Mexiletine

Mexiletine is an oral class IB antiarrhythmic that is a structural analogue of lidocaine. It is used for ventricular arrhythmias, particularly in the long QT syndrome type 3, and for the muscle stiffness of non dystrophic myotonia. It is not first line for ventricular tachycardia. Gastrointestinal and nervous system side effects are common. It is not widely available in East Africa.

Classification. Class IB antiarrhythmic (sodium channel blocker).

Mechanism. Blocks the fast sodium channel in its inactivated state, shortening the action potential in ventricular tissue and slowing conduction in ischaemic tissue. In myotonia, it reduces the repetitive discharges of skeletal muscle.

Pharmacodynamics. Oral onset within 30 minutes to 2 hours, peak at 2 to 3 hours. Little effect on the ECG at therapeutic levels; slightly shortens the QT interval. Effective plasma level 0.5 to 2 mg/L.

Pharmacokinetics. Oral bioavailability about 90%. Half life 10 to 12 hours (longer in liver disease and after myocardial infarction). Metabolised by CYP2D6 and CYP1A2 in the liver; about 10% excreted unchanged in urine. Urinary acidification speeds elimination.

Ventricular arrhythmias, adult.

• Start 200 mg every 8 hours with food (or 400 mg loading dose then 200 mg every 8 hours after 2 hours in monitored conditions).

• Increase by 50 to 100 mg a day every 2 to 3 days to the lowest effective dose.

• Usual maintenance 600 to 900 mg daily in 3 doses; maximum 1200 mg daily.

Non dystrophic myotonia (specialist), adult. Start 200 mg once daily; increase weekly to 200 mg three times daily (600 mg daily) if needed; maximum 1200 mg daily.

Long QT syndrome type 3 (specialist). 200 mg every 8 hours; maximum 900 mg daily.

Children (specialist). 1.4 to 5 mg/kg every 8 hours (maximum 900 mg daily).

Contraindications. Second or third degree atrioventricular block without a pacemaker; cardiogenic shock; severe heart failure; asymptomatic ventricular ectopy after myocardial infarction (higher mortality in a large post infarction study); hypersensitivity; severe sinoatrial disease.

Warnings. Proarrhythmia; heart failure (mild negative inotropy); seizures; liver damage (rare but serious; check enzymes); hypotension; nausea and vomiting (take with food); tremor. Smokers need higher doses because of enzyme induction.

Adverse effects. Nausea, vomiting, heartburn, tremor, dizziness, ataxia, blurred vision, drowsiness, confusion, bradycardia, rash, abnormal liver tests.

Interactions. Theophylline: raised levels. Caffeine: raised levels. CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) and CYP2D6 inhibitors (fluoxetine, quinidine): raised mexiletine levels. Rifampicin, phenytoin, carbamazepine: lower levels. Opioids and atropine: delay absorption. Cimetidine: raised levels. Beta blockers and other antiarrhythmics: additive effect.

Special groups.

• Pregnancy: avoid unless essential; limited data.

• Breastfeeding: excreted in milk; avoid.

• Patients of African ancestry: no dose change.

• Older adults: start 150 mg every 8 hours; monitor for dizziness and falls.

• Kidney impairment: reduce the dose when creatinine clearance is under 10 mL/min.

• Liver impairment: reduce the dose by 25 to 50%; monitor liver enzymes.

Formulations. Capsules 150, 200, 250 mg; injection in some markets.

Administration. Oral with food or antacid to reduce stomach upset, in 3 divided doses.

Baseline. ECG, echocardiogram, liver enzymes, full blood count, creatinine.

Monitoring. ECG after each dose change and at least yearly. Liver enzymes at baseline, 1 month, then every 6 months. Plasma level when adjusting dose with interacting drugs. Neurological symptoms and weight.

Stopping. Taper over days to weeks where possible.

Common prescribing errors. Starting at a high dose without food; forgetting theophylline level checks; combining with ciprofloxacin; failing to dose adjust in liver disease; treating ventricular ectopy after infarction.