 200 mg, 400 mg or 560 mg of fluralaner.

Each chewable tablet strength is formulated to provide a minimum dose of 10 mg/kg body weight for dogs of different weight ranges.

THERAPEUTIC CLASSIFICATION:

Antiparasitic

BRAVECTO ONE Chewable Tablet 45 mg Indications

BRAVECTO ONE is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and for the treatment and control of tick infestations with Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick) and Rhipicephalus sanguineus (brown dog tick) for one month, in dogs and puppies 8 weeks of age and older and weighing 2 kg or greater.

BRAVECTO ONE is also indicated for the treatment and control of tick infestations with Amblyomma americanum (lone star tick) for one month, in dogs and puppies 6 months of age and older and weighing 2 kg or greater.

Dosage and Administration

BRAVECTO ONE should be administered orally as a single dose every month according to the Dosage Schedule below to provide a minimum dose of 10 mg/kg body weight.

BRAVECTO ONE should be administered with food.

Dosage Schedule

* Dogs over 56 kg should be administered the appropriate combination of chewable tablets

Treatment with BRAVECTO ONE may begin at any time of the year and can continue monthly without interruption. Due to climate variations across the country, there are variable distributions and abundance of fleas and ticks. A comprehensive plan, based on regional risk assessment is recommended.

Contraindications

This product should not be given to dogs with known or suspected allergy or intolerance to fluralaner or other components of this product.

CAUTIONS:

Fluralaner is a member of the isoxazoline class. This class has been associated with neurological adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in dogs receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurological disorders.

BRAVECTO ONE is not effective against Amblyomma americanum for one month in puppies less than 6 months of age.

The safety of BRAVECTO ONE has not been evaluated in puppies less than 8 weeks of age nor in breeding, pregnant or lactating dogs.

Reproductive safety has been evaluated with BRAVECTO Chewable Tablets (see Animal Safety).

Keep BRAVECTO ONE in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Warnings

● Keep out of reach of children.

● Keep the product in the original packaging until use in order to prevent children from getting direct access to the product.

● Do not eat, drink or smoke while handling the product.

● Wash hands thoroughly with soap and water immediately after use of the product.

Adverse Reactions

Field study:

In a well-controlled U.S. field study, which included 271 dogs (201 dogs were administered BRAVECTO ONE every 30 days and 70 dogs were administered an oral active control [a drug from the isoxazoline class] every 30 days), there were no serious adverse reactions associated with treatment. Over the 90-day study period, all observations of potential adverse reactions were recorded. These adverse reactions reflect reporting and not necessarily causality.

Dogs with Adverse Reactions in the Field Study

*Alanine aminotransferase (ALT); alkaline phosphatase (ALP). No clinical signs associated with liver disease were noted in these dogs.

One dog treated with BRAVECTO ONE with a prior history of seizures and managed with two different anticonvulsant medications, had seizure activity 28 days after its first dose. The dog received its second dose of BRAVECTO ONE later the same day and no additional seizures occurred during the study. One dog in the control group with no history of seizures, had seizure activity 12 days after its second dose. The dog was started on anticonvulsant medication and no additional seizures occurred during the study.

One dog treated with BRAVECTO ONE lost >15% of body weight over the 90 days of the study. The cause of the weight loss could not be determined.

Four dogs coughed within 1 hour of dosing during the palatability assessment of BRAVECTO ONE. There was no palatability control group to compare the occurrence of coughing.

Post Approval Experience:

BRAVECTO Chewable Tablets, which contain the same active ingredient (fluralaner), have the following post-approval experience:

Although all adverse reactions are not reported, the following information is based on voluntary post-approval drug experience reporting. It is generally recognized that this results in significant under-reporting. The adverse events listed here reflect reporting and not necessarily causality. The following adverse events have been reported rarely¹ (reported in at least 1 but not more than 10 animals in 10,000 animals exposed) and very rarely² (reported in less than 1 in 10,000 animals exposed) and are listed by body system, in decreasing order of frequency:

Digestive tract disorders: vomiting¹, diarrhea², hypersalivation², hemorrhagic diarrhea²

Systemic disorders: lack of efficacy¹*, lethargy², anorexia²

Skin and appendage disorders: pruritus², alopecia²

Neurological disorders: convulsions², ataxia², muscle tremor²

*Product efficacy requires that dosing and administration instructions be carefully followed. Failure to follow label directions could result in a real or perceived lack of efficacy. Several factors, including local parasite prevalence, consistent and compliant administration and environmental control measures can contribute to a perceived inefficacy.

Clinical Pharmacology

Peak fluralaner concentrations are achieved between 1 and 3 days following single or multiple oral administrations of the recommended minimum dose of 10 mg/kg in young puppies and adult dogs. The elimination half-life ranges from 5.0 to 8.5 days for puppies and 12.6 to 15.7 days for adult dogs. Steady state is achieved after up to three monthly doses. Due to reduced drug bioavailability in the fasted state, BRAVECTO ONE should be administered with food.

MODE OF ACTION:

Fluralaner is for systemic use and belongs to the class of isoxazoline-substituted benzamide derivatives. Fluralaner is an inhibitor of the arthropod nervous system. The mode of action of fluralaner is the antagonism of the ligand-gated chloride channels (gamma-aminobutyric acid (GABA)-receptor and glutamate-receptor). Fleas and ticks must attach to the host and commence feeding in order to be exposed to the active substance.

EFFICACY:

Treatment and Prevention of Flea Infestations:

In well-controlled laboratory studies in dogs 6 months of age and older, BRAVECTO ONE killed > 82% of fleas within 4 hours after administration and was > 99% effective by 12 hours after treatment or post-infestation for 35 days. BRAVECTO ONE was 100% effective against fleas by 24 hours after treatment or post-infestation for 36 days.

