Prevention of experimentally induced heartworm (Dirofilaria immitis) infections in dogs and cats with a single topical application of selamectin.
Vet Parasitol 91[3-4]:259-68 2000 Aug 23
McTier TL, Shanks DJ, Watson P, McCall JW, Genchi C, Six RH, Thomas CA, Dickin SK, Pengo G, Rowan TG, Jernigan AD
In a series of six controlled studies (four in dogs, two in cats), heartworm-free dogs and cats were inoculated with Dirofilaria immitis larvae (L(3)) prior to topical treatment with the novel avermectin selamectin or a negative control containing inert formulation ingredients (vehicle). Selamectin and negative-control treatments were administered topically to the skin at the base of the neck in front of the scapulae. In dogs, selamectin was applied topically at dosages of 3 or 6mgkg(-1) at 30 days post-inoculation (PI), or of 3 or 6mgkg(-1) at 45 days PI, or of 6mgkg(-1) at 60 days PI. Cats were treated topically with unit doses providing a minimum dosage of 6mgkg(-1) selamectin at 30 days PI. Of the animals that were treated 30 days PI, some dogs were bathed with water or shampoo between 2 and 96h after treatment, and some cats were bathed with shampoo at 24h after treatment. Between 140 and 199 days PI, the animals were euthanized and examined for adult D. immitis. Adult heartworms developed in all control dogs (geometric mean count, 18.7 worms) and in 88% of control cats (geometric mean count, 2.1 worms). Selamectin was 100% effective in preventing heartworm development in dogs when administered as a single topical dose of 3 or 6mgkg(-1) at 30 days after infection, 3 or 6mgkg(-1) at 45 days after infection, or 6mgkg(-1) at 60 days after infection. Selamectin was 100% effective against heartworm infections in cats when administered as a single topical unit dose of 6mgkg(-1). Bathing with water or shampoo between 2 and 96h after treatment did not reduce the efficacy of selamectin as a heartworm prophylactic in dogs. Likewise, bathing with shampoo at 24h after treatment did not reduce the efficacy of selamectin in cats. These studies demonstrated that, at the recommended dosage and treatment interval, a single topical administration of selamectin was 100% effective in preventing the development of D. immitis in dogs and cats.
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Canine Heartworm Disease: Current Treatment and Prevention Approaches
Clarke Atkins, DVM, Diplomate ACVIM (Cardiology, Internal Medicine)
North Carolina State University
Prevention
The introduction of the macrolide agents ivermectin (HeartgardR), milbemycin oxime (InterceptorR), moxidectin (ProHeartR and ProHeartR 6) and selamectin (RevolutionTM) has provided the veterinary profession with effective heartworm (HW) preventatives in a variety of formulations. Such agents, because they interrupt larval development during the first 2 months after infection, have a large window of efficacy and are administered monthly or less frequently. These agents are superior to diethylcarbamazine (DEC) in: convenience; producing less severe reactions when inadvertently given to microfilaremic dogs; allowing a grace period for inadvertent lapses in administration; efficacy with treatment lapses of up to 2-3 months when used continuously for the next 12 months1; and lastly, having a dual role as microfilaricides.2-4
Ivermectin, a chemical derivative of avermectin B1 which is obtained from Streptomyces sp. is effective against a range of endo- and ectoparasites and is marketed as a once monthly heartworm preventative. It is marketed in a form with pyrantel pamoate to improve efficacy against intestinal parasites (Table 1). Macrolides offer a wide window of efficacy and provide some protection when treatment lapses (of up to two months) occur. This is extended with continuous 12-month administration post-exposure to 3 months with 98% efficacy and to 4 months with 95% efficacy.1 As stated above, ivermectin is microfilaricidal at preventative doses (6-12 µg/kg/month), resulting in a gradual decline in microfilarial numbers. Despite this gradual microfilarial destruction, generally mild, adverse reactions (transient diarrhea) can occur if administered to microfilaremic dogs.5,6 Collies have been identified as a breed in which certain individuals are at increased risk of central nervous system signs and even death due to increased concentrations of ivermectin in the central nervous system. It is important to note that such adverse reactions have not been identified at preventative or even microfilaricidal doses of ivermectin. When used appropriately, ivermectin is virtually 100% effective in preventing HWI. Additionally, recent studies have shown ivermectin to have partial adulticidal properties when used continuously for 16 months.7
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Most recently, a semi-synthetic macrolide, selamectin, has been developed and marketed. It is unique in its spectrum and in the fact that is applied topically once monthly. Its efficacy is similar to that of other macrolides (virtually 100%, when used as directed).14 At 6-12 mg/kg topically, this preventative is effective at preventing heartworm infection and kills fleas and flea eggs, sarcoptic mange mites, ticks and ear mites.14 Bathing and swimming, as soon as 2 hours after application, did not affect efficacy. Safety has been shown at 10-fold topical doses, with oral consumption of single doses, and, in ivermectin-sensitive collies, at recommended dosages and five-fold overdoses for 3 months.15 Like other macrolides, selamectin has at least a 2 month "reachback effect" and with 12 months' continuous administration, is 99% protective after 3 month lapses in prophylaxis.14,16 Selamectin has microfilaricidal activity similar to other macrolides.17
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It is now known that certain macrolides have adulticidal properties.17,21,22 Ivermectin, when administered for 31 months continuously has nearly 100% efficacy in young heartworm infections.22
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References
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Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker) Clarke Atkins, DVM, DACVIM (Cardiology, Internal Medicine)
North Carolina State University
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Selamectin (Revolution), a New Player in the Control of Fleas and Heartworms in Dogs and Cats
Author Dwight Bowman, BA, MS, PhD
Introduction
Revolution is a new, Federal Drug Administration approved, topically-applied product for the prevention of heartworm disease and the prevention and control of flea infestation in cats. The active ingredient, selamectin, is an avermectin compound that was synthesized and developed by Pfizer Animal Health, Exton, PA. Revolution also has excellent efficacy against the canine and feline ear mite (Otodectes cynotis) and is labeled for the treatment and control of this pathogen. Revolution is the only newly-approved product for the treatment of sarcoptic mange to be labeled as such since the labeling of amitraz (Mitaban). Revolution can also be used to treat intestinal hookworms and roundworms in cats, but the efficacy against intestinal helminths in dogs seems to be less than one would hope. Revolution prevents tick infestation, but in areas with high tick numbers, it is recommended that a mid-month additional treatment with this product be given.
Discussion
The benefits of Revolution are that it is a single product that prevents flea infestation and heartworm disease, it is a product that can be applied topically, and it is capable of treating ear mite infestation. Many individuals like giving monthly treats to dogs in the form of chewable heartworm prevention, but at the same time, the success of the topically applied flea-control products, imidacloprid (Advantage) and fipronil (Frontline Top Spot) indicate that people also are very happy with spot-on applications when they are efficacious. Thus, it would seem that ultimately, topical application is a mode of administration that is acceptable to clients. Also, the topical application method is a means by which cats can easily be treated. This means that cats are more likely to get the heartworm prevention that they should be receiving in areas of high heartworm prevalence. Finally, the use of selamectin for the treatment of ear mite infestation allows the steady control of this infestation and is an easy means of preventing reintroduction of this problem when new pets are added to a household.
After the application of Revolution, the selamectin passes through the skin. In dogs, the maximum plasma concentration occurs 3 days after administration and the half life of the product is about 11 days. In cats, the maximum plasma concentration occurs in less than a day after application, and the product's half life is about 8 days. Much more of the product becomes bioavailable in cats than in dogs. After administration, the product is distributed to the sebaceous glands where it is readily available to interact with fleas, ticks, and mites.