Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

MEXILETINE HCL

Chemistry - A class IB antiarrhythmic, mexiletine HCl occurs as a white or almost white, odorless, crystalline powder. It is freely soluble in water.

Storage, Stability, Compatibility

Mexiletine capsules should be stored in tight containers atroom temperature.

Pharmacology - MEXILETINE HCL

Mexiletine is similar to lidocaine in its mechanism of antiarrhythmic activity. Itinhibits the inward sodium current (fast sodium channel), thereby reducing the rate of rise of theaction potential, Phase O. In the Purkinje fibers, automaticity is decreased, action potential isshortened, and to a lesser extent, effective refractory period is decreased. Usually conduction isunaffected, but may be slowed in patients with preexisting conduction abnormalities. Mexiletine isconsidered a class IB antiarrhythmic agent.

Uses, Indications

Mexiletine may be useful to treat some ventricular arrhythmias, including
PVC's and ventricular tachycardia in small animals

Pharmacokinetics - MEXILETINE HCL

Mexiletine is relatively well absorbed from the gut and has a low first-passeffect. In humans, it is moderately bound to plasma proteins (60-75%), metabolized in the liver toinactive metabolites with an elimination half-life of about 10-12 hours. Half lives may be significantly increased in patients with moderate to severe hepatic disease, or in those having severelyreduced cardiac outputs. Half lives may be slightly prolonged in patients with severe renal diseaseor after acute myocardial infarction.

Contraindications, Precautions, Reproductive Safety

Mexiletine should be used with extremecaution if at all, in patients with pre-existing 2nd or 3rd degree AV block (without pacemaker), or inpatients with cardiogenic shock. It should be used when the following medical conditions exist onlywhen the benefits of therapy outweigh the risks: severe congestive heart failure or acute myocardialinfarction, hepatic function impairment, hypotension, intraventricular conduction abnormalities orsinus node function impairment, seizure disorder, or sensitivity to the drug.
Lab animal studies have not demonstrated teratogenicity. Because mexiletine is secreted intomaternal milk, it has been recommended to use milk replacer if the mother is taking the drug.

Adverse Effects, Warnings

The most likely adverse effect noted in animals is GI distress, including vomiting. Giving with meals may alleviate this. Potentially (reported in humans) CNSeffects (trembling, unsteadiness, dizziness), shortness of breath, PVC's and chest pain could occur.
Rarely, seizures, agranulocytosis, and thrombocytopenia have been reported in humans.

Overdosage, Acute Toxicity

Toxicity associated with overdosage may be significant. Case reports in humans have noted that CNS signs always preceded cardiovascular signs. Treatmentshould consist of GI tract emptying protocols when indicated, acidification of the urine to enhanceurinary excretion, and supportive therapy. Atropine may be useful if hypotension or bradycardiaoccur.

Drug Interactions

Urinary acidifying drugs (e.g., methionine, ammonium chloride, potassiumor sodium phosphates) may accelerate the renal excretion of mexiletine. Urinary alkalinizingdrugs (e.g., citrates, bicarb, carbonic anhydrase inhibitors) may reduce the urinary excretion ofmexiletine.
Drugs that induce hepatic enzymes (e.g., phenobarbital, griseofulvin, primidone, rifampin, tolbutamide) may accelerate the metabolism of mexiletine. Theophylline (aminophylline)metabolism may be reduced by mexiletine, thereby leading to theophylline toxicity. Cimetidinemay increase or decrease mexiletine blood levels.
Aluminum-magnesium containing antacids or opiates may slow the absorption of mexiletine.
Metoclopramide may accelerate the absorption of mexiletine.
Laboratory Considerations - Some human patients (1-3%) have had AST values increase by asmuch as three times or more above the upper limit of normal. This is reportedly a transient effectand asymptomatic.
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