Clinical experience combined with therapeutic drug monitoring of lacosamide

Abstract

Objective Lacosamide (LCM) is an antiepileptic drug (AED) with insufficient clinical experience in patients with intellectual disability (ID). They often have more severe epilepsy with comorbidities. The objective was to evaluate the efficacy and tolerability of lacosamide (LCM) in patients with refractory epilepsy with and without ID in a real‐life setting, taking drug monitoring (TDM) data into account therapeutic. Methods Retrospectively, we identified 344 patients using LCM from the TDM service covering the majority of the country, at the National Center for Epilepsy in Norway (2013‐2018). Clinical and TDM data were available for 132 patients. Results Forty‐four of the 132 patients (33%) had ID. The retention rate was significantly higher in the ID vs the non‐ID group after 1 year (84% vs 68%, P < .05). By combining clinical and TDM data, we demonstrated that 37/38 responding patients had serum concentrations above the lower limit of the reference range (>10 µmol/L), and 16/17 with lower concentrations were non‐responders. Mean serum concentration/dose ratios were similar in both groups, 0.06 and 0.07 µmol/L/mg. There were no significant differences regarding efficacy and tolerability. The risk of LCM withdrawal was significantly higher when LCM was added to sodium channel blockers, even if the latter was discontinued. Significance Lacosamide was generally well tolerated in patients with drug‐resistant epilepsy, where one third had ID, and in these patients the retention rate was higher. The combination of clinical and TDM data could possibly facilitate LCM therapy in these vulnerable patients.

Pharmacological aspects of antiseizure medications: From basic mechanisms to clinical considerations of drug interactions and use of therapeutic drug monitoring

“…43 Combinations of sodium channel blockers are often associated with increased incidence of CNS side effects in the absence of significant additive efficacy. 43,47,48 3.5.2 | Interactions between ASMs and other drug classes Valproic acid, felbamate, and, to a lesser extent, cenobamate, can decrease the clearance of drugs other than ASMs, including psychotropic drugs, calcium channel blockers, and anticoagulants, and lead to toxicity. 41,43 Cannabidiol is emerging as an inhibitor of multiple drug-metabolizing enzymes, which can inhibit the clearance of many drugs.…”

“…Although this combination can improve the therapeutic outcomes, adverse effects may be exacerbated as well 43 . Combinations of sodium channel blockers are often associated with increased incidence of CNS side effects in the absence of significant additive efficacy 43,47,48 …”

“…It must also be emphasized that the need for TDM is much more prominent in patients with refractory epilepsy than in those with new‐onset seizures. Real‐life studies examining the clinical efficacy and tolerability of ASMs in relation to serum concentrations have in our experience been valuable in improving TDM services for the recently approved ASMs 47,48,69,87,88 . There is a need for studies in selected populations and for homogeneous indications for TDM to increase the level of evidence and benefits of use in terms of improved patient treatment and care, patient safety, and economical outcomes.…”