Mexiletine Hydrochloride

Antiarrhythmic Agent (Class IB) Sodium Channel Blocker

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 4-8 mg/kg q8h Duration: As needed for arrhythmia control; often long-term
Notes: Start at lower end and titrate based on response and serum levels if available. Administer with food to reduce GI upset.
Cat PO 1-2 mg/kg q8h Duration: As needed; use cautiously due to limited safety data
Notes: May be used off-label; monitor for adverse effects.
Horse PO 2-4 mg/kg q8h Duration: As needed for arrhythmia control
Notes: Administer with feed to reduce GI irritation. Monitor ECG and serum potassium.
Cattle PO 4-6 mg/kg q8h Duration: As needed; limited data
Notes: Extra-label use; observe withdrawal times.

Clinical Indications & Species Uses

General Indications
  • Treatment of ventricular arrhythmias in dogs and horses
Dog (Canine)
  • Ventricular arrhythmias (e.g., ventricular tachycardia, premature ventricular complexes)
  • Arrhythmias associated with myocarditis, cardiomyopathy, or digitalis toxicity
  • Adjunct therapy for refractory ventricular arrhythmias
Cat (Feline)
  • Ventricular arrhythmias (less commonly used)
  • Hypertrophic cardiomyopathy with ventricular arrhythmias (off-label)
Horse (Equine)
  • Ventricular arrhythmias (e.g., ventricular tachycardia, atrial fibrillation with ventricular ectopy)
  • Exercise-induced arrhythmias
Cattle (Bovine)
  • Ventricular arrhythmias (off-label)

Pharmacology & Mechanism of Action

Drug Class: Antiarrhythmic Agent (Class IB) | Pharmacological Group: Sodium Channel Blocker

Mechanism of Action: Mexiletine is a Class IB antiarrhythmic agent that blocks fast sodium channels in cardiac myocytes, particularly in the His-Purkinje system and ventricular muscle. It shortens the action potential duration and effective refractory period, and reduces the maximal rate of depolarization (phase 0) in ischemic or depolarized tissues. It suppresses abnormal automaticity and reentrant arrhythmias by increasing the threshold for excitability and slowing conduction in abnormal tissue, while having minimal effect on normal tissue. It also has local anesthetic properties similar to lidocaine.

Pharmacodynamics: Mexiletine exhibits voltage- and frequency-dependent blockade of sodium channels. It is most effective in depolarized (ischemic) tissues and at higher heart rates. It reduces the maximum rate of depolarization (Vmax) and slows conduction in ventricular tissue, thereby terminating or preventing ventricular arrhythmias. It has minimal effects on the sinoatrial node, atrioventricular node, and atrial tissue, and does not significantly alter hemodynamics. It may cause slight prolongation of the QT interval in some patients, but this is not a prominent effect.

⚑ Pharmacokinetics Summary

Absorption: Mexiletine is well absorbed after oral administration in most species, with peak plasma concentrations occurring within 2-4 hours in dogs and 1-3 hours in horses. Food can delay absorption but does not significantly reduce the extent. In ruminants, oral bioavailability may be lower due to ruminal degradation.
Distribution: Mexiletine is widely distributed throughout the body, with a large volume of distribution (approximately 5-8 L/kg in dogs). It crosses the blood-brain barrier and placenta, and is distributed into milk. It is approximately 50-70% bound to plasma proteins (albumin and alpha-1-acid glycoprotein).
Metabolism: Mexiletine undergoes extensive hepatic metabolism, primarily via oxidative pathways (CYP2D6 in humans, but in animals, multiple CYP enzymes are involved). It undergoes first-pass metabolism, reducing oral bioavailability. Metabolites are mostly inactive, but some may have minor antiarrhythmic activity.
Excretion: Mexiletine and its metabolites are excreted primarily in the urine (about 85-90%), with a small amount excreted in feces. Renal excretion is pH-dependent; acidic urine increases excretion, while alkaline urine decreases it. In dogs, the elimination half-life is approximately 3-6 hours, but may be prolonged in hepatic or renal impairment.
Half-Life: Dogs: 3-6 hours; Horses: 2-4 hours; Cats: 4-8 hours (estimated); Humans: 10-17 hours.
Bioavailability: Oral bioavailability is approximately 80-90% in dogs, but may be lower in other species due to first-pass metabolism. In horses, bioavailability is around 50-70%.
Protein Binding: 50-70% bound to plasma proteins (albumin and alpha-1-acid glycoprotein).

