pyrantel and Dirofilariasis

Assessment of the safety of heartworm preventatives in dogs with pre-existing patent heartworm (Dirofilaria immitis) infections is necessary because rapid adult worm and microfilarial death can lead to severe clinical complications, including thromboembolism and anaphylactic shock in dogs. The aim of this study was to determine the clinical safety of Simparica Trio. Twenty-four laboratory Beagle dogs were implanted with 10 male and 10 female D. immitis (ZoeKY isolate), and once infection was patent, they were randomized equally among three groups to receive no treatment, 1× or 3× the maximum recommended label dose of Simparica Trio. Dogs in the treated groups received Simparica Trio on days 0, 28 and 56. In-life assessments included body weight, physical examinations, clinical observations, daily general health observations, a quantitative estimate of food consumption and blood collections for pharmacokinetic (PK) analysis, microfilariae (MF) counts and D. immitis antigen testing. At the end of the study the heart, lungs and pleural and peritoneal cavities were examined for adult D. immitis worms.. Simparica Trio was generally well tolerated. Emesis occurred at low frequency in all groups including control. Abnormal stool occurred occasionally in the 1× and 3× groups throughout the 3-month study. Fever (> 104 °F/40 °C) was recorded in one 1× and one 3× dog 1 day after the first dose and resolved by the following day. No severe hypersensitivity reactions occurred. The mean number of circulating microfilariae (MF) counts in the control group increased from 12,000/ml at study start (Day 0) to > 20,000/ml at Day 28 and remained > 20,000/ml for the duration of the study. The least squares means of circulating MF were reduced by 69.8% on Day 1 and 97.4% on Day 7 for the 1× group and remained at > 99% lower than the control group for the remainder of the study. Similarly, least squares means of circulating MF were reduced by 85.3% on Day 1 and 93.9% on Day 7 for the 3× group and remained > 98% lower than the control group for the remainder of the study. At the end of the study, the mean number of implanted adult worms recovered was < 10 per sex in all groups with 90%, 85% and 75% of live adult heartworms recovered in control, 1× and 3× treatment groups, respectively. Low numbers of dead adult worms were recovered in 1× and 3×, with none in control. Following each dose, the moxidectin and sarolaner AUC and C. This study demonstrated that Simparica Trio (sarolaner, pyrantel, moxidectin) was well tolerated when administered to heartworm-positive dogs at 1× and 3× the maximum recommended dose at 28-day intervals for 3 consecutive months. Simparica Trio significantly reduced microfilaria counts in both treatment groups, without significant clinical consequences. At the doses administered, Simparica Trio had minor adulticidal activity but resulted in no clinical sequelae.

Topics: Administration, Oral; Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Female; Macrolides; Male; Microfilariae; Pyrantel; Treatment Outcome

Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.. In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D. immitis larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24 µg/kg moxidectin, 2 mg/kg sarolaner and 5 mg/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24 µg/kg) or sarolaner-alone (2 mg/kg). Efficacy was evaluated ~ 5 months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs ≥ 8 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24-48 µg/kg moxidectin, 2-4 mg/kg sarolaner and 5-10 mg/kg pyrantel (n = 272) or Heartgard® Plus (ivermectin/pyrantel) at the label recommended dose rate (n = 138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection.. In the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20-44 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard® Plus tested positive. The Heartgard® Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies.. In laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard® Plus tested positive.

Topics: Administration, Oral; Animals; Antinematodal Agents; Azetidines; Chemoprevention; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Therapy, Combination; Macrolides; Placebos; Pyrantel; Spiro Compounds; Treatment Outcome; United States

This trial was conducted to test the efficacy of ivermectin/pyrantel chewables in preventing the development of Dirofilaria repens in dogs. The trial included 155 dogs from an endemic area in North-Western Italy. Prior to enrollment in the study, none of the dogs had microfilariae of D. immitis or D. repens in a concentration test, and all dogs were also seronegative for adult heartworm antigen. Animals remained with their owners and were dosed six times, at monthly intervals according to body weight. Efficacy against D. repens was evaluated approximately 6 and 12 months after the first dosing. None of the treated dogs was found to harbour microfilariae of D. repens or D. immitis on either occasion, whereas 6 of 24 untreated controls had circulating D. repens microfilariae at the final testing. The treatment was well accepted by all dogs.

