Skip to Content


Class: Class Ib Antiarrhythmics
VA Class: CV300
Chemical Name: 1-(2,6-Dimethylphenoxy)-2-propanamine hydrochloride
Molecular Formula: C11H17NO•HCl
CAS Number: 5370-01-4
Brands: Mexitil

Medically reviewed by Last updated on Nov 4, 2020.


Antiarrhythmic agent; a local anesthetic-type, class 1B agent.1 8 10 11 12 24 34

Uses for Mexiletine

Ventricular Arrhythmias

Treatment of documented life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia).1 20 34 Use for less severe arrhythmias is notrecommended.1 34 44

Can reduce ventricular premature contractions (VPCs), paired VPCs, and nonsustained ventricular tachycardia and can suppress the recurrence of ventricular tachycardia and/or fibrillation in patients with ventricular tachycardia and/or fibrillation.1 10 12 13 14 15 16 17 18 19 20 34 Avoid treatment of asymptomatic VPCs.1 34

Has been effective in some patients for the treatment of ventricular arrhythmias unresponsive to other antiarrhythmic agents.10 11 12 13 16 19 20

Diabetic Neuropathy

Has been used with equivocal results in the management of painful diabetic neuropathy;26 27 28 29 30 31 32 39 45 46 pending further accumulation of data from well-designed studies, use only in patients who do not respond to or cannot tolerate more established therapies.32 39

Mexiletine Dosage and Administration


Ventricular Arrhythmias

  • Individualize dosage carefully according to individual response, tolerance, general condition, and cardiovascular status.1 12 17 34 44 46

  • Clinical and ECG evaluation (e.g., Holter monitoring) is recommended to determine whether the desired antiarrhythmic effect has been achieved and to guide dosage titration and adjustment.1 12 14 17 18 34 44

  • Initiate therapy in a hospital.1 34 Patients at high risk for developing life-threatening arrhythmias after discontinuance of existing antiarrhythmic therapy should be hospitalized.1 34


Oral Administration

Administer orally, generally every 8 hours.1 10 12 15

Administer with food or antacids to minimize adverse GI effects.1 10 11 12 34 44 46


Available as mexiletine hydrochloride; dosage expressed in terms of the salt.1


Ventricular Arrhythmias

If rapid control of arrhythmia is essential, 400-mg loading dose followed by 200 mg in 8 hours.1 12 13 15 34 If rapid control of arrhythmia is not essential, initial dosage of 200 mg every 8 hours.1 17 20 34

If necessary, adjust dosage at intervals of at least 2–3 days in increments or decrements of 50 or 100 mg.1 13 34 200–300 mg every 8 hours usually results in satisfactory control of arrhythmias.1 10 17 34 If satisfactory control is not achieved and patient tolerates 300 mg every 8 hours, increase dosage to 400 mg every 8 hours.1 11 17 34

If adequate control of arrhythmia has been achieved at doses ≤300 mg every 8 hours, total dosage may be administered twice daily (every 12 hours) with close monitoring of degree of ventricular ectopy suppression.1 34

Switching from Another Class I Antiarrhythmic Agent

200 mg as a single dose, administered 6–12 hours after last dose of quinidine sulfate or disopyramide, 3–6 hours after last dose of procainamide, or 8–12 hours after last dose of tocainide.1 34 Adjust subsequent doses according to individual requirements.1 34

When switching to mexiletine from IV lidocaine, discontinue lidocaine infusion at the time of administration of the first dose of mexiletine; however, keep infusion line open until arrhythmia appears to be satisfactorily suppressed.1 34 Closely monitor patient.1 34

Diabetic Neuropathy†

Initial dosage of 200 mg once daily has been used;31 32 39 44 46 dosage increased at 2-day intervals to 200 mg twice daily and then 200 mg 3 times daily.32 39 46

