Mexiletine

179.25878

179.26

250-825-7

DTXSID8048446

C - Cardiovascular system

2922299090

35.2

2.1

white powder

0.979 g/cm3

203-205 °C

271.5ºC at 760 mmHg

112.2ºC

ethanol: 50 mg/mL

2-8°C

9.2None

9.2

III

6.1(b)

3249

3

20/21/22

36

KR9300000

Xn

P264, P270, P301+P312, P330, P501

H302

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory.

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.

In clinical trials, mexiletine was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations (~0.5%). Despite wide scale use, mexiletine has only rarely been linked to cases of clinically apparent liver injury. Most cases are associated with a hypersensitivity reaction. Typically, patients present with fever, rash, eosinophilia and systemic systemics (DRESS syndrome) after 2 to 6 weeks of mexiletine therapy. Eosinophilia or atypical lymphocytosis usually accompany the liver test abnormalities but may arise or continue to worsen days or weeks after onset. The pattern of serum enzyme elevations ranges from cholestatic to hepatocellular, but jaundice is usually mild or absent. Autoimmune features are uncommon. Cases of Stevens Johnson and DRESS syndrome due to mexiletine have also been reported. Corticosteroids were often used, but largely for the fever and skin rash rather than the liver disease which was typically mild. Rare instances of cholestatic hepatitis with mexiletine therapy have also been reported and may represent a different form of liver injury.

50-60%

For the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.|FDA Label

Mexiletine is an oral antiarrhythmic agent that is used for suppression of ventricular arrhythmias. Long term mexiletine therapy is associated with a low rate of serum enzyme elevations and is a rare cause of clinically apparent acute liver injury.

Antiarrhythmic Agents

Mexiletine is a local anesthetic, antiarrhythmic agent (Class Ib), structurally similar to lidocaine, but orally active. Mexiletine 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. Mexiletine either does not change the action potential duration, or decreases the action potential duration.

A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)|Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)

Well absorbed (bioavailability 90%) from the gastrointenstinal tract.|Approximately 10% is excreted unchanged by the kidney. The urinary excretion of N-methylmexiletine in man is less than 0.5%.|5 to 7 L/lg

Primarily hepatic (85%) via CYP2D6 and CYP1A2 (primarily CYP2D6).

10-12 hours

Mexiletine, 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. It achieves this reduced sodium current by inhibiting sodium channels. Mexiletine 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

KO 1173

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients