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Mexiletine for Non-Dystrophic Myotonia: the National Hospital for Neurology and Neurosurgery Prescription Guidelines Consultants: Professor M. Hanna, Consultant Neurologist, Dr D. Fialho, Consultant Neurophysiologist, Dr E Matthews, Consultant Neurologist, Dr K Savvatis, Consultant Cardiologist. Specialist Nurse: Natalie James. Clinical Fellows: Dr K Suetterlin, Dr Oliver Watkinson. Date for Guideline Review January 2021 . Suetterlin K, Bugiardini E, Kaski JP, et al. Long -term Safety and Efficacy of Mexiletine for Patients with Skeletal Muscle Channelopathies. JAMA Neurol. 2015;72(12):1531-1533. doi:10.1001/jamaneurol.2015.2338. 1 Prior to Mexiletine prescription: 1.1 Ensure baseline ECG normal, enquire about cardiac symptoms and/or history of cardiac disease (especially history of myocardial infarction in the previous 2 years, history of congestive heart failure, sinus or AV node disease). 1.2 Check no drug interactions with existing medication. 1.3 If possibility of hepatic or renal impairment, check baseline LFT/U&E/Coagulation and consider liaising with appropriate specialty prior to mexiletine prescription. 1.4 If pre-existing reflux consider investigation and or treatment e.g. H. pylori eradication as symptoms may be exacerbated by mexiletine. 2 Refer or discuss with cardiology prior to prescription if: 2.1 Abnormal baseline ECG (1st degree or higher AV-block, prolonged QRS duration). 2.2 Any cardiac history. 3 Counselling of patients: 3.1 Dyspepsia is by far the most common adverse effect (37%). Other adverse effects reported in audited patients whilst taking mexiletine (without clear alternative precipitant) included headache 8%, palpitations 6%, nausea 5%, tremor 1.5%. 3.2 Incidence of significant cardiac or other, adverse effect very low (none in our audit of 63 patients with mean follow up 4.8 years). However, patient should be counselled to seek urgent medical attention if they develop any cardiac symptoms, particularly if suggestive of syncope, arrhythmia, angina or heart failure and highlight that they are taking mexiletine. 3.3 Mexiletine is relatively contraindicated post myocardial infarction, if MI occurs whilst on mexiletine its cessation must be discussed with a cardiologist. 4 Dose Titration: Adequate dose titration is necessary to determine efficacy and slow dose titration seems to improve tolerability. Start with 100mg mexiletine once daily and increase by 100mg per week to a maximum of 200mg three times a day or dose at which symptom control is adequate whichever is the lesser amount. 4.1 If dyspepsia limits dose titration consider additional pharmacotherapy (e.g. omeprazole) to facilitate reaching sufficient mexiletine dose for adequate treatment trial (200mg TDS). 4.2 In refractory cases and where adverse effects allow, consider further dose titration to a total of 800mg mexiletine daily. However, patients should be counselled about the higher risk of side effects associated with this dose (e.g. dyspepsia). 5 Monitoring of patients on Mexiletine 5.1 Repeat ECG after initial dose titration complete (approximately 2 weeks after stabilised at effective dose). 5.2 Repeat ECG if significant dose change. 5.3 Repeat ECG if any concern over cardiac symptom and consider referral to Cardiology. 5.4 If mexiletine dose unchanged, no new cardiac symptoms, interacting medications or other related patient concerns then routine annual monitoring ECG not indicated (based on audit). 6 When to discuss or refer patients on mexiletine to a cardiologist 6.1 If significant ECG change e.g. atrial fibrillation, heart block. 6.2 If any new cardiac symptom e.g. arrhythmia, syncope, dyspnoea.