NAMUSCLA

Posology The recommended starting dose of Namuscla is 167 mg daily. After at least 1 week of treatment, based on the clinical response, the daily dose can be increased up to 333 mg daily. After at least 1 further week of treatment, based on clinical response, the dose can be further increased up to a maximum of 500 mg daily.

Depending on clinical response and tolerability, a slower dose escalation may be considered based on clinical assessment. Maintenance treatment is between 167 mg – 500 mg daily, according to the intensity of symptoms and the clinical response, taken regularly throughout the day.

Namuscla 83 mg capsules and/or 167 mg capsules can be substituted at equivalent doses to the 42mg capsules to rationalise the dosing regimen and reduce the capsules burden to the patient. The dose should not exceed 500 mg/day. Regular reassessment should be implemented, not to continue long-term treatment in a patient not responding or not experiencing benefit of the treatment.

4). 4). Elderly Experience with mexiletine in patients with myotonic disorders aged > 65 years is limited. Based on the pharmacokinetic properties of mexiletine, no dosage adjustment is required in patients aged 65 years and over. Hepatic impairment Mexiletine should be used with caution in patients with mild or moderate hepatic impairment.

In these patients, it is recommended that the dose should only be increased after at least 2 weeks of treatment. 4). Renal impairment No dosage adjustment is considered necessary in patients with mild or moderate renal impairment. The experience with mexiletine in patients with severe renal impairment is limited.

4). Paediatric population The safety and efficacy of mexiletine in children and adolescents aged 0 to 18 years have not been established. No data are available. 2). A period of at least 7 days before dose increase must be respected to ensure that steady-state levels are reached, irrespective of the patient’s CYP450 polymorphism.

Method of administration Oral use. The capsules should be swallowed with water, avoiding the supine position. In case of digestive intolerance, capsules should be taken during a meal.

Summary of the safety profile The most commonly reported adverse reactions in patients treated with mexiletine are abdominal pain (12%), vertigo (8%) and insomnia (12%). The most serious reported adverse reactions in patients treated with mexiletine are drug reaction with eosinophilia and systemic symptoms and arrhythmia (atrioventricular block, arrhythmia, ventricular fibrillation).

Tabulated list of adverse reactions Frequency categories are derived according to the following conventions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

Very common and common adverse reactions are derived from data from the MYOMEX study; less common adverse effects are derived from post-marketing data. Blood and lymphatic system disorders Not known: leukopenia, thrombocytopenia Immune system disorders Very rare: drug reaction with eosinophilia and systemic symptoms Not known: lupus-like syndrome, dermatitis exfoliative, Stevens-Johnson syndrome Psychiatric disorders Very common: insomnia Common: somnolence Not known: hallucinations, confusional state Nervous system disorders Common: headache, paraesthesia, vision blurred Uncommon: seizure, speech disorders Not known: diplopia, dysgeusia Ear and labyrinth disorders Common: vertigo Cardiac disorders Common: tachycardia Uncommon: bradycardia Not known: atrioventricular block Vascular disorders Common: flushing, hypotension Not known: circulatory collapse, hot flush Respiratory, thoracic and mediastinal disorders Not known: pulmonary fibrosis Gastrointestinal disorders Very common: abdominal pain Common: nausea Not known: diarrhoea, vomiting, oesophageal ulcers and perforation Hepatobiliary disorders Rare: hepatic function abnormal Very rare: drug-induced liver injury, liver disorder, hepatitis Skin and subcutaneous tissue disorders Common: acne Musculoskeletal and connective tissue disorders Common: pain in the extremities General disorders and administration site conditions Common: fatigue, asthenia, chest discomfort, malaise Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Cardiac arrhythmogenic effects Mexiletine may induce an arrhythmia or accentuate a pre-existing arrhythmia, either diagnosed or undiagnosed. 5 regarding association with other products with arrhythmogenic effects. Before starting mexiletine treatment, detailed and careful cardiac evaluation (ECG, 24-48-hour Holter-monitoring and echocardiography) should be carried out in all patients in order to determine the cardiac tolerability of mexiletine.

g. within 48 hours). Throughout treatment with mexiletine, and in relation with dose changes, cardiac monitoring of patients needs to be adapted as a function of the heart condition of the patient: • In patients without cardiac abnormalities, periodic ECG monitoring is recommended (every 2 years or more frequently if considered necessary).

• In patients with cardiac abnormalities, and in patients prone to such abnormalities, detailed cardiac evaluation, including ECG, should be carried out before and after any dose increase. During maintenance treatment, detailed cardiac evaluation, including ECG, 24-48 hour Holter-monitoring and echocardiography, is recommended at least annually, or more frequently if considered necessary as part of routine cardiac assessment.

Patients should be informed about the presenting symptoms of arrhythmias (fainting, palpitation, chest pain, shortness of breath, light-headedness, lipothymia, and syncope) and should be advised to immediately contact an emergency centre if there are any symptoms of arrhythmias.

3, the benefit of the antimyotonic effects of mexiletine needs to be balanced against the risk of cardiac complications on a case by case basis. 3 are detected. Electrolytic imbalance such as hypokalaemia, hyperkalaemia or hypomagnesaemia may increase the proarrhythmic effects of mexiletine.

Therefore, electrolytic evaluation should be done prior to initiating therapy with mexiletine in every patient. Electrolyte imbalance needs to be corrected before administering mexiletine and to be monitored throughout treatment (with a periodicity to be adapted patient by patient).

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