PKP-013 Levetiracetam therapeutic monitoring in patients with epilepsy: Effect of concomitant antiepileptic drugs. (14th February 2016)

• Record Type: Journal Article
• Authors: Alzueta, N; Aldaz, A; Egüés, A
• Is Part Of: European journal of hospital pharmacy. Volume 23(2016)Supplement 1
• Page Start: A183
• Page End: A184
• Publication Date: 2016-02-14
• Subjects: Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2016-000875.416
• Languages: English
• ISSNs: 2047-9956

Abstract

Abstract : Background: Levetiracetam (LEV) is one of the newer antiepileptic drugs (AEDs). Data on LEV pharmacokinetics and interactions are limited and partly contradictory. Theoretically, LEV can be expected to have a very low potential for drug interactions as it is neither protein bound in blood nor metabolised in the liver. Purpose: To evaluate the effect of concomitant AED therapy on the apparent oral clearance of LEV in patients with epilepsy. Material and methods: Retrospective study, from 2009 to 2013, in patients with epilepsy treated with LEV in a tertiary hospital. Variables collected were LEV dose, plasma concentration, age, sex, body weight and anticonvulsant comedications prescribed. They were obtained from the therapeutic drug monitoring register and medical records. Mean weight normalised LEV apparent oral clearance (CLLEV ) was compared between three groups: group A (n = 54) receiving LEV plus AED inducers of cytochrome P450 (CYP) metabolism (carbamacepine, phenobarbital, phenytoin and oxcarbacepine); group B (n = 15) receiving LEV plus AED inhibitors (valproic acid); and group C (n = 101) receiving LEV as onotherapy or LEV plus AEDs without properties to modify CYP metabolism (lamotrigine, topiramate and lacosamide). LEV plasma concentrations were measured by high performance liquid chromatography with spectrophotometric detection. Statistica Statasoft software was used for statistical analysis. Results: 170 patients were included; 60% of patients were prescribed polytherapy. Mean morning trough LEV plasma concentrations were significantly lower in patients in group A than in group B (18.6 ± 11.6 μg/mL vs 27.5 ± 16.2 μg/mL, p < 0.001) or group C (18.6 ± 11.6 μg/mL vs 22.1 ± 12.6 μg/mL, p < 0.001). Mean CLLEV was significantly higher in patients in group A compared with group B (116.1 ± 49 mL/Kg/h vs 76.1 ± 39.5 mL/Kg/h, p < 0.001) and group C (116.1 ± 49 mL/Kg/h vs 83.3 ± 44.8 mL/Kg/h, p < 0.001). Conclusion: Concomitant AED can contribute to variability in LEV disposition in patients with epilepsy. This study showed that comedication with an enzyme inducing AED was associated with 52.6% higher clearance compared with group B and 39.4% higher clearance compared with group C. These findings emphasise the need to monitor LEV, especially when other anticonvulsant comedications are prescribed or discontinued in the treatment regimen. No conflict of interest.