Efficacy and toxicity of tocainide for the treatment of ventricular tachyarrhythmias in Doberman pinschers with occult cardiomyopathy.

Abstract

Tocainide was administered to 23 cardiomyopathic Doberman Pinschers at doses of 15 to 25 mg/kg tid. These doses produced peak (2-hour) serum concentrations of 6.2 to 19.1 mg/L and trough (8-hour) serum concentrations of 2.3 to 11.1 mg/L. Anorexia and gastrointestinal disturbances occurred in 8 dogs (35%) at doses (15.6 to 25.0 mg/kg) that were not different from those (16.0 to 26.0 mg/kg) received by dogs that did not experience toxicity. Doses producing peak serum concentrations that were either greater or less than 14 mg/L were not different. Likewise, doses producing trough values that were either greater or less than 6 mg/L were not different. The mean dose that produced peak serum concentrations of 10 to 13.6 mg/L and trough concentrations of 4.2 to 10.0 mg/L was 17.9 mg/kg, and was associated with anorexia in 4 dogs. Mean peak serum concentrations associated with toxicity (14.4 mg/L) were significantly higher (P = .02) than dogs not experiencing toxicity (11.8 mg/L). Serious adverse effects occurred in 7 of 12 dogs (58%) receiving tocainide for longer than 4 consecutive months. Progressive corneal endothelial dystrophy occurred in 3 dogs. Although a causal effect could not be proven, 6 dogs experienced renal dysfunction during treatment. Drug doses in these 7 dogs were similar to those received by other dogs. At least a 70% reduction of the total numbers of ventricular premature contractions occurred in 80% of dogs treated, and ventricular tachycardia was eliminated in 90% of affected dogs by the time of the first posttreatment Holter recording. Long-term control of ventricular tachyarrhythmias was difficult to achieve in some dogs when the left ventricular shortening fraction was less than approximately 17%.