Lacosamide

Indications

Lacosamide is used for: Partial seizures

Adult Dose

Adult : PO/IV Monotherapy/adjunctive therapy: Initial: 50 mg bid (100 mg bid may also be given as monotherapy), w/ increments of 50 mg bid/wk based on response and tolerability. Max: 300 mg bid (monotherapy); 200 mg bid (as adjunct). Hepatic impairment Mild-to-moderate: No dose adjustment required Severe: Not recommended Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction

Child Dose

Child: 16-18 yr PO/IV Monotherapy/adjunctive therapy: Initial: 50 mg bid (100 mg bid may also be given as monotherapy), w/ increments of 50 mg bid/wk based on response and tolerability. Max: 300 mg bid (monotherapy); 200 mg bid (as adjunct). Hepatic impairment Mild-to-moderate: No dose adjustment required Severe: Not recommended Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction

Renal Dose

Renal impairment Mild-to-moderate: no dose adjustment required Severe (CrCl <30 mL/min) or ESRD: Reduce maximum dosage by 25% Hemodialysis: Consider supplementing with up to 50% of dose after 4-hr dialysis session Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction

Administration

May be taken with or without food. IV Preparation May be administered without dilution or diluted in compatible solutions; (see IV Compatibility) Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit Product with particulate matter or discoloration should not be used Vials is for single-dose only; discard any unused portion of lacosamide injection IV Administration Infuse IV over 15-60 min; 30-60 min preferable, and should be used when a 15 min administration is not required IV lacosamide may cause bradycardia or AV bock in patients with underlying cardiac disease Monitor infusion closely patients with known cardiac conduction problems, on concomitant medications that prolong PR interval, or with severe cardiac disease (eg, myocardial ischemia, heart failure)

Contra Indications

2nd- or 3rd-degree AV block (w/o pacemaker). Severe hepatic impairment.

Precautions

Patient w/ severe cardiac disease (e.g. MI, heart failure), conduction problems (e.g. marked 1st degree AV block or sick sinus syndrome w/o pacemaker), Na channelopathies (e.g. Brugada syndrome), structural heart disease. Childn. Hepatic and renal impairment. Pregnancy and lactation.

Pregnancy-Lactation

Interactions

Increased systemic exposure w/ strong inhibitors of CYP2C9 (e.g. fluconazole) and CYP3A4 (e.g. ketoconazole, itraconazole, clarithromycin, ritonavir) enzymes. Reduced systemic exposure w/ rifampicin, phenobarbital, phenytoin, carbamazepine. Risk of PR prolongation w/ class I antiarrhythmics, lamotrigine, pregabalin, carbamazepine, eslicarbazepine.

Adverse Effects

Side effects of Lacosamide : >10% Tablets and oral solution Dizziness (16-53%) Diplopia (6-16%) Blurred vision (2-16%) Nausea (7-17%) Vomiting (6-16%) Fatigue (7-15%) Ataxia (11-14%) Nystagmus (2-10%) IV Fatigue (20-63%) Somnolence (26-34%) Headache (4-16%) Diplopia (4-20%) Nausea (14-24%) Dry mouth (6-12%) Vomiting (4-12%) Fatigue (12-18%) Chest pain (3-12%) 1-10% Tablets and oral solution Nystagmus (2-10%) Memory impairment (1-6%) Balance disorder (1-6%) Diarrhea (3-5%) Gait disturbance (<1-4%) Asthenia (1-3%) Vertigo (1-4%) Pruritus (2-3%) Depression (2%) IV Oral paresthesia (4-8%) Oral hypoesthesia (5-8%) Diarrhea (4-8%) Paresthesia (4-8%) Gait disturbance (2-8%) Hyperhidrosis (2-8%) Tremor (4-6%) Abnormal coordination (3-6%) Pruritus (4-6%)

Mechanism of Action

Lacosamide is a functionalised amino acid structurally related to serine. Its precise mechanism of action is unknown, however in vitro studies suggest that it selectively enhances the slow inactivation of Na channels w/o affecting fast inactivation. This results in stabilisation of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. Additionally, it may affect collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and axonal growth.