Version July 2025
In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non–life-threatening ventricular arrhythmias who had an myocardial infarction (MI) more than 6 days but less than 2 years previously, an excessive mortality or nonfatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3%). The average duration of treatment with encainide or flecainide in this study was 10 months.
The applicability of the CAST results to other populations (eg, those without recent MI) is uncertain. Considering the known proarrhythmic properties of mexiletine and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of mexiletine as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
In postmarketing experience, abnormal liver function tests have been reported, some in the first few weeks of therapy with mexiletine. Most of these have been observed in the setting of congestive heart failure or ischemia and their relationship to mexiletine has not been established.
Myotonic dystrophy (type 1) (off-label use): Oral: 150 mg 3 times daily (Ref). Note: It is prudent to obtain a cardiology consult prior to beginning therapy.
Ventricular arrhythmias (life-threatening): Oral: Initial: 150 to 200 mg every 8 to 12 hours (may load with 400 mg if necessary); adjust dose as needed in 50 or 100 mg increments no more frequently than every 2 to 3 days up to 300 mg every 8 to 12 hours; usual dose: 150 to 300 mg every 8 to 12 hours (Ref); maximum dose: 1.2 g/day.
Conversion:
Switching from other oral antiarrhythmics (eg, disopyramide, quinidine sulfate): Initiate 200 mg dose of mexiletine 6 to 12 hours after the last dose of the former agent.
Switching from IV lidocaine: Initiate 200 mg dose of mexiletine when lidocaine infusion is stopped.
Switching from oral procainamide: Initiate a 200 mg dose of mexiletine 3 to 6 hours after the last dose of procainamide.
Ventricular premature beat (symptomatic) suppression (off-label use): Oral: Initial: 100 to 150 mg every 8 to 12 hours; adjust dose as needed in 50 or 100 mg increments no more frequently than every 2 to 3 days up to 300 mg every 8 to 12 hours; usual dose: 150 to 300 mg every 8 to 12 hours (Ref); maximum dose: 1.2 g/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (large Vd): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Not significantly dialyzed: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. Patients with hepatic impairment or hepatic congestion secondary to heart failure may require dose reduction; half-life is approximately doubled in patients with hepatic impairment.
Refer to adult dosing.
(For additional information see "Mexiletine: Pediatric drug information")
Ventricular arrhythmias, life-threatening (including Long QT Syndrome Type 3): Limited data available: Children and Adolescents: Oral: Initial: 6 to 8 mg/kg/day in 2 or 3 divided doses for 2 to 3 days, then increase to 2 to 5 mg/kg/dose every 8 to 12 hours; continue to increase by 1 to 2 mg/kg/dose every 2 to 3 days until desired effect; monitor serum concentrations. Maximum daily dose: 15 mg/kg/day not to exceed 1,200 mg/day. Based on experience in adult patients, do not exceed the maximum single adult doses of 400 mg every 8 hours or 450 mg every 12 hours (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; in adult patients, no adjustment is necessary.
There are no dosage adjustments provided in the manufacturer's labeling. In adult patients with hepatic impairment or hepatic congestion secondary to heart failure, dose adjustment may be required.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Exacerbation of cardiac arrhythmia (10% to 15%; patients with malignant arrhythmia)
Central nervous system: Dizziness (11% to 25%), ataxia (10% to 20%), nervousness (5% to 10%), unsteady gait
Gastrointestinal: Gastrointestinal distress (41%), nausea (≤40%), vomiting (≤40%)
Neuromuscular & skeletal: Tremor (13%)
1% to 10%:
Cardiovascular: Palpitations (4% to 8%), chest pain (3% to 8%), angina pectoris (2%), ventricular premature contractions (1% to 2%)
Central nervous system: Insomnia (5% to 7%), numbness (fingers or toes: 2% to 4%), depression (2%), paresthesia (2%), confusion, headache
Dermatologic: Skin rash (4%)
Gastrointestinal: Constipation (≤5%), diarrhea (≤5%), xerostomia (3%), abdominal pain (1%)
Neuromuscular & skeletal: Weakness (5%), arthralgia (1%)
Ophthalmic: Blurred vision (5% to 7%), nystagmus (6%)
Otic: Tinnitus (2% to 3%)
Respiratory: Dyspnea (3%)
