Abstract
Rivaroxaban is commonly used for the prophylaxis of venous thromboembolism (VTE) for patients undergoing major orthopedic surgery. Rivaroxaban is primarily eliminated by hepatic CYP450 metabolism and renal excretion. Rifampin is a commonly used antibiotic for prosthetic joint infections (PJI) and a potent inducer of CYP450 enzymes. Clinical data about drug-drug interactions of rivaroxaban and rifampin are limited. The present study is to describe DDI of rivaroxaban and rifampin in several prosthetic joint infections patients undergoing major orthopedic surgery. We retrospectively identified six patients concomitantly administered with rivaroxaban and rifampin between 2019 and 2020. Plasma samples of these patients with accurate sampling time were chosen from the biobank and plasma levels of rivaroxaban were measured at each time point. A physiologically based pharmacokinetic model for the rivaroxaban-rifampin interaction was developed to predict the optimal dosing regimen of rivaroxaban in the case of co-medication with rifampin. The model was validated by the observed plasma concentration of rivaroxaban from the above patients. From this model, it could be simulated that when rifampin starts or stops, gradually changing rivaroxaban dose during the first few days would elevate the efficacy and safety of rivaroxaban.
Highlights
Rivaroxaban, a direct oral FXa inhibitor, is commonly used for the prophylaxis and treatment of venous thromboembolism (VTE), especially for patients undergoing major orthopedic surgery (Capodanno et al, 2012)
Patients with prosthetic joint infections (PJI) after major orthopedic surgery is involved with an increased risk of thromboembolic events, and in these circumstances rivaroxaban is generally prescribed for the long-term prophylaxis of VTE
While it is generally difficult to know how to optimize the dosing regimen of rivaroxaban when combined with rifampin, our simulations show that when rifampin is added or removed from patient’s therapy, a gradual change in rivaroxaban dose would potentially increase the efficacy and safety profiles of rivaroxaban
Summary
Rivaroxaban, a direct oral FXa inhibitor, is commonly used for the prophylaxis and treatment of venous thromboembolism (VTE), especially for patients undergoing major orthopedic surgery (Capodanno et al, 2012). Patients with PJI after major orthopedic surgery is involved with an increased risk of thromboembolic events, and in these circumstances rivaroxaban is generally prescribed for the long-term prophylaxis of VTE. There are case reports of patients suffering from embolism events as a result of decreased rivaroxaban exposure due to the co-medication of CYP/P-gp inducer (rifampin and phenytoin), and the drug labeling of rivaroxaban does not recommend the concomitant use with rifampin (FDA, 2011; Altena et al, 2014; Becerra et al, 2017). The concomitant use of rivaroxaban and rifampin may not be completely avoided and optimization of dosing regimen is needed in these cases
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