VIMPAT

1 Dosing Considerations VIMPAT may be taken with or without food. VIMPAT®, lacosamide Product Monograph Page 5 of 49 Initiation  VIMPAT therapy can be initiated with either oral or intravenous (IV) administration.  VIMPAT solution for injection for IV use is an alternative when oral administration is temporarily not feasible.

 Conversion to or from oral and IV administration can be done directly without titration. The total daily dose and twice daily administration should be maintained. 2 Recommended Dose and Dosage Adjustment Monotherapy The recommended starting dose is 100 mg twice a day (200 mg/day), with or without food.

Depending on patient response and tolerability, the dose can be further increased at weekly intervals by 50 mg twice a day (100 mg/day), to a maximum recommended maintenance daily dose of 300 mg twice a day (600 mg/day). 2 Study Results, Monotherapy).

In patients having reached VIMPAT ≥400mg/day and who need an additional antiepileptic drug, the dosing that is recommended for adjunctive therapy below should be followed. Maximum recommended daily dose for adjunctive therapy is 400 mg/day.

Adjunctive Therapy The recommended starting dose for VIMPAT is 50 mg twice a day, with or without food, which should be increased to an initial therapeutic dose of 100 mg twice a day after one week. Depending on patient response and tolerability, the maintenance dose can be further increased by 50 mg twice a day every week, to a maximum recommended daily dose of 400 mg (200 mg twice a day).

Doses above 400 mg/day do not confer additional benefit, are associated with more severe and substantially higher frequency of adverse reacti ons and are not recommended (see

). Patients should be informed that if visual disturbances occur, they should notify their physician promptly. If visual disturbance persists, further assessment, including dose reduction and possible discontinuation of VIMPAT, should be considered.

More fre quent assessments should VIMPAT®, lacosamide Product Monograph Page 14 of 49 be considered for patients with known vision-related issues or those who are already routinely monitored for ocular conditions. Psychiatric Suicidal Ideation and Behaviour Suicidal ideation and behaviour have been reported in pati ents treated with antiepileptic agents in several indications.

All patients treated with antiepileptic drugs, irrespective of indication, should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

An FDA meta-analysis of randomized placebo controlled trials, in which antiepileptic drugs were used for various indications, has shown a small increased risk of suicidal ideation and behaviour in patients treated with these drugs.

The mechanism of this risk is not known. There were 43892 patients treated in the placebo controlled clinical trials that were included in the meta-analysis. Approximately 75% of patients in these clinical trials were treated for indications other than epilepsy and, for the majority of non-epilepsy indications the treatment (antiepileptic drug or placebo) was administered as monotherapy.

, patients in both treatment arms were being treated with one or more antiepileptic drug). 24% for patients on placebo) is based largely on patients that received monotherapy treatment (antiepileptic drug or placebo) for non -epilepsy indications.

2 Recommended Dose and Dosage Adjustment, Discontinuation). Carcinogenesis and Mutagenesis See 16 NON-CLINICAL TOXICOLOGY, Carcinogenesis and Mutagenesis for discussion on animal data. Cardiovascular Cardiac Rhythm and Conduction Abnormalities  PR Interval Prolongation In post-marketing experience, atrioventricular (AV) block (including second degree or higher AV block) has been reported.

In patients with proarrhythmic conditions, ventricular tachyarrhythmia has been rarely reported. In rare cases, these events have led to asystole, cardiac arrest and death in patients with underlying proarrhythmic conditions. g. slow, rapid, or irregular pulse, palpitations, shortness of breath, feeling lightheaded, fainting), and told to seek immediate medical advice if these symptoms occur.

In patients who develop serious cardiac arrhythmia, VIMPAT should be discontinued and a thorough clinical benefit/risk assessment should be performed before possibly restarting therapy. g. g. 2 Drug Interactions Overview). In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state, is recommended.

g. 2 Drug Interactions Overview). In these patients it should be considered to perform an ECG before a VIMPAT dose increase above 400mg/day and after VIMPAT is titrated to steady-state. 2 Pharmacodynamics, Cardiac Electrophysiology). Patients with significant electrocardiographic (ECG) abnormalities were systematically excluded from these trials.

3ms for the placebo group. 3ms for the placebo group. 2ms in the placebo group. 2 Clinical Trial Adverse Reactions, Cardiac).  Atrial Fibrillation and Atrial Flutter VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease.

g. palpitations, rapid or irregular pulse, shortness of breath) and told to contact their physician should any of these symptoms occur. Atrial fibrillation and flutter have been reported in open-label epilepsy trials and in post- marketing experience.

 Patients who are hypersensitive to VIMPAT or to any of the excipients. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.  Patients with a history of, or presence of, second- or third-degree atrioventricular (AV) block.