"Potential drug treatments are tested on paper, in laboratories and eventually in thousands of people. But every drug that goes through this cycle â€“ every drug that FDA approves â€“ carries some risk. One of the first lines of defense against "...
(Generic versions may still be available.)
Tocainide, like lidocaine, produces dose dependent decreases in sodium and potassium conductance, thereby decreasing the excitability of myocardial cells. In experimental animal models, the dose-related depression of sodium current is more pronounced in ischemic tissue than in normal tissue.
Tocainide is a Class I antiarrhythmic compound with electrophysiologic properties in man similar to those of lidocaine, but dissimilar from quinidine, procainamide, and disopyramide.
In studies of isolated dog Purkinje fibers, tocainide in concentrations of 1-50 mcg/mL had no significant effect on resting membrane potential, but reduced the amplitude and rate of depolarization (dv/dt) of the action potential. Tocainide decreased the effective refractory period (ERP) to a lesser extent than the action potential duration (APD) resulting in an increase in the ERP/APD ratio.
In patients with cardiac disease, TONOCARD (tocainide hcl) produced no clinically significant changes in sinus nodal function, effective refractory periods, or intracardiac conduction times when studied under electrophysiologic testing procedures.
Tocainide, like lidocaine, characteristically does not prolong ventricular depolarization (QRS duration) or repolarization (QT intervals) as measured by electrocardiography. Theoretically, therefore, TONOCARD (tocainide hcl) may be useful in the treatment of ventricular arrhythmias associated with a prolonged QT interval.
Patients who respond to lidocaine also respond to TONOCARD (tocainide hcl) in a majority of cases. Failure to respond to lidocaine usually predicts failure to respond to TONOCARD, (tocainide hcl) but there are exceptions to this.
In a controlled comparison with quinidine, 600 mg b.i.d. of TONOCARD (tocainide hcl) produced a mean reduction of 42 percent in PVC count, compared to a 54 percent reduction by quinidine 300 mg every 6 hours. Among all patients entered into the study, about one-fifth of tocainide recipients and one-third of quinidine recipients had 75 percent or greater reductions in PVC count or had elimination of ventricular tachycardia.
Following oral administration of tocainide, peak plasma concentrations occur within 0.5 to 2 hours. The average plasma half-life in patients is approximately 15 hours. Although the effective plasma concentration may vary from patient to patient, the usual therapeutic plasma range (as defined by 50-80 percent PVC suppression) is 4-10 mcg/mL (18-45 micromole/L), expressed as tocainide hydrochloride. Tocainide is approximately 10 percent bound to plasma protein.
In contrast to lidocaine, tocainide undergoes negligible first pass hepatic degradation. Following oral administration, the bioavailability of TONOCARD (tocainide hcl) approaches 100 percent. The extent of its bioavailability is unaffected by food. Tocainide has no cardioactive metabolites. Approximately 40 percent of the administered dose of tocainide is excreted unchanged in the urine. Acidification of the urine has not been shown to significantly alter tocainide excretion in the urine, but alkalinization of the urine results in a significant decrease in the percent of tocainide excreted unchanged in the urine. Animal data indicate that tocainide crosses the blood-brain barrier; however, it has less lipid solubility than lidocaine.
Cardiac catheterization studies in man utilizing intravenous tocainide infusions (0.5-0.75 mg/kg/mm over 15 min) have shown that tocainide usually produces a small degree of depression of parameters of left ventricular function, such as left ventricular dP/dt, and left ventricular end diastolic pressure. There were usually no changes in cardiac output or clinical evidence of increasing congestive heart failure in the well-compensated patients studied. Small but statistically significant increases in aortic and pulmonary arterial pressures have been consistently observed and are probably related to small increases in vascular resistance. When used concomitantly with a beta-blocking drug, tocainide further reduced cardiac index and left ventricular dP/dt and further increased pulmonary wedge pressure.
No clinically significant changes in heart rate, blood pressure, or signs of myocardial depression were observed in a study of 72 post-myocardial infarction patients receiving long-term therapy with oral TONOCARD (tocainide hcl) at usual doses (400 mg q8h). When tocainide was administered orally at a dose of 120 mg/kg to anesthetized dogs (14 times the initial maximum dose recommended for humans), a negative inotropic effect was observed: the rate of change of left ventricular pressure decreased by up to 29 percent of control at 3 hours after administration. This effect was not observed at lower doses (60 mg/kg). Tocainide has been used safely in patients with acute myocardial infarction and various degrees of congestive heart failure. It has, however, a small negative inotropic effect and can increase peripheral resistance slightly. It therefore should be used cautiously in patients with known heart failure, particularly if a beta-blocker is given as well. (See PRECAUTIONS.)
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
Additional Tonocard Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.