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Advantage Multi for Dogs

This page contains information on Advantage Multi for Dogs for veterinary use.
The information provided typically includes the following:
  • Advantage Multi for Dogs Indications
  • Warnings and cautions for Advantage Multi for Dogs
  • Direction and dosage information for Advantage Multi for Dogs

Advantage Multi For Dogs

This treatment applies to the following species:

(imidacloprid + Moxidectin) Topical Solution

Manufacturer: Bayer Animal Health

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.

Advantage Multi for Dogs Caution

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


Advantage Multifor 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.

Advantage Multi for Dogs Indications

Advantage Multi for Dogs is indicated for the prevention of heartworm disease caused by Dirofilaria immitis. Advantage Multi for Dogs kills adult fleas and is indicated for the treatment of flea infestations (Ctenocephalides felis). Advantage Multi for Dogs is also indicated for the treatment and control of the following intestinal parasites:

Intestinal Parasite

Intestinal Stage


Immature Adult

Fourth Stage Larvae

Hookworm Species

Ancylostoma caninum




Uncinaria stenocephala




Roundworm Species

Toxocara canis





Toxascaris leonina





Trichuris vulpis





Do Not Administer This Product Orally. (see Warnings.)

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


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.b

a 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 Site For Two (2) Hours After Application.

Causes eye irritation. Harmful if swallowed. Do not get in eyes or on clothing. Avoid contact with 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, moxidectin, or imidacloprid 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.


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. Advantage Multi for Dogs is not effective against adult D. immitis. While the number of circulating microfilariae may decrease following treatment, Advantage Multi for Dogs is not effective for microfilariae clearance. (See ANIMAL SAFETY - Safety Study in Heartworm-Positive Dogs.)

Adverse Reactions

Field Studies

Following treatment with Advantage Multi for 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.

Advantage Multi for Dogs 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 Multifor Dogs tube that correctly corresponds with the body weight of the dog.

Dog (lbs.)

Advantage Multi for Dogs

Volume (ml)

Imidacloprid (mg)

Moxidectin (mg)

3 - 9

Advantage Multi 9




9.1 - 20

Advantage Multi 20




20.1 - 55

Advantage Multi 55




55.1 - 88*

Advantage Multi 88




* Dogs over 88 lbs. should be treated with the appropriate combination of Advantage Multi for Dogs tubes.

2. While holding the tube in an upright position, remove the cap from the tube.

3. Turn the cap over and push the other end of cap onto the tip of the tube.

4. Twist the cap to break the seal and then remove cap from the tube.

5. The dog should be standing for application. Part the hair on the back of the dog between the shoulder blades until the skin is visible. For dogs weighing 20 lbs. or less, place the tip of the tube on the skin and apply the entire contents directly on the exposed skin at one spot between the shoulder blades. For dogs weighing more than 20 lbs., place the tip of the tube on the skin and apply the entire contents directly on the exposed skin at 3 or 4 spots on the top of the backline from the base of the neck to the upper back in an area inaccessible to licking. Do not apply an amount of solution at any one location that could run off the side of the dog.

Do not let this product get in your dog's mouth or eyes. Do not allow the dog to lick any of the application sites for 30 minutes. In households with multiple pets, keep each treated dog separated from other treated dogs and other pets for 30 minutes after application to prevent licking the application sites. (See WARNINGS.)

Stiff hair, a damp appearance of the hair, pink skin, or a slight powdery residue may be observed at the application site on some animals. This is temporary and does not affect the safety and effectiveness of the product.

Shampooing 90 minutes after treatment does not reduce the effectiveness of Advantage Multi for Dogs in the prevention of heartworm disease.

Shampooing or water immersion 4 days after treatment will not reduce the effectiveness of Advantage Multi for Dogs in the treatment of flea infestations. However, shampooing as often as once weekly may reduce the effectiveness of the product against fleas.

Heartworm Prevention

For prevention of heartworm disease, Advantage Multi for Dogs should be administered at one-month intervals. Advantage Multi for Dogs may be administered year-round or at a minimum should start one month before the first expected exposure to mosquitoes and should continue at monthly intervals until one month after the last exposure to mosquitoes. If a dose is missed and a 30-day interval between doses is exceeded, administer Advantage Multi for Dogs immediately and resume the monthly dosing schedule. When replacing another heartworm preventative product in a heartworm prevention program, the first treatment with Advantage Multi for Dogs should be given within one month of the last dose of the former medication.

Flea Treatment

For the treatment of flea infestations, Advantage Multi for Dogs should be administered at one-month intervals. If the dog is already infested with fleas when the first dose of Advantage Multi for Dogs is administered, adult fleas on the dog will be killed. However, reinfestation from the emergence of pre-existing pupae in the environment may continue to occur for six weeks or longer after treatment is initiated. Dogs treated with imidacloprid, including those with pre-existing flea allergy dermatitis have shown clinical improvement as a direct result of elimination of fleas from the dog.

Treatment And Control Of Intestinal Nematode Infections

For the treatment and control of intestinal hookworm infections caused by Ancylostoma caninum and Uncinaria stenocephala (adults, immature adults and fourth stage larvae) and roundworm infections caused by Toxocara canis (adults and fourth stage larvae), and Toxascaris leonina (adults), and whipworm infections caused by Trichuris vulpis (adults), Advantage Multi for Dogs should be administered once as a single topical dose.

Animal Safety

In a controlled, double-masked, field safety study, Advantage Multi 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 Multi for 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 Multi for 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 postdosing 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.)

Storage Information

Store at temperatures between 4°C (39°F) and 30°C (86°F), avoiding excess heat or cold.

How Supplied


Applications Per Package


6 x 0.4 mL tubes


6 x 1.0 mL tubes


6 x 2.5 mL tubes


6 x 4.0 mL tubes

Advantage Multi is protected by one or more of the following U.S. patents: 6,232,328 and 6,001,858.

08944698, R.0

October 2006

NADA # 141-251, Approved by FDA

© 2006 Bayer HealthCare LLC

Bayer, the Bayer Cross and Advantage Multi are trademarks of Bayer.

Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201 U.S.A.

Regulations for product use are established by country. Information contained on this site pertains only to the United States of America, and is not intended to provide adequate information for product use. Before using or dispensing any product, read and carefully observe the label directions.

Animal Health Division

P.O. BOX 390, SHAWNEE MISSION, KS, 66201-0390
Customer Service Tel.:   800-633-3796
Customer Service Fax:   800-344-4219
Every effort has been made to ensure the accuracy of the Advantage Multi for Dogs information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Advantage Multi for Dogs product label or package insert.

Copyright © 2018 North American Compendiums. Updated: 2018-03-29