DESCRIPTION

The class IC antidysrhythmic agents include flecainide, propafenone, and moricizine.

FORMS AND USES

• Antidysrhythmic class IC agents are used in the treatment of life-threatening ventricular dysrhythmia.
• Flecainide (Tanbocor, in 50-, 100-, and 150-mg tablets). Adult dose is 100 to 200 mg twice daily. Pediatric dose is 100 to 200 mg/m²/day or 1 to 8 mg/kg/day in divided doses.
• Propafenone (Rhythmol, in 150- and 300-mg tablets). Adult dose is 600 to 900 mg/day orally. Pediatric dose is up to 600 mg/m²/24 hours, or 8 to 10 mg/kg/day.
• Moricizine (Ethmozine, in 200-, 250-, and 300-mg tablets). Adult dose is 200 and 300 mg orally three times daily. Pediatric dose is not applicable because it is rarely needed in this group.
• Encainide, ajmaline, and prajmaline are used in Europe and the Middle East.

TOXIC DOSE

• Death has occurred after a flecainide ingestion of as little as three times the daily dose.
• Toxicity may develop at therapeutic drug levels in patients with underlying cardiac disease.

PATHOPHYSIOLOGY

• Antidysrhythmic class IC agents slow depolarization and conduction in normal cardiac tissue by inducing a blockade of the fast inward sodium channel during phase 0 (depolarization) of the action potential.
• Nonlinear kinetics are common for all agents; hence, a twofold increase in dosage may lead to a much greater elevation in the plasma level.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects are typically mild to moderate.
• Death occurs primarily in patients who collapse before medical care is received.

CAUSES

• Toxic ingestion is usually intentional.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

RISK FACTORS

A preexisting cardiac conduction defect predisposes the patient to proarrhythmic effects even at therapeutic doses.

DRUG AND DISEASE INTERACTIONS

• Levels of antidysrhythmic class IC agents are increased by inhibitors of cytochrome P450: cimetidine, quinidine, ketoconazole, erythromycin, and birth control pills, among others.
• Class IC agents may cause lethal ventricular dysrhythmias when used to treat minimally symptomatic ventricular dysrhythmias after myocardial infarction.

PREGNANCY AND LACTATION

• Moricizine. US FDA Pregnancy Category B. Animal studies indicate no fetal risk, and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in women do not.
• Flecainide and propafenone. US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of CNS depression, seizure, and ECG conduction abnormality include class I antidysrhythmic agents, antihistamine, cocaine, beta-receptor or calcium channel blockers, quinine, chloroquine, digoxin, phenothiazine, and cyclic antidepressants, among others.
• Other causes of CNS depression and seizure include head trauma, elevated intracranial pressure, and electrolyte abnormalities.

SIGNS AND SYMPTOMS

A large overdose that goes untreated often leads to severe cardiac dysrhythmia, depressed mentation, seizure, and cardiac arrest.

Vital Signs

Bradycardia and hypotension are common in a serious overdose.

Cardiovascular

• Conduction defects and wide-complex ventricular tachydysrhythmias are characteristic.
• Superventricular tachycardia with aberrant conduction also occurs.
• Atypical chest pain is reported in some patients in therapeutic doses.

Pulmonary

Propafenone may induce wheezing due to beta-receptor blockade.

Gastrointestinal

Nausea and vomiting are common after an overdose.

Hepatic

An increase in liver transaminases may develop but is rarely severe.

Neurologic

• Visual hallucinations and dysarthria can occur in acute toxicity.
• Generalized depression of mental status, seizures may occur with serious overdose.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• ECG with continuous monitoring is used to assess QRS widening, ST-T wave abnormalities, and QT prolongation. QT prolongation greater than 50% indicates toxicity. QRS widening or QT prolongation should prompt immediate intervention.
• Serum electrolytes, calcium, magnesium, BUN, and creatinine levels are measured to assess other causes of dysrhythmia.
• Arterial blood gas is measured in patients with clinical effects or receiving bicarbonate therapy.

Recommended Tests

• Serum acetaminophen and aspirin levels should be measured in an overdose setting to detect occult ingestion.
• Head CT, lumbar puncture, and bacterial cultures should be performed in patients with altered mental status of unknown etiology.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment is focused on early airway management, seizure control and treatment of dysrhythmia.
• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Altered mental status, cardiac toxicity, or other severe effects are present.
• Toxic effects are not consistent with class IC antidysrhythmic poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Toxic effects are present.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

DECONTAMINATION

Out of Hospital

Do not induce emesis; coma or seizure may develop abruptly.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

Admission Consideration

Inpatient management is warranted for patients with apparent toxic effects or suspected suicidal ingestion of class IC antidysrhythmic agents.

ANTIDOTES

There is no specific antidote for class IC antidysrhythmic agent poisoning.

ADJUNCTIVE TREATMENT

Bradydysrhythmia

Standard agents including atropine and isoproterenol are usually ineffective. Early use of a pacemaker is recommended.

