Apixaban Use With Rifampin in a Pediatric Congenital Heart Disease Patient

Introduction: Pediatric direct oral anticoagulant (DOAC) use has been increasing, and the most recent pediatric venous thromboembolism (VTE) guidelines recommend DOACs as first line therapy. While there are few drug interactions for DOACs requiring drug modification, rifampin use with DOACs is not recommended as rifampin is a potent inducer of cytochrome P450 (CYP3A4) and P-glycoprotein, which increase DOAC metabolism. We describe a patient with complex congenital heart disease (CHD) on apixaban who required rifampin for endocarditis.


Description: A 16-year-old male with truncus arteriosus with a right ventricle-pulmonary artery conduit and truncal valve regurgitation presented in cardiac arrest due to ventricular fibrillation requiring VA ECMO. He was decannulated after 5 days and an AICD was placed due to ventricular arrhythmia. He was transitioned to apixaban for a subsegmental pulmonary embolism, persistent factor VIII elevation and conduit presence. Apixaban levels were assessed due to fluctuating renal function post-cardiac arrest, which normalized within 2 weeks. Initial apixaban level was 120 ng/mL on 5 mg oral twice daily. He was discharged but required readmission 12 days later due to Staphylococcus aureus septicemia. Given his truncal valve regurgitation and conduit presence, it was deemed necessary to treat for endocarditis with 6 weeks of cefazolin and rifampin along with 2 weeks of gentamicin. In discussion with the family and patient, they did not want to transition to low molecular weight heparin (LMWH) for rifampin duration so we reassessed apixaban levels during use. Two days prior to rifampin initiation, his level was 312 ng/mL and after 5 rifampin doses, the level was 356 ng/mL. After 4 weeks of rifampin therapy, his level was 136 ng/mL and the current level off rifampin is 271 ng/mL.


Discussion: Given increased DOAC use in CHD patients, it may be possible to continue DOACs with rifampin. Many CHD patients with artificial shunts and conduits require long-term anticoagulants, and if these patients develop endocarditis, they may require extended rifampin use. With ease of DOAC use, patients are reluctant to transition to LMWH for such conditions. Assessment of apixaban levels with rifampin use may help to evaluate the efficacy of DOAC for VTE prevention or treatment.