Vosamide

VOSAMIDE 50: Pink, oval, biconvex film coated tablet with engraved 50 on one side and plain on the other.
Each film coated tablet contains Lacosamide 50 mg.
VOSAMIDE 100: Yellow, oval, biconvex film coated tablet with engraved 100 on one side and plain on the other.
Each film coated tablet contains Lacosamide 100 mg.

Pharmacology: Pharmacodynamics: In vitro studies have shown that lacosamide stabilizes hyperexcitable neuronal membranes by enhancing the slow inactivation of sodium channels (with no effects on fast inactivation of sodium channels).
Pharmacokinetics: Absorption: Tmax, oral: 1 to 4 hours.
Bioavailability, oral: 100%.
Effects of food: None.
Distribution: Protein binding: 14%.
V_d: 0.6 L/kg.
Metabolism: Major metabolite: O-desmethyl-lacosamide (inactive).
Substrate of CYP3A4, CYP2C9, and CYP2C19.
Excretion: Fecal excretion: Less than 0.5%.
Renal excretion: 95% (40% as unchanged drug, 30% as inactive metabolite, 20% as uncharacterized metabolite).
Dialyzable: Yes (hemodialysis), 50% removed.
Elimination Half Life: Adult: 13 hours.

Monotherapy in the treatment of partial-onset seizures in patients with epilepsy aged 16 years and older.
Adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in patients with epilepsy aged 16 years and older.

Monotherapy: Initial and titration dosage: 100 mg orally twice daily (200 mg/day); may be increased to 150 mg twice daily (300 mg/day) after one week. The dose can be further increased up to a maximum recommended maintenance daily dose of 200 mg twice daily (400 mg/day) based on response and tolerability.
Converting from another single antiepileptic: After lacosamide has titrated to therapeutic dosage for at least 3 days, may begin gradual withdrawal of the other antiepileptic over at least 6 weeks.
Adjunctive therapy: Initial and titration dosage: 50 mg orally twice daily (100 mg/day); may be increased to 100 mg twice daily (200 mg/day) after one week. The dose can be further increased by 50 mg twice daily every week, to a maximum recommended maintenance daily dose of 200 mg twice daily (400 mg/day) based on response and tolerability.
Initial treatment with a loading dose: Single loading dose of 200 mg followed approximately 12 hours later by 100 mg twice daily for 1 week; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability.
Administer loading doses under medical supervision because of the increased incidence of CNS adverse reactions.
Discontinuation of therapy: In patients receiving lacosamide long term, unless safety concerns require a more rapid withdrawal, lacosamide should be withdrawn gradually over a few weeks to several months to minimize the potential of seizures or other withdrawal symptoms.
Renal impairment: Mild to moderate impairment (CrCl more than 30 mL/min): No dosage adjustment is necessary. Cautiously titrate dosage.
Severe impairment (CrCl less than or equal to 30 mL/min) or ESRD: Maximum dosage is 250 mg/day.
For patients requiring haemodialysis, a supplement of up to 50% of the divided daily doses directly after the end of haemodialysis is recommended.
Renal impairment and taking a concomitant strong inhibitor of CYP3A4 or CYP2C9: Dose reduction may be necessary.
Hepatic impairment: Mild to moderate impairment: Titrate dose cautiously.
Maximum dose is 300 mg/day.
Severe impairment: Use is not recommended.
Hepatic impairment and taking a concomitant strong inhibitor of CYP3A4 or CYP2C9: Dose reduction may be necessary.
Elderly (over 65 years of age): No dosage reduction is necessary in elderly patients. Age associated decreased renal clearance with an increase in AUC levels should be considered in elderly patients.
Pediatric: The safety and efficacy of lacosamide in children aged below 16 years have not yet been established.
Administration: VOSAMIDE must be taken twice a day (usually once in the morning and once in the evening).
May be administered with or without food. Swallow tablets whole, do not divide.

