2mo 100% efficacy 3 mo 98% efficacy 4 mo with 95% efficacy

[guest]

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.

******
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

<snip>

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

<snip>

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
<snip>

References

1. McCall, JW, et al. Evaluation of ivermectin and milbemycin oxime efficacy against Dirofilaria immitis infections of three and fours months' duration. Amer J Vet Res 1996; 57:1189-1192.

2. Bowman, D.D., Johnson, R.C., Ulrich, M.E., et al.: Effects of Long-Term Administration of Ivermectin and Milbemycin Oxime on Circulating Microfilariae and Parasite Antigenemia in Dogs with Patent Heartworm Infections. In Soll, M.D, ed. Proc Amer Heartworm Sym '92. Austin, TX: American Heartworm Society 1992; 151.

3. Hendrix CM, Blagburn BL, Bowles JV, et al. The safety of moxidectin in dogs with microfilariae and adults of Dirofilaria immitis. In Soll, M.D, ed. Proc Amer Heartworm Sym '92. Austin, TX: American Heartworm Society 1992; 183-187.

4. Dzimianski MT, McCall JW, Steffens, WL, et al. The safety of selamectin in heartworm infected dogs and its effect on adult worms and microfilariae. In Seward, L., ed. Proc Amer Heartworm Sym '01. Batavia, IL: American Heartworm Society, 2001; in press.

5. American Heartworm Society: Recommended Procedures for the Diagnosis and Management of Heartworm (Dirofilaria immitis) Infection. In Soll, M.D, ed. Proc Amer Heartworm Symp '92, Austin, TX: American Heartworm Society 1992; 289-294.

6. American Heartworm Society: 1999 Guidelines for the Diagnosis, Prevention, and Management of Heartworm (Dirofilaria immitis) Infection in Dogs. In Seward, L., ed. Proc Amer Heartworm Sym '98. Batavia, IL: American Heartworm Society 1998; 257-264.

7. McCall, J.W., Ryan, W.G, Roberts, R.E., Dzimianski, M.T. Heartworm adulticidal activity of prophylactic doses of ivermectin (6 µg/kg) plus pyrantel pamoate administered monthly to dogs. In Soll, M.D., ed. Proc Amer Heartworm Sym '98. Batavia, IL: American Heartworm Society 1998, 209-215.

8. Blagburn, B.L., Hendrix, C.M., Lindsay, D.S., et al. Post-adulticide milbemycin oxime microfilaricidal activity in dogs naturally infected with Dirofilaria immitis. In Soll, M.D., ed. Proc Amer Heartworm Sym '92. Batavia, IL: American Heartworm Society 1992; 159-164.

9. McCall, J.W., McTier, T.L., Homes, R.A., et al.: Prevention of Naturally Acquired Heartworm Infection in Heartworm-Naive Beagles by Oral Administration of Moxidectin at an Interval of One or Two Months. In Soll, M.D., ed. Proc Amer Heartworm Sym '92. Batavia, IL: American Heartworm Society 1992; 169.

10. Hendrix, C.M., Blagburn, B.L, Bowles, J.V., et al.: The Safety of Moxidectin in Dogs Infected with Microfilariae and Adults of Dirofilaria Immitis.In Soll, M.D., ed. Proc Amer Heartworm Sym '92. Batavia, IL: American Heartworm Society 1992; 183.

11. Paul, A.J., Tranquilli, W.J., Todd, K.S., Aguilar, R.: Evaluation of Moxidectin in Collies. In Soll, M.D., ed. Proc Amer Heartworm Sym '92. Batavia, IL: American Heartworm Society 1992; 189.

12. Lok JB, Knight DH, Wang GT, et al. Activity of an injectable, sustained-release formulation of moxidectin administered prophylactically to mixed-breed dogs to prevent infection with Dirofilaria immitis. Am Jour Vet Res 2001 62:1721-1726.

13. McCall JW, Suprakorndej P, Dzimianski MT, et al. Evaluation of retroactive and adulticidal activity of moxidectin canine SR (sustained release) injectable formulation against dirofilaria immitis infections in beagles. In Seward, L., ed. Proc Amer Heartworm Sym '01. Batavia, IL: American Heartworm Society, 2001; in press.

14. Thomas, C.A. RevolutionTM: A unique endectocide providing comprehensive, convenient protection. Compend Contin Educ Pract Vet (Suppl) 1999; 21:2-25.

