Mexiletine: class 1b antiarrhythmic in myotonia and arrhythmias
Mexiletine (brand name Namuscla in the EU for myotonia, Mexitil in some countries for arrhythmias) is an oral class 1b antiarrhythmic according to Vaughan Williams. Structurally and pharmacologically it resembles the local anaesthetic lidocaine but, unlike lidocaine, it is orally bioavailable and therefore suitable for long term therapy. Mexiletine was introduced in Germany and the US as an antiarrhythmic in 1976.
In 2018 Namuscla received EU approval for the symptomatic treatment of non dystrophic myotonia in adults. This made mexiletine the first approved oral therapy for this rare neuromuscular disease. In the US, mexiletine has this specific indication as an orphan drug.
Mechanism of action
Mexiletine blocks voltage gated sodium channels (mainly Nav1.5 in the heart and Nav1.4 in skeletal muscle) in their inactivated state. Class 1b is characterised by short binding duration with minimal effect on phase 0 of the action potential in normal cells but pronounced effect in pathologically depolarised or ischaemic tissue.
In the heart mexiletine acts antiarrhythmically by inhibiting repetitive activations, particularly in damaged myocardium. In skeletal muscle the sodium channel block reduces the persistent hyperexcitability after voluntary movement that is typical of myotonia. The result is a perceptible improvement of myotonic symptoms with reduced stiffness and better mobility.
Mexiletine is metabolised hepatically via CYP2D6. The half life is 10 to 12 hours, requiring twice or three times daily dosing.
Indications
- Non dystrophic myotonia: symptomatic therapy in adults with myotonia congenita (Becker and Thomsen), paramyotonia congenita, potassium aggravated myotonia
- Ventricular arrhythmias: in structurally normal hearts, particularly in long QT syndrome type 3 with SCN5A mutation
- Off label: myotonic dystrophy, neuropathic pain (limited data), erythromelalgia
Dosing and administration
Non dystrophic myotonia (Namuscla): starting dose 167 mg once daily, gradually increasing to 167 mg three times daily (equivalent to 200 mg mexiletine hydrochloride three times daily). Maximum dose according to clinical response.
Ventricular arrhythmias: 200 to 400 mg every 8 hours, depending on response and tolerability.
Take with meals to reduce gastrointestinal complaints. Step up gradually over several days.
Level monitoring: in risk patients or with suspected toxicity. Therapeutic range 0.5 to 2.0 mg per litre.
Renal impairment: usually no dose adjustment. Liver disease: prolonged half life, caution and possible dose reduction.
Adverse effects
Common: gastrointestinal complaints (nausea, abdominal pain, heartburn), tremor, dizziness, headache, sleep disturbance, visual disturbance.
Uncommon: slurred speech, concentration difficulties, hypotension, bradycardia, rash, mildly raised liver transaminases.
Rare: proarrhythmia with ventricular arrhythmias, seizures, severe skin reactions (DRESS syndrome, Stevens Johnson syndrome), hepatitis, pulmonary fibrosis.
Important points:
- In non dystrophic myotonia therapy is generally well tolerated; severe adverse events are rare
- Before starting therapy: ECG, liver enzymes, pregnancy test
- If a rash appears, exclude DRESS syndrome and stop therapy immediately
- In structural heart disease use with caution and careful indication
Interactions
- CYP2D6 substrates (codeine, tricyclics, antipsychotics, other antiarrhythmics): level changes, individual assessment
- Other antiarrhythmics: additive effect, risk of proarrhythmia
- QT prolonging substances: theoretical interaction, clinically rarely relevant under mexiletine
- Theophylline: raised theophylline levels with concurrent therapy
- Phenytoin and rifampicin: reduced levels through CYP induction
- Cimetidine: moderate level increase
Special considerations
Pregnancy: limited data. Mexiletine is occasionally used maternally for fetal tachycardia. In myotonia individual evaluation.
Breastfeeding: small amounts pass into milk, individual assessment.
Children: use is rare and limited to specialised centres.
Contraindications: cardiogenic shock, second or third degree AV block without pacemaker, sinoatrial block, severe bradycardia, manifest heart failure, severe hypotension, acute porphyria.
Follow up: ECG before start and during the first weeks, then every 3 to 6 months. Liver enzymes and blood count regularly. In myotonia clinical assessment of symptoms with standardised tests.
Patient communication: in myotonia mexiletine means a clear improvement of quality of life for many patients. Realistic expectations and information about possible adverse events support adherence.
Related substances
- Flecainide, class 1c antiarrhythmic
- Propafenone, another class 1c
- Quinidine, class 1a antiarrhythmic
- Lidocaine, class 1b local anaesthetic with similar mechanism
Frequently asked questions
What is non dystrophic myotonia?
A rare neuromuscular disease with delayed muscle relaxation after voluntary movement. Unlike myotonic dystrophy patients are otherwise muscularly healthy. Common forms are myotonia congenita (Becker and Thomsen) and paramyotonia congenita.
How quickly does mexiletine work in myotonia?
First effects are often visible within a few days, full effect develops over 2 to 4 weeks after up titration. Patients often report reduced stiffness on movement, fewer falls and better day to day function.
What checks are needed?
Before starting therapy ECG, liver enzymes, blood count, pregnancy test. Regular ECGs and assessment of efficacy and tolerability during therapy. Medical evaluation for rash or new symptoms.
Can I take mexiletine long term?
Yes, in myotonia long term therapy is usual. Therapy is adapted individually with regular re evaluation. With stable course the dose can sometimes be reduced; when worse it is increased.
Sources
- EMA Namuscla (mexiletine) EPAR
- BfArM German Federal Institute for Drugs and Medical Devices
- AWMF guidelines neurology and cardiology
- Gelbe Liste mexiletine monograph
Legal notice and disclaimer
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