Carbamazepine toxicity with concomitant levetiracetam therapy in patients with epilepsy.

Abstract

Aim: Drug interactions are crucial in understanding the efficacy and safety of co-administered antiepileptic drugs, which underscores the need for cautious prescribing and close monitoring of patients receiving multiple antiepileptics. This study aims to investigate drug interactions between carbamazepine(CBZ) and levetiracetam(LEV) and whether the CBZ toxicity is LEV drug-dose or dose-ratio-dependent(LEV:CBZ).

Methods: The present record-based case-control study analyzed data from 158 patients. A univariate analysis was done to identify the association of various factors with toxic trough CBZ concentrations. Frequentist disproportionality analysis was done to determine a signal for the association between concomitant LEV administration and CBZ toxicity. Receiver operating characteristic (ROC) analysis was done to identify the LEV:CBZ dose ratio or LEV dose to differentiate between toxic and non-toxic CBZ concentrations.

Results: The odds of developing manifestations of CBZ toxicity in CBZ + LEV versus CBZ group was 16.65(95%CI:3.52-78.70;p < 0.001). The univariate analysis showed no association between CBZ dose and toxic trough CBZ levels, while an association between LEV administration and toxic trough CBZ levels was evident. A reporting odds ratio(ROR) of 2.25(95%CI:1.07-4.72;p = 0.030) and a proportional reporting ratio (PRR) of 1.77(95%CI:1.07-2.94) was observed for toxic levels of CBZ with co-administration of LEV. A LEV: CBZ dose ratio of 1.86 was identified as a threshold for differentiating between toxic and non-toxic serum concentrations with an accuracy of 72.9%.

Conclusions: There is a temporal association between LEV administration and toxic blood levels and toxic symptoms of CBZ. The chances of achieving toxic concentrations of CBZ are significantly higher when the dose strength of LEV is nearly double the dose of CBZ.