Apixaban in low-weight patients with cancer-associated thrombosis: A cross sectional study of drug levels

Abstract

Introduction: Apixaban, a direct factor Xa inhibitor, has been shown to be at least as safe and probably more effective than dalteparin for the treatment of cancer-associated thrombosis (CAT) as reported in the ADAM-VTE and Caravaggio studies, which included a low percentage of underweight patients. Lower-weight–based dosing is supported by cancer-specific studies such as half-dose edoxaban in the Hokusai-VTE cancer trial in individuals weighing <60 kg. Objective: To examine apixaban plasma trough levels in low-weight individuals with CAT, stably anticoagulated with full or half-dose apixaban. Methods: This was a cross-sectional study of 61 routinely treated patients with active cancer and venous thromboembolism comparing three groups: patients weighing >60 kg treated with apixaban 5 mg twice daily, patients weighing ≤60 kg also receiving apixaban 5 mg twice daily, and patients weighing ≤60 kg given half-dose apixaban (2.5 mg twice daily). Apixaban plasma steady-state trough levels were determined on a single occasion. Results: Mean apixaban plasma trough levels were similar for patients weighing >60 kg on full-dose apixaban to those weighing ≤60 kg taking 2.5 mg twice daily (mean, 109 ng/dL; 95% confidence interval [CI], 74-145; standard deviation [SD]: 77.6; and mean,101 ng/dL, 95% CI, 67-135; SD: 80, respectively). Mean values for low-weight patients (≤60 kg) on the full 5 mg twice-daily dosing tended to be higher (mean, 136 ng/dL; 95%CI, 70-201; SD:114), without statistical significance (P =.22). Conclusions: This study supports the rationale for studying weight-based adjustments in apixaban dosing in prospective studies evaluating safety and efficacy of dose reduction in low-weight patients with cancer.