Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.
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Contin M, Albani F, Riva R, Candela C, Mohamed S, Baruzzi A
Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.
Ther Drug Monit. 2013 Dec;35(6):849-52. doi: 10.1097/FTD.0b013e318290eacc.
- PubMed ID
- 23942540 [ View in PubMed]
- Abstract
BACKGROUND: Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentrations of LCM in a population of patients with epilepsy. METHODS: Steady state plasma concentrations of LCM were assessed in a cohort of 75 consecutive patients with epilepsy referred to the Laboratory of Clinical Neuropharmacology for AED therapeutic monitoring over 16 months. Plasma LCM concentrations were measured by high-performance liquid chromatography with spectrophotometric detection. RESULTS: Median morning trough plasma concentration-to-weight-adjusted dose ratio of LCM [(mg/L)/(mg/kg/d)] was significantly reduced (0.94 versus 1.35, P < 0.001) in patients treated with LCM plus AED strong inducers of cytochrome P450 metabolism, namely, carbamazepine, phenobarbital, and phenytoin (group A, n = 33), compared with a pool of patients not comedicated with AED strong inducers, predominantly including oxcarbazepine, levetiracetam, lamotrigine, and valproic acid (group B, n = 42). The 2 groups were comparable for age, gender, weight, LCM daily dose, and dosing frequency. LCM plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 75 to 600 mg/d, although, at a given drug dose, a large interpatient variability was observed in matched, plasma drug concentration. CONCLUSIONS: Our findings confirm, in a real-patient clinical setting, preliminary evidence from randomized, clinical trials showing that carbamazepine, phenobarbital, or phenytoin significantly reduces the overall systemic exposure to LCM. From a practical point of view, patients on concomitant AED strong inducers may require a 30% higher dose of LCM compared with patients not receiving strongly inducing AED cotherapy, to achieve the same plasma drug concentration.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Lacosamide Cytochrome P450 2C19 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareLacosamidePhenytoin The serum concentration of Lacosamide can be decreased when it is combined with Phenytoin. LacosamideFosphenytoin The serum concentration of Lacosamide can be decreased when it is combined with Fosphenytoin. LacosamideCarbamazepine The serum concentration of Lacosamide can be decreased when it is combined with Carbamazepine. LacosamidePrimidone The metabolism of Lacosamide can be increased when combined with Primidone. LacosamideMethylphenobarbital The metabolism of Lacosamide can be increased when combined with Methylphenobarbital.