Efficacy and safety of selamectin against fleas on dogs and cats presented as veterinary patients in Europe

Two controlled and masked multi-centre studies were conducted to examine the efficacy of a novel topical avermectin, selamectin, against natural flea infestations on 418 dogs and 345 cats. Veterinary patients with viable flea infestations were enrolled in the studies, which were conducted in United Kingdom, France, Germany, and Italy. Animals were allocated randomly in a 2:1 ratio to one of two treatments: either selamectin alone at a minimum dosage of 6mgkg(-1) or fenthion at recommended dose rates. Concurrent use of an environmental spray (containing methoprene and either pyrethrins or permethrin) was permitted only for fenthion-treated animals. In-contact cats and dogs (animals living in the same home) received the same treatment as the first animal enrolled from the household, if recommended by the veterinarian. Study day 0 was defined as the day of first treatment. Animals were treated on days 0, 30, and 60, and flea comb counts and clinical evaluations were conducted on days 0, 14, 30, 60, and 90. Analysis of variance of ln(flea count+1) showed that values were significantly lower for selamectin alone compared with fenthion (with or without the concurrent use of an environmental spray) in dogs on days 30, 60, and 90 (P<0.05) and in cats on days 14, 30, 60, and 90 (P<0.01). For selamectin, the reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day 0, were 92.5, 90.7, 98.1, and 99.1%, respectively, for dogs and 92.8, 92.7, 97.7, and 98.4%, respectively, for cats. Selamectin was shown to be safe and highly effective in the control of naturally acquired flea infestations on dogs and cats presented as veterinary patients in Europe.     

Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).     

Field evaluation of the efficacy and safety of a combination of spinosad and milbemycin oxime in the treatment and prevention of naturally acquired flea infestations and treatment of intestinal nematode infections in dogs in Europe

Two separate randomised, blinded, multicentre field trials were conducted to evaluate the efficacy and safety of a combination of spinosad and milbemycin oxime (MO) (Trifexis^®, Elanco Animal Health) in the treatment and prevention of naturally acquired flea infestations and intestinal nematode infections in European dogs. Treatments using Trifexis^® and each control veterinary product (CVP) were administered once on Day 0 in both field studies.In the flea field trial, 11 veterinary clinics in France participated in the study. On Day 0, whole body flea comb counts were conducted on all dogs being evaluated for enrolment. Dogs with ≥7 fleas on Day 0 were enrolled, treated once on Day 0 with spinosad/MO or the CVP (Stronghold^®; selamectin) and then underwent post-treatment flea counts on Days 14 and 30. There were 150 spinosad/MO treated dogs and 71 CVP treated dogs included in the flea effectiveness population. Effectiveness against fleas (% reduction in geometric means; GM) was 98.97% and 97.37% for the spinosad/MO treated dogs, and 97.43% and 93.96% for the CVP dogs on Days 14 and 30, respectively, compared to the pre-treatment baseline flea counts. Of the spinosad/MO dogs, 89.3% and 80.0% had no live fleas on Days 14 and 30, compared to 77.5% and 70.4% of the CVP dogs, respectively.In the nematode field trial, data from 10 veterinary clinics in France and 19 in Ireland were pooled. Faecal samples from dogs at each clinic were analysed. A positive result at screening (parasite eggs from Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum) allowed for enrolment. Dogs were randomised to spinosad/MO or the CVP (Milbemax^®; MO/praziquantel). On Day 8, a post-treatment faecal sample was taken and analysed. Of 2333 dogs screened for nematode eggs, 238 dogs were positive with one or more of these nematodes, and 229 were enrolled in the study. Of the 229 dogs, 151 were treated with a single dose of spinosad/MO, and 77 were treated with a single dose of CVP. Post-treatment effectiveness against all nematodes (% reduction GM) was achieved with reductions of 98.57% and 97.57% for the spinosad/MO treated dogs and CVP dogs, respectively, as compared to the pre-treatment baseline faecal egg counts.Trifexis^® was shown to be safe and effective against natural infestations of fleas as well as mixed and single intestinal nematode infections in client owned dogs in Europe when administered as a single oral administration at the recommended dose.     