<1%, postmarketing, and/or case reports: Agranulocytosis, alopecia, amnesia (short-term), atrioventricular block, cardiac conduction disturbance, cardiac failure (patients with pre-existing ventricular dysfunction), cardiogenic shock, decreased libido, diaphoresis, diplopia, dysphagia, edema, esophageal ulcer, exfoliative dermatitis, hallucination, hepatic necrosis, hepatitis, hot flash, hypertension, hypotension, impotence, increased liver enzymes, increased serum transaminases, leukopenia, lupus-like syndrome (drug-induced), malaise, myelofibrosis (patients with pre-existing myeloid abnormalities), pancreatitis (rare), peptic ulcer, pharyngitis, positive ANA titer, psychological disorder, psychosis, pulmonary fibrosis, salivary gland disease, seizure, sinoatrial arrest, Stevens-Johnson syndrome, syncope, thrombocytopenia, torsades de pointes, upper gastrointestinal hemorrhage, urinary hesitancy, urinary retention, urticaria
Cardiogenic shock; second- or third-degree AV block (except in patients with a functioning artificial pacemaker)
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to mexiletine, amide-type local anesthetics (eg, pramoxine), or any component of the formulation
Concerns related to adverse effects:
• Blood dyscrasias: Rare marked leukopenia, agranulocytosis, and thrombocytopenia have been reported; often occurs in seriously ill patients receiving other medications that can cause these effects. If significant hematologic changes occur, discontinue therapy (blood counts usually return to normal within a month of discontinuation).
• Drug reactions with eosinophilia and systemic symptoms: Drug reactions with eosinophilia and systemic symptoms (DRESS) has been reported. Discontinue if DRESS is suspected. Symptoms of DRESS include eosinophilia, fever, rash, and/or lymphadenopathy in association with other organ involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection.
• Hepatotoxicity: [US Boxed Warning]: Abnormal liver function tests have been reported, some in the first few weeks of therapy. Most of these have been observed in the setting of congestive heart failure or ischemia and their relationship to mexiletine has not been established. Marked elevations of AST (>1000 units/L) and rare instances of severe liver injury, including hepatic necrosis, have also been reported. Carefully monitor patients who develop abnormal LFTs or who have signs/symptoms of liver dysfunction. If persistent or worsening elevation of hepatic enzymes occurs, consider discontinuing therapy.
• Proarrhythmic effects: Proarrhythmia may occur with the use of mexiletine especially in those with life-threatening arrhythmias (eg, sustained ventricular tachycardia). Aggravation of arrhythmia may also occur; monitor for proarrhythmic effects (Podrid 1987; Podrid 1999; Velebit 1982).
Disease-related concerns:
• Conduction disturbances: Use with caution in patients with intraventricular conduction delays, first-degree heart block and/or preexisting sinus node dysfunction. Use is contraindicated in patients with second- or third-degree AV block (except in patients with a functioning artificial pacemaker).
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy (Podrid 1999).
• Heart failure (HF): Use with caution in patients with severe HF; may precipitate or exacerbate condition.
• Hepatic impairment: Use with caution in patients with hepatic impairment; may prolong the elimination half-life of mexiletine and increase the risk of adverse effects.
• Seizure: Use with caution in patients with seizure disorder.
Other warnings/precautions:
• Appropriate use: Initiate therapy in the hospital when used to treat life-threatening arrhythmias. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Has not been shown to enhance survival in patients with ventricular arrhythmias.
• CAST trial: [US Boxed Warning]: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, nonlife-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias. In a double-blind placebo controlled trial in patients with recent MI, the use of mexiletine to reduce premature ventricular contractions demonstrated a numerically greater number of deaths compared to placebo (IMPACT Research Group, 1984).
• Urinary pH: Alterations in urinary pH may change urinary excretion; avoid dietary regimens that may markedly alter urinary pH.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Generic: 150 mg, 200 mg, 250 mg
Yes
Capsules (Mexiletine HCl Oral)
150 mg (per each): $1.46 - $2.54
200 mg (per each): $1.69 - $3.03
250 mg (per each): $2.43 - $3.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 100 mg
Capsule, Oral, as hydrochloride:
Generic: 200 mg
Administer around-the-clock rather than 3 times daily to promote less variation in peak and trough serum levels; administer with food or antacid
Oral: Administer around-the-clock (every 8 or 12 hours) rather than 2 or 3 times daily to promote less variation in peak and trough serum concentrations; administer with food or antacid (Ref).
