Fluralaner

Dogs (Dogs and Puppies 6 Months and Older)

Bravecto® kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick), and Haemaphysalis longicornis (Asian longhorned tick)] for 12 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater. Bravecto® is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

Bravecto®

BRAVECTO® 1- MONTH kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick) and Haemaphysalis longicornis (Asian longhorned tick)] for one month in dogs and puppies 8 weeks of age and older, and weighing 4.4 pounds or greater. BRAVECTO® 1-MONTH is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for one month in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

BRAVECTO® 1-MONTH

BRAVECTO® QUANTUM kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and for the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick), Haemaphysalis longicornis (Asian longhorned tick), and Amblyomma maculatum (Gulf Coast tick)] for 12 months in dogs and puppies 6 months of age and older. BRAVECTO® QUANTUM is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 months in dogs and puppies 6 months of age and older.

BRAVECTO® QUANTUM

Kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick),and Rhipicephalus sanguineus (brown dog tick)] for 12 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater. It is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

BRAVECTO®

BRAVECTO® kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) for 12 weeks in cats and kittens 12 weeks of age and older, and weighing 2.6 pounds or greater. BRAVECTO® is also indicated for the treatment and control of Ixodes scapularis (black-legged tick), Haemaphysalis longicornis (Asian longhorned tick), and Amblyomma maculatum (Gulf Coast tick) infestations for 12 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater. BRAVECTO® is also indicated for the treatment and control of Dermacentor variabilis (American dog tick) infestations for 8 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater.

BRAVECTO®

For the prevention of heartworm disease caused by Dirofilaria immitis and for the treatment of infections with intestinal roundworm (Toxocara cati; 4th stage larvae, immature adults and adults) and hookworm (Ancylostoma tubaeforme; 4th stage larvae, immature adults and adults). Kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Haemaphysalis longicornis (Asian longhorned tick), and Amblyomma maculatum (Gulf Coast tick)] for 2 months in cats and kittens 6 months of age and older and weighing 2.6 lb or greater.

BRAVECTO® PLUS

Laying hens, replacement chickens, and breeder chickens

For the treatment and control of northern fowl mites (Ornithonyssus sylviarum).

Exzolt™

Beef cattle 2 months of age and older and replacement dairy heifers less than 20 months of age

For the prevention and treatment of infestations caused by New World screwworm (Cochliomyia hominivorax) larvae (myiasis) and treatment and control of cattle fever tick (Rhipicephalus microplus) in beef cattle 2 months of age and older and replacement dairy heifers less than 20 months of age.

Exzolt™ Cattle-CA1

Bravecto Plus is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and for the treatment of infections with intestinal roundworm (Toxocara cati; 4th stage larvae, immature adults and adults) and hookworm (Ancylostoma tubaeforme; 4th stage larvae, immature adults and adults). Bravecto Plus kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Haemaphysalis longicornis (Asian longhorned tick), and Amblyomma maculatum (Gulf Coast tick)] for 2 months in cats and kittens 6 months of age and older and weighing 2.6 lb or greater.

BRAVECTO® PLUS (fluralaner and moxidectin topical solution) for Cats

Bravecto kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) for 12 weeks in cats and kittens 12 weeks of age and older, and weighing 2.6 pounds or greater. Bravecto is also indicated for the treatment and control of Ixodes scapularis (black-legged tick), Haemaphysalis longicornis (Asian longhorned tick), and Amblyomma maculatum (Gulf Coast tick) infestations for 12 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater. Bravecto is also indicated for the treatment and control of Dermacentor variabilis (American dog tick) infestations for 8 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater.

BRAVECTO® (fluralaner topical solution) for Cats

Bravecto 1-Month kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick) and Haemaphysalis longicornis (Asian longhorned tick)] for one month in dogs and puppies 8 weeks of age and older, and weighing 4.4 pounds or greater. Bravecto 1-Month is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for one month in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

BRAVECTO® 1-MONTH (fluralaner) Chews for Dogs

Bravecto kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick), and Haemaphysalis longicornis (Asian longhorned tick)] for 12 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater. Bravecto is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

BRAVECTO® (fluralaner) Chews

BRAVECTO QUANTUM kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and for the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick), Haemaphysalis longicornis (Asian longhorned tick), and Amblyomma maculatum (Gulf Coast tick)] for 12 months in dogs and puppies 6 months of age and older. BRAVECTO QUANTUM is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 months in dogs and puppies 6 months of age and older.

