metaflumizone and Tick-Infestations

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated in four laboratory studies to confirm efficacy against fleas and ticks on dogs for 1 month. Three different strains of cat flea (Ctenocephalides felis felis) and four tick species were used. Rhipicephalus sanguineus and Dermacentor variabilis were evaluated concurrently in two studies and Ixodes scapularis and Amblyomma americanum in one study each. In all studies, dogs were randomly allocated to treatment groups and compared with nontreated dogs. One study also included a placebo treatment and a commercial product containing fipronil plus S-methoprene. All treatments were applied to the skin at a single spot between the scapulae on Day 0. Dogs were infested with fleas and/or ticks prior to treatment and then reinfested at weekly intervals for 6 weeks after treatment and evaluated for efficacy at 1 or 2 days after treatment and each reinfestation. These studies confirmed that treatment with ProMeris for Dogs at the proposed commercial dose rate rapidly controlled existing infestations of fleas and ticks on dogs. Treatment provided control of reinfesting fleas for up to 6 weeks and at least 4 weeks control of ticks. Efficacy was confirmed in a variety of dog breeds against three different flea strains and four common species of ticks found on dogs in the United States.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Ixodidae; Male; Semicarbazones; Siphonaptera; Tick Control; Tick Infestations; Toluidines

Four laboratory studies were conducted in Beagle dogs to evaluate the safety of a novel ectoparasiticide combination of metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) when applied according to the recommended dosage of >/=20mgmetaflumizonekg(-1) plus >/=20mgamitrazkg(-1), at exaggerated and repeated dosages, and if accidentally orally ingested. Parameters evaluated included body weight, food consumption, clinical, physical and neurological examinations, clinical pathology and gross and microscopic pathology. Exaggerated and repeated topical treatment with metaflumizone plus amitraz administered at 1x, 3x and 5x the recommended dose had no effect on clinical findings, heart rates, body weight, food consumption, physical/neurological examinations, macroscopic and microscopic pathology. Very slight, transient, clinically insignificant increases in serum urea nitrogen were noted in some dogs treated at all dose rates tested. This effect was not persistent, was not dose-responsive, nor aggravated by repeated applications and was not associated with a corresponding increase in creatinine or renal pathology. Therefore, these increases in urea nitrogen were suspected to be of non-renal origin and were not considered toxicologically significant. Exaggerated doses (3x and 5x) caused very mild, transient hyperglycemia, most notably in some adult females. Transient and inconsistently noted mild increases in leukocytes, neutrophils and monocytes were observed in some 3x and 5x treated dogs at some intervals. None of the effects noted were aggravated by repeated administration. When 10% of the recommended topical dose was orally administered to mimic exposure due to licking the application, avoidance behaviors including spitting, head shaking, and salivation were noted immediately in all animals. Consequently, voluntary oral ingestion is considered unlikely. Transient decreased activity, slightly reduced body temperature and pale oral mucous membranes were noted in some animals beginning 1-2h posttreatment. Ataxia, resolving within 4h posttreatment, was noted in one female. Oral administration had no effect on clinical pathology. Results from these four studies indicate repeated use of metaflumizone plus amitraz causes no adverse health effects when used as recommended in dogs as young as 8 weeks of age.

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Drug-Related Side Effects and Adverse Reactions; Ectoparasitic Infestations; Female; Insect Control; Insecticides; Male; Semicarbazones; Tick Control; Tick Infestations; Toluidines

A novel spot-on formulation containing metaflumizone and amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated in a laboratory study to determine the appropriate dose for efficacy against fleas and ticks on dogs for 1 month. Thirty-six Beagles were randomly allocated to six equal groups and individually housed. One group remained nontreated. Another was treated with a placebo formulation (solvents with no active ingredients). Three groups of dogs were treated topically with the metaflumizone plus amitraz formulation (150mg of each of metaflumizone and amitraz/ml), at volumes providing doses of 10, 20 and 40mgeachactive/kg. The final group was treated with a commercial spot-on providing 6.7mgfipronil/kg. All treatments were applied to the skin at a single spot between the scapulae on Day 0. Dogs were infested with 50 adult brown dog ticks (Rhipicephalus sanguineus) on each of Days -2, 5, 12, 19, 26, 33 and 40, and with 100 cat fleas (Ctenocephalides felis felis) on Days -1, 6, 13, 20, 27, 34 and 41. Dogs were examined and parasites "finger counted" on Day 1 to estimate knock down efficacy, and all animals were comb counted to determine the numbers of viable fleas and ticks on Days 7, 14, 21, 28, 35 and 42. There were no significant differences in parasite counts between the nontreated control and the placebo-treated control groups for either fleas or ticks (P>0.05) except for very slight reductions on Day 7 for fleas and Day 14 for ticks, demonstrating that the formulation excipients had no activity. The qualitative finger counts on Day 1 indicated that all of the insecticidal treatments resulted in a noticeable reduction in flea and tick numbers within 1 day of treatment. All of the metaflumizone and amitraz treatments and fipronil resulted in significantly lower flea and tick numbers relative to nontreated controls on all posttreatment count days (P<0.05). For the metaflumizone plus amitraz treatments, mean flea and tick counts for the 10mg/kg dose were significantly higher than those for the 20mg/kg dose (P<0.05) from Day 21 on. There was no significant advantage provided by the 40mg/kg dose over the 20mg dose throughout the entire study (P>0.05). The two higher metaflumizone plus amitraz doses provided >95% control of fleas and >90% control of ticks for at least 35 days after treatment, and this level of control was similar to that of the commercial fipronil product. The 20mg/kg dose was selected as the min

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Drug Combinations; Ectoparasitic Infestations; Insect Control; Insecticides; Rhipicephalus sanguineus; Semicarbazones; Siphonaptera; Tick Control; Tick Infestations; Toluidines

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.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ectoparasitic Infestations; Europe; Female; Insecticides; Male; Pyrazoles; Random Allocation; Semicarbazones; Tick Infestations; Toluidines; Water

A topical spot-on solution was developed for treating pets that contained of active ingredients metaflumizone and amitraz and intended for use as an ectoparasiticide. The formulation vehicle system was designed by balancing the following three attributes of various solvents: evaporation/drying, surface spreading, and percutaneous absorption. The solvents were selected by evaluating the solubilization capacity of individual solvents with respect to the above active ingredients. The evaporation rates of various solvent systems were then determined. The visual observations of the treatment sites was also performed a day after treating the dogs to understand the cosmetic effect of various solvent systems. The lead formulations dried off within a day after application with no noticeable residue at the treatment site, while others produced appreciable powdery residue or a large wet and oily spot. The stability of the lead formulations was also evaluated over 2 years to demonstrate a 2-year shelf life of this product.

Topics: Administration, Topical; Animals; Dog Diseases; Dogs; Drug Combinations; Drug Stability; Ectoparasitic Infestations; Female; Insecticides; Male; Semicarbazones; Solubility; Solvents; Tick Infestations; Time Factors; Toluidines