Does Oxcarbazepine Warrant Therapeutic Drug Monitoring?

Abstract

Oxcarbazepine, the 10-keto analogue of carbamazepine, is approved for the treatment of partial seizures or generalized tonic-clonic seizures. The primary metabolite of oxcarbazepine is monohydroxylated derivative (MHD). This review follows a decision-making algorithm to determine if therapeutic drug monitoring of MHD is warranted.Important factors to take into account include the appropriateness of oxcarbazepine for the therapeutic indication; ability to measure MHD concentrations; existence of a good concentration-response relationship, narrow therapeutic range or unpredictable pharmacokinetic parameters; assessability of the pharmacological response of oxcarbazepine; adequate duration of therapy; and potential influence of MHD concentrations in the clinical decision-making process. Based on the available evidence, therapeutic drug monitoring of MHD is not routinely warranted but may be beneficial in optimizing seizure control at the extremes of age, during pregnancy, in renal insufficiency, or to determine the significance of potential drug interactions or rule out noncompliance.

Population pharmacokinetics modeling of oxcarbazepine to characterize drug interactions in Chinese children with epilepsy

“…It has been suggested in previous studies that factors affecting the pharmacokinetics of MHD might include comedication, age, renal impairment, pregnancy, and compliance [6,21] . Our findings suggest that comedication with other AEDs is a significant predictor for MHD clearance in the target population.…”

Drug Interaction and Pharmacokinetic Modeling of Oxcarbazepine in Korean Patients With Epilepsy

“…4 Because there was no correlation between the concentration and response noted to date, some patients might develop ADRs from OXC even if the levels are within the ''suggested reference range.'' The reported minimal and maximum OHC concentration range was from 3 to 15 mg/L and from 20 to 55 mg/L, respectively.…”

“…4 Because there was no correlation between the concentration and response noted to date, some patients might develop ADRs from OXC even if the levels are within the ''suggested reference range.'' 4 The possibility of ADRs by cross-reaction with comedications such as CBZ could not be excluded. Marked hyponatremia (serum sodium concentration G125 mEq/L) has been reported in 2.7% of patients treated with OXC.…”

“…8,9 The dose to proportional pharmacokinetics of OHC has been reported to be in the dose range of 300 to 2700 mg/d. 4 The relationship between comedications and the pharmacokinetics of OHC may be complex. 1,4Y7,10 It has been suggested that factors affecting the pharmacokinetics of OHC might include comedication, age, renal impairment, pregnancy, and compliance.…”

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

“…Monitoring MHD and OXB concentrations could therefore help in the management of patients with OXB therapy. Based on the available evidence, therapeutic drug monitoring of MHD is not routinely warranted but may be beneficial in optimizing seizure control at the extremes of age, during pregnancy, in renal insufficiency, or to determine the significance of potential drug interactions or rule out noncompliance [197]. There are many HPLC [198,199] and GC [200,201] methods for the measurement of MHD and OXB in biological fluids.…”