BRAVECTO® QUANTUM (fluralaner for extended-release injectable suspension)

Exzolt Cattle-CA1 is indicated for the prevention and treatment of infestations caused by New World screwworm (Cochliomyia hominivorax) larvae (myiasis) and treatment and control of cattle fever tick (Rhipicephalus microplus) in beef cattle 2 months of age and older and replacement dairy heifers less than 20 months of age. Not for use in bulls intended for breeding 1 year of age and older, dairy calves, and veal calves.

Exzolt™ Cattle-CA1 (fluralaner topical solution)

Indications for Use: Exzolt is indicated for the treatment and control of northern fowl mites (Ornithonyssus sylviarum) in laying hens, replacement chickens, and breeder chickens.

Exzolt® (fluralaner oral solution)

Peak fluralaner concentrations are achieved between 1 and 3 days following single or multiple oral administrations of Bravecto 1-Month to 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. Due to reduced drug bioavailability in the fasted state, Bravecto 1-Month should be administered with food.

BRAVECTO® 1-MONTH (fluralaner) Chews for Dogs

Peak fluralaner concentrations are achieved between 2 hours and 3 days following oral administration, and the elimination half-life ranges between 9.3 to 16.2 days. Quantifiable drug concentrations can be measured (lower than necessary for effectiveness) through 112 days. Due to reduced drug bioavailability in the fasted state, fluralaner should be administered with food.

BRAVECTO® (fluralaner) Chews

Peak fluralaner concentrations are achieved between 3 and 21 days following topical administration and the elimination half-life ranges between 11 and 18 days. Peak moxidectin concentrations are achieved between 1 and 5 days following topical administration and the elimination half-life ranges between 20 and 30 days.

BRAVECTO® PLUS (fluralaner and moxidectin topical solution) for Cats

Peak fluralaner concentrations are achieved between 7 and 42 days following topical administration and the elimination half-life ranges between 14 and 29 days. The bioavailability of fluralaner following oral and topical administration is approximately 25%.

BRAVECTO® (fluralaner topical solution) for Dogs

Peak fluralaner concentrations are achieved between 7 and 21 days following topical administration and the elimination half-life ranges between 11 and 13 days.

BRAVECTO® (fluralaner topical solution) for Cats

Clinical Pharmacology:

Exzolt™ Cattle-CA1 (fluralaner topical solution)

There are no known contraindications for the use of the product.

BRAVECTO® 1-MONTH (fluralaner) Chews for Dogs

User Safety Warnings: Not for use in humans. Keep out of reach of children. This drug product is a skin and eye irritant; special care should be taken to avoid contact. Personal protective equipment should be worn, such as gloves, long sleeve shirt and pants, as well as glasses or goggles to prevent skin, eye and mucous membrane contact and/or drug absorption, while handling the product. In case of skin contact, wash with soap and water. If contact with eyes occurs, immediately rinse thoroughly with water. In case of accidental spill, immediately remove affected clothing and wash contacted skin with soap and water. In case of accidental ingestion, immediately rinse the mouth with plenty of water and seek medical advice. Do not eat, drink, or smoke while handling the product. Wash hands thoroughly with soap and water immediately after use of the product. The product is highly flammable. Keep away from heat, sparks, open flame or other sources of ignition. To obtain a Safety Data Sheet (SDS) or for technical assistance, call Merck Animal Health at 1-800-211-3573.

Exzolt™ Cattle-CA1 (fluralaner topical solution)

Not for human use. Keep this and all drugs out of the reach of children. Do not contact or allow children to contact the application site until 2 hours post application. 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. Avoid contact with skin and eyes. If contact with eyes occurs, then flush eyes slowly and gently with water. If wearing contact lenses, eyes should be rinsed first, then remove contact lenses and continue rinsing, then seek medical advice immediately. Wash hands and contacted skin thoroughly with soap and water immediately after use of the product. If the product accidentally contacts skin and a sticky residue persists after washing, rubbing alcohol (70% isopropyl alcohol) can be applied to the area to remove the residue. The product is highly flammable. Keep away from heat, sparks, open flame or other sources of ignition.