Prescribing Limits


Ventricular Arrhythmias

Maximum 400 mg every 8 hours1 11 17 34 (1.2 g daily).1 13 34 46

If given twice daily, maximum 450 mg every 12 hours.1 34

Diabetic Neuropathy†

Dosage generally should not exceed 1.2 g daily.32 39 46

Special Populations

Hepatic Impairment

Consider dosage reduction in patients with hepatic impairment (including those with hepatic dysfunction secondary to CHF).1 8 12 34 44

Renal Impairment

Dosage adjustment not required.1 8 12 21 34

Cautions for Mexiletine


  • Second- or third-degree AV block (unless a cardiac pacemaker is in place).1 34 46

  • Cardiogenic shock.1 34 46




In CAST study, excessive rate of mortality and nonfatal cardiac arrest reported in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) who were receiving encainide or flecainide compared with placebo.1 2 3 4 5 34

Limit use of mexiletine in patients with ventricular arrhythmias to those with life-threatening arrhythmias1 34 due to mexiletine’s arrhythmogenic potential (see Cardiovascular Effects under Cautions) and the lack of evidence for improved survival for class I antiarrhythmic agents.33 34 40 41 42 Use for treatment of less severe arrhythmias currently is not recommended; avoid treatment of asymptomatic VPCs.1 34

Major Toxicities

Cardiovascular Effects

Possible development or exacerbation of arrhythmias; clinical and ECG evaluations are essential prior to and during therapy.1 34 Initiate therapy in a hospital.1 34

Use with caution in patients with preexisting first-degree AV block, sinus node dysfunction, or intraventricular conduction disturbances.1 34 Continuous monitoring recommended for patients with second- or third-degree AV block and an operative ventricular pacemaker.1 34 (See Contraindications under Cautions.)

Possible exacerbation of hypotension and CHF; use with caution in patients with these conditions.1 34

Hepatic Effects

Possible abnormal liver function test results (AST elevations ≥3 times the ULN),1 34 44 especially during initial weeks of therapy in patients with CHF or AMI and/or patients who have received blood transfusions or other drug therapies.1 34 Discontinuance of therapy usually is not required.1 34 Severe hepatic injury, including hepatic necrosis, reported rarely.1 34

Carefully evaluate patients who develop elevated serum concentrations of hepatic enzymes and those with signs or symptoms suggestive of liver dysfunction; consider discontinuance of therapy if enzyme elevations are persistent or increasing.1 34

Hematologic Effects

Possible leukopenia, agranulocytosis, and thrombocytopenia, 1 34 especially in severely ill patients receiving concurrent therapy with drugs known to cause adverse hematologic effects (e.g., procainamide, vinblastine).1 34

Carefully evaluate patients in whom substantial hematologic changes occur; consider discontinuing therapy.1 34 Blood cell counts generally return to normal within 1 month following discontinuance.1 34

General Precautions


Seizures reported rarely; discontinuance of therapy may be necessary.1 34 Use with caution in patients with a history of seizure disorder.1 34

Effects on Urinary Excretion

Substantial changes in urinary pH may affect urinary excretion of mexiletine; avoid concomitant drug therapy or dietary regimens that may markedly affect urinary pH.1 11 12 21 34

Specific Populations


Category C.1


Distributed into milk.1 21 34 Discontinue nursing or the drug.1 34

Pediatric Use

Safety and efficacy not established.1 34 44 47

Hepatic Impairment

Possible prolonged elimination.1 8 9 12 13 34 Careful monitoring recommended (including in those with hepatic impairment secondary to CHF).1 8 9 34 Consider dosage reduction.1 8 12 34 44

Common Adverse Effects

Nausea,1 14 18 19 20 34 vomiting,1 18 19 20 34 heartburn,1 14 20 34 dizziness1 5 18 19 34 or lightheadedness,1 34 tremor,1 18 20 34 nervousness,1 34 chest pain, 1 34 coordination difficulties,1 34 headache,1 15 34 blurred vision/visual disturbances.1 20 34