Ventricular Dysrhythmias

• For stable patients, begin with drug therapy as described below. For unstable patients use defibrillation followed by pharmacologic therapy as guided by the ACLS algorithm.
• Sodium bicarbonate. Administer NaHCO₃ 1 to 2 mEq/kg intravenous bolus and repeat as needed to narrow the QRS complex. Arterial pH should not exceed 7.55. Simultaneous hyperventilation and bicarbonate therapy must be administered cautiously because it may cause severe alkalemia. Control seizures concurrently.
• Lidocaine
  • Adult dose is 1.0 to 1.5 mg/kg intravenous push. Titrate infusion from 1 to 4 mg/min to maintain suppression. Repeat with 0.5 to 0.75 mg/kg boluses and increase maintenance infusion every 5 to 10 minutes until ventricular tachycardia resolves or a total of 3 mg/kg has been given.
  • Pediatric dose is 1 mg/kg intravenous push. May repeat same dose in 10 to 15 minutes. If a second dose is required, start infusion at 20 to 50 µg/kg/min.
  • The dose should be reduced in patients with hepatic insufficiency, congestive heart failure, or cardiogenic shock, or in those over 70 years of age.
• Phenytoin or Fosphenytoin
  • Phenytoin loading dose. Adults and pediatric dose is 15 to 20 mg/kg intravenous. The rate of infusion should not exceed 50 mg/min (adult) or 1.5 mg/kg/min (pediatric).
  • Maintenance dose. Adult dose is 100 mg every 6 to 8 hours. Pediatric dose is 4 to 7 mg/kg/day in two divided doses.
  • Monitor ECG and blood pressure during infusion; stop if dysrhythmia or hypotension occurs.
  • Fosphenytoin loading dose is 15 to 20 or phenytoin equivalents/kg given at a rate of 100 to 150 phenytoin equivalents/min.
• Avoid bretylium because alpha blocking effects may worsen hypotension. Avoid class IA antidysrhythmic agents because they may worsen dysrhythmias.

Torsade de Pointes

• Correct electrolyte abnormalities if present.
• Avoid quinidine, disopyramide, procainamide, amiodarone or bretylium, which also prolong the QT interval.
• Magnesium sulfate (MgSO₄)
  • Adult dose is 1 to 2 g intravenous push, and may be repeated in 10 to 15 minutes. Begin intravenous infusion at 2 to 10 mg/min, titrate to antidysrhythmic effect.
  • Pediatric dose is 25 to 50 mg/kg intravenously over 5 minutes.
• Isoproterenol
  • Adult dose is 2 to 4 µg/kg/min intravenous infusion, titrated to effect.
  • Pediatric dose is 0.1 µg/kg/min intravenous infusion, titrated to effect.
  • If unresponsive, overdrive pacing may be used.

Hypotension

The primary treatment is correction of the dysrhythmia. Also administer 10 to 20 ml/kg 0.9% saline, place patient in the Trendelenburg position, and administer a vasopressor, if needed. Dopamine is preferred and norepinephrine is added for refractory hypotension.

Seizures

• A patent airway must be ensured.
• A benzodiazepine is administered for initial control. If seizures persist or recur, another anticonvulsant such as phenobarbital may be added.

Cardiac Pacing

Cardiac pacing may be useful in patients with bradycardia or atrioventricular block not responsive to other measures.

Not Recommended

Hemodialysis, hemofiltration, hemoperfusion, forced diuresis, and urinary acidification are not recommended.

Section Outline:

• DIRECTING PATIENT COURSE
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
  • Admission Consideration
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Bradydysrhythmia
  • Ventricular Dysrhythmias
  • Torsade de Pointes
  • Hypotension
  • Seizures
  • Cardiac Pacing
  • Not Recommended

PATIENT MONITORING

• Respiratory and cardiac function should be monitored continuously.
• Permanent neurologic injury may occur from hypotension, seizures, or hypoxia.

EXPECTED COURSE AND PROGNOSIS

• Most adverse effects develop soon after ingestion.
• Recovery is expected unless sequelae of hypoxia intercede.

DISCHARGE CRITERIA/INSTRUCTIONS

• From emergency department. There are no accepted criteria for discharge. Due to potential for delayed toxicity, most patients should be admitted if suicidal ingestion is possible.
• From the hospital. Discharge patient after toxic effects have resolved and after psychiatric evaluation, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

Small increases in dosage may produce toxicity.

Poisoning by other central nervous system depressants and anesthetics.

See Also: SECTION II, Bradycardia, Hypotension, Seizure, and Ventricular Dysrhythmias chapters.

RECOMMENDED READING

Bigger JT, Hoffman BF. Antidysrhythmic drugs. In: Gilman et al., eds. Pharmacologic basis of therapeutics. New York: MacMillan, 1985:767-772.

Lewin NA, Osborn H. Antidysrhythmic agents. In: Goldfrank et al., eds. Toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Gerald F. O'Malley

Reviewer: Katherine M. Hurlbut