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U.S. Department of Health and Human Services

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Enforcement Actions

Bayer Health Care LLC 11-Jun-07

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

Rockville MD 20857


JUN 11 2007

WARNING LETTER

Certified Mail
Return Receipt Requested

NADA 141-251 (L0024) & 141-254 (L0022)

Janet Cunningham
Regulatory Affairs Consultant
Bayer Health Care LLC
Animal Health Division
P.O. Box 390
Shawnee Mission, KS 66201

RE: NADA 141-251 Advantage MuIti™ (imidacloprid/moxidectin) For Dogs &
141-254 Advantage Multi™ (imidacloprid/moxidectin) For Cats; exhibit at
2007 AAHA meeting and TV advertisement entitled "Field Trip."

Dear Ms. Cunningham:

The Division of Surveillance has reviewed a 60-second direct-to-consumer (DTC) television advertisement (TV ad) entitled "Field Trip" for Advantage Multi™ (imidacloprid/moxidectin) for Dogs, NADA 141-251. This TV ad misbrands the drug within the meaning of 502(n) [21 U.S.C. § 352(n)] of the Federal Food, Drug, and Cosmetic Act ("Act"). This TV ad minimizes risks associated with use of the drug and fails to reveal material facts about the product in violation of the Act and its implementing regulations. See 21 CFR § 202.1(e). By omitting and minimizing the risks associated with Advantage Multi™ for Dogs, the TV ad misleadingly suggests that Advantage Multi™ for Dogs is safer than has been demonstrated by substantial evidence or substantial clinical experience.

We have also reviewed exhibit booth materials from the March 17-21, 2007, AAHA meeting in Denver, Colorado, for your Advantage Multi™ (imidacloprid/moxidectin) products for Dogs and Cats. The promotional piece for the products, produced by Bayer Health Care LLC, was located in your exhibit booth at the conference. We consider the exhibit booth materials to be misleading because they fail to reveal relevant risk information. Therefore, the drugs are misbranded within the meaning of sections 502(a) and 201(n) of the Act.

Background

Advantage Multi™ for Dogs (10% imidacloprid/2.5% moxidectin) is a once-a-month topical solution for dogs and puppies that are at least seven weeks of age, weighing at least three pounds, and 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 felfs). Advantage Multi™ for Dogs is also indicated for the treatment and control of intestinal parasites.

Advantage Multi™ for Cats (10% imidacloprid/l % moxidectin) is a once-a-month topical solution for the prevention of heartworm disease, kills adult fleas, and is indicated for the treatment of flea infestations, as well as the treatment and control of ear mite infestations and intestinal parasite infections in cats and kittens that are nine weeks of age and older and that weigh at least two pounds.

The FDA-approved labeling for Advantage Multi™ (imidacloprid/moxidectin) For Dogs contains the following statements:

in the Warnings section, (Boxed Warning):

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, in coordination, panting, and generalized muscle tremors.

In avermectin sensitive dogs, the signs may be more severe and may include coma and death.

in the Precaution section:

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 Mult™ 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 seven weeks of age or less than three 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)

in the Human Warnings section:

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. 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 FDA-approved labeling for Advantage Multi™ (imidacloprid/m.oxidectin) For Cats contains the following statements:

in the Warnings section:

WARNINGS: Do not use on sick, debilitated, or underweight cats (See ADVERSE REACTIONS). Do not use on cats less than 9 weeks of age or less than 2 lbs body weight.

in the Human Warnings section:

HUMAN WARNINGS:
Not for human use. Keep out of the reach of children.
Children should not come in contact with the application site for 30 minutes 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.

in the Precaution section:

Do not dispense dose applicator tubes without complete safety and administration information.
Avoid oral ingestion. Cats may experience hypersalivation, tremors, vomiting and decreased appetite if Advantage Multi™ for Cats is inadvertently administered orally or through grooming/licking of the application site.
The safety of Advantage Multi™ for Cats has not been established in breeding, pregnant, or lactating cats.
Use of this product in geriatric patients with subclinical conditions has not been adequately studied. Several otherwise healthy, thin geriatric cats experienced prolonged lethargy and sleepiness after using this drug (See ADVERSE REACTIONS).

Minimization of Risk

The TV ad "Field Trip" fails to adequately communicate the risks associated with Advantage Multi™ For Dogs. Specifically, while the TV ad mentions that in avermectin sensitive dogs more severe adverse effects may be seen, the possibility of coma and death, which is stated in the boxed warning, is not mentioned, thereby minimizing these risks and misleadingly suggesting that Advantage Multi™ For Dogs is safer than have been demonstrated by substantial evidence or substantial clinical experience. See 21 CFR 202.1(e)(6)(i).

To comply with the Act and its implementing regulations, promotional pieces must reveal material facts about the product being promoted, including facts about the consequences that can result from use of the product as suggested in the promotional piece; and should present information about effectiveness and information about risk in a balanced manner.

Omission of Risk Information

With respect to the exhibit booth materials at the March 17-21, 2007, AAHA meeting in Denver, Colorado, although the exhibit materials present several effectiveness claims for Advantage Multi for Dogs and Advantage Multi™ for Cats, they fail to include any risk information. As noted above, improper use of Advantage Multi™ for Dogs and Advantage Multi™ for Cats may result in serious adverse reactions. The label clearly states a number of serious risks associated with incorrect use or with inadvertent exposure to humans or non-target animals. These are important facts that veterinarians and consumers should be aware of, and the absence of adequate information regarding these risks is misleading and may lead to the unsafe use of Advantage Multi™ for Dog and Advantage Multi™ for Cats. The exhibit booth materials therefore cause the drugs to be misbranded. See Section 502(a) of the Act.

Conclusion and Requested Action

As discussed above, the TV ad for Advantage Multi for Dogs and the exhibit booth materials for both Advantage Multi products do not contain important safety and risk information. Accordingly, the drugs are misbranded under sections 502(a) and 502(n) of the Act.

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to see that your promotional materials for Advantage Multi™ for Dogs and Advantage Multi™ for Cats, as well as other Bayer Health Care LLC products, comply with the requirements of the Act and its implementing regulations. Failure to correct the violations discussed above may result in FDA regulatory action without further notice such as seizure and/or injunction.

The Division of Surveillance requests that Bayer Health Care LLC immediately cease the use of these and/or similar materials. Future promotional materials should adequately address risk information. You should notify this office in writing of the steps you have taken to bring your firm into compliance with the law within fifteen (15) working days of receiving this letter. Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made. Specifically, you should correct your future exhibit booth materials, existing TV advertisements and any other promotional materials to adequately reflect the risks associated with use of the products. Because the violations described above are serious, we request that your submission include a comprehensive plan of action to disseminate a truthful, non-misleading, and complete corrective message about the issues discussed in this letter to the audience(s) that received the violative promotional materials.

Please direct your response to me at the Food and Drug Administration, Center for Veterinary Medicine, Division of Surveillance, HIV-216, 7519 Standish Place, Rockville, MD 20855. We remind you that only written communications are official.

Sincerely yours,

/S/

Lynn O. Post, DVM, PhD, DABVT
Director, Division of Surveillance
HFV-210
Center for Veterinary Medicine