Carbamazepine Induction Impacting Apixaban Concentrations: A Case Report

Abstract

Avoidance of apixaban with carbamazepine (CBZ) is recommended owing to an anticipated reduction in apixaban concentration, although this drug interaction is poorly described. We report a case wherein apixaban concentration was measured before and 2 weeks after CBZ. Apixaban concentrations were substantially reduced; hence, the dose of apixaban was doubled alongside a small increase in CBZ. Subsequent apixaban concentrations were essentially unchanged. This extent of reduction in apixaban concentration appears to be related to the dose of CBZ, with the interaction occurring over 2-4 weeks. This combination should be avoided unless apixaban concentrations can be assessed using a calibrated assay.

The Problem With Predictions: A Cautionary Tale of Empirically Adjusting Apixaban Dosing With Carbamazepine

“…We initiated apixaban 10 mg BID based on a previous case report 3 that demonstrated the need to escalate apixaban to 10 mg BID in the setting of CBZ dose escalation to 600 mg in the morning and 400 mg in the evening (less than the current case’s CBZ dose of 600 mg BID). Two case reports exist for patients on low-dose CBZ (200 mg BID)—one demonstrated reduced apixaban concentrations (undetectable trough; low peak of 29 ng/mL) leading to a transient ischemic attack, 4 and the other demonstrated little or no impact on apixaban concentration.…”

“…Carbamazepine (CBZ) is a known strong inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) and is to be “generally avoided” with apixaban, given that apixaban is a substrate for P-gp and is metabolized by CYP3A4. 1 Few case reports of this drug interaction exist; one showed no impact with concomitant apixaban 5 mg twice daily (BID) and CBZ 200 mg BID 2 whereas another required up-titration to apixaban 10 mg BID alongside CBZ 600 mg in the morning and 400 mg in the evening 3 to sustain apixaban trough/peak concentrations. Additionally, a different case report with concomitant apixaban 5 mg BID and CBZ 200 mg BID demonstrated relevant reductions in apixaban plasma concentrations, leading to a transient ischemic attack in a patient with atrial fibrillation.…”

DOAC drug interactions management resource

“…Rivaroxaban: rivaroxaban 20 mg/day + carbamazepine 900 mg/day with reduced rivaroxaban concentration <20 ng/mL with recurrent venous thromboembolism (VTE; case report 36 ); PE after total knee replacement taking rivaroxaban 10 mg/day + carbamazepine 600 mg bid without rivaroxaban concentration (case report 37 ); avoid use 2 46. Apixaban: Transient ischemic attack with apixaban 5 mg bid + carbamazepine 400 mg/day with peak apixaban concentration 94 ng/mL (case report 38 ); apixaban 5 mg bid + carbamazepine 400 mg/day with peak apixaban concentration 110 ng/mL and trough 64 ng/mL—concentrations higher than while not taking carbamazepine (case report 39 ); titration of carbamazepine with apixaban 5 mg bid + carbamazepine 800 mg/day had apixaban trough concentration 30 ng/mL + peak 114 ng/mL, apixaban 10 mg bid + carbamazepine 1000 mg/day with repeat trough/peak of 41/99 ng/mL (case report 40 ); avoid use 3 47. Dabigatran: dabigatran 150 mg bid + carbamazepine dose not specified yielded reduced dabigatran concentration of <30 ng/mL (2 case reports 41 ); avoid use 4 48.…”

“… 46. Apixaban: Transient ischemic attack with apixaban 5 mg bid + carbamazepine 400 mg/day with peak apixaban concentration 94 ng/mL (case report 38 ); apixaban 5 mg bid + carbamazepine 400 mg/day with peak apixaban concentration 110 ng/mL and trough 64 ng/mL—concentrations higher than while not taking carbamazepine (case report 39 ); titration of carbamazepine with apixaban 5 mg bid + carbamazepine 800 mg/day had apixaban trough concentration 30 ng/mL + peak 114 ng/mL, apixaban 10 mg bid + carbamazepine 1000 mg/day with repeat trough/peak of 41/99 ng/mL (case report 40 ); avoid use 3 …”