Topics: Administration, Oral; Animals; Dirofilariasis; Dog Diseases; Dogs; Filaricides; Ivermectin; Mastication; Pyrantel

Several reports have confirmed that macrocyclic lactone-resistant isolates of Dirofilaria immitis are circulating in the United States; however, the prevalence and potential impact of drug resistance is unknown. We wished to assess computer-aided measurements of motility as a method for rapidly assessing the resistance status of parasite isolates.. Blood containing microfilariae (MF) from two clinical cases with a high suspicion of resistance was fed to mosquitoes and the resultant L3 injected into dogs that were then treated with six doses of Heartgard® Plus (ivermectin + pyrantel; Merial Limited) at 30-day intervals. In both cases patent heartworm infections resulted despite the preventive treatment. Microfilariae isolated from these dogs and other isolates of known resistance status were exposed to varying concentrations of ivermectin in vitro and their motility assessed 24 h later using computer-processed high-definition video imaging.. We produced two isolates, Yazoo-2013 and Metairie-2014, which established patent infections despite Heartgard® Plus treatments. Measurements of the motility of MF of these and other isolates (Missouri, MP3 and JYD-27) following exposure to varying concentrations of ivermectin did not distinguish between susceptible and resistant heartworm populations. There was some evidence that the method of MF isolation had an influence on the motility and drug susceptibility of the MF.. We confirmed that drug-resistant heartworms are circulating in the southern United States, but that motility measurements in the presence of ivermectin are not a reliable method for their detection. This implies that the drug does not kill the microfilariae via paralysis.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Drug Resistance; Filaricides; Ivermectin; Microfilariae; Pyrantel

This study was designed to evaluate the efficacy of prolonged monthly ivermectin treatment against Dirofilaria immitis in client-owned dogs with naturally acquired infections and to clinically monitor the animal's response to the slow killing of heartworms, with death of the worms distributed over a period of up to 2 years. A total of 17 male and female dogs of different breeds and ages were used. Prior to treatment, all of the dogs tested positive for heartworm antigen (Ag) and all but two had microfilariae (mf). The dogs were randomly allocated to one group of seven dogs which received a commercial formulation of ivermectin (minimum, 6 mcg IVM/kg) plus pyrantel (minimum, 5 mg PP/kg) (Heartgard Plus Chewables, Merial, Ltd.), another group of seven dogs which received a commercial formulation of IVM (min, 6 mcg/kg) (Heartgard Chewables, Merial Ltd.), and a group of three dogs which served as an untreated controls. All dogs were evaluated prior to initiation of treatment and thereafter at 3- to 5-month-intervals for mf, Ag, and radiographic and echocardiographic findings. All of the 17 dogs, with the exception of two dogs in the IVM group, had circulating mf of D. immitis prior to the 1st monthly dose, and a few also had mf of Dirofilaria repens. After 4 monthly doses, only one dog in the IVM/PP group and two dogs in the IVM group had a patent heartworm infection, and no heartworm mf were seen in the 14 treated dogs thereafter. After 10 monthly doses, the number of Ag-positive dogs in both of the treated groups decreased gradually. Efficacy, based on the reduction in number of Ag-positive dogs, was similar for the IVM/PP and IVM groups, with overall efficacy scores for the 14 dogs of 21, 21, 43, and 71% after 10, 14, 19, and 24 monthly doses, respectively. Two of the seven dogs treated with IVM/PP, one of the seven treated with IVM, and two of the three untreated controls showed echocardiographic evidence of a parasitic burden prior to treatment, and all of these scores had decreased by the end of the study. Only one dog (IVM/PP group) had a cardiovascular pattern of heartworm disease by echocardiography prior to treatment, but this dog's score increased to two and the scores of two additional dogs increased from zero to two (IVM group) or three (IVM/PP group) by the end of the study. Only 1 (IVM/PP group) of the 17 dogs showed a pulmonary pattern of heartworm disease by radiography prior to treatment, but this dog's score increased to three by the end of

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Filaricides; Ivermectin; Male; Pyrantel; Random Allocation; Time Factors; Treatment Outcome