Effect of carbamazepine on the pharmacokinetics of paliperidone extended‐release tablets at steady‐state

Given the potential concomitant use of carbamazepine and paliperidone extended‐release (ER) in the treatment of schizophrenia or schizoaffective disorder, this open‐label, two‐treatment sequential study investigated the effect of repeated administration of carbamazepine on the steady‐state pharmacokinetics of paliperidone. Sixty‐four patients with a diagnosis of schizophrenia or bipolar‐I disorder received the following treatments in a fixed sequential order, without washout between treatments: (i) paliperidone ER 6 mg tablet once daily for 7 days, and (ii) paliperidone ER 6 mg once daily concomitantly with carbamazepine 200 mg twice daily for the subsequent 21 days. Upon coadministration with carbamazepine, paliperidone steady‐state total exposure (AUC 24 h ) and peak plasma concentrations (C max ) decreased by approximately 37% [LSM ratio—AUC 24 h : 63.4 (90% CI: 57.19; 70.29); C max : 62.47 (90% CI: 55.77; 69.98)]. This decrease is accounted for to a substantial degree by a 35% increase in renal clearance of paliperidone, likely as a result of induction of renal P‐glycoprotein by carbamazepine. A 14% decrease in the amount of drug excreted unchanged in the urine suggests that carbamazepine coadministration has a limited effect on the intestinal absorption or cytochrome metabolism of paliperidone.