MEXILETINE HYDROCHLORIDE

Posology Treatment with mexiletine should be initiated and monitored by a specialist experienced in the treatment of cardiac arrhythmias. The optimal dosage should be determined individually based on the patient's response and tolerance.

Adults In patients in whom rapid control of ventricular arrhythmia is needed, a loading dose of 400 mg may be given. A maintenance dose of 150 mg to 300 mg, two to three times daily is recommended. If necessary, dose may be adjusted in 50 or 100 mg increments.

A minimum of two to three days between dose adjustments is recommended. Dosage should not exceed 1200 mg per day. Paediatric population The safety and efficacy of Mexiletine Hard Capsules in children and adolescents aged 0 to 18 years have not yet been established.

No data are available. Elderly No dosage adjustment is required for older patients with normal renal function. Renal impairment No dosage adjustment is considered necessary in patients with mild or moderate renal impairment. 2). Hepatic impairment It is recommended to exercise caution in patients with mild or moderate hepatic impairment due to the potential for higher plasma exposure.

In those patients, a minimum of two weeks between dose adjustments is recommended. 2). Poor CYP2D6 metabolisers The major elimination pathway for mexiletine is through CYP2D6. There is a potential for increased plasma levels in CYP2D6 poor metabolisers (7% of the European population).

In those patients, a minimum of one week between dose adjustments is recommended. 2). Method of administration For oral use. Capsules should be swallowed whole with ample liquid, preferably with the patient in an upright position. It is advisable to take Mexiletine Hard Capsules with food to minimise gastrointestinal adverse effects.

Adverse effects have been ranked under headings of frequency using the following convention: very common (≥1/10); common (≥1/100; <1/10); uncommon (≥1/1,000; <1/100); rare (≥1/10,000; <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

System Organ Class 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 established from the available data) Blood and lymphatic system disorders neutropenia, agranulocyto sis leukopenia, thrombocyto penia Immune system disorders drug reaction with eosinophilia and systemic symptoms (DRESS) lupus like syndrome, dermatitis exfoliative, Stevens- Johnson syndrome System Organ Class 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 established from the available data) Psychiatric disorders insomnia somnolence hallucination s, confusional state Nervous system disorders dizziness, tremor, headache, paraesthesia, vision blurred, numbness seizure, speech disorders, amnesia, lost consciousnes s diplopia, dysgeusia Ear and labyrinth disorders vertigo, tinnitus Cardiac disorders tachycardia, palpitations, angina pain, atrial fibrillation, bradycardia heart failure atrioventricu lar block Vascular disorders flushing, hypotension circulatory collapse, hot flush Respiratory, thoracic and mediastinal disorders hiccups pulmonary fibrosis Gastrointesti nal disorders abdomina l pain, dyspepsia nausea, constipation, dry mouth diarrhoea, vomiting, oesophageal ulcers and perforation Hepatobiliary disorders hepatic function abnormal drug- induced liver injury, liver disorder, hepatitis Skin and subcutaneous tissue disorders acne, rash dry skin, alopecia Musculoskele tal and connective tissue disorders pain in the extremities arthralgia System Organ Class 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 established from the available data) General disorders and administratio n site conditions fatigue, asthenia, chest discomfort, malaise, ataxia Investigation s abnormal liver function tests Reproductive system and breast disorders impotence Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Considering the pro-arrhythmic potential of mexiletine and the lack of evidence of improved survival for class I antiarrhythmic agents in patients without life- threatening arrhythmias, the use of mexiletine should be reserved for patients with life-threatening ventricular arrhythmia.

Congestive Heart Failure (CHF) or Hypotension Mexiletine should be used with caution in patients with hypotension or congestive heart failure because of its potential for depressing myocardial contractility. Conduction Abnormalities Caution should be exercised when mexiletine is used in patients with first degree AV block or intraventricular conduction abnormalities.

If a ventricular pacemaker is operative, patients with second- or third-degree AV block may be treated with mexiletine if continuously monitored. Blood Dyscrasias Leukopenia and thrombocytopenia have been reported in clinical studies.

It is recommended that careful hematologic monitoring should be carried out in patients on mexiletine. Haemogram including WBC differential and platelet count should be performed prior to initiation of therapy. If significant hematologic changes are observed, the patients should be carefully evaluated, and, if warranted, mexiletine should be discontinued.

Blood counts usually returned to normal within one month of discontinuation. Drug reaction with eosinophilia and systemic symptoms (DRESS) DRESS refers to syndrome characterised by severe cutaneous eruptions, fever, lymphadenopathy, hepatitis, haematological abnormalities with eosinophilia and atypical lymphocytes and can involve other organs.

The latency between drug initiation and onset of disease is prolonged, typically between one to eight weeks. Severe systemic manifestations are responsible for a 10% mortality rate. Incidence of DRESS has been reported between 1:100 and 1:10,000 patients treated.

Several medicinal products including mexiletine have been identified as possible causes. Mexiletine should not be administered to patients with known hypersensitivity to mexiletine or any of the excipients of this product or to any local anaesthetic.

2). 5). If necessary, dose increase is recommended after a period of at least 7 days to ensure that steady-state levels are reached and mexiletine is well tolerated. 5). Patients with Liver Disease Mexiletine should be used with caution in patients with mild or moderate hepatic dysfunction.

Mexiletine should not be used in patients with severe hepatic impairment. Liver Injury Abnormalities of the liver function and rare instances of severe liver injury, including hepatic necrosis have been reported in association with mexiletine treatment.

It is recommended that patients in whom an abnormal liver test has occurred, or who have signs or symptoms suggesting liver dysfunction, be carefully evaluated. If persistent or worsening elevation of hepatic enzymes is detected, considerations should be given to discontinuing therapy.

Urinary pH Since renal excretion of mexiletine is greatly increased with acidification of urine, concomitant drug therapy or dietary regimens which substantially change urinary pH should be avoided while being treated with mexiletine.

Seizures Mexiletine Capsules should be used with caution in patients with history of seizures. Occupational Hazards Mexiletine causes CNS effects and patients should be warned about engaging in activities requiring mental alertness, judgement and physical coordination when these effects occur.

Electrolyte Disturbances Antiarrhythmic drugs may be ineffective in patients with electrolyte disturbances. Therefore, any electrolyte disturbances should be corrected as part of the management of ventricular arrhythmia. Electrolytic evaluation should be done prior to initiating and during therapy with mexiletine in every patient.

Mexiletine hydrochloride 100 mg Hard Capsules and Mexiletine hydrochloride 200 mg Hard Capsules contain sodium. These medicines contain less than 1 mmol sodium (23 mg) per capsule, that is to say essentially “sodium-free”.

1 • Sinus node dysfunction (unless a pacemaker is present) • Severe atrioventricular (AV) conduction disturbances (unless a pacemaker is present) • Severe heart failure (HF); cardiogenic shock