BRAVECTO® PLUS (fluralaner and moxidectin topical solution) for Cats

WITHDRAWAL PERIODS AND RESIDUE WARNINGS: Environmental temperature affects the withdrawal period. Cattle must not be slaughtered for human consumption within 98 days of treatment. If cattle are continuously exposed to temperatures at or above 60° F after product administration, then cattle may be slaughtered for human consumption 44 days after treatment. Violative residues may result if cattle are exposed to temperatures below 60° F after administration and are slaughtered at 44 days. Not for use in female dairy cattle 20 months of age or older, including dry dairy cows; use in these cattle may cause drug residues in milk and/or in calves born to these cows or heifers. Not for use in beef calves less than 2 months of age, dairy calves, and veal calves. A withdrawal period has not been established for this product in pre-ruminating calves.

Exzolt™ Cattle-CA1 (fluralaner topical solution)

Not for human use. Keep this and all drugs out of the 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. Keep Bravecto 1-Month in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

BRAVECTO® 1-MONTH (fluralaner) Chews for Dogs

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

BRAVECTO® (fluralaner topical solution) for Cats

In a well-controlled U.S. field study, 225 dogs were administered two doses of BRAVECTO QUANTUM at a 1-year interval and 96 dogs were administered an oral active control every 12 weeks for a total of 6 doses. Over the 455-day study period, all observations of potential adverse reactions were recorded. Percentage of Dogs with Adverse Reactions in the Field Study Adverse Reaction (AR) BRAVECTO QUANTUM (n = 225 dogs) Active Control (n = 96 dogs) Lethargy 4.9% 3.1% Decreased appetite 4.4% 4.2% Vomiting 4.0% 0% Diarrhea 2.7% 3.1% Liver enzymes (serum ALT or ALP) greater than twice the upper reference rangeAlanine aminotransferase (ALT); Alkaline phosphatase (ALP) 2.7% 2.1% Pruritus 1.8% 2.1% Injection site lumps or swellingMild injection site reactions, described as a lump, bump or knot, occurred in three BRAVECTO QUANTUM treated dogs and were all observed within 3 days of the injection. All injection site reactions were self-limiting and resolved following 1, 4, and 27 days after the initial observation. 1.3% 0% SeizuresTwo dogs treated with BRAVECTO QUANTUM experienced seizures during the study. One dog with a history of at least one seizure within three months prior to the start of the study, reported 6 seizures in 9 months starting 23 days after the initial dose. Although anticonvulsant medications were not started, no additional seizures were observed during the study following the second dose administered 12 months after the initial dose. A second dog reported 8 seizures starting 57 days after the initial dose. The dog was removed from the study on Day 84 and managed with anticonvulsant medications. 0.9% 0% One dog treated in the BRAVECTO QUANTUM group had a hypersensitivity reaction which included hives, facial edema, vomiting, and heavy breathing within the first 12 hours following the initial treatment. The dog was treated with oral antihistamines and recovered within 24 hours of treatment. No additional hypersensitivity reactions were observed in subsequent dosing 12 months later when premedicated with diphenhydramine. In well-controlled foreign laboratory effectiveness studies, after administration of BRAVECTO QUANTUM, two dogs exhibited slight mucosal hyperemia the day following administration that resolved the following day, one dog exhibited transient erythema 10 minutes post-injection that resolved within 1 hour, and one dog had a nonpainful swollen upper eyelid observed 24 hours post treatment. In a large European field study, pain on injection of BRAVECTO QUANTUM was reported in 5 dogs.

BRAVECTO® QUANTUM (fluralaner for extended-release injectable suspension)

In a well-controlled U.S. field study, which included a total of 165 households and 321 treated dogs (221 with fluralaner and 100 with a topical active control), there were no serious adverse reactions. Percentage of Dogs with Adverse Reactions in the Field Study Adverse Reaction (AR) Bravecto Group: Percent of Dogs with the AR During the 105-Day Study (n= 221 dogs) Active Control Group: Percent of Dogs with the AR During the 84-Day Study (n= 100 dogs) Vomiting 6.3 % 6.0 % Alopecia 4.1 % 2.0 % Diarrhea 2.7 % 11.0 % Lethargy 2.7 % 2.0 % Decreased Appetite 1.4 % 0.0 % Moist Dermatitis/Rash 0.9 % 0.0 % In the field study, two dogs treated with Bravecto with no prior history of seizures each experienced a seizure. One dog had two seizures a day apart about 18 days after its first dose. The dog was started on antiepileptic medication and had no additional seizures during the study. A second dog had a seizure 76 days after its first dose and 3 days after starting fluoxetine for separation anxiety. The fluoxetine was discontinued and the dog experienced no additional seizures during the study. One dog treated with Bravecto was observed by the owner to be off balance for about 30 minutes five days after its first dose and had no similar observations after the second dose. One dog with a history of seizures had a seizure the day after the second dose of the active control. In two well-controlled laboratory dose confirmation studies, one dog developed mild to moderate redness, flaking, crusts/scabs and alopecia at the treatment site from Day 1 through 14 after application of Bravecto on Day 0, and one dog developed self-limiting generalized erythema (possible allergic reaction) one day after treatment with Bravecto. In a European field study in cats, there were three reports of facial dermatitis in humans after close contact with the application site which occurred within 4 days of application.

BRAVECTO® (fluralaner topical solution) for Dogs

In a well-controlled U.S. field study, which included a total of 161 households and 311 treated cats (224 with fluralaner and 87 with a topical active control), there were no serious adverse reactions. Percentage of Cats with Adverse Reactions (AR) in the Field Study Adverse Reaction (AR) Bravecto Group: Percent of Cats with the AR During the 105-Day Study (n=224 cats) Active Control Group: Percent of Cats with the AR During the 84-Day Study (n=87 cats) Vomiting 7.6% 6.9% Pruritus 5.4% 11.5% Diarrhea 4.9% 1.1% Alopecia 4.9% 4.6% Decreased Appetite 3.6% 0.0% Lethargy 3.1% 2.3% Scabs/Ulcerated Lesions 2.2% 3.4% In the field study, two cats treated with fluralaner topical solution experienced ataxia. One cat became ataxic with a right head tilt 34 days after the first dose. The cat improved within one week of starting antibiotics. The ataxia and right head tilt, along with lateral recumbency, reoccurred 82 days after administration of the first dose. The cat recovered with antibiotics and was redosed with fluralaner topical solution 92 days after administration of the first dose, with no further abnormalities during the study. A second cat became ataxic 15 days after receiving its first dose and recovered the next day. The cat was redosed with fluralaner topical solution 82 days after administration of the first dose, with no further abnormalities during the study. In a European field study, two cats from the same household experienced tremors, lethargy, and anorexia within one day of administration. The signs resolved in both cats within 48-72 hours. In a European field study, there were three reports of facial dermatitis in humans after close contact with the application site which occurred within 4 days of application.

BRAVECTO® (fluralaner topical solution) for Cats

In a well-controlled U.S. field study, which included 271 dogs (201 dogs were administered Bravecto 1-Month every 30 days and 70 dogs were administered an oral active control [an isoxazoline] 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. Dogs with Adverse Reactions in the Field Study Adverse Reaction (AR) Fluralaner Group: Percentage of Dogs with the AR during the 90-Day Study (n= 201 dogs) Active Control Group: Percentage of Dogs with the AR during the 90-Day Study (n= 70 dogs) Pruritus 7.0% 10.0% Diarrhea 3.0% 4.3% Vomiting 3.0% 4.3% Decreased Appetite 3.0% 0.0% Liver enzymes (serum ALT or ALP) greater than twice the upper reference rangeAlanine aminotransferase (ALT); alkaline phosphatase (ALP) 1.0% 1.4% Lethargy 1.0% 1.4% Weight loss (>15%) 0.5% 0.0% One dog in the Bravecto 1-Month group with a history of seizures managed with anticonvulsant medication had seizure activity 28 days after its first dose; the dog received its second dose later the same day. 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. During the palatability assessment, four dogs coughed within 1 hour of dosing with Bravecto 1-Month. Palatability was not assessed in the control group. In well-controlled laboratory effectiveness studies, one dog and three puppies administered Bravecto 1-Month had diarrhea (with or without blood).

