Mexiletine
/api/v1/drug/mexiletineMechanism of action
Sourced from openFDAMechanism-of-action class: Sodium Channel Interactions.
Indications
Sourced from openFDA- 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.
Contraindications
Sourced from openFDA- Mexiletine hydrochloride capsules are contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree AV block (if no pacemaker is present).contraindicated
Dosage & administration
Sourced from openFDAThe dosage of mexiletine hydrochloride must be individualized on the basis of response and tolerance, both of which are dose-related. Administration with food or antacid is recommended. Initiate mexiletine therapy with 200 mg every eight hours when rapid control of arrhythmia is not essential. A minimum of two to three days between dose adjustments is recommended. Dose may be adjusted in 50 or 100 mg increments up or down. As with any antiarrhythmic drug, clinical and electrocardiographic evaluation (including Holter monitoring if necessary for evaluation) are needed to determine whether the desired antiarrhythmic effect has been obtained and to guide titration and dose adjustment. Satisfactory control can be achieved in most patients by 200 to 300 mg given every eight hours with food or antacid. If satisfactory response has not been achieved at 300 mg q8h, and the patient tolerates mexiletine well, a dose of 400 mg q8h may be tried. As the severity of CNS side effects increases with total daily dose, the dose should not exceed 1200 mg/day. In general, patients with renal failure will require the usual doses of mexiletine hydrochloride. Patients with severe liver disease, however, may require lower doses and must be monitored closely. Similarly, marked right-sided congestive heart failure can reduce hepatic metabolism and reduce the needed dose. Plasma level may also be affected by certain concomitant drugs (see PRECAUTIONS, Drug Interactions ).
Warnings & precautions
Sourced from openFDABOXED WARNING WARNINGS Mortality In the National Heart, Lung and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicentered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously, an excessive mortality or non-fatal 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 ten months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) 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 arrhythmia. Acute Liver Injury In postmarketing experience abnormal liver function tests have been reported, some in the first few weeks of therapy with mexiletine hydrochloride. Most of these have been observed in the setting of congestive heart failure or ischemia and their relationship to mexiletine hydrochloride has not been established.
Adverse reactions
Sourced from openFDAMexiletine hydrochloride commonly produces reversible gastrointestinal and nervous system adverse reactions but is otherwise well tolerated. Mexiletine has been evaluated in 483 patients in one month and three month controlled studies and in over 10,000 patients in a large compassionate use program. Dosages in the controlled studies ranged from 600 to 1200 mg/day; some patients (8%) in the compassionate use program were treated with higher daily doses (1600 to 3200 mg/day). In the three month controlled trials comparing mexiletine to quinidine, procainamide and disopyramide, the most frequent adverse reactions were upper gastrointestinal distress (41%), lightheadedness (10.5%), tremor (12.6%) and coordination difficulties (10.2%). Similar frequency and incidence were observed in the one month placebo-controlled trial. Although these reactions were generally not serious, and were dose-related and reversible with a reduction in dosage, by taking the drug with food or antacid or by therapy discontinuation, they led to therapy discontinuation in 40% of patients in the controlled trials. Table 1 presents the adverse events reported in the one-month placebo-controlled trial.
Overdosage
Sourced from openFDAClinical findings associated with mexiletine overdosage have included drowsiness, confusion, nausea, hypotension, sinus bradycardia, paresthesia, seizures, bundle branch block, AV heart block, asystole, ventricular tachyarrythmia, including ventricular fibrillation, cardiovascular collapse and coma. The lowest known dose in a fatality case was 4.4 g with postmortem serum mexiletine level of 34 to 37 mcg/mL (Jequier P. et. al., Lancet 1976: 1 (7956): 429). Patients have recovered from ingestion of 4 g to 18 g of mexiletine (Frank S. E. et. al., Am J Emerg Med 1991: 9:43-48). There is no specific antidote for mexiletine. Management of mexiletine overdosage includes general supportive measures, close observation and monitoring of vital signs. In addition, the use of pharmacologic interventions (e.g., pressor agents, atropine or anticonvulsants) or transvenous cardiac pacing is suggested, depending on the patient’s clinical condition.
Approval history
Sourced from openFDA- May 16, 1995ANDAANDA074377Teva
- May 16, 1996ANDAANDA074450Ani Pharms
- Jul 22, 2020ANDAANDA213500Crossmedika Sa
- Jan 25, 2021ANDAANDA214352Ingenus Pharms Llc
- Oct 1, 2021ANDAANDA214089Senores Pharms
- May 25, 2022ANDAANDA202111Hospira
- Aug 26, 2022ANDAANDA215315Rising
- Nov 9, 2022ANDAANDA216463Annora Pharma
FAERS reports
- 1Drug Ineffective4210%
- 2Fatigue327.7%
- 3Ventricular Tachycardia317.5%
- 4Dyspnoea276.5%
- 5Nausea245.8%
- 6Poor Quality Sleep245.8%
- 7Impaired Work Ability235.6%
- 8Impaired Quality Of Life225.3%
- 9Pyrexia225.3%
- 10Pneumonia194.6%
- 11Cardiac Failure184.3%
- 12Hypertension184.3%
- 13Contusion153.6%
- 14Alanine Aminotransferase Increased143.4%
- 15Cardiac Failure Congestive143.4%
Literature
Recent PubMed references pinned to Mexiletine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.