Available Formulations & Strengths

Oral Capsule 50 mg, 100 mg, 150 mg, 200 mg (PO)
Oral Tablet 150 mg, 200 mg, 250 mg (PO)
Injectable Solution (for IV use; not commonly used in veterinary medicine) 25 mg/mL (human formulation) (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to mexiletine or other amide local anesthetics
  • Severe cardiogenic shock or second- or third-degree atrioventricular block (unless a pacemaker is in place)
  • Severe hepatic impairment
  • Concurrent use with other Class I antiarrhythmics (e.g., quinidine, procainamide) without careful monitoring
Warnings & Clinical Precautions:
  • Use with caution in animals with pre-existing sinus node dysfunction, conduction disturbances, or hypotension.
  • Monitor ECG and serum potassium levels during therapy.
  • May cause GI upset; administer with food.
  • Use with caution in animals with renal impairment; dose adjustment may be necessary.
  • Safety in pregnant or lactating animals has not been established; use only when clearly needed.
  • In horses, use with caution in animals with hepatic or renal disease.
  • Do not crush or open capsules; administer whole.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Tremors
  • Ataxia
  • Weakness

Serious / Severe:

  • Cardiac arrhythmias (bradycardia, AV block, worsening of arrhythmias)
  • Seizures
  • Hypotension
  • Hepatotoxicity (rare)

Rare:

  • Blood dyscrasias (leukopenia, thrombocytopenia)
  • Pulmonary fibrosis (long-term use in humans)
  • Allergic reactions (rash, urticaria)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other Class I antiarrhythmics (e.g., quinidine, procainamide) Additive sodium channel blockade and increased risk of proarrhythmia and conduction disturbances. High
Beta-blockers (e.g., propranolol) May increase mexiletine levels and additive negative chronotropic effects. Moderate
Cimetidine May increase mexiletine plasma concentrations by inhibiting hepatic metabolism. Moderate
Phenobarbital or other hepatic enzyme inducers May decrease mexiletine plasma concentrations by increasing metabolism. Moderate
Urinary alkalinizers (e.g., sodium bicarbonate) May decrease renal excretion of mexiletine, increasing plasma levels. Mild
Urinary acidifiers (e.g., ammonium chloride) May increase renal excretion of mexiletine, decreasing plasma levels. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Nausea, vomiting
  • Tremors, ataxia
  • Seizures
  • Bradycardia, hypotension
  • AV block, asystole
  • Respiratory depression
  • Coma

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids for hypotension. Treat seizures with diazepam or barbiturates. For severe cardiac toxicity, use atropine for bradycardia, and consider temporary pacemaker for AV block. Sodium bicarbonate may be used to reverse sodium channel blockade. Monitor ECG and vital signs closely.

Food Animal Withdrawal Times

πŸ₯© Meat: 7 daysπŸ₯› Milk: 3 days

Withdrawal times are not established for mexiletine in food animals. The values provided are conservative estimates based on pharmacokinetic data. Consult regulatory authorities for specific guidance.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25Β°C or 68-77Β°F).

Handling & Special Conditions: Protect from moisture. Keep in tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, mexiletine is not FDA-approved for veterinary use; it is used extra-label under AMDUCA. For food animals, a valid veterinarian-client-patient relationship is required, and withdrawal times must be observed.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Mexiletine is a valuable antiarrhythmic for managing ventricular arrhythmias in dogs and horses, particularly when other agents (e.g., lidocaine, procainamide) are ineffective or not suitable. It is often used in combination with other antiarrhythmics (e.g., sotalol) for refractory cases. Therapeutic drug monitoring is recommended to optimize dosing and minimize toxicity. Because of its narrow therapeutic index, careful dose titration and ECG monitoring are essential. In dogs, the starting dose is typically 4-6 mg/kg PO q8h, with adjustments based on response and adverse effects. In horses, it is used for ventricular tachycardia and may be combined with other drugs. Gastrointestinal side effects are common and can be mitigated by administering with food. Mexiletine should be used with caution in animals with hepatic or renal impairment. For food animals, extra-label use requires careful attention to withdrawal times to ensure food safety.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)