Interactions for Mexiletine

Metabolized by various CYP isoenzymes,1 9 principally by CYP2D and CYP1A2.39

Drugs Affecting Hepatic Microsomal Enzymes

Hepatic enzyme inducers: Potential pharmacokinetic interaction (decreased plasma mexiletine concentrations).1 8 9 10 11 12 13 21 25 34

Hepatic enzyme inhibitors: Potential pharmacokinetic interaction (decreased mexiletine clearance).1 49 50

Drugs Affecting Gastric Emptying

Drugs that delay gastric emptying may reduce rate of mexiletine absorption1 34 (since mexiletine is absorbed in the small intestine1 11 12 13 21 34 ); conversely, drugs that accelerate gastric emptying may increase rate of mexiletine absorption.1 10 11 21 34

Drugs Affecting Urinary pH

Drugs that markedly alter urinary pH may affect elimination of mexiletine; urinary acidification accelerates elimination; alkalinization slows elimination.1 Avoid concomitant drug therapy that markedly affects urinary pH.1 11 12 21 34

Specific Drugs




Antacids (aluminum- and magnesium-containing)

Possible decreased rate of absorption of mexiletine1 10 11 21 34

Antianginal agents

Adverse pharmacokinetic interactions not reported1 34

Antiarrhythmic agents (e.g., quinidine, propranolol)

Possible improved control of ventricular ectopy;1 34 prolongation of PR and QT intervals or QRS complex not reported with concomitant propranolol use1 10 11 12 34


Adverse pharmacokinetic interactions not reported1 34

Antihypertensive agents

Adverse pharmacokinetic interactions not reported1 34


Possible decreased rate of absorption of mexiletine1 10 11 21 34


Pharmacokinetic interactions not reported1 34


Possible increased, decreased, or unchanged plasma mexiletine concentrations1 8 11 12 34

Closely monitor plasma mexiletine concentrations1 34


Prolongation of PR and QT intervals or QRS complex not reported1 10 11 12 34


Prolongation of PR and QT intervals or QRS complex not reported1 10 11 12 34


Reduced mexiletine clearance49 50

Monitor patient closely and monitor serum mexiletine concentrations 49 50


Potential additive adverse effects1 34

Close monitoring recommended when patients are switched from IV lidocaine to mexiletine1 34

Methylxanthines (caffeine, theophylline)

Possible decreased methylxanthine clearance and increased plasma theophylline concentrations1 34

Monitor plasma theophylline concentrations; adjust theophylline dosage if necessary1 34


Possible increased rate of absorption of mexiletine1 10 11 21 34

Opiate agonists

Possible decreased rate of absorption of mexiletine1 10 11 21 34


Possible decreased plasma mexiletine concentrations1 8 9 10 11 12 13 21 25 34

Closely monitor plasma mexiletine concentrations1 34


Possible decreased plasma mexiletine concentrations1 8 9 10 11 12 13 21 25 34

Closely monitor plasma mexiletine concentrations1 34


Possible increased plasma mexiletine concentrationsa b

Rifampin and rifapentine

Possible decreased plasma mexiletine concentrations1 8 9 10 11 12 13 21 25 34

Closely monitor plasma mexiletine concentrations1 34

Mexiletine Pharmacokinetics



About 90% absorbed following oral administration, with peak plasma concentrations attained in 2–3 hours.1 Undergoes low first-pass metabolism.1 34


Onset of action is usually within 30–120 minutes.1 34

Plasma Concentrations

Plasma mexiletine concentrations of ≥0.5 mcg/mL generally required to suppress ventricular arrhythmias; concentrations >2 mcg/mL associated with adverse CNS effects.1

Special Populations

Decreased rate of absorption in patients with AMI or other conditions that delay gastric emptying.1


Plasma Protein Binding




Extensively metabolized in the liver1 9 10 34 by various CYP isoenzymes,9 including CYP2D and CYP1A2.39 Pharmacologic activity results principally from the parent drug.9 10

Elimination Route

About 8–15% of a dose is excreted in urine as unchanged drug.12 13


10–12 hours.1

Special Populations

In patients with hepatic impairment, possible decreased metabolism1 8 12 34 44 and prolonged elimination.1 8 9 12 13 34







