Mexiletine Side Effects: What to Expect and When to Call Your Doctor

Mexiletine is an effective medication for ventricular arrhythmias and other conditions, but it comes with a notable side effect profile. Most side effects are gastrointestinal or neurological, manageable through dose adjustment and food timing. But some side effects are serious warning signs that require immediate attention. This guide walks you through what to expect — and what to watch for.

Most Common Side Effects of Mexiletine

The majority of mexiletine side effects are mild-to-moderate and improve as your body adjusts to the medication. The most frequently reported include:

Nausea and vomiting: The most commonly reported side effect. Taking mexiletine with food or an antacid (e.g., calcium carbonate) significantly reduces nausea.

Heartburn and dyspepsia: Stomach upset is common, particularly when taken on an empty stomach.

Dizziness and lightheadedness: Can occur, particularly when standing up quickly. Avoid driving or operating machinery until you know how mexiletine affects you.

Tremor and shaking: Fine tremor of the hands or fingers is a common neurological side effect.

Coordination problems: Difficulty with fine motor tasks or balance may occur.

Headache and drowsiness: Both common, especially early in therapy.

Chest discomfort: Mild chest discomfort is reported by some patients, though chest pain that is new, worsening, or severe requires immediate evaluation.

How to Minimize Common Side Effects

Always take mexiletine with food or antacid — this is the most effective way to reduce nausea and heartburn

Space doses evenly — mexiletine is typically taken every 8 hours; uneven spacing can lead to peaks and troughs that worsen side effects

Report persistent side effects to your doctor — dose adjustments of 50-100 mg increments can significantly improve tolerability without sacrificing effectiveness

Serious Side Effects: Call Your Doctor Immediately

Some mexiletine side effects are medically serious. Seek emergency care or call your doctor immediately if you experience:

Worsened or new arrhythmia: Mexiletine can occasionally cause new arrhythmias (proarrhythmic effect). Contact your provider if you feel a new or worsening irregular heartbeat, palpitations, or fainting.

Signs of liver damage: Yellowing of the skin or eyes (jaundice), dark urine, upper right stomach pain, unusual fatigue, or loss of appetite. Rare liver toxicity has been reported, particularly in the first few weeks.

Chest pain or shortness of breath: May indicate worsening heart failure, new pulmonary infiltrates (lung inflammation), or serious cardiac arrhythmia.

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): A rare but serious allergic reaction involving sudden rash, fever, mouth sores, chills, body aches, or swollen lymph nodes. Can lead to organ failure if untreated.

Blood disorders: Mexiletine may rarely lower white blood cells or platelets. Signs include unusual bleeding, bruising, or signs of infection.

Severe dizziness or fainting: More than mild dizziness may indicate low blood pressure or serious arrhythmia.

Mexiletine and the CAST Trial Warning

The Cardiac Arrhythmia Suppression Trial (CAST) found that certain antiarrhythmic drugs similar to mexiletine increased the risk of sudden death in patients who had recently had a heart attack. While mexiletine is a Class 1B drug (not Class 1C like the drugs directly studied in CAST), it shares the same general caution: it is reserved for patients with life-threatening ventricular arrhythmias where the benefit clearly outweighs the risk. It is not recommended for treating mild or asymptomatic arrhythmias.

Side Effects During Initial Dose Adjustment

Most side effects are most prominent when starting mexiletine or when the dose is increased. Your doctor will usually start you at 200 mg every 8 hours and adjust slowly — waiting at least 2-3 days between dose changes. During this period, your provider should be monitoring your EKG and may draw blood tests to check liver function and blood counts.

For more, see our guides on mexiletine drug interactions and what mexiletine is and what it's used for.