BRAVECTO® 1-MONTH (fluralaner) Chews for Dogs

In a well-controlled U.S. field study, which included a total of 176 treated cats (135 with Bravecto Plus and 41 with a monthly topical active control), there were no serious adverse reactions. Percentage of Cats with Adverse Reactions (AR) in the Field Study Adverse Reaction Bravecto Plus Group: Percent of Cats with the AR During the 120-Day Study (n=135 cats) Active Control Group: Percent of Cats with the AR During the 120-Day Study (n=41 cats) Vomiting 5.9% 12.2% Alopecia (not at application site) 5.2% 2.4% Pruritus 4.4% 12.2% Application site pruritus 4.4% 4.9% Diarrhea 3.7% 7.3% Lethargy 3.7% 9.8% Dry Skin 3.0% 0.0% Elevated alanine aminotransferase (ALT)ALT was greater than twice the upper reference range of 100 IU/L. These cats also had mild elevations of aspartate aminotransferase (AST) (less than twice the upper reference range of 100 IU/L). No clinical signs associated with liver disease were noted in these cats. 3.0% 0.0% Hypersalivation 1.5% 1.5% Application site alopecia 0.7% 0.0% In well-controlled laboratory effectiveness studies, the following adverse reactions were seen after application of Bravecto Plus: pyrexia, tachypnea, mydriasis, pruritus, scabbing, and bloody stool.

BRAVECTO® PLUS (fluralaner and moxidectin topical solution) for Cats

In a well-controlled U.S. field study, which included 294 dogs (224 dogs were administered Bravecto every 12 weeks and 70 dogs were administered an oral active control every 4 weeks and were provided with a tick collar); there were no serious adverse reactions. All potential adverse reactions were recorded in dogs treated with Bravecto over a 182-day period and in dogs treated with the active control over an 84-day period. The most frequently reported adverse reaction in dogs in the Bravecto and active control groups was vomiting. Percentage of Dogs with Adverse Reactions in the Field Study Adverse Reaction (AR) Bravecto Group: Percentage of Dogs with the AR During the 182-Day Study (n=224 dogs) Active Control Group: Percentage of Dogs with the AR During the 84-Day Study (n=70 dogs) Vomiting 7.1 14.3 Decreased Appetite 6.7 0.0 Diarrhea 4.9 2.9 Lethargy 5.4 7.1 Polydipsia 1.8 4.3 Flatulence 1.3 0.0 In a well-controlled laboratory dose confirmation study, one dog developed edema and hyperemia of the upper lips within one hour of receiving Bravecto. The edema improved progressively through the day and had resolved without medical intervention by the next morning.

BRAVECTO® (fluralaner) Chews

Dogs (Dogs and Puppies 6 Months and Older)

May be administered every 8 weeks in case of potential exposure to Amblyomma americanum ticks.

Oral

Bravecto®

Administer as a single subcutaneous dose every 12 months or every 8 months in the case of potential exposure to Amblyomma americanum ticks. The subcutaneous dose volume is 0.1 mL of the constituted suspension/kg body weight (0.045 mL per pound (/lb)). This volume provides a dose of 15 mg fluralaner per kilogram body weight (6.8 mg/lb).

Subcutaneous

BRAVECTO® QUANTUM

Administer topically as a single dose every 12 weeks according to the label dosage schedule to provide a minimum dose of 11.4 mg/lb (25 mg/ kg) body weight. May be administered every 8 weeks in case of potential exposure to Amblyomma americanum ticks.

Topical

BRAVECTO®

Administer orally as a single dose monthly to provide a minimum dose of 4.5 mg/lb (10 mg/kg) fluralaner. Administer with food.

Oral

BRAVECTO® 1-MONTH

Administer topically as a single dose every 12 weeks according to the label dosage schedule to provide a minimum dose of 18.2 mg/lb (40 mg/ kg) body weight. May be administered every 8 weeks in case of potential exposure to Dermacentor variabilis ticks.

Topical

BRAVECTO®

Administer topically as a single dose every 2 months to provide a minimum dose of 18.2 mg/lb (40 mg/kg) fluralaner and 0.9 mg/lb (2 mg/kg) moxidectin.

Topical

BRAVECTO® PLUS

Laying hens, replacement chickens, and breeder chickens

Administer orally to chickens via the drinking water as 2 single doses spaced 7 days apart, with each dose consumed over a period of 6 to 24 hours. Each dose is 0.5 mg fluralaner/kg (0.227 mg/lb) body weight, equivalent to 0.05 mL fluralaner oral solution/kg body weight (0.023 mL/lb).