Efficacy of selamectin against experimentally induced and naturally acquired ascarid (Toxocara canis and Toxascaris leonina) infections in dogs

The efficacy of selamectin against adult ascarids was evaluated in eight controlled and masked studies in dogs. Three laboratory studies evaluated selamectin against experimentally induced infections of Toxocara canis; three laboratory studies evaluated selamectin against naturally acquired infections of T. canis; one laboratory study evaluated selamectin against naturally acquired infections of both T. canis and Toxascaris leonina; one field study evaluated selamectin against naturally acquired infections of ascarids (T. canis and/or T. leonina) in dogs presented as veterinary patients. Selamectin was administered topically to the skin of dogs in unit doses designed to deliver a minimum of 6mgkg(-1) (range, 6-12mgkg(-1)). In all studies, dogs were allocated randomly to treatment assignments (selamectin or vehicle control in laboratory studies: selamectin or reference product in the field study) on the basis of pretreatment fecal egg counts. For induced infections, there were significant reductions in geometric mean numbers of adult T. canis after a single application of selamectin (93.9-98.1%, P=0.0001), after two monthly applications (> or =88.3%, P< or =0.0001), and after three monthly applications (100%, P< or =0.0002). In the natural infection laboratory studies, when selamectin was administered twice at an interval of 30 days, the percentage reductions in geometric mean numbers of adult T. canis at necropsy were 84.6, 91.3, and 97.9%, and when selamectin was administered on days 0, 14, and 30, the percentage reductions were 91.1 and 97.6%. Geometric mean fecal T. canis egg counts were reduced by > or =92.9% (P< or =0.0067) at the end of the studies. In the field study, geometric mean fecal ascarid egg counts were reduced by 89.5 and 95. 5% (P=0.0001) for 14 and 30 days, respectively, after a single treatment with selamectin, and by 94.0% (P=0.0001) 30 days after the second treatment with selamectin. These reductions compared favorably with the egg count reductions from dogs treated with a reference product containing praziquantel, pyrantel embonate, and febantel. There were no adverse drug experiences or treatment-related mortalities during any of the studies. Selamectin, when administered topically in a unit dose providing a minimum dosage of 6mgkg(-1), was safe and effective against adult T. canis and T. leonina and in reducing the fecal excretion of T. canis eggs in dogs.     

Efficacy of selamectin in the treatment and prevention of flea (Ctenocephalides felis felis) infestations on dogs and cats housed in simulated home environments

The efficacy of selamectin, a novel avermectin, in protecting dogs and cats against experimentally induced environmental flea (Ctenocephalides felis felis) infestations, was evaluated in a series of controlled and masked studies. Purpose-bred shorthaired cats and Beagles were randomly allocated to treatment with either selamectin at a minimum dosage of 6mgkg(-1) of body weight in the commercial formulation or the negative control treatment (vehicle only), and housed in controlled simulated home environments capable of supporting the flea life cycle. Day 0 was defined as the first day of treatment. Treatments were administered topically in a single spot on the skin at the base of the neck in front of the scapulae. In environmental challenge studies, which were designed to evaluate the efficacy of selamectin in the treatment and control of established flea infestations, dogs and cats were each infested with 100 fleas on days -28 and -21 and placed in carpeted rooms in order to establish high levels of active flea infestation prior to day 0. Treatments were administered monthly for 3 months. Flea comb counts were performed on days 14, 29, 44, 59, 74, and 90. Reductions in geometric mean flea comb counts for selamectin, compared with vehicle, were >99% from day 14 onwards for dogs, and >92% on day 29 and >99% on days 44, 59, 74, and 90 for cats (P=0.0001). In prevention of environmental infestation studies, dogs and cats were placed in environments capable of supporting flea infestations and given monthly treatments for 2 months, commencing on day 0. Animals were infested with 100 fleas on days 1 and 7, and flea comb counts were performed on days 29, 44, and 60. Reductions in geometric mean flea comb counts for selamectin, compared with vehicle, were >99% on days 29, 44, and 60 (P=0.0001) for dogs and cats. Monthly administration of selamectin to dogs and cats housed in environments highly suited to completion of the flea life cycle was shown to be highly effective in the treatment and prevention of flea infestations, without the need for supplementary environmental control measures.     