  • Combines with fast sodium channels within the myocardium and inhibits rapid sodium influx, which decreases the maximal rate of depolarization of phase 0 of the action potential.1 8 10 11 12 21 34

  • Inhibits recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.35 36 37 39

  • Increases the effective refractory period (ERP) relative to the duration of the action potential (ERP/APD)1 8 9 10 12 14 21 34 and reduces ventricular automaticity by raising the threshold for spontaneous firing of ventricular pacemaker cells.10

  • Exhibits electrophysiologic effects characteristic of class IB antiarrhythmic agents,8 10 12 35 36 37 38 which rapidly attach to and dissociate from transmembrane sodium channels.1 8 9 12 35 36 37

  • Causes little or no prolongation of PR and QT intervals or QRS complex.1 8 9 10 12 14 21 34 Has no clinically important effect on heart rate, systemic arterial BP, or myocardial function in healthy individuals or patients with cardiovascular disease.1 10 11 12 14 21 34

Advice to Patients

  • Potential for toxicity (e.g., cardiovascular, hepatic).1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 34

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 34

  • Importance of informing patients of other important precautionary information. (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mexiletine Hydrochloride


Dosage Forms


Brand Names




150 mg*

Mexiletine Hydrochloride Capsules


Boehringer Ingelheim

200 mg*

Mexiletine Hydrochloride Capsules


Boehringer Ingelheim

250 mg*

Mexiletine Hydrochloride Capsules


Boehringer Ingelheim

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 14, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


1. Mexitil (mexiletine hydrochloride) capsules prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT; 2003 May 30.

2. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989; 321:406-12.

3. Ruskin JN. The Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med. 1989; 321:386-8.

4. Echt DC, Liebson PR, Mitchell LB et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991; 324:781-8.

5. Food and Drug Administration. Enkaid and Tambocor use in non-life-threatening arrhythmias halted. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1989 Apr 25.

6. Department of Health and Human Services. Background statement regarding encainide, flecainide, and moricizine. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1989 Apr.

7. The Cardiac Arrhythmia Suppression Trial II investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992; 327:227-33.

8. Kowey PR. Pharmacological Effects of Antiarrhythmic Drug: Review and Update. Arch Intern Med. 1998; 158: 325-32.

9. Kowey PR, Marinchak RA, Rials SJ et al. Classification and pharmacology of antiarrhythmic drugs. Am Heart J. 2000;140: 12-20.

10. . Fenster PE, Comess KA. Pharmacology and clinical use of mexiletine. Pharmacotherapy. 1986; 6:1-9.

11. Campbell RWF. Mexiletine. N Engl J Med. 1987; 316:29-34.

12. Monk JP, Brogden RN. Mexiletine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. Drugs. 1990; 40:374-411.

13. Mexiletine for arrhythmias. Med Lett Drugs Ther. 1986; 28:65-6.

14. Masotti G, Morettini A, Casolo GC et al. Efficacy of mexiletine in the medium-term treatment of ventricular arrhythmias: a randomized, double-blind, crossover trial against placebo in ambulatory patients. J Int Med Res. 1984; 12:73-80.

15. Singh JB, Rasul AM, Shah A et al. Efficacy of mexiletine in chronic ventricular arrhythmias compared with quinidine: a single-blind, randomized trial. Am J Cardiol. 1984; 53: 84-7.

16. Mason JW, for the Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. N Engl J Med. 1993; 329:452-8.

17. Assey ME, Hudson WM, Hanger KH et al. Comparative study of mexiletine and quinidine in the treatment of ventricular ectopia. South Med J. 1985; 78:565-8.

18. Frank MJ, Watkins LO, Prisant LM et al. Mexiletine versus quinidine as first-line antiarrhythmia therapy: results from consecutive trials. J Clin Pharmacol. 1991; 31:222-8.