15. Thomas, C.A. RevolutionTM safety profile. Compend Contin Educ Pract Vet (Suppl) 1999; 21:26-31.

16. McCall JW, Suprakorndej P, Dzimianski MT, et al. Evaluation of retroactive and adulticidal activity of moxidectin canine SR (sustained release) injectable formulation against dirofilaria immitis infections in beagles. In Seward, L., ed. Proc Amer Heartworm Sym '01. Batavia, IL: American Heartworm Society, 2001; in press.

17. McCall JW, Hack R, McCall SD, et al. Evaluation of repeated monthly dosing of selamectin against Dirofilaria immitis beginning at three months after experimental inoculation of heartworm larvae in dogs. In Seward, L., ed. Proc Amer Heartworm Sym '01. Batavia, IL: American Heartworm Society, 2001, in press.

18. Knight, D.H.: How Current Knowledge Has Affected the Diagnosis, Prevention, and Treatment of Heartworm Infection. In Soll, M.D, ed. Proc Amer Heartworm Sym '92. Austin, TX: American Heartworm Society 1992; 253.

19. Vezzoni, A., Genchi, C., Raynaud, J-P.: Adulticide Efficacy of RM 340 in Dogs with Mild and Severe Natural Infections. In Soll, M.D, ed. Proc Amer Heartworm Sym '92. Austin, TX: American Heartworm Society 1992; 231.

20. Keister, D.M., Dzimianski, M.T., McTier, T.L., et al.: Dose Selection and C onfirmation of RM 340, a New Filaricide for the Treatment of Dogs with Immature and Mature Dirofilaria Immitis. In Soll, M.D, ed. Proc Amer Heartworm Sym '92. Austin, TX: American Heartworm Society 1992; 225.

21. McCall JW, Ryan WG, Roberts RE, Dzimianski MT. Heartworm adulticidal activity of prophylactic doses of ivermectin (6 µg/kg) plus pyrantel administered monthly to dogs. In Seward, L., ed. Proc Amer Heartworm Sym '98. Batavia, IL: American Heartworm Society, 1998; 209-215.

22. McCall JW, Roberts RE, Suprakorndej N, et al. Further evidence of clinical prophylactic (reach-back) and adulticidal activity of monthly administration of ivermectin and pyrantel pamoate in dogs experimentally infected with heartworms. In Seward, L., ed. Proc Amer Heartworm Sym '01. Batavia, IL: American Heartworm Society, 2001; in press.

23. Rawlings CA, Bowman DD, Howerth EW, et al. Response of dogs treated with ivermectin or milbemycin starting at various intervals after Dirofilaria immitis infection. Vet Ther 2001; 2:193-207.

24. Sasaki, Y., Kitagawa, H, Ishihara, K.: Clinical and Pathological Effects of Heartworm Removal from the Pulmonary Arteries Using Flexible Alligator Forceps. In Otto GF, ed. Proc Amer Heartworm Sym '89.Washington, DC: 1989; 45-51.

25. Morini S, Venco L, Fagioli P, Genchi C. Surgical removal of heartworms versus melarsomine treatment of naturally-infected dogs with risk of thromboembolism. In Seward, L., ed. Proc Amer Heartworm Sym '98. Batavia, IL: American Heartworm Society, 1998; 235-240.

26. Rawlings, C.A., Keith, J.C., Schaub, R.G., et al. Post Adulticide Treatment Pulmonary Disease and its Modification with Prednisolone and Aspirin. In Otto GF, ed. Proc Amer Heartworm Sym '83, Edwardsville, KS: Veterinary Medical Publishing Co, 1983; 122.

27. Calvert C.A., Rawlings C.A.: Treatment of Heartworm Disease in Dogs. Canine Pract 1994;18:13.

28. Atwell, R.B., Sutton, R.H., Carlisle, C.H.: The Reduction of Pulmonary Thromboembolic Disease (D. Immitis) in the Dog Associated with Aspirin Therapy. In Otto GF, ed. Proc Amer Heartworm Sym '83, Edwardsville, KS: Veterinary Medical Publishing Co, 1983; 115.

29. Keith, J.C., Rawlings, C.A., Schaub, R.G.: Effect of Aspirin on Canine Pulmonary Artery Disease Caused by Dirofilaria Immitis. In Otto GF, ed. Proc Amer Heartworm Sym '83, Edwardsville, KS: Veterinary Medical Publishing Co, 1983; 119.

30. Leuthy, M.W., Sisson, D.D., Kneller, S.K., et al.: Angiographic Assessment of Aspirin for the Prevention of Pulmonary Thromboembolism Following Adulticide Therapy. In Otto GF, ed. Proc Amer Heartworm Sym '89.Washington, DC: 1989; 53.

31. Boudreaux, M.K., Dillon, A.R., Ravis, W.R., et al.: Effects of Treatment with Aspirin or Aspirin/dipyridamole Combination in Heartworm-negative, Heartworm-infected, and Embolized Heartworm-infected Dogs. Amer J Vet Res 1992; 52:1991.

32. Neer, T.M., Hoskins, J.D.: Clinical Experience with Ivermectin Used as a Microfilaricide and for Prophylaxis in the Dog. In Otto GF, ed. Proc Amer Heartworm Sym '89.Washington, DC: 1989; 95.

33. Blagburn, B.L, Hendrix, C.M., Lindsay, D.S., et al.: Post-adulticide Milbemycin Oxime Microfilaricidal Activity in Dogs Naturally Infected with Dirofilaria Immitis. In Soll, M.D, ed. Proc Amer Heartworm Sym '92. Austin, TX: American Heartworm Society, '92, 1992; 159.

34. Atwell, RB, et al: Studies on the adverse reactions to dethylcarbamazine to microfilaria-positive (D. immitis) dogs. In Otto GF, ed. Proc Amer Heartworm Sym '83, Edwardsville, KS: Veterinary Medical Publishing Co, 1983;105-109.

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
****
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.

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Here are some quotes from the canadian vet journal volume 41 December 2000 page 929-937 we can talk about.

"the principals of evidence-based medicine were used to determine the prevalence of heartworm infection in various dog populations and the effectiveness of screening these populations"

"The evidence indicates that a heartworm diagnostic test applied to an asymptotic dog on preventative medication contributes little information regarding the heartworm infection status of that dog. However testing of a dog characterized as being high risk will provide clinically useful information"

"eligibility of articles for critical review was based on the use of a gold standard for detection of heartworm, namely necropsy and the use of blinding the study design where the person performing the heartworm test was unaware of the necropsy results."

"The specificity of most of eh antigen tests appears to be very high, although the cited specificity's of 100% are likely a reflection of the low numbers of dogs tested. False-postive results can occur when adults have died less than 3mo prior to testing, as antigen may take this long to dissipate (35), when the monoclonal antibody binds to antigens from other nematodes or to other agents in the sera (especially if hemolysis or lipolysis is evident),and when nonspecific binding to a solid surface occurs (36)"

"Unreliability appears to be a problem with heartworm antigen test as many pratictioners are concerned with discrepant results on retesting of dogs. Data on reliability are sparse but appear to indicate that there may be some cause for concern. In a study conducted by Hoover et al.27) discordant replicated test results for 8 different tests were reported to have eliminated samples from further analysis."

"A dog that has tested negative in the past and has been on heartworm preventive medication consistently during the parasite transmission season, whether in Canada or abroad, will have a pretest probability of being infected of virtually 0%."

"Thus for dogs on a consistent preventative medication program, only 1 out of every 28 positive antigen test is likely to be a true positive."

"Heartworm infection does not invariably lead to disease and death. In fact it is generally accepted, that low heartworm burdens < 20 worms are rarely of clinical significance (41)"

"It would appear from surveys that, in Canada, more dogs are euthanized because they tested positive than would ever become symptomatic or die from heartworm infection."

[guest]

Heartworm Medication Raises Questions

A CBS 2 Special Report

Mar 1, 2004 10:59 pm US/Eastern
NEW YORK (CBS) The focus of an investigative story by our sister-station WBZ-TV Boston is a popular medication being used to prevent heartworm, a potentially deadly disease. WBZ's Joe Bergantino has learned that after taking this drug thousands of dogs have gotten sick, hundreds have even died.

Joanne Plumer treats all of her dogs like members of the family.

So she immediately noticed something was wrong with her 13-year-old named April. "She couldn't stand up any more, she couldn't eat, her mouth was full of blisters, her fur was falling out."

It all started the day after April got a shot of the heartworm medication ProHeart 6. Three weeks later, April had to be put to sleep.

"We were devastated with April. We were totally devastated with April. She was my baby," Joanne recalled.

Within a few weeks, Joanne's other dog, 10-year-old Cuji, also treated with ProHeart 6, got very sick. Cuji died three months after getting her shot.

"She went completely blind. Then you know, she started coughing and coughing and she couldn't catch her breath and we checked her out and she had complete kidney failure," Joanne remembered.

These are not isolated cases.

WBZ's I-Team investigation found that in the past two and a half years the FDA has received more than 4,000 reports of dogs getting sick after getting a shot of ProHeart 6. And more than 400 dogs have died nationwide.

The FDA says it's been able to link ProHeart 6 to a small percentage of those cases but even those numbers are, in the FDA's words, "a cause for concern." The FDA is investigating.

In fact, the FDA has twice told the makers of ProHeart 6 to change its labeling, most recently asking the company to add that there have been rare reports of death.

"I think this is just the tip of the iceberg," says Veterinarian Bob Rogers. He wonders why the FDA has not taken the drug off the market.

The FDA's answer: it believes the medication could potentially save the lives of more dogs than it harms.

But Dr. Rogers disagrees. "I have seen veterinary drugs pulled off the market when there were less deaths involved than this."

As for the manufacturer of ProHeart 6, a company called Fort Dodge Animal Health, it declined an on-camera interview but released this statement saying "Millions of U.S. dogs have benefited from the heartworm protection provided by ProHeart 6. The reports submitted to the FDA represent a fraction of 1% of total doses sold…and the product has been proven to be safe."

Donna Sadoski doesn't believe that. Her 11-year-old dog Sammy went blind after getting a shot of ProHeart 6.

"I wonder how many animals will be put to sleep? How many animals will have life threatening problems they will have to deal with for the rest of their lives before someone stops this medicine from actually being given to them," Donna told WBZ.

The makers of ProHeart 6 say they do not believe their heartworm medication caused Donna's and Joanne's dogs to get sick.

But the FDA continues to investigate, at this point asking the company to find out if there are any impurities in the drug's formula that may be causing problems.

[guest]

canada vet journal volume 41 dec 2000 page 935"test interpretation
In order for practitioners to rationally interpret the results of a heartworm test, information on sensitivity and specificity of the test and the estimated pretest probability of infection in the dog have to be combined to obtain positive and negative predictive values. The predictive values aid the practitioner in making a decision about the infection status of a dog. The positive predictive value (PPV) is the probabiltiy that a test-positive animal is truly infected with d. immitis.""if the pretest probability of heartworm infection is less than 5.0% the PPV drops off rapidly,making the decision to treat uncertain."" It is only when the pretest probability of heartworm infection is at least 3% to 5% that a positive test result, by itself,should change the practitioners opinion of the infection status of an unporotected,asymptomatic,as a PPV of 90% will be achieved."

[malernee]

PARASITICIDES : ENDECTOCIDES (systemic parasiticides) : Spot treatments
PFIZER INC.
235 E. 42ND ST., NEW YORK, NY, 10017
General: 610-363-3100
Customer Service (Orders): 800-733-5500
Technical Services (USA): 800-366-5288
Technical Services (Canada): 800-461-0917
Website: www.pfizer.com/ah



--------------------------------------------------------------------------------
Every effort has been made to ensure the accuracy of the information published.
However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the product label or package insert.

--------------------------------------------------------------------------------

REVOLUTION®
Rx
Pfizer Animal Health
NADA #141-152, Approved by FDA
(selamectin)
Topical Parasiticide For Dogs and Cats
CAUTION:
US Federal law restricts this drug to use by or on the order of a licensed veterinarian.
DESCRIPTION:
Revolution (selamectin) Topical Parasiticide is available as a colorless to yellow, ready to use solution in single dose tubes for topical (dermal) treatment of dogs and cats six weeks of age and older. The content of each tube is formulated to provide a minimum of 2.7 mg/lb (6 mg/kg) of body weight of selamectin. The chemical composition of selamectin is (5Z, 25S)-25-cyclohexyl-4'-O-de(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)-5-demethoxy-25-de(1-methylpropyl)-22, 23-dihydro-5-hydroxyiminoavermectin A1a.
INDICATIONS:
Revolution is recommended for use in dogs and cats six weeks of age or older for the following parasites and indications:
Dogs:
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).
Cats:
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.
WARNINGS:
Not for human use. Keep out of the reach of children.
In humans, Revolution may be irritating to skin and eyes. Reactions such as hives, itching and skin redness have been reported in humans in rare instances. Revolution contains isopropyl alcohol and the preservative butylated hydroxytoluene (BHT). Wash hands after use and wash off any product in contact with the skin immediately with soap and water. If contact with eyes occurs, then flush eyes copiously with water. In case of ingestion by a human, contact a physician immediately. The material safety data sheet (MSDS) provides more detailed occupational safety information. For a copy of the MSDS or to report adverse reactions attributable to exposure to this product, call 1-800-366-5288.
Flammable - Keep away from heat, sparks, open flames or other sources of ignition.
PRECAUTIONS:
Use with caution in sick, debilitated or underweight animals (see SAFETY).
Prior to administration of Revolution, dogs should be tested for existing heartworm infections. At the discretion of the veterinarian, infected dogs should be treated to remove adult heartworms. Revolution is not effective against adult D. immitis and, while the number of circulating microfilariae may decrease following treatment, Revolution is not effective for microfilariae clearance.
Hypersensitivity reactions have not been observed in dogs with patent heartworm infections administered three times the recommended dose of Revolution. Higher doses were not tested.
ADVERSE REACTIONS:
Pre-approval clinical trials:
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 rarely (<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.
Post-approval experience:
In addition to the aforementioned clinical signs that were reported in pre-approval clinical trials, there have been reports of pruritus, urticaria and erythema. There have also been rare reports of seizures and ataxia in dogs.
DOSAGE:
The recommended minimum dose is 2.7 mg selamectin per pound (6 mg/kg) of body weight.
Administer the entire contents of a single dose tube (or two tubes used in combination for dogs weighing over 85 pounds) of Revolution topically in accordance with the following tables. (See ADMINISTRATION for the recommended treatment intervals.)
Cats (lb)
Package
color
mg per tube
Potency
(mg/mL)
Administered
volume (mL)

Up to 5
Mauve
15 mg
60
0.25

5.1-15
Blue
45 mg
60
0.75

For cats over 15 lbs use the appropriate combination of tubes.
Dogs (lb)
Package
color
mg per tube
Potency
(mg/mL)
Administered
volume (mL)

Up to 5
Mauve
15 mg
60
0.25

5.1-10
Purple
30 mg
120
0.25

10.1-20
Brown
60 mg
120
0.5

20.1-40
Red
120 mg
120
1.0

40.1-85
Teal
240 mg
120
2.0

85.1-130
Plum
120 mg + 240 mg*
120
3.0

*Two tubes used in combination.
For dogs over 130 lbs use the appropriate combination of tubes.
Recommended for use in animals 6 weeks of age and older.
ADMINISTRATION:
Firmly depress the cap to puncture the seal on the Revolution tube; then remove the cap to administer the product. Part the hair on the back of the animal at the base of the neck in front of the shoulder blades until the skin is visible. Place the tip of the tube on the skin, release the hair and squeeze the tube to empty its entire contents directly onto the skin in one spot. Do not massage the product into the skin. Due to alcohol content, do not apply to broken skin. Avoid contact between the product and fingers. Do not apply when the hair coat is wet. Bathing or shampooing the animal 2 or more hours after treatment will not reduce the effectiveness of Revolution. Stiff hair, clumping of hair, hair discoloration, or a slight powdery residue may be observed at the treatment site in some animals. These effects are temporary and do not affect the safety or effectiveness of the product. Discard empty tubes in your ordinary household refuse.
Flea Control in Dogs and 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.
Heartworm Prevention in Dogs and Cats
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.
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 safely be given Revolution monthly to prevent further infections.
Ear Mite Treatment in Dogs and Cats
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.
Sarcoptic Mange Treatment in Dogs
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.
Tick Control in Dogs
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.
Nematode Treatment in Cats
For the treatment of intestinal hookworm (A. tubaeforme) and roundworm (T. cati) infections, Revolution should be applied once as a single topical dose.
SAFETY:
Revolution has been tested safe in over 100 different pure and mixed breeds of healthy dogs and over 15 different pure and mixed breeds of healthy cats, including pregnant and lactating females, breeding males and females, puppies and kittens six weeks of age and older, and avermectin-sensitive collies. However, a kitten, estimated to be 5-6 weeks old (0.3 kg), died 8 1/2 hours after receiving a single treatment of Revolution at the recommended dosage. The kitten displayed clinical signs which included muscle spasms, salivation and neurological signs. The kitten was a stray with an unknown history and was malnourished and underweight (see PRECAUTIONS).
DOGS: In safety studies Revolution was administered at 1, 3, 5, and 10 times the recommended dose to 6 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.
CATS: 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.
STORAGE CONDITIONS: Store below 30°C (86°F).
HOW SUPPLIED: Available in six separate dose strengths for dogs and cats of different weights (see Dosage). Revolution for puppies and kittens is available in cartons containing 3 single dose tubes. Revolution for cats and dogs is available in cartons containing 3 or 6 single dose tubes. Revolution for dogs weighing more than 85 lbs is available in cartons containing 6 or 12 single dose tubes.
Distributed by:
Pfizer Animal Health
Exton, PA 19341, USA
Div. of Pfizer Inc
NY, NY 10017
www.revolutionpet.com
69-9876-00-1

