Mexiletine

Mexiletine is an oral antiarrhythmic medicine. Here is what it is approved to treat:

• Life-threatening ventricular arrhythmias — Mexiletine Hydrochloride capsules are indicated for documented, life-threatening irregular heart rhythms originating in the ventricles (lower chambers of the heart), such as sustained ventricular tachycardia.
• It is not appropriate for minor ventricular arrhythmias or for arrhythmias that cause no symptoms — using it in those settings is generally not recommended and carries unnecessary risk.

Mexiletine is a Class 1B antiarrhythmic drug — closely related in structure and action to lidocaine, the local anesthetic, but designed to work when swallowed rather than injected. It blocks sodium channels in the heart's electrical cells, which slows down the abnormally fast or chaotic electrical signals that cause dangerous arrhythmias. Importantly, at normal doses it does not significantly prolong the QT interval (the heart's electrical recovery time) or reduce the heart's pumping strength, which sets it apart from some other antiarrhythmics.

In patients with already-impaired heart conduction pathways, mexiletine can occasionally slow the heart's natural pacemaker or affect how signals travel — so careful monitoring is essential in those individuals.

Mexiletine Hydrochloride capsules are taken by mouth, usually three times a day (every eight hours). Taking each dose with food or an antacid is strongly recommended — it significantly reduces stomach upset. Your prescriber will start at a lower dose and adjust it gradually, waiting at least two to three days between changes, until your arrhythmia is controlled and you tolerate the medicine well.

• Some patients who respond well may be switched to a twice-daily (every twelve hours) schedule for convenience — but only under close medical supervision.
• If you are being transferred to mexiletine from another antiarrhythmic drug, your prescriber will follow a specific timing schedule to safely make the switch.
• Mexiletine is always started in a hospital setting so your heart rhythm can be monitored during the early phase of treatment.

The most common side effects of mexiletine involve the stomach and the nervous system, and they are often dose-related — meaning they may improve if the dose is lowered or the capsule is taken with food.

• Nausea, vomiting, or heartburn
• Dizziness or lightheadedness
• Tremor (shakiness, usually in the hands)
• Difficulty with coordination
• Nervousness or anxiety
• Blurred or disturbed vision
• Headache
• Changes in sleep habits

More serious reactions — including new or worsened arrhythmias, signs of liver injury (yellowing of skin or eyes, dark urine), a severe immune reaction called DRESS (rash, fever, swollen glands, organ involvement), low blood cell counts, or rare severe skin reactions — require immediate medical attention.

• Proarrhythmic risk: Mexiletine can occasionally make heart rhythm problems worse. It must only be used for life-threatening arrhythmias and must be started in a hospital with monitoring.
• Not for minor arrhythmias: Using mexiletine for symptom-free or low-risk irregular heartbeats is not recommended and may increase the risk of death based on evidence from similar drugs.
• DRESS reaction: A rare but potentially life-threatening immune reaction — with fever, rash, swollen lymph nodes, and internal organ involvement — has been reported. Stop the medicine and get medical help immediately if these symptoms appear.
• Liver injury: Abnormal liver tests have been reported, especially in people with heart failure or poor blood flow to the liver. Rare cases of severe hepatitis have occurred. Report any yellowing of skin or eyes, dark urine, or severe stomach pain to your doctor promptly.
• Blood cell changes: Rare decreases in white blood cells (which fight infection) and platelets (which help clotting) have been seen. Watch for unusual bruising, bleeding, or signs of infection.
• Liver disease or severe heart failure: Both conditions slow how the body processes mexiletine, so lower doses may be needed and closer monitoring is required.

Mexiletine is processed by two liver enzymes (CYP2D6 and CYP1A2), so drugs that affect those enzymes — or that mexiletine affects in return — can cause meaningful changes in drug levels.

• Fluvoxamine (antidepressant/OCD drug): inhibits CYP1A2, raising mexiletine levels — use cautiously and titrate slowly.
• Propafenone (heart rhythm drug): can raise mexiletine levels significantly in many patients — titrate mexiletine slowly when starting together.
• Phenytoin, rifampin, phenobarbital (seizure or infection medications): induce liver enzymes, lowering mexiletine levels and potentially making it less effective — blood level monitoring recommended.
• Theophylline (for lung conditions): mexiletine can raise theophylline blood levels by about 70%, increasing risk of theophylline toxicity — monitor theophylline levels and adjust the dose if needed.
• Cimetidine (heartburn/ulcer drug): may unpredictably raise or lower mexiletine levels — monitor closely.
• Caffeine: mexiletine slows caffeine clearance by about 50%, so you may feel stronger effects from caffeine.
• Narcotics, atropine, and magnesium-aluminum antacids: can slow how quickly mexiletine is absorbed — timing of doses may matter.
• Metoclopramide (anti-nausea drug): can speed up mexiletine absorption.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not take mexiletine if you have second- or third-degree AV block (a serious conduction problem) without a functioning pacemaker — it is contraindicated.
• Do not take mexiletine if you are in cardiogenic shock (when the heart cannot pump enough blood to the body).
• Tell your doctor about any liver disease — mexiletine stays in the body much longer when the liver is impaired, and lower doses are usually needed.
• Tell your doctor about severe right-sided congestive heart failure, which can also reduce the liver's ability to process mexiletine.
• Tell your doctor about all current medications, especially other antiarrhythmics, seizure medications, antibiotics, and antidepressants.
• Tell your doctor about kidney disease — though the dose generally does not change, your prescriber should know.
• Tell your doctor about a recent heart attack — absorption of mexiletine can be slower after a heart attack, and starting the drug in this setting requires extra care.

Taking too much mexiletine can cause drowsiness, confusion, nausea, low blood pressure, very slow heart rate, numbness or tingling, seizures, and serious heart rhythm problems including ventricular fibrillation (a life-threatening chaotic heartbeat) or cardiac arrest. There is no specific antidote. If an overdose is suspected, seek emergency medical care immediately — treatment focuses on supporting vital signs, monitoring the heart, and using medications or pacing as needed.

Mexiletine stabilizes the electrical activity of the heart by blocking sodium channels in heart cells, which slows the abnormal electrical signals responsible for dangerous ventricular arrhythmias. At recommended doses, it does not significantly lower blood pressure, reduce the heart's pumping strength, or prolong the QT interval (the heart's electrical recovery time). In patients with already-abnormal electrical pathways, mexiletine can occasionally slow the sinus (natural pacemaker) rate or reduce how quickly impulses travel through the heart's conduction system.

Mexiletine is well absorbed from the gut (about 90%) and reaches peak blood levels within two to three hours of a dose. In people with normal liver function, it stays in the body for roughly 10 to 12 hours (half-life) — but this extends to about 25 hours in people with moderate-to-severe liver disease, so those patients need closer monitoring. About 90% of mexiletine is broken down in the liver, primarily through an enzyme called CYP2D6 (with CYP1A2 also involved); only about 10% is excreted unchanged by the kidneys. The therapeutic blood level range is narrow, and levels above the upper end of that range are associated with increased nervous system side effects.

Store at 20°C to 25°C (68 to 77°F); excursions permitted to 15°C to 30°C (59 to 86°F) . Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).