Carbamazepine toxicity with concomitant levetiracetam therapy in patients with epilepsy

Drug interactions are crucial in understanding the efficacy and safety of co-administered antiepileptic drugs. This study aims to investigate drug interactions between carbamazepine (CBZ) and levetiracetam (LEV) and the factors associated with CBZ toxicity.

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 to differentiate between toxic and non-toxic CBZ concentrations.

The odds of developing manifestations of CBZ toxicity in CBZ + LEV versus CBZ group were 16.65 (95% confidence interval [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 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.

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%.

There is a temporal association between LEV administration and toxic blood levels and toxic symptoms of CBZ, the chances of which significantly higher when the dose ratio of LEV:CBZ is 1.86.