[anom]

As a veterinarian my goal is to take care of your pets the best I can using the best meds available. I have been following the
info on Proheart6, and I was using it exclusive of all other heart worm meds. My patients have had some bad experiences with
the pills and remembering to give them to their pets on time. These meds are to protect your dog from a worm that eats their
heart. Something you never want to see or deal with. I ended up using up an entire weekend checking this out.
There have been 600 dog deaths and over 5,000 adverse reactions. That meant nothing to me. I needed to know how many dogs
got the injection. That information would put the deaths and adverse reactions into perspective for me. Dr. Glickman's Banfield report
finally released a report with some of that data. 735,654 dogs got the injection, in his study.
735,654 dogs were protected from worms eating their hearts and 0.29% died, Do the math. That would make Proheart about as risky as crossing the street, same odds.
So why has the FDA asked for a recall on PH6? At a meeting I was able to ask an FDA official about that. He said " we don't
look at the total number of of dogs it was administered to just the number of adverse reactions, and it was greater than any
of the other meds used for heart worm," and."we have never had hearings on veterinarian product before," that he could remember. I found a pdf that reports that half of the Advisory Committee has financial connections to the competition, Dr. John Glisson, Dr. Katrina L. Mealey, and Dr. Mark G Papich, and would be voting. http://www.fda.gov/cvm/Documents/VMACWinter05Trans.pdf
I just stared at him, the FDA was using a flawed methodology. They didn't know if it was given to 5,000 dogs or 100,000,000
dogs. And that makes a big difference.
If I had quit using the other meds and was using PH6 exclusively, then prob ally many other vets were doing the same. Now
stay with me here, fore the sake of argument lets say the three other meds were all having 3,000 adverse reactions EACH,
that would be 9,000 adverse reactions total. Now just for the sake of argument lets say Ph6 got 100% of the market, and the
other 3 had none, and PH6 got 5,000 adverse reactions. That is a significant improvement over the 9,000 previously, but the
FDA still took it off the market!
This just points out the FDA's method has nothing to do with safety, just looking at number of adverse reactions.
Is Ph6 good? Based on the number of dogs that received protection vs adverse reactions and no worry on my part about the
owners forgetting to give a pill, Ph6 is a God send.
A further look around the INTERNET shows almost everyone of the 600 owners that had a pet die put up a web site, strange.
There are many links pointing to a "proheart petition", I read it, nothing to do with Ph6.
http://www.google.com/search?q=proheart ... S&filter=0
petition:
http://www.petitiononline.com/ProHeart/petition.html
And a Dr. Bob Rogers, and many links pointing to a "Proheart Class Action suit"/
http://www.google.com/search?num=100&hl ... tnG=Search
I read the suit and again nothing to do with
Ph6! http://www.childresslaw.net/CM/Custom/Custom52.asp
It feels like something funny is going on here.
I just want the best meds for heartworm, the statistics indicate it is Ph6.
What is going on, my patients are not getting my best because of the FDA and some wacko web sites.
The thing that confuses me is Fort Dodges's wimpy ATTITUDE to this Internet WHIPPING?
Board Certified DVM

[malernee]