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Adverse reactions to oral administration of milbemycin oxime were investigated in heartworm (hw)-free and hw-infected dogs given either the minimal hw prophylactic dose (0.25 mg/kg of body weight) or the hookworm anthelmintic dose (0.5 mg/kg). In 12 hw-free control dogs treated with lactose excipient (100 mg/kg), abnormal signs were not observed. There were no differences between the 2 doses in prevalence of clinical signs of disease and laboratory test results. In 60 hw-free dogs (50 dogs administered the low dose, and 10 dogs given the high dose) and 46 nonmicrofilaremic hw-infected dogs (35 dogs administered the low dose, and 11 dogs given the high dose), only a transient and slight paleness of the visible mucous membranes, intestinal hyperperistalsis, or both were observed in some dogs. In 77 microfilaremic (mf) dogs (41 dogs administered the low dose, and 36 dogs given the high dose), weakness or loss of appetite was observed in 13 dogs (16.9%). Paleness of the visible mucous membranes was observed in 16 dogs (20.8%), intestinal hyperperistalsis was observed in 27 dogs (35.1%), and respiratory signs, such as mild labored respiration, were observed in 13 dogs (16.9%). Dullness of heart sounds was noticed in 4 dogs (5.2%). In 12 (9 dogs administered the low dose, and 3 dogs given the high dose) of 89 mf dogs (13.5%), adult heartworms migrated from the pulmonary arteries to the right atrium, causing signs of caval syndrome, including heart murmurs, jugular pulsations, and weakness.

C and neutrophil counts increased slightly at 3 hours. Serum alanine transaminase, alkaline phosphatasIn hw-free dogs, rectal temperature tended to decrease gradually, and heart and respiratory rates were transiently decreased. Mean blood pressure, rbc count, serum total protein concentration, serum osmolality, and serum sodium (Na) and potassium (K) concentrations decreased 3 or 6 hours after administration. The total WBe, and lactate dehydrogenase activities did not change significantly. In hw-infected, nonmicrofilaremic dogs, trends in laboratory changes were almost the same as those in hw-free dogs.

In mf dogs, circulating microfilaria count decreased starting at 6 hours after treatment. Heart rate, rbc count, and serum total protein concentration decreased transiently, similar to values in hw-free dogs. Rectal temperature, respiratory rate, and serum enzyme activities increased, and neutrophil and eosinophil counts, serum osmolality, and serum Na and K concentrations decreased. Changes in test results for dogs with hw migration were almost the same as those in mf hw-infected dogs.

Heartworm-free and nonmicrofilaremic hw-infected dogs did not have clinically relevant problems after treatment with milbemycin oxime. Administration of milbemycin oxime does not involve risks for these dogs. However, reactions in mf dogs appear to be related to the death of microfilariae, and caution must be used when these dogs are treated with this compound.

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in American Journal of Veterinary Research