Lacosamide

Concomitant use may cause CNS depression and cognitive/neuropsychiatric adverse reactions. Should be used with extreme caution.

Lacosamide should be used with caution with sodium channel blockers due to risk of AV block, bradycardia, or ventricular tachyarrhythmia. ECG monitoring recommended.

Concomitant use may cause CNS depression and cognitive/neuropsychiatric adverse reactions. Should be used with extreme caution.

7 DRUG INTERACTIONS 7.1 Strong CYP3A4 or CYP2C9 Inhibitors Patients with renal or hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to lacosamide oral solution. 7.2 Concomitant Medications that Affect Cardiac Conduction Lacosamide oral solution should be used with caution in patients on concomitant medications that affect cardiac conduction (sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers) including those that prolong PR interval (including sodium channel blocking AEDs), because of a risk of AV block, bradycardia, or ventricular tachyarrhythmia. In such patients, obtaining an ECG before beginning lacosamide oral solution, and after lacosamide oral solution is titrated to steady-state, is recommended.

Strong CYP3A4 inhibitors may significantly increase lacosamide exposure in patients with renal or hepatic impairment. Dose reduction may be necessary.

Lacosamide should be used with caution with beta-blockers due to risk of AV block, bradycardia, or ventricular tachyarrhythmia. ECG monitoring recommended.

Carbamazepine 400 mg/day had no influence on lacosamide 400 mg/day pharmacokinetics, and lacosamide had no influence on carbamazepine pharmacokinetics.

Steady-state plasma concentrations of clonazepam were not affected by concomitant lacosamide at any dose in clinical studies.

Steady-state plasma concentrations of gabapentin were not affected by concomitant lacosamide at any dose in clinical studies.

Steady-state plasma concentrations of lamotrigine were not affected by concomitant lacosamide at any dose in clinical studies.

Steady-state plasma concentrations of levetiracetam were not affected by concomitant lacosamide at any dose in clinical studies.

In vivo study with omeprazole did not show an inhibitory effect on omeprazole pharmacokinetics despite in vitro potential to inhibit CYP2C19.

Steady-state plasma concentrations of oxcarbazepine monohydroxy derivative were not affected by concomitant lacosamide at any dose in clinical studies.

Steady-state plasma concentrations of phenobarbital were not affected by concomitant lacosamide at any dose in clinical studies.

Steady-state plasma concentrations of phenytoin were not affected by concomitant lacosamide at any dose in clinical studies.

Steady-state plasma concentrations of topiramate were not affected by concomitant lacosamide at any dose in clinical studies.

Valproic acid 600 mg/day had no influence on lacosamide 400 mg/day pharmacokinetics, and lacosamide had no influence on valproic acid pharmacokinetics.

Steady-state plasma concentrations of zonisamide were not affected by concomitant lacosamide at any dose in clinical studies.

Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine, lacosamide Antiplatelets Ticagrelor Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite.

o Midazolam Midazolam is a 3A4 substrate. There was no effect of lacosamide (200 mg single dose or repeat doses of 400 mg/day given as 200 mg BID) on the pharmacokinetics of midazolam (single dose, 7.5 mg), indicating no inhibitory or inducing effects on CYP3A4.

Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Anticoagulants Apixaban, dabigatran, edoxaban, rivaroxaban Antiepileptic drugs The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine, lacosamide Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiplatelets Ticagrelor Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite.