advantage multi for dogs

Bayer HealthCare LLC Animal Health Division
Bayer HealthCare LLC Animal Health Divisions

FULL PRESCRIBING INFORMATION: CONTENTS*

• WARNING
• CAUTION:
• ADVANTAGE MULTI FOR DOGS DESCRIPTION:
• INDICATIONS:
• ADVANTAGE MULTI FOR DOGS CONTRAINDICATIONS:
• WARNINGS:
• HUMAN WARNINGS:
• PRECAUTIONS:
• ADVANTAGE MULTI FOR DOGS ADVERSE REACTIONS:
• ADVANTAGE MULTI FOR DOGS DOSAGE AND ADMINISTRATION:
• ANIMAL SAFETY:
• STORAGE INFORMATION:
• HOW SUPPLIED:
• PACKAGE/LABEL PRINCIPAL DISPLAY PANEL - 3-9 lbs dogs:
• PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 9.1-20 lbs dogs:
• PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 20.1-55 lbs dogs:
• PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 55.1-88 lbs dogs:
• PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 88.1-110 lbs dogs:

FULL PRESCRIBING INFORMATION

Once-a-month topical solution for the prevention of heartworm disease, the treatment of circulating microfilariae, kills adult fleas, is indicated for the treatment of flea infestations, the treatment and control of sarcoptic mange, as well as the treatment and control of intestinal parasite infections in dogs and puppies that are at least 7 weeks of age and that weigh at least 3 lbs.

CAUTION:

Federal (U.S.A.) Law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION:

Advantage Multi^® for Dogs (10% imidacloprid + 2.5% moxidectin) is a colorless to yellow ready-to-use solution packaged in single dose applicator tubes for topical treatment of dogs. The formulation and dosage schedule are designed to provide a minimum of 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin based on body weight.

Imidacloprid is a chloronicotinyl nitroguanidine insecticide. The chemical name for imidacloprid is 1-[(6-Chloro-3- pyridinyl)methyl]-N-nitro-2-imidazolidinimine. Moxidectin is a semisynthetic macrocyclic lactone endectocide derived from the actinomycete Streptomycetes cyaneogriseus noncyanogenus. The chemical name for moxidectin is [6R, 23E, 25S(E)]-5-O-Demethyl-28-deoxy-25-(1,3-dimethyl-1-butenyl)- 6,28-epoxy-23-(methoxyimino) milbemycin B.

INDICATIONS:

Advantage Multi for Dogs is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and the treatment of Dirofilaria immitis circulating microfilariae in heartworm-positive dogs. Advantage Multi for Dogs kills adult fleas and is indicated for the treatment of flea infestations (Ctenocephalides felis). Advantage Multi for Dogs is indicated for the treatment and control of sarcoptic mange caused by Sarcoptes scabiei var. canis. Advantage Multi for Dogs is also indicated for the treatment and control of the following intestinal parasites:

CONTRAINDICATIONS:

Do not administer this product orally. (See WARNINGS.)

Do not use this product (containing 2.5% moxidectin) on cats.

WARNINGS:

For the first 30 minutes after application:

Ensure that dogs cannot lick the product from application sites on themselves or other treated dogs, and

Separate treated dogs from one another and from other pets to reduce the risk of accidental ingestion.

Ingestion of this product by dogs may cause serious adverse reactions including depression, salivation, dilated pupils, incoordination, panting, and generalized muscle tremors.

In avermectin sensitive dogs,^a the signs may be more severe and may include coma and death.<sup>b


a</sup> Some dogs are more sensitive to avermectins due to a mutation in the MDR1 gene. Dogs with this mutation may develop signs of severe avermectin toxicity if they ingest this product. The most common breeds associated with this mutation include Collies and Collie crosses.

^b Although there is no specific antagonist for avermectin toxicity, even severely affected dogs have completely recovered from avermectin toxicity with intensive veterinary supportive care.

HUMAN WARNINGS:

Not for human use. Keep out of the reach of children.
Children should not come in contact with application sites for two (2) hours after application.
Causes eye irritation. Harmful if swallowed. Do not get in eyes or on clothing. Avoid contact with skin. Exposure to the product has been reported to cause headache; dizziness; and redness, burning, tingling, or numbness of the skin. Wash hands thoroughly with soap and warm water after handling.

If contact with eyes occurs, hold eyelids open and flush with copious amounts of water for 15 minutes. If eye irritation develops or persists, contact a physician. If swallowed, call poison control center or physician immediately for treatment advice. Have person sip a glass of water if able to swallow. Do not induce vomiting unless told to do so by the poison control center or physician. People with known hypersensitivity to benzyl alcohol, imidacloprid or moxidectin should administer the product with caution. In case of allergic reaction, contact a physician. If contact with skin or clothing occurs, take off contaminated clothing. Wash skin immediately with plenty of soap and water. Call a poison control center or physician for treatment advice.

The Material Safety Data Sheet (MSDS) provides additional occupational safety information. For a copy of the Material Safety Data Sheet (MSDS) or to report adverse reactions call Bayer Veterinary Services at 1-800-422-9874. For consumer questions call 1-800-255-6826.

PRECAUTIONS:

Do not dispense dose applicator tubes without complete safety and administration information.

Use with caution in sick, debilitated, or underweight animals. The safety of Advantage Multi for Dogs has not been established in breeding, pregnant, or lactating dogs. The safe use of Advantage Multi for Dogs has not been established in puppies and dogs less than 7 weeks of age or less than 3 lbs. body weight.