In a well-controlled laboratory study in puppies 8 weeks of age and older, BRAVECTO ONE demonstrated 100% efficacy against fleas 48 hours after treatment or post-infestation for 30 days.

In a well-controlled 90-day U.S. field study conducted in households with existing flea infestations, the efficacy of BRAVECTO ONE against fleas on Day 30, 60, and 90 visits compared with baseline was 99.6%, 99.9%, and 99.9%, respectively. Dogs with signs of flea allergy dermatitis showed improvement in erythema, alopecia, papules, scales, crusts, and excoriation as a direct result of eliminating flea infestations.

Treatment and Control of Tick Infestations:

In well-controlled laboratory studies in dogs 6 months of age and older, BRAVECTO ONE demonstrated ≥ 99.5% efficacy against Rhipicephalus sanguineus ticks 48 hours after treatment or post-infestation for 37 days, and demonstrated ≥ 94.8% efficacy against Amblyomma americanum ticks 72 hours after treatment or post-infestation for 31 days. Data generated with Rhipicephalus sanguineus also support efficacy against Ixodes scapularis and Dermacentor variabilis as these two tick species have a greater sensitivity to fluralaner.

In well-controlled laboratory studies in puppies 8 weeks of age and older, BRAVECTO ONE demonstrated ≥ 97.7% efficacy against Rhipicephalus sanguineus ticks 48 hours after treatment or post-infestation for 30 days. BRAVECTO ONE failed to demonstrate > 90% efficacy against Amblyomma americanum for 31 days in 8- or 12-week-old puppies. Data generated with Rhipicephalus sanguineus also support efficacy against Ixodes scapularis and Dermacentor variabilis as these two tick species have a greater sensitivity to fluralaner.

Palatability:

In a well-controlled U.S. field study, which included 579 doses administered to 201 dogs, 81.5% of dogs voluntarily consumed BRAVECTO ONE within 5 minutes and an additional 9.0% voluntarily consumed BRAVECTO ONE within 5 minutes when offered with food. For 9.5% of dogs, owners administered the tablet by placing it on the tongue at the back of the mouth.

ANIMAL SAFETY:

Margin of Safety Study in 8-week-old puppies:

In a margin of safety study, BRAVECTO ONE was administered orally to 8-week old puppies at 1X, 3X, and 5X the maximum labeled dose of 22.5 mg/kg at three, 30-day intervals (8 dogs per group). The dogs in the control group (0X) were administered water. There were no clinically relevant, treatment-related effects on body weights, food consumption, clinical pathology (hematology, clinical chemistries, coagulation tests and urinalysis), gross pathology, histopathology, or organ weights. Vomiting was noted in one dog in the 5X group and one dog in the control group on Day 2.

Safety in adult dogs:

The safety of BRAVECTO ONE in adults is based on the results of a toxicokinetic study conducted in 14-month old Beagles. Eight dogs (4/sex) were orally administered a dose of 67.5 mg/kg (3X the maximum labeled dose) once monthly for 4 months. There were no notable clinical observations or effects on body weight or food consumption associated with the treatment.

Reproductive Safety Study:

Reproductive safety was evaluated with BRAVECTO Chewable Tablets, which contain the same active ingredient (fluralaner) as BRAVECTO ONE. BRAVECTO Chewable Tablets were administered orally to intact, reproductively-sound male and female Beagles at a dose of up to 168 mg/kg (equivalent to 7.5X the maximum labeled dose of BRAVECTO ONE) on three to four occasions at 8-week intervals. The dogs in the control group were untreated. There were no clinically-relevant, treatment-related effects on the body weights, food consumption, reproductive performance, semen analysis, litter data, gross necropsy (adult dogs) or histopathology findings (adult dogs and puppies). One adult dog in the treated group suffered a seizure during the course of the study (46 days after the third treatment). Abnormal salivation was observed on 17 occasions: in six treated dogs (11 occasions) after dosing and four control dogs (6 occasions).

The following abnormalities were noted in 7 pups from 2 of the 10 dams in only the treated group during gross necropsy examination: limb deformity (4 pups), enlarged heart (2 pups), enlarged spleen (3 pups), and cleft palate (2 pups). During veterinary examination at Week 7, two pups from the control group had inguinal testicles, and two and four pups from the treated group had inguinal and cryptorchid testicles, respectively. No undescended testicles were observed at the time of necropsy (days 50 to 71).

Field study:

In a well-controlled field study, BRAVECTO ONE was used concurrently with other medications, such as vaccines, anthelmintics, antibiotics (including topicals), steroids, analgesics and anesthetics. BRAVECTO ONE was well tolerated under these real-life conditions of use.

STORAGE CONDITIONS:

Store between 15°C - 30°C.

How Supplied

BRAVECTO ONE (Fluralaner Chewable Tablet) is available in five strengths (45 mg, 100 mg, 200 mg, 400 mg and 560 mg fluralaner per chewable tablet). Each chewable tablet is packaged individually into aluminum foil blister packs sealed with a peelable paper backed foil lid stock. Product may be supplied in 1, 3, or 4 chewable tablets per package. Not all pack sizes may be marketed.

Intervet Canada Corp., subsidiary of Merck & Co., Inc., 16750, route Transcanadienne, Kirkland, QC H9H 4M7 1 866 683-7838

Version: 9JULY2020

^® Registered trademark of Intervet International B.V. Used under license.

354933 R1

CPN: 1208324.0