Ventricular arrhythmias: Management of life-threatening ventricular arrhythmias
Note: The American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) states that mexiletine may be considered for those with long QT syndrome type 3 who present with torsades de pointes (ACC/AHA/HRS [Al-Khatib 2017]; Mazzanti 2016).
Amyotrophic lateral sclerosis, painful muscle spasms; Myotonic dystrophy (type 1); Ventricular premature beats
Substrate of CYP1A2 (Major), CYP2D6 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (Moderate);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Agomelatine. Risk C: Monitor
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Alosetron: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Risk D: Consider Therapy Modification
Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase active metabolite exposure of Anagrelide. Risk C: Monitor
Antihepaciviral Combination Products: May increase serum concentration of Mexiletine. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Bendamustine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider Therapy Modification
Broccoli: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Cannabis: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ClomiPRAMINE. Risk C: Monitor
CloZAPine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of CloZAPine. Risk C: Monitor
CYP1A2 Inducers (Moderate): May decrease serum concentration of Mexiletine. Risk C: Monitor
CYP1A2 Inhibitors (Strong): May increase serum concentration of Mexiletine. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of Mexiletine. Risk C: Monitor
Diazoxide Choline: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of DULoxetine. Risk C: Monitor
Etravirine: May decrease serum concentration of Mexiletine. Risk C: Monitor
Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Fezolinetant. Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of Mexiletine. Risk C: Monitor
Lacosamide: Mexiletine may increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Lidocaine (Topical): May increase adverse/toxic effects of Antiarrhythmic Agents (Class IB). Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Melatonin: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Melatonin. Risk C: Monitor
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of OLANZapine. Risk C: Monitor
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pentoxifylline. Risk C: Monitor
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider Therapy Modification
Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pomalidomide. Risk C: Monitor
Primaquine: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor
Propafenone: May increase serum concentration of Mexiletine. Risk C: Monitor
Propranolol: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Propranolol. Risk C: Monitor
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Ramelteon. Risk C: Monitor
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Ramosetron. Risk C: Monitor
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Risk D: Consider Therapy Modification
RifAMPin: May decrease serum concentration of Mexiletine. Risk C: Monitor
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ROPINIRole. Risk C: Monitor
ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ROPivacaine. Risk C: Monitor
Simeprevir: May increase serum concentration of Mexiletine. Risk C: Monitor
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Tasimelteon. Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider Therapy Modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with moderate CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
Tobacco (Smoked): May decrease serum concentration of Mexiletine. Risk C: Monitor
Vorasidenib: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Vorasidenib. Management: Avoid concurrent use with moderate CYP1A2 inhibitors when possible. If combined use cannot be avoided, monitor for evidence of adverse effects and adjust vorasidenib dose accordingly if necessary. Risk D: Consider Therapy Modification
Food may decrease the rate, but not the extent of oral absorption; diets which affect urine pH can increase or decrease excretion of mexiletine. Management: Avoid dietary changes that alter urine pH.
Mexiletine crosses the placenta (Timmis 1980).
Outcome data following maternal use of mexiletine during pregnancy are available from case reports (Gregg 1988; Lownes 1987; Timmis 1980).
Mexiletine is present in human milk.
Data related to the presence of mexiletine in breast milk are available from case reports (Lewis 1981; Monfort 2023; Timmis 1980). Concentrations in breast milk are similar to those in the maternal plasma.
Breastfeeding is not recommended by the manufacturer.
Liver function tests, ECG
Therapeutic range: 0.5 to 2 mcg/mL; potentially toxic: >2 mcg/mL
Class IB antiarrhythmic, structurally related to lidocaine, which inhibits inward sodium current, decreases rate of rise of phase 0, increases effective refractory period/action potential duration ratio
Onset of action: 30 to 120 minutes (with loading regimen)
Absorption: Well absorbed
Distribution: Vd: 5 to 7 L/kg
Protein binding: 50% to 60%
Metabolism: Hepatic via CYP2D6 metabolism to inactive metabolites (~90%) and major metabolites p-hydroxymexiletine, hydroxy-methylmexiletine, and N-hydroxy-mexiletine (minimal antiarrhythmic activity); low first-pass effect
Bioavailability: 90%
Half-life elimination: ~10 to 12 hours; ~ 15 hours in severe renal impairment (CrCl < 10 ml/min); ~ 25 hours in moderate to severe hepatic impairment
Time to peak, serum: 2 to 3 hours
Excretion: Urine (10% as unchanged drug); urinary acidification increases excretion, alkalinization decreases excretion