Evaluation of spinosad for the oral treatment and control of flea infestations on dogs in Europe

The novel ectoparasiticide spinosad is a naturally occurring mixture of spinosyns A and D formed during a fermentation process. The spinosyns are tetracyclic macrolides with a unique ring system. Their mode of action differs from that of other commercially available insecticides. Laboratory and field trials were conducted to evaluate the use of spinosad in a chewable tablet at a dose range of 45 to 70 mg/kg for the treatment and control of flea infestations on dogs in Europe. Laboratory studies with artificially infested dogs confirmed persistent activity against Ctenocephalides felis of higher than 99 per cent at three weeks post-treatment with values of 96.5 to 97.8 per cent at four weeks. Two multicentric field trials with naturally infected client-owned animals in five European countries used selamectin as comparator. Monthly doses were given during the summer when many homes were heavily infested. Households with spinosad-treated dogs showed cumulative benefits with flea burdens reduced by about 97 per cent at 14 and 30 days and by 99.6 per cent at 60 and 90 days. Corresponding figures for selamectin were significantly lower (P<0.05) at all time points: between 88.5 and 91 per cent at 14 and 30 days, then 97.8 and 98.2 per cent at 60 and 90 days. Thus, the performance of spinosad compared favourably with that of the established reference product.     

Evaluation of the effects of selamectin against adult and immature stages of fleas (Ctenocephalides felis felis) on dogs and cats

The adulticidal, ovicidal, and larvicidal effects of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats were evaluated in a series of seven controlled and masked studies (three in cats, four in dogs). Animals were randomly allocated to treatment with either selamectin at a minimum dosage of 6mgkg(-1) in the commercial formulation or one of two negative-controls (0.9% NaCl solution or the vehicle from the commercial formulation). Treatments were administered topically in a single spot on the skin at the base of the neck in front of the scapulae. Speed of kill, measured by flea comb counts at 12h intervals during the 48h immediately following a single treatment on day 0, was evaluated in two studies. One study was in dogs and the other in cats, and each animal was infested with approximately 100 unfed viable adult fleas prior to treatment. Reductions in geometric mean flea counts for selamectin compared with saline were >98% between 24 and 36h after treatment in dogs, and between 12 and 24h after treatment in cats (P< or =0.0006). Efficacy in reducing flea egg hatch and larval development was evaluated in four studies, in which dogs and cats were treated once on day 0 and then repeatedly infested with approximately 600 fleas. Flea eggs were collected approximately for 72h after each infestation, on days 3, 7, 14, 21, and 30, counted, and cultured to determine their hatchability and subsequent larval development. Compared with the vehicle, selamectin was highly effective in reducing flea egg hatch (>92% in cats) and larval development (> or =95% for dogs and cats), and emergence of adults (97.8-100% for dogs, 85.6-100% for cats) for 30 days. Effects of exposure to hair coat debris were investigated in a study with dogs treated once on day 0 and repeatedly infested with 100 adult fleas. Debris (dander, flea faeces, hair, scales) was collected on days 1, 7, 14, 21, and 30 and added to normal flea eggs or larvae for incubation. Compared with debris from vehicle-treated dogs, debris from selamectin-treated dogs was highly effective in preventing egg hatch (>96%), in killing larvae (>98%) and in preventing larval development to adults (>99%) (P相似文献   

Efficacy of selamectin administered topically to pregnant and lactating female dogs in the treatment and prevention of adult roundworm (Toxocara canis) infections and flea (Ctenocephalides felis felis) infestations in the dams and their pups