- Stability assessment of a novel 3D-printed oral dosage form of Mexiletine Hydrochloride: a six-month shelf-life study.Pharmaceutical development and technology · 2025 · Ait Hoummad A, Ramcharan A, Shokri F, et al.PMID 41239893DOI 10.1080/10837450.2025.2590122
- Towards development of Nav1.7 channel modulators for pain treatment: A comparison of mexiletine effect in two cell models by automated patch clamp.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025 · Cerchiara AG, Marinelli M, Boccanegra B, et al.PMID 40795473DOI 10.1016/j.biopha.2025.118450
- Antiarrhythmic efficacy and safety of oral mexiletine in dogs with ventricular arrhythmias: a multicentre, retrospective analysis.Journal of the American Veterinary Medical Association · 2025 · Romito G, Mazzoldi C, Travaglini S, et al.PMID 40523634DOI 10.2460/javma.25.02.0088
- Pharmacogenetic pilot study of CYP2D6 and CYP1A2 genes in Italian patients with non-dystrophic myotonia and myotonic dystrophy treated with mexiletine.Gene · 2025 · Brugnoni R, Salvi E, Moresco E, et al.PMID 40324568DOI 10.1016/j.gene.2025.149536
- Evaluation of professional practices in the use of mexiletine for the management of childhood myotonia in French pediatric neuromuscular centers (MEXI-PEDI survey).Archives de pediatrie : organe officiel de la Societe francaise de pediatrie · 2025 · Barrière S, Manel V, Barnerias C, et al.PMID 39875220DOI 10.1016/j.arcped.2024.10.009
- Effects of SZV-2649, a new multiple ion channel inhibitor mexiletine analogue.Scientific reports · 2024 · Mohammed ASA, Naveed M, Szabados T, et al.PMID 39369049DOI 10.1038/s41598-024-73576-5
- Recommendations of an expert group for the cardiac assessment of non-dystrophic myotonia adult patients treated with mexiletine.Neuromuscular disorders : NMD · 2024 · Vicart S, Wahbi K, Duchateau J, et al.PMID 39368428DOI 10.1016/j.nmd.2024.104464
- Severe caffeine poisoning with mexiletine successfully treated by extracorporeal methods.The American journal of emergency medicine · 2024 · Kohara S, Kamijo Y, Kyan R, et al.PMID 39343625DOI 10.1016/j.ajem.2024.09.034
Clinical trials
The 10 most recently updated of 34 ClinicalTrials.gov registrations naming Mexiletine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- Anti-arrhythmic Therapy vs Catheter Ablation as First Line Treatment for AICD Shock PreventionTerminated · Phase 4 · Interventional · 3 enrolled · Ottawa Heart Institute Research CorporationNCT02114528updated 2026-05-04
- Non-Invasive Programmed Stimulation (NIPS) to Guide the Subsequent VT Therapeutic StrategiesRecruiting · Interventional · 51 enrolled · IRCCS Ospedale San RaffaeleNCT06669299updated 2026-03-27
- The Efficacy and Safety of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2Recruiting · Phase 3 · Interventional · 176 enrolled · Lupin Ltd.NCT06523400updated 2026-02-06
- An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2 Who Have Completed MEX-DM-302 Study.Enrolling by invitation · Phase 3 · Interventional · 176 enrolled · Lupin Ltd.NCT06549400updated 2026-01-26
- An Open-Label, Randomized, Cross-Over Study to Investigate the Efficacy and Safety of Mexiletine PR Compared to Mexiletine IRRecruiting · Phase 3 · Interventional · 24 enrolled · Lupin Ltd.NCT07097701updated 2025-12-22
- Prospective, Long Term, Observational Study (Patient Registry) of Paediatric Myotonic DisordersRecruiting · Observational · 10 enrolled · Lupin Ltd.NCT07154654updated 2025-09-23
- Open-label Extension Study in Paediatric Patients Who Have Completed the MEX-NM-301 Study.Active not recruiting · Interventional · 14 enrolled · Lupin Ltd.NCT04622553updated 2025-07-25
- An Observational Study in Adult Patients With Non-dystrophic Myotonic DisordersActive not recruiting · Observational · 53 enrolled · Lupin Ltd.NCT04616807updated 2025-07-25
- Clinical Trial of Mexiletine Hydrochloride for Spinal and Bulbar Muscular AtrophyRecruiting · Phase 2 · Phase 3 · Interventional · 68 enrolled · Masahisa KatsunoNCT06862596updated 2025-04-16
- Open Label Study in Adolescents and Children With Myotonic DisordersCompleted · Phase 3 · Interventional · 12 enrolled · Lupin Ltd.NCT04624750updated 2024-11-25
Frequently asked questions
- How does Mexiletine work?
- Mechanism-of-action class: Sodium Channel Interactions.
- What is Mexiletine used for?
- According to FDA labeling, Mexiletine carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Mexiletine?
- Mexiletine is classified as Antiarrhythmics, class Ib, Antiarrhythmic, Sodium Channel Interactions, Cardiac Rhythm Alteration.
- What are the contraindications for Mexiletine?
- Mexiletine labeling lists contraindications including: Mexiletine hydrochloride capsules are contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree AV block (if no pacemaker is present).. Always consult the full prescribing information and a clinician.
mexiletine is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.