Tonocard (Tocainide HCL): 400 mg, 600 mg Tablets

By | April 21, 2016

Tocainide HCL (Tonocard)

ORAL ANTIARRHYTHMIC

Highlights of Prescribing Information

  • Oral antiarrhythmic with similar activity as lidocaine; not commonly used in veterinary medicine
  • Contraindications: Hypersensitivity reactions to it or amide-type local anesthetics, 2nd or 3rd degree AV block & not being artificially paced. Caution: Heart failure, hematologic abnormalities, or preexisting bone marrow failure.
  • Adverse Effects: CNS effects (depression, ataxia, muscle tremors, etc.), nausea & vomiting (usually transient), cardiovascular effects (hypotension, bradycardia, tachycardia, other arrhythmias, & exacerbation of CHF)
  • Case reports of dogs on long-term therapy (>3 mos.) developing ocular & renal toxicity

What Is Drug Used For?

Veterinary experience with tocainide is limited. At this time, dogs are the only veterinary species where enough clinical experience has been garnered to recommend its use. It is indicated for the oral therapy of ventricular arrhythmias, principally ventricular tachycardia and ventricular premature complexes. In humans, response to lidocaine can usually predict whether tocainide might be effective.

Pharmacology / Actions

Tocainide is considered a class IB (membrane-stabilizing) antidysrhythmic agent that demonstrates rapid rates of attachment and dissociation to sodium channels. Like lidocaine, tocainide produces a dose-dependent decrease in potassium and sodium conductance that results in decreased excitability of myocardial cells. Automaticity, conduction velocity, and effective refractory periods are decreased at therapeutic levels. Little or no increases in PR intervals, QRS complexes, or QT intervals are seen at therapeutic levels. Like lidocaine, tocainide has little, if any effect, on autonomic tone.

Pharmacokinetics

Following oral administration, tocainide is rapidly and almost completely absorbed. 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 plasma levels 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 of distribution ranges from 1.5-4 L/kg and has been reported to be 1.7 L/kg in dogs. Tocainide is minimally 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 the kidneys into the urine. Alkalinization of the urine may result in a substantial decrease in the amount of tocainide that is excreted unchanged into the urine, but acidification of the urine reportedly does not enhance the excretion rate. Elimination half-life is dose-dependent and at the clinical doses used for dogs, not well-described.

Before you take Drug

Contraindications / Precautions / Warnings

Tocainide is contraindicated in patients who have demonstrated previous hypersensitivity reactions to it or amide-type local anesthetics, or who have 2nd or 3rd degree AV block and are not being artificially paced.

Use tocainide cautiously in patients with heart failure as it has the potential to aggravate the condition. Use with caution in patients with hematologic abnormalities or preexisting bone marrow failure.

Adverse Effects

It is expected that tocainide would exhibit a similar adverse reaction profile as lidocaine with anorexia, and vomiting being most likely. In dogs, tocainide serum concentrations of greater than 12 meg/ mL have been associated with neurotoxicity (ataxia, head tremor). There are case reports of dogs receiving tocainide for more than 3 months developing ocular (corneal dystrophy) and renal toxicity. Although side effects are common in human patients, they are usually dose related, 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 CHE Rarely (<1% incidence), clinical signs of bone marrow depression or pulmonary effects (pulmonary fibrosis, pneumonia, respiratory arrest, pulmonary edema, etc.) have been reported in humans.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)

Tocainide enters milk in significant quantities and may potentially cause adverse effects in nursing offspring.

Overdosage / Acute Toxicity

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 and symptomatic. For more information, see the Lidocaine monograph. Tocainide can be removed with hemodialysis.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving tocainide and may be of significance in veterinary patients:

■ ANTIARRHYTHMICS, OTHER CLASS IB (e.g., lidocaine, phenytoin, mexi-letine): Toxicities may be additive, with little or no therapeutic gain, if tocainide is used concurrently with other Class IB antidysrhythmics; use caution, when converting from one Class IB agent to another

■ CIMETIDINE (and other H2 blockers): May reduce tocainide bio-availability

■ METOPROLOL: Tocainide used concomitantly with metoprolol (a beta-adrenergic antagonist) can have additive effects on cardiac index and wedge pressure; may clinically significant, particularly in patients with sick sinus syndrome and impaired AV conduction

■ RIFAMPIN: May decrease tocainide effects by increasing metabolism

How to use Drug

Drug dosage for dogs:

  1. a) 10-20 mg/kg (up to 25 mg/kg) PO q8h ()
  2. b) 5-10 mg/kg PO three times daily ()
  3. c) 10-20 mg/kg PO q8h ()
  4. d) 10-20 mg/kg PO two to three times a day ()

Monitoring

■ ECG

■ Clinical signs of toxicity (see Adverse Reactions); may wish to monitor CBC’s if treating chronically (Note: For human patients, the manufacturer recommends weekly CBC’s with differential and platelets, be run at weekly intervals for the first 3 months of therapy and periodically thereafter)

■ Serum levels (therapeutic levels in humans are usually 3-10 mi-crograms/mL), especially if clinical signs of toxicity or lack of efficacy are noted.

Client Information

■ To be effective, the animal must receive all doses as prescribed

■ Notify veterinarian if the animal exhibits any abnormal bleeding or bruising, develops wheezing, shortness of breath, or a cough

■ If dog vomits or becomes anorexic after dosing, give with food; if vomiting persists or animal develops a change in behavior or attitude, contact veterinarian

Chemistry / Synonyms

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 is structurally related to lidocaine, but it is a primary amine where lidocaine is a tertiary amine. This modification allows tocainide to be resistant to extensive first-pass metabolism after oral administration.

Tocainide HCL may also be known as W-36095, Tonocard or Xylotocan.

Storage / Stability

Protect tablets from light and store in well-closed containers. An expiration date of 4 years after manufacture is assigned to the commercially available tablets when packaged in high-density polyethylene bottles.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Tocainide HCL Oral Tablets: 400 mg, 600 mg; Tonocard (Astra Merck); (Rx)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008