19. Rutledge JC, Harris F, Amsterdam EA et al. Clinical evaluation of oral mexiletine therapy in the treatment of ventricular arrhythmias. J Am Coll Cardiol. 1985; 6:780-4.

20. Kerin NZ, Aragon E, Marinescu G et al. Mexiletine: long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias. Arch Intern Med. 1990; 150:381-4.

21. Woosley RL, Wang T, Stone W et al. Pharmacology, electrophysiology, and pharmacokinetics of mexiletine. Am Heart J. 1984; 107:1058-65.

22. Solvay Pharmaceuticals. Luvox (fluvoxamine maleate) tablets prescribing information. Marietta, GA; 2001 Jun.

23. Abbott Laboratories. Norvir (ritonavir) capsules and oral solution prescribing information (dated 2001 Sep). In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:482-9.

24. AstraZeneca. EMLA Cream and Anesthetic Disc (lidocaine 2.5% and prilocaine 2.5% cream) prescribing information (dated 2002 Feb). In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:599-602.

25. Aventis. Priftin (rifapentine) tablets prescribing information. In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:753-6.

26. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Diabetic Neuropathies: the nerve damage of diabetes. From NIDDK website ( 2003 Apr 2.

27. Russell D, Stading J. Diabetic Peripheral Neuropathy: minimizing and treating its pain. US Pharmacist. 2002; 27:56-67.

28. Galer BS. Neuropathic pain of peripheral origin: advances in pharmacologic treatment. Neurology. 1995; 45(Suppl 9):S17-25.

29. Oskarsson P, Ljunggren JG, Lins PE et al. Efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy. Diabetes Care. 1997; 20:1594-7.

30. Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet. 1988; 1:9-11.

31. Stracke H, Meyer UE, Schumacher HE et al. Mexiletine in the treatment of diabetic neuropathy. Diabetes Care. 1992; 15:1550-5.

32. Wright JM, Oki JC, Graves L 3rd. Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy. Ann Pharmacother. 1997; 31:116-7.

33. Hine LK, Laird NM, Hewitt P et al. Meta-analysis of empirical long-term antiarrhythmic therapy after myocardial infarction. JAMA. 1989; 262:3037-40.

34. Watson. Mexiletine hydrochloride capsules prescribing information. Corona, CA; 2000 May.

35. Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984; 24:129-47.

36. Harrison DC. Antiarrhythmic drug classification: new science and practical applications. Am J Cardiol. 1985; 56:185-7.

37. Campbell TJ. Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983; 17:344-52.

38. Harrison DC. Current classification of antiarrhythmic drugs as a guide to their rational clinical use. Drugs. 1986; 31:93-5.

39. Jarvis B, Coukell AJ. Mexiletine: a review of its therapeutic use in painful diabetic neuropathy. Drugs. 1998; 56:691-707.

40. Anon. Drugs for cardiac arrhythmias. Med Lett Drugs Ther. 1989; 31:35-40.

41. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. JAMA. 1993; 270:1589-95.

42. Pratt CM, Moye L. The Cardiac Arrhythmia Suppression Trial: implications for antiarrhythmic drug development. J Clin Pharmacol. 1990; 30:967-74.

44. Reviewers’ comments (personal observations).

45. Vinik AI. Diagnosis and management of diabetic neuropathy. Clin Geriatr Med. 1999; 2:293-320.

46. Guay DRP.Adjunctive agents in the management of chronic pain. Pharmacotherapy. 2001; 9: 1070-81.

47. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT: Personal communication.

49. Barr Laboratories, Inc. Fluvoxamine maleate tablets prescribing information. Pomona, NY; 2005 Jan.

50. Kusumoto M, Ueno K, Oda A et al. Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. Clin Pharmacol Ther. 2001; 69:104-7.

a. Libersa C, Caron J, Broly F et al. Interaction of propafenone and mexiletine. J Am Coll Cardiol. 1993; 22:2061.

b. Yeung-Lai-Wah JA, Murdock CJ, Boone J et al. Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia. J Am Coll Cardiol. 1992; 20:547-51.