REVOLUTION

Revolution kills adult fleas and prevents flea eggs from hatching for one month and is indicated for the prevention and control of flea infestations (Ctenocephalides felis), prevention of heartworm disease caused by Dirofilaria immitis, and the treatment and control of ear mite (Otodectes cynotis) infestations. Revolution also is indicated for the treatment and control of sarcoptic mange (Sarcoptes scabiei) and for the control of tick infestations due to Dermacentor variabilis.

Revolution kills adult fleas and prevents flea eggs from hatching for one month and is indicated for the prevention and control of flea infestations (Ctenocephalides felis), prevention of heartworm disease caused by Dirofilaria immitis, and the treatment and control of ear mite (Otodectes cynotis) infestations. Revolution is also indicated for the treatment and control of roundworm (Toxocara cati) and intestinal hookworm (Ancylostoma tubaeforme) infections in cats.

For the prevention and control of flea infestations, Revolution should be administered at monthly intervals throughout the flea season, starting one month before fleas become active. In controlled laboratory studies >98% of fleas were killed within 36 hours. Results of clinical field studies using Revolution monthly demonstrated >90% control of flea infestations within 30 days of the first dose. Dogs and cats treated with Revolution, including those with pre-existing flea allergy dermatitis, showed improvement in clinical signs associated with fleas as a direct result of eliminating the fleas from the animals and their environment.

If the dog or cat is already infested with fleas when the first dose of Revolution is administered, adult fleas on the animal are killed and no viable fleas hatch from eggs after the first administration. However, an environmental infestation of fleas may persist for a short time after beginning treatment with Revolution because of the emergence of adult fleas from pupae.

For the prevention of heartworm disease, Revolution must be administered on a monthly basis. Revolution may be administered year-round or at least within one month after the animal's first exposure to mosquitoes and monthly thereafter until the end of the mosquito season. The final dose must be given within one month after the last exposure to mosquitoes. If a dose is missed and a monthly interval between dosing is exceeded then immediate administration of Revolution and resumption of monthly dosing will minimize the opportunity for the development of adult heartworms. When replacing another heartworm preventive product in a heartworm disease prevention program, the first dose of Revolution must be given within a month of the last dose of the former medication.

Selamectin, the active ingredient in Revolution, is a macrocyclic lactone compound. These compounds effectively prevent the development of adult heartworms when administered to dogs and cats within one month of exposure to infective (L₃) Dirofilaria immitis larvae. Efficacy of macrocyclic lactones decreases below 100% in dogs, however, if first administered >2 months after exposure to infective larvae. Thus, in heartworm endemic regions, delaying initiation of heartworm prevention using Revolution beyond 2 months of first exposure to infective larvae (e.g., starting puppies and kittens at >8 weeks of age), or gaps of >2 months in the administration of Revolution during periods of heartworm transmission, increases the risk of the animal acquiring heartworms. Animals with unknown heartworm history that test negative for heartworms prior to the initiation of Revolution may be harboring pre-patent infections at the time Revolution was started. Testing such animals 3–4 months after initiation of Revolution would be necessary to confirm their negative heartworm status.

At the discretion of the veterinarian, cats ≥6 months of age may be tested to determine the presence of existing heartworm infections before beginning treatment with Revolution. Cats already infected with adult heartworms can be given Revolution monthly to prevent further infections.

For the treatment of ear mite (O. cynotis) infestations in dogs and cats, Revolution should be administered once as a single topical dose. A second monthly dose may be required in some dogs. Monthly use of Revolution will control any subsequent ear mite infestations. In the clinical field trials ears were not cleaned, and many animals still had debris in their ears after the second dose. Cleansing of the infested ears is recommended to remove the debris.

For the treatment of sarcoptic mange (S. scabiei) in dogs, Revolution should be administered once as a single topical dose. A second monthly dose may be required in some dogs. Monthly use of Revolution will control any subsequent sarcoptic mange mite infestations. Because of the difficulty in finding sarcoptic mange mites on skin scrapings, effectiveness assessments also were based on resolution of clinical signs. Resolution of the pruritus associated with the mite infestations was observed in approximately 50% of the dogs 30 days after the first treatment and in approximately 90% of the dogs 30 days after the second monthly treatment.

For the control of tick (Dermacentor variabilis) infestations in dogs, Revolution should be administered on a monthly basis. In heavy tick infestations, complete efficacy may not be achieved after the first dose. In these cases, one additional dose may be administered two weeks after the previous dose, with monthly dosing continued thereafter.

For the treatment and control of intestinal hookworm (A. tubaeforme) and roundworm (T. cati) infections, Revolution should be applied once as a single topical dose.

Following treatment with Revolution, transient localized alopecia with or without inflammation at or near the site of application was observed in approximately 1% of 691 treated cats. Other signs observed (≤0.5% of 1743 treated cats and dogs) included vomiting, loose stool or diarrhea with or without blood, anorexia, lethargy, salivation, tachypnea, and muscle tremors.

The following adverse events are based on post-approval adverse drug experience reporting for Revolution. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data.

The following adverse events reported for dogs are listed in decreasing order of reporting frequency:
Lethargy, vomiting, diarrhea, anorexia, generalized pruritus, seizures, application site reactions (including alopecia, lesions, erythema, pruritus, and inflammation), tremors, ataxia, death, and dermatitis.

The following adverse events reported for cats are listed in decreasing order of reporting frequency:
Application site reactions (including alopecia, lesions, erythema, pruritus, inflammation, vesicles, blisters, and excoriations), lethargy, anorexia, vomiting, death, generalized pruritus, diarrhea, ataxia, fever, generalized alopecia, tremors, hypersalivation, dermatitis, and seizures.

In safety studies, Revolution was administered at 1, 3, 5, and 10 times the recommended dose to six-week-old puppies, and no adverse reactions were observed. The safety of Revolution administered orally also was tested in case of accidental oral ingestion. Oral administration of Revolution at the recommended topical dose in 5- to 8-month-old beagles did not cause any adverse reactions. In a pre-clinical study selamectin was dosed orally to ivermectin-sensitive collies. Oral administration of 2.5, 10, and 15 mg/kg in this dose escalating study did not cause any adverse reactions; however, eight hours after receiving 5 mg/kg orally, one avermectin-sensitive collie became ataxic for several hours, but did not show any other adverse reactions after receiving subsequent doses of 10 and 15 mg/kg orally. In a topical safety study conducted with avermectin-sensitive collies at 1, 3 and 5 times the recommended dose of Revolution, salivation was observed in all treatment groups, including the vehicle control. Revolution also was administered at 3 times the recommended dose to heartworm infected dogs, and no adverse effects were observed.

In safety studies, Revolution was applied at 1, 3, 5, and 10 times the recommended dose to six-week-old kittens. No adverse reactions were observed. The safety of Revolution administered orally also was tested in case of accidental oral ingestion. Oral administration of the recommended topical dose of Revolution to cats caused salivation and intermittent vomiting. Revolution also was applied at 4 times the recommended dose to patent heartworm infected cats, and no adverse reactions were observed.

In well-controlled clinical studies, Revolution was used safely in animals receiving other frequently used veterinary products such as vaccines, anthelmintics, antiparasitics, antibiotics, steroids, collars, shampoos and dips.