Oral

Exzolt™

Beef cattle 2 months of age and older and replacement dairy heifers less than 20 months of age

2.5 milligrams per kilogram (1.13 milligram per one pound) body weight.

Topical

Exzolt™ Cattle-CA1

Bravecto Plus should be administered topically as a single dose every 2 months according to the Dosage Schedule below to provide a minimum dose of 18.2 mg/lb (40 mg/kg) fluralaner and 0.9 mg/lb (2 mg/kg) moxidectin. For prevention of heartworm disease, Bravecto Plus should be administered at 2-month intervals. Bravecto Plus may be administered year-round without interruption or at a minimum should be administered at 2-month intervals beginning at the cat's first seasonal exposure to mosquitoes and continuing until the cat's last seasonal exposure to mosquitoes. If a dose is missed and a 2-month interval between doses is exceeded, administer Bravecto Plus immediately and resume the dosing every 2 months. When replacing a monthly heartworm preventative product, the first dose of Bravecto Plus should be given within one month of the last dose of the former medication. Dosing Schedule: Body Weight Ranges (lb) Fluralaner content (mg/tube) Moxidectin content (mg/tube) Tubes Administered 2.6 – 6.2 112.5 5.6 One >6.2 – 13.8 250 12.5 One >13.8 – 27.5Cats over 27.5 lb should be administered the appropriate combination of tubes. 500 25 One A veterinarian or veterinary technician should demonstrate or instruct the pet owner regarding the appropriate technique for applying Bravecto Plus topically to cats prior to first use. Step 1: Immediately before use, open the pouch and remove the tube. Put on gloves. Hold the tube at the crimped end with the cap in an upright position (tip up). The cap should be rotated clockwise or counter clockwise one full turn. The cap is designed to stay on the tube for dosing and should not be removed. The tube is open and ready for application when a breaking of the seal is felt. Step 2: The cat should be standing or lying with its back horizontal during application. Part the fur at the administration site. Place the tube tip vertically against the skin at the base of the skull of the cat. Step 3: Squeeze the tube and gently apply the entire contents of Bravecto Plus directly to the skin at the base of the skull of the cat. Avoid applying an excessive amount of solution that could cause some of the solution to run and drip off of the cat. If a second spot is needed to avoid run off, then apply the second spot slightly behind the first spot. Greasy, oily, or wet appearance may occur at the application site in some cats.

TOPICAL

BRAVECTO® PLUS (fluralaner and moxidectin topical solution) for Cats

Bravecto should be administered topically as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 11.4 mg/lb (25 mg/kg) body weight. Bravecto may be administered every 8 weeks in case of potential exposure to Amblyomma americanum ticks (see Effectiveness ). Dosage Schedule Body Weight Ranges (lb) Fluralaner content (mg)/tube Tubes Administered 4.4 – 9.9 112.5 One >9.9 – 22.0 250 One >22.0 – 44.0 500 One >44.0 – 88.0 1000 One >88.0 – 123.0Dogs over 123.0 lb should be administered the appropriate combination of tubes 1400 One A veterinarian or veterinary technician should demonstrate or instruct the pet owner regarding the appropriate technique for applying Bravecto topically to dogs prior to first use. Step 1: Immediately before use, open the pouch and remove the tube. Put on gloves. Hold the tube at the crimped end with the cap in an upright position (tip up). The cap should be rotated clockwise or counter clockwise one full turn. The cap is designed to stay on the tube for dosing and should not be removed. The tube is open and ready for application when a breaking of the seal is felt. Step 2: The dog should be standing or lying with its back horizontal during application. Part the fur at the administration site. Place the tube tip vertically against the skin between the shoulder blades of the dog. Step 3: Squeeze the tube and gently apply Bravecto in one or more spots starting between the shoulder blades and continuing along the dog's back. Avoid applying an excessive amount of solution in any one spot which may cause some solution to run or drip off of the dog. Bathing or water immersion 3 days after administration will not reduce the effectiveness of Bravecto against fleas and Ixodes ricinus ticks (see Effectiveness ). Treatment with Bravecto may begin at any time of the year and can continue year round without interruption.

