Acode 50 Drug Interactions

Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation (e.g., carbamazepine, lamotrigine, pregabalin) and in patients treated with class I antiarrhythmic drugs. However, subgroup analysis did not identify an increased magnitude of PR prolongation in patients with concomitant administration of carbamazepine or lamotrigine in clinical trials.
In vitro data: Data generally suggest that lacosamide has a low interaction potential.
In vitro metabolism studies indicate that lacosamide does not induce the enzyme activity of drug metabolizing cytochrome P450 isoforms CYP1A2, 2B6, 2C9, 2C19 and 3A4.
Lacosamide did not inhibit CYP 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 2E1, 3A4/5 at plasma concentrations observed in clinical studies.In vitro data suggest that lacosamide has the potential to inhibit CYP2C19 at therapeutic concentrations. Lacosamide was not a substrate or inhibitor for P-glycoprotein.
In vivo data: Clinical data indicate that lacosamide does not inhibit or induce CYP2C19 and 3A4.
Furthermore, an interaction trial with omeprazole (CYP2C19 inhibitor) demonstrated no clinically relevant changes in lacosamide plasma concentrations and no inhibitory effect on omeprazole pharmacokinetics.
Antiepileptics: In interaction trials lacosamide did not significantly affect the plasma concentrations of carbamazepine and valproic acid. Lacosamide plasma concentrations were not affected by carbamazepine and by valproic acid.
A population PK analysis estimated that concomitant treatment with other anti-epileptics known to be enzyme inducers (carbamazepine, phenytoin, phenobarbital, in various doses) decreased the overall systemic exposure of lacosamide by 25%.
Oral contraceptives: In an interaction trial there was no clinically relevant interaction between lacosamide and the oral contraceptives ethinylestradiol and levonorgestrel. Progesterone concentrations were not affected when the medicinal products were co-administered.
Others: Interaction trials showed that lacosamide had no effect on the pharmacokinetics of digoxin. There was no clinically relevant interaction between lacosamide and metformin.
Co-administration of warfarin with lacosamide does not result in a clinically relevant change in the pharmacokinetics and pharmacodynamics of warfarin.
Protein binding: Lacosamide has a low protein binding of less than 15%. Therefore, clinically relevant interactions with other drugs through competition for protein binding sites are considered unlikely.