The efficacy of selamectin in the treatment and prevention of naturally acquired Toxocara canis infections and experimentally induced flea (Ctenocephalides felis felis) infestations in dams and their suckling pups was evaluated by administering selamectin to the adult females only, approximately 40 and 10 days before parturition and 10 and 40 days after parturition. Unit doses of the commercial formulation of selamectin were administered to the dams to provide at least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(-1)). Dams and their pups were housed in carpeted environments able to support the flea life cycle. Flea infestations were established initially by experimental infestation before treatment administration and by repeated re-infestation of dams at approximately weekly intervals throughout the study, which was completed 45 days after parturition. There were no adverse drug experiences related to treatment with selamectin and no treatment-related mortalities. Percentage reductions in geometric mean T. canis faecal egg counts for the selamectin-treated dams, compared with those receiving the negative-control treatment (vehicle only) were 99.7% at the end of the study (P=0.0001). Geometric mean faecal egg counts in pups from selamectin-treated females were reduced by > or =96% on the 24th and 34th days after birth (P=0.0001), and the number of adult worms recovered from the gastrointestinal tract of pups from selamectin-treated dams was reduced by 98.2% (P=0.0001), compared with that for pups from dams treated with the vehicle only. Percentage reductions in geometric mean flea counts for selamectin-treated dams and their pups, compared with vehicle-treated dams and their pups, were > or =99.8% (P=0.0001) and 100% (P=0.0001), respectively, throughout the study. Thus, selamectin administered topically at a minimum unit dosage of 6mgkg(-1) to dams with naturally acquired T. canis infections and experimentally induced C. felis infestations was safe and highly effective in the treatment, control, and prevention of adult T. canis infection and C. felis infestation affecting both the dams and their pups.     

Efficacy and safety of selamectin against fleas and heartworms in dogs and cats presented as veterinary patients in North America

A series of randomized, controlled, masked field studies was conducted to assess the efficacy and safety of selamectin in the treatment of flea infestations on dogs and cats, and in the prevention of heartworm infection in dogs. In addition, observations were made on the beneficial effect of selamectin treatment on dogs and cats showing signs of flea allergy dermatitis (FAD). In all studies selamectin was applied topically, once per month, in unit doses providing a minimum dosage of 6mgkg(-1). Dogs and cats with naturally occurring flea infestations, some of which also had signs associated with FAD, were assigned randomly to receive three months of topical treatment with selamectin (220 dogs, 189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins, n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as the day that the animal first received treatment. Flea burdens were assessed by flea comb counts and clinical evaluations of FAD were performed before treatment, and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%, respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%, respectively, compared with day 0 counts. Selamectin also was beneficial in alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397 dogs free of adult heartworm infection from four heartworm-endemic areas of the USA were allocated randomly to six months of treatment with selamectin (n=298) or ivermectin (n=99). Selamectin achieved a heartworm prevention rate of 100%, with all dogs testing negative for microfilariae and adult heartworm antigen on days 180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats having an age range of 6 weeks to 19 years (3954 doses). The animals included 19 purebred or crossbred Collies (Bearded, Border, and unspecified). There were no serious adverse events. Results of these studies indicated that selamectin was highly effective in the control of flea infestations in dogs and cats without the need for simultaneous treatment of the environment or of in-contact animals and also was beneficial in alleviating signs associated with FAD. Selamectin also was 100% effective in preventing the development of canine heartworms and was safe for topical use in dogs and cats.     

Evaluation of the comparative efficacy of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats in simulated home environments

The comparative efficacy of monthly administration of selamectin or lufenuron against Ctenocephalides felis felis on dogs and cats was evaluated over a 5-month period in flea-infested environments. Twenty-four dogs and 32 cats were randomly allocated to receiving a topical treatment with selamectin or an oral administration of tablets containing lufenuron/milbemycin oxime (for dogs) or lufenuron only (for cats). Each product was administered in accordance with the manufacturer's label recommendations. Eight dogs and four cats served as untreated sentinels. Treatments were administered on days 0, 30, 60, 90, and 120. Each animal received an application of 100 fleas on days -28 and -21, and then weekly applications of 20 fleas from days 91 through 147. Flea comb counts were performed on day -6, and every 2 weeks after day 0. From day 29 (dogs) or day 44 (cats) to day 150, geometric mean flea counts for selamectin were < or =0.4. Mean flea counts for animals assigned to treatment with selamectin were significantly lower (P=0.0001) than for animals assigned to treatment with lufenuron at all assessments after day 0.     

