moxidectin and fipronil

For a number of reasons, several of the more 'traditional' ectoparasiticides in the small animal veterinarian's armoury have been withdrawn over the past few years. New, safer products which are long-acting and easier to apply than the conventional dips, rinses and aerosol sprays of the past have replaced them. However, relatively few such novel acaricidal preparations have become commercially available. Consequently, practitioners and researchers frequently experiment with the drugs they have at their disposal to assess their efficacy against a variety of target acarids when used at different dosages and/or via different routes of administration, compared with those recommended by the manufacturer. This paper reviews the anecdotal and peer-reviewed reports describing the use of modern acaricides in dogs and cats that have recently appeared in the veterinary literature. It should be stressed, however, that no medicine should be prescribed for extra-label use without the informed consent of the owner.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Cat Diseases; Cats; Clinical Trials as Topic; Dog Diseases; Dogs; Insecticides; Ivermectin; Macrolides; Mite Infestations; Mites; Pyrazoles; Scabies; Toluidines

Safety and efficacy of the combined monthly use of spot-on fipronil 6.76% w/v / permethrin 50.48% w/v (Frontline Tri-Act®) and chewable tablets of afoxolaner 1.9% w/w / milbemycin oxime 0.4% w/w (NexGard Spectra®) in dogs was evaluated in a field study over a period of 6 months.. Forty-one healthy dogs living in highly endemic area for canine leishmaniosis and other canine vector borne diseases (VBD) were included in the study at the beginning of the Leishmania transmission season. Sixteen dogs were pet dogs living each in a single household; twenty-five dogs were hunting dogs living in three kennels. At inclusion, the dogs were ELISA (rapid test) negative for antibodies to Anaplasma, Borrelia, Ehrlichia, and for antigens of Dirofilaria. The dogs were also negative for blood microfilariae at the Knott's test, and no clinical or haematological abnormalities were observed. Of the included dogs, six hunting, apparently healthy, dogs were ELISA (rapid test) positive to Leishmania, and some were naturally infected by gastrointestinal nematodes (58.5%) and/or infested by fleas (58.5%) and ticks (9.8%). All the included dogs were treated at Days 0, 28, 56, 84, 112 and 140, and followed-up for efficacy until the study end (Day 168).. No adverse events related to the two products, nor skin reactions, general signs, or changes in the haematological profile, were observed during the study. At Day 14, anthelminthic efficacy was 100% for Toxocara canis, Toxascaris leonina and Capillaria aerophila, while few hunting dogs were still shedding eggs of Trichuris vulpis (1/25 hunting dog) and Ancylostomatidae (9/25 hunting dogs). All pet dogs were nematode free at the end of the study. Hunting dogs were free of roundworms and whipworms. Twenty-four hours after the first treatment, 95.8% of the ectoparasite infested dogs were free from fleas and ticks. Ectoparasites were significantly controlled during the 6-month study period, with 100% efficacy on both fleas and ticks from Day 56 to Day 168. Blood and serum samples collected on Day 168 were tested for vector-borne pathogens using same methods of the inclusion and no new seroconversions or circulating blood microfilariae were observed.. Concomitant use of Frontline Tri-Act® and NexGard Spectra® in dogs for six months was well tolerated. The combination was effective in controlling fleas, ticks, gastro-intestinal nematodes, and neither new seroconversion to the tested vector-borne pathogens nor blood microfilariae were detected in treated dogs at the end of the study.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Female; Insect Vectors; Insecticides; Isoxazoles; Macrolides; Male; Naphthalenes; Parasitic Diseases, Animal; Permethrin; Pyrazoles

A spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) has been developed to provide broad spectrum parasite protection for cats. The effectiveness and safety of this product against ticks and fleas was assessed in a randomized, controlled, 12-week study in client-owned cats in Germany and Spain.. Eligible households containing at least one cat with at least two fleas and/or two ticks were allocated randomly in a 2:1 ratio to a single treatment with fluralaner plus moxidectin on Day 0, or three 4-weekly treatments with fipronil (Frontline®). Veterinary staff, masked to treatment, completed tick and flea counts on each cat at 14 ± 2 (2 weeks), 28 ± 2 (4 weeks), 56 ± 2 (8 weeks) and 84 ± 2 days (12 weeks) after the initial treatment.. In total, 707 cats (257 with ticks) from 332 households (236 with fleas) were included. Ixodes ricinus (78%) and Rhipicephalus sanguineus complex (18%) ticks were the most commonly identified. Tick and flea counts were lower in the fluralaner plus moxidectin group than in the fipronil group throughout the study and the efficacy of fluralaner plus moxidectin exceeded 97 and 98%, respectively. At 12 weeks, 94.1 and 93.3% of cats from the fluralaner plus moxidectin and 92.2 and 60.3% of cats from the fipronil group were free of ticks and fleas, respectively. Fluralaner plus moxidectin was non-inferior to fipronil (P < 0.0001) at all assessments and superior to fipronil at 2 and 8 weeks for the proportion of cats free of ticks (P < 0.0001). Fluralaner plus moxidectin was superior to fipronil for the proportion of both households and cats free of fleas (P < 0.0001). Both products were safe and well tolerated.. A single application of fluralaner plus moxidectin spot-on was well tolerated by cats and highly effective for 12 weeks against ticks and fleas. Fluralaner plus moxidectin was non-inferior to fipronil for the proportion of ectoparasite-free and consistently superior to fipronil in controlling fleas.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Flea Infestations; Germany; Insecticides; Isoxazoles; Ixodes; Macrolides; Ownership; Pyrazoles; Random Allocation; Rhipicephalus sanguineus; Single-Blind Method; Spain; Tick Infestations; Treatment Outcome

Topics: Administration, Topical; Animals; Antiparasitic Agents; Cat Diseases; Cats; Europe; Female; Flea Infestations; Imidazoles; Isoxazoles; Ivermectin; Macrolides; Male; Neonicotinoids; Nitro Compounds; Pyrazoles; Tick Infestations; Treatment Outcome

Invertebrate ligand-gated chloride channels are well recognized as important targets for several insecticides and anthelmintics. Hco-UNC-49 is a GABA-gated chloride channel from the parasitic nematode Haemonchus contortus and is an orthologue to the neuromuscular receptor (Cel-UNC-49) from the free-living nematode Caenorhabditis elegans. While the receptors from the two nematodes are similar in sequence, they exhibit different sensitivities to GABA which may reflect differences in in vivo function. The aim of the current study was to further characterize the pharmacology of the Hco-UNC-49 receptor by examining its sensitivity to various insecticides and anthelmintics using two-electrode voltage clamp. Specifically, the insecticides fipronil and picrotoxin appear to inhibit the channel in a similar manner. The IC(50) of picrotoxin on the homomeric channel was 3.65 ± 0.64 μM and for the heteromeric channel was 134.56 ± 44.12 μM. On the other hand, dieldrin, a well-known insect GABA receptor blocker, had little effect on the UNC-49 channel. The anthelmintics ivermectin and moxidectin both moderately potentiated the activation of Hco-UNC-49 by GABA, while piperazine was able to directly activate both the Hco-UNC-49 homomeric and heteromeric channels with EC(50) values of 6.23 ± 0.45 mM and 5.09 ± 0.32 mM, respectively. This piperazine current was reversibly blocked by picrotoxin which demonstrates that the anthelmintic specifically targets Hco-UNC-49. These results demonstrate that Hco-UNC-49 exhibits binding sites for several molecules including piperazine and macrocyclic lactone anthelmintics. In addition, this is the first report of the heterologous expression and subsequent characterization of a receptor for piperazine.

Topics: Animals; Anthelmintics; Chloride Channels; gamma-Aminobutyric Acid; Gene Expression Regulation; Haemonchus; Helminth Proteins; Insecticides; Ion Channel Gating; Ivermectin; Lactams, Macrocyclic; Macrolides; Oocytes; Picrotoxin; Piperazine; Piperazines; Pyrazoles; Receptors, Cell Surface; Xenopus laevis