TOCAINIDE HCL
Chemistry - An amide-type local anesthetic, tocainide HCl occurs as a bitter-tasting, white, crystalline powder with a pKa of 7.8. It is freely soluble in both water and alcohol. Tocainide isstructurally related to lidocaine, but it is a primary amine where lidocaine is a tertiary amine. Thismodification allows tocainide to be resistant to extensive first-pass metabolism after oraladministration.
An expiration date of 4 years after manufacture is assigned to the commercially available tabletswhen packaged in high-density polyethylene bottles.
QRS complex, or QT interval is seen at therapeutic levels. Like lidocaine, tocainide has little, if anyeffect, on autonomic tone.
Unlike lidocaine, the hepatic first-pass effect is minimal with tocainide. In humans, peak plasmalevels occur between 0.5-2 hours when administered on an empty stomach.
The distribution aspects of tocainide have not been fully described. In humans, the volume ofdistribution ranges from 1.5 - 4 L/kg and has been reported to be 1.7 L/kg in dogs. Tocainide isminimally bound to plasma proteins. It is unknown if it crosses the placenta or enters into the milk.
Tocainide is metabolized by the liver, but up to 50% of a dose is excreted unchanged by thekidneys into the urine. Alkalinization of the urine may result in a substantial decrease in the amountof tocainide that is excreted unchanged into the urine, but acidification of the urine reportedly doesnot enhance the excretion rate.
Contraindications/Precautions - Tocainide is contraindicated in patients who have demonstratedprevious hypersensitivity reactions to it or amide-type local anesthetics, or who have 2nd or 3rddegree AV block and are not being artificially paced.
Use tocainide cautiously in patients with heart failure as it has the potential to aggravate thecondition. Use with caution in patients with hematologic abnormalities or preexisting bone marrowfailure.
Cardiovascular effects reported include hypotension, bradycardia, tachycardia, other arrhythmias, and exacerbation of CHF. Rarely (<1% incidence), symptoms of bone marrow depression orpulmonary effects (pulmonary fibrosis, pneumonia, respiratory arrest, pulmonary edema, etc.) havebeen reported in humans.
Overdosage - Dogs tend to be rather resistant to the acute toxic effects of the drug. In one study, dogs were administered 750 mg/kg over 6 hours and emesis was the only frequent effect seen, but
ECG changes were also seen in some animals.
There is no specific antidote for tocainide overdose and treatment tends to be supportive andsymptomatic. For more information, see the Lidocaine monograph. Tocainide can be removed withhemodialysis.
Use caution, when converting from one Class IB agent to another.
Tocainide used concomitantly with metoprolol (a beta-adrenergic antagonist) can have additiveeffects on cardiac index and wedge pressure. This may clinically significant, particularly in patientswith sick sinus syndrome and impaired AV conduction. Because experience with tocainide is stilllimited, use caution when administering to patients on multiple-drug therapy.
Storage, Stability, Compatibility
Protect tablets from light and store in well-closed containers.An expiration date of 4 years after manufacture is assigned to the commercially available tabletswhen packaged in high-density polyethylene bottles.
Pharmacology - TOCAINIDE HCL
Tocainide is considered to be a class IB (membrane-stabilizing) antidysrhythmicagent which demonstrates rapid rates of attachment and dissociation to sodium channels. Likelidocaine, tocainide produces a dose-dependent decrease in potassium and sodium conductancewhich results in decreased excitability of myocardial cells. Automaticity, conduction velocity andeffective refractory periods are decreased at therapeutic levels. Little or no increases in PR interval,QRS complex, or QT interval is seen at therapeutic levels. Like lidocaine, tocainide has little, if anyeffect, on autonomic tone.
Uses, Indications
Tocainide is a relatively recent addition to the armamentarium, and veterinaryexperience with it is quite limited. At this time, dogs are the only veterinary species where enoughclinical experience has been garnered to recommend its use. It is indicated for the oral therapy ofventricular arrhythmias, principally ventricular tachycardia and ventricular premature complexes. Inhumans, response to lidocaine can usually predict whether tocainide might be effective.Pharmacokinetics - TOCAINIDE HCL
Following oral administration, tocainide is rapidly and almost completelyabsorbed. The presence of food in the stomach may alter the rate, but not the extent of absorption.Unlike lidocaine, the hepatic first-pass effect is minimal with tocainide. In humans, peak plasmalevels occur between 0.5-2 hours when administered on an empty stomach.
The distribution aspects of tocainide have not been fully described. In humans, the volume ofdistribution ranges from 1.5 - 4 L/kg and has been reported to be 1.7 L/kg in dogs. Tocainide isminimally bound to plasma proteins. It is unknown if it crosses the placenta or enters into the milk.
Tocainide is metabolized by the liver, but up to 50% of a dose is excreted unchanged by thekidneys into the urine. Alkalinization of the urine may result in a substantial decrease in the amountof tocainide that is excreted unchanged into the urine, but acidification of the urine reportedly doesnot enhance the excretion rate.
Contraindications/Precautions - Tocainide is contraindicated in patients who have demonstratedprevious hypersensitivity reactions to it or amide-type local anesthetics, or who have 2nd or 3rddegree AV block and are not being artificially paced.
Use tocainide cautiously in patients with heart failure as it has the potential to aggravate thecondition. Use with caution in patients with hematologic abnormalities or preexisting bone marrowfailure.
Adverse Effects, Warnings
It is expected that tocainide would exhibit a similar adverse reactionprofile as lidocaine. Although side effects are common in human patients, they are usually doserelated, mild, and reversible upon discontinuation of the drug. CNS effects can include drowsiness, depression, ataxia, muscle tremors, etc. Nausea and vomiting may occur, but are usually transient.Cardiovascular effects reported include hypotension, bradycardia, tachycardia, other arrhythmias, and exacerbation of CHF. Rarely (<1% incidence), symptoms of bone marrow depression orpulmonary effects (pulmonary fibrosis, pneumonia, respiratory arrest, pulmonary edema, etc.) havebeen reported in humans.
Overdosage - Dogs tend to be rather resistant to the acute toxic effects of the drug. In one study, dogs were administered 750 mg/kg over 6 hours and emesis was the only frequent effect seen, but
ECG changes were also seen in some animals.
There is no specific antidote for tocainide overdose and treatment tends to be supportive andsymptomatic. For more information, see the Lidocaine monograph. Tocainide can be removed withhemodialysis.
Drug Interactions
Toxicities may be additive, with little or no therapeutic gain, if tocainide isused concurrently with other Class IB antidysrhythmics (e.g., lidocaine, phenytoin, mexiletine).Use caution, when converting from one Class IB agent to another.
Tocainide used concomitantly with metoprolol (a beta-adrenergic antagonist) can have additiveeffects on cardiac index and wedge pressure. This may clinically significant, particularly in patientswith sick sinus syndrome and impaired AV conduction. Because experience with tocainide is stilllimited, use caution when administering to patients on multiple-drug therapy.