Overdose: Mild to moderate toxicity: The signs and symptoms of an acute overdose are expected to be similar to adverse effects seen at therapeutic doses. Dizziness, nausea, and seizures (generalized tonic-clonic seizures, status epilepticus) have been reported with lacosamide ingestions of more than 800 mg (twice the maximum recommended daily dosage).
Severe toxicity: Cardiac conduction disorders, confusion, QRS prolongation, AV blocks, cardiogenic shock, and cardiac arrest have been reported.
Treatment: Treatment is symptomatic and supportive. Patients may require airway management. Closely monitor neurologic function. Treat QRS prolongation with sodium bicarbonate; an initial dose of 1 to 2 mEq/kg is reasonable. Monitor ECG and arterial blood gases.

Hypersensitivity to lacosamide or any component of the formulation.
Current or history of second- or third-degree atrioventricular (AV) block.

Based on the notification of the Ministry of Public Health: This drug may cause drowsiness. Patients should not drive, operate machinery, or drink alcohol containing products while taking this drug.
This drug may cause hematologic disorders.
Do not use this drug while pregnant due to the risk of teratogenicity.
Use this drug with caution in patients with liver and kidney disease.

Cardiovascular: Dose-dependent PR interval prolongation has been reported in adults and further PR prolongation is possible when given with other PR-prolonging agents.
Cardiac arrhythmias (including bradycardia, AV block, and ventricular tachyarrhythmia) have been reported and have rarely resulted in asystole, cardiac arrest, and death.
Use with caution in patients with underlying proarrhythmic conditions (eg, marked first-degree AV block, second-degree or higher AV block, sick sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome) and in those receiving concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval.
Atrial fibrillation and flutter have been reported; use may predispose to atrial arrhythmias, especially in patients with diabetic neuropathy and/or cardiovascular disease.
Immunologic: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS; ie, multiorgan hypersensitivity) including life-threatening cases and fatalities has been reported; discontinue use if an alternative etiology cannot be established.
Neurologic: Dose-related dizziness and ataxia have been reported.
Abrupt discontinuation of therapy may precipitate withdrawal seizure; discontinue gradually over a minimum of 1 week.
Psychiatric: Suicidal ideation and behavior have been reported; monitoring recommended.
Special populations: Use caution during dose titration for elderly patients.

Pregnancy: Lacosamide crosses the placenta. Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of lacosamide may be altered. Information related to pregnancy outcomes following maternal use of lacosamide is limited. In general, maternal polytherapy with antiepileptic drugs may increase the risk of congenital malformations, monotherapy with the lowest effective dose is recommended. Newborns of women taking antiepileptic medications may be at an increased risk of adverse events.
Breastfeeding: Lacosamide is present in breast milk. Drowsiness and poor feeding were observed in a breastfeeding newborn following maternal use of lacosamide (in combination with other medications) throughout pregnancy and postpartum. The decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Common: Gastrointestinal: Nausea (Up to 24%).
Neurologic: Dizziness (16-30%), Headache (11-16%).
Ophthalmic: Diplopia (9-11%).
Serious: Cardiovascular: Atrial fibrillation and flutter, First degree atrioventricular block, Asymptomatic (0.4%), Prolonged PR interval.
Immunologic: Drug reaction with eosinophilia and systemic symptoms.
Psychiatric: Suicidal behavior, Suicidal thoughts.

The levels/effects of lacosamide may be increased by: Antiarrhythmic agents (class III), antiepileptic agents (sodium channel blockers), bradycardia-causing agents, CYP3A4 inhibitors (strong), lidocaine (systemic), mexiletine, QT-prolonging class IA antiarrhythmics (highest risk), QT-prolonging class IC antiarrhythmics (moderate risk).
The levels/effects of lacosamide may be decreased by: Mefloquine, mianserin, orlistat.

Store below 30°C.

Anticonvulsants

N03AX18 - lacosamide ; Belongs to the class of other antiepileptics.

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