The efficacy of selamectin in the treatment of naturally acquired aural infestations of otodectes cynotis on dogs and cats

The efficacy of a novel avermectin, selamectin, was evaluated against naturally acquired aural infestations of Otodectes cynotis on dogs and cats. In four controlled and masked studies conducted in the USA and Europe, animals were allocated randomly to treatment with either selamectin at a minimum dosage of 6mgkg(-1) (range, 6-12. 5mgkg(-1)) or the vehicle only from the commercial formulation of selamectin (negative control). Treatments were administered topically in a single spot to the skin of each animal's back at the base of the neck in front of the scapulae. Cats were treated on day 0 only, and dogs were treated either on day 0 only or on days 0 and 30. The ears of dogs were examined otoscopically on day 14 for the presence of viable mites. Mite counts were conducted on day 30 for animals that had received one dose and on day 60 for animals that had received two doses. Percentage reductions in geometric mean mite counts for selamectin treatment compared with the vehicle were 100% for all animals on all count days. Analysis of variance, confirmed by Savage Scores, showed that ln(mite count+1) values were significantly (P< or =0.0015) lower for selamectin than for the vehicle for all animals on all count days. Thus, selamectin administered topically at a minimum dosage of 6mgkg(-1) was safe and 100% effective against naturally acquired aural infestations of O. cynotis in dogs and cats after a single dose or after two doses administered 1 month apart.     

Efficacy of selamectin against adult flea infestations (Ctenocephalides felis felis and Ctenocephalides canis) on dogs and cats

Selamectin was evaluated in eight controlled studies (4 in dogs, 4 in cats) to determine the efficacy of a single topical unit dose providing the recommended minimum dosage of 6mgkg(-1) against Ctenocephalides felis felis and Ctenocephalides canis fleas on dogs and against C. felis on cats. In addition, the effect of bathing on the efficacy of selamectin against C. felis was evaluated. Identical studies were performed in Beagles and domestic shorthaired cats. For each study, animals were allocated randomly to treatments of 8-12 animals each. All studies (dog studies A, B, C, and D and cat studies A, B, C, and D) evaluated the efficacy of selamectin without bathing. In addition, study C in both dogs and cats evaluated efficacy with a shampoo bath at 24h after dosing, and study D evaluated the efficacy of selamectin with water soaking at 2h after dosing or with a shampoo bath at 2-6h after dosing. Dog study B evaluated efficacy against C. canis, whereas all other studies used C. felis. In each study, selamectin was administered on day 0 as a topical dose that was applied directly to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with approximately 100 viable unfed C. felis or C. canis on days 4, 11, 18, and 27. On days 7, 14, 21, and 30, approximately 72h after infestation, a comb count of the number of viable fleas present on each animal was made. For C. felis and C. canis for dogs and cats, compared with controls, selamectin achieved significant reductions in geometric mean adult flea comb counts of > or =98.9% on days 7, 14, and 21 in all eight studies. On day 30, the reduction for C. felis remained at or above 98.0%. This included the dogs and cats that were soaked with water or bathed with shampoo at 2, 6, or 24h after treatment. There were no significant (P>0.05) differences between the flea counts from selamectin-treated animals in these studies, regardless of bathing status. On day 30, a significant reduction of 91.8% was achieved against C. canis on dogs. Thus, these studies demonstrated that a single topical unit dose of selamectin was highly effective against adult fleas on dogs and cats for at least 27 days.     

Preliminary studies on the effectiveness of the novel pulicide, spinosad, for the treatment and control of fleas on dogs

Spinosad is a novel mode-of-action insecticide produced from a family of natural products derived from fermentation of the actinomycete, Saccharopolyspora spinosa. Separate studies were undertaken to determine the minimum effective dose of spinosad given orally for the treatment of experimentally induced flea infestations (Ctenocephalides felis) on dogs, and to assess any potential impacts of feeding canned or dry food at the time of dosing. Both were randomized block (blocked by gender and pre-treatment flea counts), blinded parallel-arm studies, with dogs selected on health and ability to maintain pre-treatment flea populations. For dose selection, 48 dogs were allocated among six groups (8 dogs/group; 4 males, 4 females): placebo-treated negative control, spinosad in gelatin capsules at 15, 20, 30 and 40 mg/kg administered per os; and topical imidacloprid (10 mg/kg) as a positive control. Placebo and spinosad treatments were administered on Days 0, 30 and 60, imidacloprid only on Day 0. In a second study to assess the impact of food type at the time of dosing, three groups were formed: placebo-treated control (8 dogs; 4 males, 4 females), spinosad (30 mg/kg) administered with canned food (8 male dogs, 8 females); and spinosad (30 mg/kg) with dry food (8 males, 8 females). Treatments were administered on Days 0 and 30. To assess post-treatment persistent efficacy, flea infestations were repeated at regular post-treatment intervals, beginning on Day 5 through Day 89 in the dose selection study and Day 58 in the impact of food type and dosing study. Flea counts were performed 48 h post-infestation by study personnel who were blinded to treatments. In the dose selection study, compared to geometric mean live flea counts in the control group, each spinosad dose was highly effective (99.8–100%) at 7, 14 and 21 days after treatment. Only the 30 and 40 mg/kg doses maintained high efficacy (97.2–100%) until 30 days after treatment, with no difference between the two. Imidacloprid was highly effective at Day 30, with significant difference only from the 15 mg/kg spinosad group. Because there was no significant difference between the higher spinosad rates, 30 mg/kg was selected as the optimal minimum effective dose. In the second study, spinosad was highly effective at all post-treatment flea counts (98–100%). Taken together, these studies demonstrate that repeated monthly oral treatments with spinosad at 30 mg/kg provide sustained control of C. felis on dogs. There were no treatment-related adverse events in either study, indicating that spinosad has potential to be used monthly as a safe and effective flea adulticide, providing sustained activity that matches that of currently used topical products.     

Prevention of experimentally induced heartworm (Dirofilaria immitis) infections in dogs and cats with a single topical application of selamectin

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.     

Repellency and efficacy of 65% permethrin and selamectin spot-on formulations against Ixodes ricinus ticks on dogs

Two topically applied spot-on products used for flea and tick control on dogs, 65% permethrin (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp., Union, NJ) and selamectin (Revolution [United States] or Stronghold [Europe], Pfizer Animal Health, New York, NY), were evaluated for repellency and efficacy against Ixodes ricinus, the primary vector of Lyme disease in Europe. Eighteen dogs were evenly and randomly allocated to the following treatments: 1) 65% permethrin, 2) selamectin, 3) untreated control. Dogs were treated by topical application of the assigned product in accordance with product label directions on Day 0. At 7, 14, 21, 28, and 35 days after treatment, each dog was exposed for 2 hours to 50 unfed, adult ticks in a cage with a carpet that covered approximately 70% of the floor area. After the exposure period, dogs were removed from the cages and live and dead ticks were counted on the dogs and in the cages. The number of live ticks recovered was reduced by 90.3% to 99.5% for dogs treated with 65% permethrin (P <.0001 versus controls and selamectin), compared with 10.9% to 31.1% for dogs treated with selamectin (P >.05 versus controls). The repellency of 65% permethrin was 63.4% to 80.2% against I. ricinus ticks (P <.0001 versus controls, P <.0007 versus selamectin), compared with 0% to 10.9% repellency for selamectin (P >.05 versus controls).     

Evaluation of the efficacy and safety of a novel formulation of metaflumizone plus amitraz in dogs naturally infested with fleas and ticks in Europe

The efficacy and safety of a novel spot-on formulation of metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was assessed in dogs naturally infested with ticks and/or fleas in a multiregional, clinical field study. Nineteen veterinary clinics in Germany and 11 clinics in France enrolled patients to the study. One hundred eighty one dogs with tick infestation and 170 dogs with flea infestation (plus three dogs harboring both ticks and fleas) qualified as primary patients and were randomly allocated to one of two treatments in a ratio of approximately 2:1 for metaflumizone plus amitraz (minimum dosage of 20 plus 20mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Tick and/or flea counts and safety evaluations were repeated at intervals of about 2 weeks for 8 weeks. Both products resulted in consistent reductions in tick numbers (>81%) throughout the study, with metaflumizone plus amitraz giving consistently higher reductions in tick numbers. The efficacy against tick count compared with Day 0 was 97.6%, 93.5%, 89% and 94% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 86.3%, 81.1%, 84.8% and 86.1%. Within groups, the tick reduction was highly significant (P<0.0001) compared to baseline at all observation periods. Both treatments resulted in consistent (>89%) and highly significant (P<0.0001) reductions in flea numbers relative to the baseline counts throughout the study, although fipronil resulted in numerically higher reductions on each count day. The efficacy against fleas compared to baseline was 91.8%, 88.7%, 91.5% and 92.0% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 98.2%, 96.3%, 95.9% and 96.7%. Metaflumizone plus amitraz was highly effective in controlling existing infestations of fleas and ticks on dogs and was effective against reinfestation for at least 56 days. Metaflumizone plus amitraz showed a good tolerance profile in dogs.     

