Safety evaluation of tocainide in the American emergency use program

Abstract This is a report of the safety evaluation of tocainide in the first 369 patients entered into the American Tocainide Emergency Use Program. This humanitarian protocol has made tocainide available for emergency use in the treatment of life-threatening, intractable ventricular arrhythmias in patients who were unresponsive to or unable to take the approved antiarrhythmic drugs. The most frequent adverse experiences reported were neurologic and gastrointestinal in nature and included dizziness, lightheadedness, tremors, nausea, vomiting, and anorexia. Adverse experiences resulted in the discontinuation of tocainide in 16% of these patients and were transient and reversible with no conclusive evidence of permanent organ injury. Adverse experiences having special relevance to the safety assessment of new antiarrhythmic agents are discussed, including congestive heart failure, arrhythmias and conduction disturbances, convulsions, lupus erythematosus-like illness, and deaths while on therapy. No significant abnormal trends were observed in routine hematologic and biochemical laboratory screening tests or in ophthalmologic or chest x-ray examinations. An evaluation of the effects of chronic tocainide administration on ECG intervals showed no significant change in P-R or QRS intervals but demonstrated a statistically significant decrease in Q-T duration. It is concluded that in patients with life-threatening ventricular arrhythmias, tocainide is a safe agent with a favorable risk-benefit ratio.