Adult: Doses are expressed in terms of mexiletine base (200 mg mexiletine hydrochloride is equivalent to approx 166.2 mg of mexiletine base). In patients with non-dystrophic myotonic disorders: Initially, 167 mg once daily for at least 1 week. Dose may be increased to 333 mg once daily for at least 1 week, then may be further increased to 500 mg once daily according to clinical response. Maintenance: 167-500 mg daily, depending on intensity of symptoms and clinical response. Max: 500 mg daily. Treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Oral Life-threatening ventricular arrhythmias
Adult: Doses are expressed in terms of mexiletine hydrochloride (200 mg mexiletine hydrochloride is equivalent to approx 166.2 mg mexiletine base). For rapid control: 400 mg as loading dose, followed by maintenance dose of 150-300 mg 8-12 hourly. When rapid control is not essential: Initially, 200 mg 8 hourly. Doses may be adjusted in increments or decrements of 50 mg or 100 mg at intervals of at least 2-3 days. Usual dose: 200-300 mg 8 hourly. Max: 400 mg 8 hourly. In treatment-responsive patients receiving 300 mg or less 8 hourly, dosing may be adjusted to 12 hourly schedule; up to a Max of 450 mg 12 hourly may be given if necessary. Dosage recommendations may vary among countries and between individual products (refer to specific product guidelines).
Hepatic Impairment
Mild or moderate: Dose may be increased after at least 2 weeks of treatment.
Administration
Should be taken with food.
Contraindications
Cardiogenic shock, 2nd- or 3rd-degree AV block (unless a functional artificial pacemaker is in place). Contraindications may vary between individual products (refer to specific product guidelines).
Special Precautions
Patient with severe heart failure, sinus node dysfunction or other conduction disorders, 1st-degree AV block, MI, hypotension, epilepsy or history of seizures. Avoid use in patients with asymptomatic ventricular premature contractions. Avoid concomitant use or dietary regimens that may significantly affect urinary pH. Hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Abnormal LFTs (e.g. elevations in AST >3 times the ULN); proarrhythmic effects or aggravation of arrhythmia (particularly in patients with life-threatening arrhythmia); blood dyscrasias (e.g. leucopenia, agranulocytosis, thrombocytopenia), seizures, drug reactions with eosinophilia and systemic symptoms (DRESS). Rarely, severe liver injury, including hepatic necrosis. Cardiac disorders: Palpitations, angina pectoris. Ear and labyrinth disorders: Tinnitus, vertigo. Eye disorders: Blurred vision, nystagmus. Gastrointestinal disorders: Gastrointestinal distress, oesophageal ulceration, abdominal pain, constipation, diarrhoea, nausea, vomiting, dry mouth. General disorders and administration site conditions: Asthenia, fatigue, malaise, chest discomfort. Investigations: Positive antinuclear factor titres. Musculoskeletal and connective tissue disorders: Arthralgia, pain in extremities. Nervous system disorders: Dizziness, ataxia, paraesthesia, tremor, headache. Psychiatric disorders: Nervousness, insomnia, somnolence, confusion. Respiratory, thoracic and mediastinal disorders: Dyspnoea, pulmonary fibrosis. Skin and subcutaneous tissue disorders: Rash, alopecia. Vascular disorders: Flushing, hypotension.
This drug may cause tiredness, confusion or blurred vision, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor and correct electrolyte disturbances (particularly hypokalaemia, hypomagnesaemia) before starting and during treatment. Monitor LFTs, cardiac status (e.g. ECG, Holter monitoring); CBC (before and during therapy). Assess for CNS changes (e.g. tremors, ataxia, dizziness, nervousness).
Management: Symptomatic and supportive treatment. Perform gastric lavage. May administer IV atropine for CV complications. Administer benzodiazepines in case of seizures. Urine acidification may enhance mexiletine elimination.
Drug Interactions
May increase serum concentration with CYP1A2 inhibitors (e.g. fluvoxamine) and CYP2D6 inhibitors (e.g. propafenone). May decrease serum concentration with CYP1A2 inducers (e.g. omeprazole). Delayed absorption with drugs that slow gastric emptying (e.g. opioid analgesics, atropine, antacids). Increased rate of absorption with metoclopramide. May increase the plasma concentration of CYP1A2 substrates (e.g. caffeine, theophylline).
Action
Description: Overview: Mexiletine is a class Ib antiarrhythmic agent with muscle relaxant properties. Mechanism of Action: Mexiletine binds to receptors in the fast sodium channel, inhibiting inward sodium current and resulting in decreased maximal rate of depolarisation of phase 0 of the action potential. It decreases the effective refractory period (ERP) in Purkinje fibres, which is of lesser magnitude than the reduction in action potential duration (ADP), resulting in an increased ERP/ADP ratio. Pharmacodynamics: Mexiletine produces a significant reduction of ventricular premature beats, paired beats and non-sustained ventricular tachycardia episodes. It causes little to no prolongation of the QT and PR interval or QRS complex, and it has no clinically important effect on heart rate, systolic arterial blood pressure, or myocardial function. Additionally, it does not generally affect conduction velocity, although it may slow conduction in patients with preexisting conduction abnormalities. In patients with preexisting sick sinus syndrome, it can produce a more marked depression of sinus rate and/or prolonged sinus node recovery time. Onset: Life-threatening ventricular arrhythmias: 30-120 minutes (with loading regimen). Pharmacokinetics: Absorption: Readily and almost completely absorbed from the gastrointestinal tract. Bioavailability: Approx 90%. Time to peak plasma concentration: 2-3 hours. Distribution: Widely distributed in the body. Crosses the placenta and enters breast milk. Volume of distribution: 5-7 L/kg. Plasma protein binding: Approx 50-70%. Metabolism: Metabolised in the liver mainly by CYP2D6 isoenzyme and to a lesser extent by CYP1A2 via various pathways, including aromatic and aliphatic hydroxylation, dealkylation, deamination, and N-oxidation, into inactive metabolites (approx 90%) and major metabolites (p-hydroxymexiletine, hydroxy-methylmexiletine, and N-hydroxymexiletine), which undergo further metabolism via conjugation with glucuronic acid. Undergoes minimal first-pass metabolism. Excretion: Via urine (approx 10% as unchanged drug). Elimination half-life: Approx 10-12 hours.
Chemical Structure
Mexiletine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4178, Mexiletine. https://pubchem.ncbi.nlm.nih.gov/compound/Mexiletine. Accessed Oct. 26, 2020.
C01BB02 - mexiletine ; Belongs to class Ib antiarrhythmics.
References
Brayfield A, Cadart C (eds). Mexiletine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/10/2025.Joint Formulary Committee. Mexiletine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/10/2025.Mexiletine Hydrochloride 50 mg Hard Capsules (Clinigen Healthcare Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 15/10/2025.Mexiletine Hydrochloride Capsule (Lannett Company, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 15/10/2025.Mexiletine Hydrochloride. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 15/10/2025.Mexiletine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 15/10/2025.Namuscla 167 mg Hard Capsules (Lupin Europe GmbH). MHRA. https://products.mhra.gov.uk. Accessed 15/10/2025.Namuscla 42 mg Hard Capsules (Lupin Europe GmbH). MHRA. https://products.mhra.gov.uk. Accessed 15/10/2025.Namuscla 83 mg Hard Capsules (Lupin Europe GmbH). MHRA. https://products.mhra.gov.uk. Accessed 15/10/2025.
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