In vivo anthelmintic activity of Phytolacca icosandra against Haemonchus contortus in goats

Two separate controlled and blinded studies were conducted to confirm the dose and non-interference of spinosad and milbemycin oxime (MO) administered orally in combination or alone to dogs for the treatment and control of experimentally induced flea infestations (Ctenocephalides felis) and adult hookworm infections (Ancylostoma caninum). For each study, dogs were allocated randomly based on pre-treatment adult flea and hookworm egg counts to one of four treatment groups of 10 animals each. In each study, spinosad and MO in combination, using the lower half (30-45 mg/kg spinosad; 0.5-0.75 mg/kg MO) of the US commercial dose band (30-60 mg/kg spinosad; 0.5-1.0mg/kg MO) of each active ingredient, or individually alone using the full dose range, were given orally to dogs on Day 0 using a tablet formulation. A placebo control was treated similarly. In one study, on Days -1, 5, 12, 19, 28 and 35 each dog was infested with approximately 100 unfed adult C. felis obtained from the investigator's established flea colony. All dogs were infested via the same method. Forty-eight hour post-infestation flea comb counts were conducted on Days 1, 7, 14, 21, 30 and 37 and were used to determine the knockdown and residual flea activity. In the second study, on Day -27 each of 48 dogs were experimentally inoculated with 100 third-stage infective larvae of the hookworm, A. caninum. Dogs were treated on Day 0 and necropsied on Day 7 or Day 8. All nematodes in the intestinal tract were collected on Day 7 or Day 8, identified and counted by species and stage. Post-treatment, the geometric mean live flea counts were significantly different (p-value<0.0001) between the spinosad/MO combination and the spinosad only treatment groups as compared to the vehicle control group. The flea counts in the MO only group and the control group were not statistically different. The spinosad and MO combination group and the spinosad only treatment group demonstrated significantly different knockdown (100%) and post-treatment residual flea efficacy at Day 30 was 100% for both groups as compared to the vehicle control. The presence of MO in combination with spinosad did not interfere with the flea efficacy of spinosad as compared to the spinosad only group. MO alone did not demonstrate any flea efficacy. Post-treatment, the geometric mean A. caninum worm counts were significantly different (p-value<0.0001) between the spinosad and MO combination group as compared to the vehicle control group. The worm counts in the MO only group and the combination group were not statistically different. The spinosad and MO combination group (99.8% reduction) and the MO only treatment group (99.5% reduction) both demonstrated significantly different hookworm efficacy as compared to the vehicle control group. The presence of spinosad in combination with MO did not interfere with the hookworm efficacy of MO as compared to the MO only group. Spinosad alone did not demonstrate any hookworm efficacy. In summary, flavored spinosad and MO combination tablets administered orally to dogs at the lower end (30-45 mg/kg spinosad; 0.5-0.75 mg/kg MO) of the US commercial tablet unit dose range (30-60 mg/kg spinosad; 0.5-1.0mg/kg MO) were both safe and highly efficacious delivering 100% knockdown and 30 days of residual adult flea control on experimentally infested dogs as well as >99% adult hookworm efficacy evaluated under laboratory conditions. Interference between either drugs was not demonstrated for both of these dose limiting parasites.     

