Advantage Multi for Dogs

Name: Advantage Multi for Dogs

advantage multi® for dogs (imidacloprid + moxidectin) Topical Solution

Once-a-month topical solution for the prevention of heartworm disease, kills adult fleas, is indicated for the treatment of flea infestations, 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.


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

Advantage Multi for Dogs 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.


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 dogs1, the signs may be
   more severe and may include coma and death.2

1 Some dogs are more sensitive to avermectins due to a mutation in the MDR1 gene. Dogs with this mutation may develop signs of sever avermectin toxicity if they ingest this product. the most common breeds associated with this mutation include Collies and Collie crosses. 2 Although there is no specific antagonist for avermectin toxicity, even severely affected dogs have completely recovered from avermectin toxicity with intensive veterinary supportive care.

Adverse reactions

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


Advantage Multi n=128

Active Control n=68


19 dogs (14.8%)

7 dogs (10.3%)


9 dogs (7.0%)

5 dogs (7.4%)

Medicinal Odor

5 dogs (3.9%)

None observed


1 dog (0.8%)

1 dog (1.5%)


1 dog (0.8%)

1 dog (1.5%)


1 dog (0.8%)

None observed

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%).

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.

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.

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

Animal safety

In a controlled, double-masked, field safety study, AdvantageMulti for Dogs was administered to 128 dogs of various breeds, 3 months to 15 years of age, weighing 4 to 157 pounds. Advantage Multi for Dogs was used safely in dogs concomitantly receiving ACE inhibitors, anticonvulsants, antihistamines, antimicrobials, chondroprotectants, corticosteroids, immunotherapeutics, MAO inhibitors, NSAIDs, ophthalmic medications, sympathomimetics, synthetic estrogens, thyroid hormones, and urinary acidifiers. Owners reported the following signs in their dogs after application of Advantage Multifor Dogs: pruritus, flaky/greasy residue at the treatment site, medicinal odor, lethargy, inappetence, and hyperactivity. (See ADVERSE REACTIONS.)

Safety Study in Puppies: Advantage Multi for Dogs was applied topically at 1, 3 and 5X the recommended dose to 7-week-old Beagle puppies once every 2 weeks for 6 treatments on days 0, 14, 28, 42, 56, and 70. Loose stools and diarrhea were observed in all groups, including the controls, throughout the study. Vomiting was seen in one puppy from the 1X treatment group (day 57), in two puppies from the 3X treatment group (days 1 and 79), and in one puppy from the 5X treatment group (day 1). Two puppies each in the 1X, 3X, and 5X groups had decreased appetites within 24 hours post-dosing. One puppy in the 1X treatment group had pruritus for one hour following the fifth treatment. A puppy from the 5X treatment group displayed rapid, difficult breathing from 4 to 8 hours following the second treatment.

Dermal Dose Tolerance Study: Advantage Multi for Dogs was administered topically to 8-month-old Beagle dogs at 10X the recommended dose once. One dog showed signs of treatment site irritation after application. Two dogs vomited, one at 6 hours and one at 6 days post-treatment. Increased RBC, hemoglobin, activated partial thromboplastin, and direct bilirubin were observed in the treated group. Dogs in the treated group did not gain as much weight as the control group.

Safety Study in Heartworm-Positive Dogs: Advantage Multifor Dogs was administered topically at 1 and 5X the recommended dose every 14 days for 3 treatments to dogs with adult heartworm infections and circulating microfilariae. At 5X, one dog was observed vomiting three hours after the second treatment. Hypersensitivity reactions were not seen in the 5X treatment group. Microfilariae counts decreased with treatment.

Oral Safety Study in Beagles: Advantage Multi for Dogs was administered once orally at the recommended topical dose to 12 dogs. Six dogs vomited within 1 hour of receiving the test article, 2 of these dogs vomited again at 2 hours, and 1 dog vomited again up to 18 hours post-dosing. One dog exhibited shaking (nervousness) 1 hour post-dosing. Another dog exhibited abnormal neurological signs (circling, ataxia, generalized muscle tremors, and dilated pupils with a slow pupillary light response) starting at 4 hours post-dosing through 18 hours post-dosing. Without treatment, this dog was neurologically normal at 24 hours and had a normal appetite by 48 hours post-dosing. (See CONTRAINDICATIONS.)

Dermal Safety Study in Ivermectin-Sensitive Collies:Advantage Multi for Dogs was administered topically at 3 and 5X the recommended dose every 28 days for 3 treatments to Collies which had been pre-screened for avermectin sensitivity. No clinical abnormalities were observed.

Oral Safety Study in Ivermectin-Sensitive Collies: Advantage Multi for Dogs was administered orally to 5 pre-screened ivermectin-sensitive Collies. The Collies were asymptomatic after ingesting 10% of the minimum labeled dose. At 40% of the minimum recommended topical dose, 4 of the dogs experienced neurological signs indicative of avermectin toxicity including depression, ataxia, mydriasis, salivation, muscle fasciculation, and coma, and were euthanized. (See CONTRAINDICATIONS.)

Dog 55 sample carton image

Advantage Multi for Dogs 
imidacloprid moxidectin solution
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:0859-2342
Route of Administration TOPICAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
# Item Code Package Description
1 2.5 mL in 1 TUBE
2 2.5 mL in 1 TUBE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NADA NADA141251 12/20/2006
Labeler - Bayer HealthCare LLC Animal Health Division (152266193)
Registrant - Bayer HealthCare LLC Animal Health Divisions (152266193)
Revised: 05/2009   Bayer HealthCare LLC Animal Health Division