TOPICAL

BRAVECTO® (fluralaner topical solution) for Dogs

Bravecto should be administered topically as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 18.2 mg/lb (40 mg/kg) body weight. Bravecto may be administered every 8 weeks in case of potential exposure to Dermacentor variabilis ticks (see Effectiveness ). Dosage Schedule: Body Weight Ranges (lb) Fluralaner content (mg/tube) Tubes Administered 2.6 – 6.2 112.5 One >6.2 – 13.8 250 One >13.8 – 27.5Cats over 27.5 lb should be administered the appropriate combination of tubes. 500 One A veterinarian or veterinary technician should demonstrate or instruct the pet owner regarding the appropriate technique for applying Bravecto topically to cats prior to first use. Step 1: Immediately before use, open the pouch and remove the tube. Put on gloves. Hold the tube at the crimped end with the cap in an upright position (tip up). The cap should be rotated clockwise or counter clockwise one full turn. The cap is designed to stay on the tube for dosing and should not be removed. The tube is open and ready for application when a breaking of the seal is felt. Step 2: The cat should be standing or lying with its back horizontal during application. Part the fur at the administration site. Place the tube tip vertically against the skin at the base of the skull of the cat. Step 3: Squeeze the tube and gently apply the entire contents of Bravecto directly to the skin at the base of the skull of the cat. Avoid applying an excessive amount of solution that could cause some of the solution to run and drip off of the cat. If a second spot is needed to avoid run off, then apply the second spot slightly behind the first spot. Greasy, oily, or wet appearance may occur at the application site in some cats. Treatment with Bravecto may begin at any time of the year and can continue year round without interruption.

TOPICAL

BRAVECTO® (fluralaner topical solution) for Cats

Bravecto should be administered orally as a single dose every 12 weeks according to the Dosage Schedule below to provide a minimum dose of 11.4 mg/lb (25 mg/kg) body weight. Bravecto may be administered every 8 weeks in case of potential exposure to Amblyomma americanum ticks (see Effectiveness ). Bravecto should be administered with food. Dosage Schedule Body Weight Ranges (lb) Fluralaner Content (mg) Chews Administered 4.4 – 9.9 112.5 One >9.9 – 22.0 250 One >22.0 – 44.0 500 One >44.0 – 88.0 1000 One >88.0 – 123.0Dogs over 123.0 lb should be administered the appropriate combination of chews 1400 One Treatment with Bravecto may begin at any time of the year and can continue year round without interruption.

ORAL

BRAVECTO® (fluralaner) Chews

Bravecto 1-Month should be administered orally as a single dose monthly according to the Dosage Schedule below to provide a minimum dose of 4.5 mg/lb (10 mg/kg) fluralaner. Bravecto 1-Month should be administered with food. Dosage Schedule Body Weight Ranges (lb) Fluralaner content (mg) Chews Administered 4.4 – 9.9 45 One >9.9 – 22.0 100 One >22.0 – 44.0 200 One >44.0 – 88.0 400 One >88.0 – 123.0Dogs over 123.0 lb should be administered the appropriate combination of chews 560 One Treatment with Bravecto 1-Month may begin at any time of the year and can continue year-round without interruption.

ORAL

BRAVECTO® 1-MONTH (fluralaner) Chews for Dogs

Exzolt Cattle-CA1 is a ready-to-use topical formulation intended for direct application to the hair and skin in a narrow strip extending along the dorsal midline from the withers to the base of the tail (see Figure 1). The recommended rate of administration is 1 mL/44.1 lbs. (1 mL/20 kg) body weight, which is equivalent to 1.13 mg of fluralaner for each pound (2.5 mg/kg) body weight. Effectiveness has not been evaluated in cattle with wet hides.

TOPICAL

Exzolt™ Cattle-CA1 (fluralaner topical solution)

Dosage and Administration: Exzolt must be administered orally to chickens via the drinking water as 2 single doses spaced 7 days apart, with each dose consumed over a period of 6 to 24 hours. Each dose is 0.5 mg fluralaner/kg (0.227 mg/lb) body weight, equivalent to 0.05 mL of Exzolt/kg body weight (0.023 mL/lb).

ORAL

Exzolt® (fluralaner oral solution)