What is the use of Mexiletine (mexiletine hydrochloride)?

From the Guidelines

Mexiletine should be used as a second- or third-line treatment for neuropathic pain, particularly in patients who are refractory to other treatments, due to its poor side effect profile and limited efficacy compared to other antiarrhythmic medications. The typical dosage of mexiletine ranges from 225-675 mg/day, with common side effects including nausea, headache, sleep disturbances, and tiredness 1. Mexiletine works by blocking sodium channels in cardiac and nerve cells, which stabilizes cell membranes and reduces abnormal electrical activity, making it effective for controlling irregular heartbeats and dampening overactive pain signals in damaged nerves.

Some key points to consider when using mexiletine include:

• Starting with a lower dose and gradually increasing as needed based on patient response
• Taking the medication with food to reduce gastrointestinal side effects
• Regular monitoring of blood levels and cardiac function during treatment, as the therapeutic window is relatively narrow
• Using caution in patients with liver disease, heart block, or seizure disorders, and being aware of potential interactions with other medications that affect heart rhythm or are metabolized by the liver
• Considering alternative treatments, such as gabapentin or pregabalin, which have been shown to be effective in treating neuropathic pain and have a more favorable side effect profile 1.

It's also important to note that mexiletine has been used in specific circumstances, such as congenital long QT syndrome, and may be considered for use in patients with drug- and ablation-refractory VT 1. However, its use should be carefully weighed against the potential risks and benefits, and alternative treatments should be considered whenever possible.

From the FDA Drug Label

INDICATIONS AND USAGE Mexiletine Hydrochloride Capsules USP are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life- threatening. Because of the proarrhythmic effects of mexiletine, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of mexiletine treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.

Mexiletine is indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that are life-threatening 2.

• The use of mexiletine is generally not recommended for lesser arrhythmias due to its proarrhythmic effects.
• Treatment should be avoided in patients with asymptomatic ventricular premature contractions.
• Initiation of mexiletine treatment should be carried out in the hospital.

From the Research

Overview of Mexiletine

• Mexiletine is a medication used to treat ventricular arrhythmias, which are abnormal heart rhythms that can be life-threatening 3, 4, 5, 6, 7.
• It has been used for over 40 years to prevent recurrent ventricular arrhythmias and myotonia, a condition characterized by muscle stiffness 3.

Efficacy of Mexiletine

• Studies have shown that mexiletine is effective in reducing the frequency of ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation 3, 4, 5, 6, 7.
• A systematic review of 221 studies found that mexiletine decreased ventricular arrhythmias by more than 50% in 72% of studies for premature ventricular complexes, 64% for ventricular tachycardia, and 33% for ventricular fibrillation 3.
• Another study found that mexiletine significantly reduced the number of electrical storm events, VT/VF episodes, and ICD interventions in patients with recurrent ventricular tachyarrhythmias 6.

Safety and Tolerability of Mexiletine

• Mexiletine is generally well-tolerated, but common side effects include gastrointestinal complaints, such as nausea and vomiting, and neurologic effects, such as dizziness and tremors 3, 4, 5, 6, 7.
• Severe side effects, such as cardiac arrhythmias and allergic reactions, can occur, but are rare 4, 5, 6, 7.
• The rate of side effects requiring dosage reduction or interruption is not negligible, with 6-18% of patients discontinuing treatment due to adverse effects 6, 7.

Clinical Use of Mexiletine

• Mexiletine is used to treat patients with recurrent ventricular arrhythmias, including those with implantable cardioverter-defibrillators (ICDs) 6, 7.
• It is often used in combination with other antiarrhythmic medications, such as class Ia agents, to enhance its effectiveness 4, 5.
• Mexiletine may be effective in patients with chronic coronary syndrome and recurrent ventricular arrhythmias, when conventional antiarrhythmic therapy has failed 7.