Multifactorial Alterations in Lacosamide Exposure in an Elderly Woman with Symptomatic Epilepsy and Tuberculous...

An elderly woman taking lacosamide (LCM) for epilepsy was diagnosed with tuberculous pleurisy. In the hospital, she received a four-drug combination therapy with rifampicin (RFP), isoniazid, pyrazinamide, and ethambutol for tuberculous pleurisy, in addition to medications for symptomatic epilepsy. At admission, her renal function was mildly impaired but remained stable throughout hospitalization. Serum albumin levels were slightly below the normal range. C-reactive protein was markedly elevated on day 4 but returned to normal by the time of discharge. On day 4, therapeutic drug monitoring (TDM) was initiated for LCM, a substrate for CYP2C19 and P-glycoprotein, because RFP can induce multiple cytochrome P450s (CYPs) and P-glycoprotein. Initially, the doses of RFP and LCM were 450 and 100 mg/d, respectively, and the serum concentration of LCM was 9.5 μg/mL (day 4). On day 12, the serum concentration of LCM decreased to 4.1 μg/mL, and the dose of LCM was increased to 200 mg/d. The dose of LCM was further increased to 300 mg/d on day 60 to maintain the serum concentration of LCM at approximately 10 μg/mL. The estimated serum concentration (C) of LCM normalized by the dose (D) ratio, or C/D ratio, was 0.095 on day 4 and decreased to 0.03-0.04 after day 12. The LCM concentration during RFP co-administration may have been affected by the combined effects of RFP-mediated CYP2C19 and P-glycoprotein induction, the patient's inflammatory status, and concomitant anti-tuberculosis drugs. TDM is necessary to attain clinically effective serum concentrations of LCM when RFP is used concomitantly.