Efficacy of selamectin against experimentally induced tick (Rhipicephalus sanguineus and Dermacentor variabilis) infestations on dogs

Seven controlled studies were conducted to investigate the efficacy of selamectin against weekly infestations of dogs with Rhipicephalus sanguineus and Dermacentor variabilis. Treatments (selamectin or vehicle alone) were applied topically at weekly, 2-week, or monthly intervals or in a "Monthly Plus" regimen (monthly treatment with an additional treatment at 14 days after the first treatment). Selamectin was supplied in unit dose tubes designed to deliver a minimum dosage of 6mgkg(-1). The studies ranged in duration from 37 to 90 days. Fifty adult ticks (+/-2) were applied approximately weekly, and tick counts were performed 3, 4, and 5 days after each infestation. The efficacy of selamectin was expressed as the percentage reduction in geometric mean tick counts on selamectin-treated dogs compared with those for dogs treated with the vehicle alone (negative-control). In one study, the engorgement of Dermacentor variabilis was assessed by weighing ticks after removal on the fifth day after each infestation. Weekly and 2-week interval treatments with selamectin provided efficacies against R. sanguineus of >89% across the entire study periods, with 100% efficacy being achieved from 21 days after the first dose and thereafter (study duration, 37 days for the weekly regimen and 44 days for the 2-week interval regimen). D. variabilis also was well controlled by the 2-week interval treatment regimen, with >96% efficacy being achieved from 21 days after the first treatment and thereafter until the end of the study (study duration: 90 days). In five of six studies incorporating three treatments at monthly intervals, the percentage reduction in R. sanguineus and D. variabilis counts 5 days after infestation ranged from 90 to 100% in the second and third months after treatment began. In the sixth study, reductions of > or =95% in D. variabilis counts 5 days after infestation were achieved for 2 weeks after each treatment in the second and third months. For the Monthly Plus regimen, from the second treatment (day 14) onwards, selamectin achieved 83-100% reductions in R. sanguineus and D. variabilis counts 3 days after infestation, and 94-100% reductions 5 days after infestation in three of the four studies. In the fourth study, selamectin demonstrated good efficacy against D. variabilis for 2 weeks after each treatment. In all seven studies, the counts from the selamectin-treated dogs were significantly (P< or =0.018) lower than those from the vehicle-treated dogs on 77 of the 80 assessments made 5 days after infestation. Selamectin also significantly (P< or =0.0105) reduced engorgement of female D. variabilis. These studies demonstrated that selamectin, administered topically to the skin in a single spot at a minimum dosage of 6mgkg(-1) at monthly intervals, was effective in the control of experimentally induced R. sanguineus and D. variabilis infestations on dogs.     

The efficacy of selamectin in the treatment of naturally acquired infestations of sarcoptes scabiei on dogs

Selamectin, a novel avermectin, was evaluated for its effect on naturally occurring infestations of Sarcoptes scabiei in 42 dogs. In two controlled and masked laboratory studies conducted in the USA and Italy, infested dogs received treatment with either selamectin (6mgkg(-1); range: 6-12mgkg(-1)) or the vehicle only (negative control). Treatments were administered topically to the skin on each animal's back at the base of the neck in front of the scapulae. Study day 0 was defined as the first day of treatment administration. Dogs were treated on days 0 and 30, and efficacy was assessed by counting viable mites recovered from skin scrapings performed on each dog on days 14, 29 or 30, 44, and 60, and by categorising the clinical signs of canine scabies on the same days. Percentage reductions in geometric mean mite counts for selamectin, compared with vehicle, on days 14, 29 or 30, 44, and 60 were > or =98.1, > or =93.5, 100, and 100%, respectively. Analysis of variance, confirmed by Savage Scores, showed that ln(mite counts+1) values for selamectin-treated dogs were significantly lower (P< or =0.0391) than those for vehicle-treated dogs on all post-treatment assessment days. Clinical signs of scabies were markedly reduced in selamectin-treated dogs, compared with vehicle-treated dogs. Topical administration to the skin in a single spot of a single unit dose of selamectin, or of two unit doses given 1 month apart, each providing at least the recommended minimum dosage of 6mgkg(-1), was highly effective against naturally acquired infestations of S. scabiei in dogs, reducing mite counts by >93% (single dose) and 100% (two doses).     

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.