Prior to administration of Advantage Multi for Dogs, dogs should be tested for existing heartworm infection. At the discretion of the veterinarian, infected dogs should be treated with an adulticide to remove adult heartworms. The safety of Advantage Multi for Dogs has not been evaluated when administered on the same day as an adulticide. Advantage Multi for Dogs is not effective against adult D. immitis. Although the number of circulating microfilariae is substantially reduced in most dogs following treatment with Advantage Multi for Dogs, the microfilariae count in some heartworm-positive dogs may increase or remain unchanged following treatment with Advantage Multi for Dogs alone or in a dosing regimen with melarsomine dihydrochloride.
(See ADVERSE REACTIONS and ANIMAL SAFETY – Safety Study in Heartworm-Positive Dogs.)

Advantage Multi for Dogs has not been evaluated in hearworm-positive dogs with Class 4 heartworm disease.

ADVERSE REACTIONS:

Heartworm-Negative Dogs

Field Studies: Following treatment with Advantage Multi for Dogs or an active control, dog owners reported the following post-treatment reactions:

During a field study using 61 dogs with pre-existing flea allergy dermatitis, one (1.6%) dog experienced localized pruritus immediately after imidacloprid application, and one investigator noted hyperkeratosis at the application site of one dog (1.6%).

In a field safety and effectiveness study, Advantage Multi for Dogs was administered to 92 client-owned dogs with sarcoptic mange. The dogs ranged in age from 2 months to 12.5 years and ranged in weight from 3 to 231.5 pounds. Adverse reactions in dogs treated with Advantage Multi for Dogs included hematochezia, diarrhea, vomiting, lethargy, inappetence, and pyoderma.

Laboratory Effectiveness Studies: One dog in a laboratory effectiveness study experienced weakness, depression, and unsteadiness between 6 and 9 days after application with Advantage Multi for Dogs. The signs resolved without intervention by day 10 post-application. The signs in this dog may have been related to peak serum levels of moxidectin, which vary between dogs, and occur between 1 and 21 days after application of Advantage Multi for Dogs.

The following clinical observations also occurred in laboratory effectiveness studies following application with Advantage Multi for Dogs and may be directly attributed to the drug or may be secondary to the intestinal parasite burden or other underlying conditions in the dogs: diarrhea, bloody stools, vomiting, anorexia, lethargy, coughing, ocular discharge and nasal discharge. Observations at the application sites included damp, stiff or greasy hair, the appearance of a white deposit on the hair, and mild erythema, which resolved without treatment within 2 to 48 hours.

Heartworm-Positive Dogs

Field Study: A 56-day field study was conducted in 214 D. immitis heartworm and microfilariae positive dogs with Class 1, 2 or 3 heartworm disease. All dogs received Advantage Multi for Dogs on Study Days 0 and 28; 108 dogs also received melarsomine dihydrochloride on Study Days – 14, 14, and 15. All dogs were hospitalized for a minimum of 12 hours following each treatment. Effectiveness against circulating D. immitis microfilariae was > 90% at five of six sites; however, one site had an effectiveness of 73.3%. The microfilariae count in some heartworm-positive dogs increased or remained unchanged following treatment with Advantage Multi for Dogs alone or in a dosing regimen with melarsomine dihydrochloride.

Following treatment with Advantage Multi for Dogs alone or in a dosing regimen with melarsomine dihydrochloride, the following adverse reactions were observed:

Three dogs treated with Advantage Mutli for Dogs in a dosing regimen with melarsomine dihydrochloride died of pulmonary embolism from dead and dying heartworms. One dog, treated with Advantage Multi for Dogs and melarsomine dihydrochloride, experienced pulmonary hemorrhage and responded to supportive medical treatment. Following the first treatment with Advantage Multi for Dogs alone, two dogs experienced adverse reactions (coughing, vomiting, and dyspnea) that required hospitalization. In both groups, there were more adverse reactions to Advantage Multi for Dogs following the first treatment than the second treatment.

To report a suspected adverse reaction, call 1-800-422-9874.

Foreign Market Experience

Because the following events were reported voluntarily during post-approval use of the product in foreign markets, it is not always possible to reliably establish a causal relationship to drug exposure.

The following adverse events were reported in humans: eye irritation, allergic reactions, skin irritation, skin tingling, sore throat, and chemical odor. Adverse events reported in dogs topically treated with imidacloprid + moxidectin for dogs included: vomiting, diarrhea, bloody diarrhea, salivation, poor appetite, lethargy, weakness, restlessness, agitation, disorientation, ataxia, muscle tremors, seizures, panting, labored breathing, acute pulmonary edema, hives, rash, swollen face and ears, pruritus, erythema, alopecia, hot spots, local discomfort, and discoloration of the hair at the application site. Accidental oral ingestion in dogs caused salivation, vomiting, muscle tremor, seizures, mydriasis, ataxia, lethargy, disorientation, agitation, and poor appetite. Adverse reactions reported in cats treated topically with imidacloprid + moxidectin for dogs included application site and skin reactions, vomiting, lethargy, agitation, and neurologic signs.

DOSAGE AND ADMINISTRATION:

The recommended minimum dose is 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month, by topical administration.

Do not apply to irritated skin.

1. Remove one dose applicator tube (tube) from the package. As specified in the following table, administer the entire contents of the Advantage Multi for Dogs tube that correctly corresponds with the body weight of the dog.