Mexitil

Mexitil - General Information

Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [PubChem]

Pharmacology of Mexitil

Mexitil is a local anesthetic, antiarrhythmic agent (Class Ib), structurally similar to lidocaine, but orally active. Mexitil has fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. It shortens the action potential duration, reduces refractoriness, and decreases Vmax in partially depolarized cells with fast response action potentials. Mexitil either does not change the action potential duration, or decreases the action potential duration.

Mexitil for patients

Mexitil Interactions

Since MEXITIL is a substrate for the metabolic pathways involving CYP2D6 and CYP1A2 enzymes, inhibition or induction of either of these enzymes would be expected to alter mexiletine plasma concentrations. In a formal, single-dose interaction study (n = 6 males) the clearance of mexiletine was decreased by 38% following the coadministration of fluvoxamine, an inhibitor of CYP1A2. In another formal study (n = 8 extensive and n = 7 poor metabolizers of CYP2D6), coadministration of propafenone did not alter the kinetics of mexiletine in the poor CYP2D6 metabolizer group. However, the metabolic clearance of mexiletine in the extensive metabolizer phenotype decreased by about 70% making the poor and extensive metabolizer groups indistinguishable. In this crossover steady state study, the pharmacokinetics of propafenone were unaffected in either phenotype by the coadministration of mexiletine. Addition of mexiletine to propafenone did not lead to further electrocardiographic parameters changes of QRS, QTc, RR, and PR intervals than propafenone alone. When concomitant administration of either of these two drugs with mexiletine is initiated, the dose of mexiletine should be slowly titrated to desired effect.

In a large compassionate use program Mexitil has been used concurrently with commonly employed antianginal, antihypertensive, and anticoagulant drugs without observed interactions. A variety of antiarrhythmics such as quinidine or propranolol were also added, sometimes with improved control of ventricular ectopy. When phenytoin or other hepatic enzyme inducers such as rifampin and phenobarbital have been taken concurrently with Mexitil, lowered Mexitil plasma levels have been reported. Monitoring of Mexitil plasma levels is recommended during such concurrent use to avoid ineffective therapy.

In a formal study, benzodiazepines were shown not to affect Mexitil plasma concentrations. ECG intervals (PR, QRS, and QT) were not affected by concurrent Mexitil and digoxin, diuretics, or propranolol.

Concurrent administration of cimetidine and Mexitil has been reported to increase, decrease, or leave unchanged Mexitil plasma levels; therefore patients should be followed carefully during concurrent therapy.

Mexitil does not alter serum digoxin levels but magnesium-aluminum hydroxide, when used to treat gastrointestinal symptoms due to Mexitil, has been reported to lower serum digoxin levels.

Concurrent use of Mexitil and theophylline may lead to increased plasma theophylline levels. One controlled study in eight normal subjects showed a 72% mean increase (range 35-136%) in plasma theophylline levels. This increase was observed at the first test point which was the second day after starting Mexitil. Theophylline plasma levels returned to pre-Mexitil values within 48 hours after discontinuing Mexitil. If Mexitil and theophylline are to be used concurrently, theophylline blood levels should be monitored, particularly when the Mexitil dose is changed. An appropriate adjustment in theophylline dose should be considered.

Additionally, in one controlled study in five normal subjects and seven patients, the clearance of caffeine was decreased 50% following the administration of Mexitil.

Mexitil Contraindications

Mexitil (mexiletine hydrochloride, USP) is contraindicated in the presence of cardiogenic shock or pre-existing second- or third-degree AV block (if no pacemaker is present).

Additional information about Mexitil

Mexitil Indication: For the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.
Mechanism Of Action: Mexitil, like lidocaine, inhibits the inward sodium current required for the initiation and conduction of impulses, thus reducing the rate of rise of the action potential, Phase 0. Mexitil decreases the effective refractory period (ERP) in Purkinje fibers in the heart. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), which results in an increase in the ERP/APD ratio. It does not significantly affect resting membrane potential or sinus node automaticity, left ventricular function, systolic arterial blood pressure, atrioventricular (AV) conduction velocity, or QRS or QT intervals
Drug Interactions: Aminophylline Mexitil increases the effect and toxicity of theophylline
Dyphylline Mexitil increases the effect and toxicity of theophylline
Oxtriphylline Mexitil increases the effect and toxicity of theophylline
Theophylline Mexitil increases the effect and toxicity of theophylline
Ethotoin The hydantoin decreases the effect of mexiletine
Fosphenytoin The hydantoin decreases the effect of mexiletine
Mephenytoin The hydantoin decreases the effect of mexiletine
Phenytoin The hydantoin decreases the effect of mexiletine
Fluvoxamine Fluvoxamine increases the effect and toxicity of mexiletine
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Rifampin Rifampin decreases the effect of mexiletine
Propafenone Propafenone increases the effects/toxicity of mexiletine
Food Interactions: Not Available
Generic Name: Mexiletine
Synonyms: Mexiletina [INN-Spanish]; Mexiletine HCL; Mexiletinum [INN-Latin]; Mexilitine
Drug Category: Anti-Arrhythmia Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Mexiletine: Mexitil;
Absorption: Well absorbed (bioavailability 90%) from the gastrointenstinal tract.
Toxicity (Overdose): Symptoms of overdose include nausea, hypotension, sinus bradycardia, paresthesia, seizures, bundle branch block, AV heart block, asystole, ventricular tachyarrythmia, including ventricular fibrillation, cardiovascular collapse, and coma.
Protein Binding: 50-60%
Biotransformation: Primarily hepatic (85%) via CYP2D6 and CYP1A2 (primarily CYP2D6).
Half Life: 10-12 hours
Dosage Forms of Mexitil: Capsule Oral
Chemical IUPAC Name: 1-(2,6-dimethylphenoxy)propan-2-amine
Chemical Formula: C11H17NO
Mexiletine on Wikipedia: https://en.wikipedia.org/wiki/Mexiletine
Organisms Affected: Humans and other mammals