Direct Oral Anticoagulants (Rivaroxaban and Apixaban) in Patients With Liver Cirrhosis

Exclusion Criteria22

• Positive pregnancy test (only for women in childbearing age with intact uterus), pregnancy or nursing women
• Intake of prophylactic or therapeutic oral anticoagulant (phenprocoumon, acenocoumarol, dabigatran etc.) 2 weeks prior to inclusion in the study
• Application of parenteral anticoagulant, e.g. unfractionated heparin, low molecular weight heparins, heparin derivatives (fondaparinux etc.) 1 week prior to inclusion in the study
• Pharmacologic platelet inhibition within 2 weeks prior to inclusion in the study
• Known coagulation disorders (e.g. von Willebrand's disease, hemophilia)
• Active, clinically significant bleeding
• Congenital or acquired bleeding disorder
• High risk of bleeding (e.g. active ulcerative gastrointestinal disease)
• Uncontrolled severe hypertension
• Vascular retinopathy
• Acute infection
• Acute bacterial endocarditis
• Severe anemia (haemoglobin ≤100 g/L)
• Hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
• Severe liver dysfunction (Child-Pugh Score grade C)
• Hepatic encephalopathy ≥ grade 3
• Severe renal impairment with a creatinine clearance (GFR) of \<30 ml/min
• Known intolerance to the study medications rivaroxaban and/or apixaban
• Concomitant treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, lopinavir, ritonavir, indinavir).
• Concomitant treatment with a P-glycoprotein inhibitor and a weak or moderate CYP3A4 inhibitor (e.g., erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine).
• Concomitant treatment with a P-glycoprotein inducer and a strong CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampicin).
• Wash-out period of less than two weeks prior to the application of study drug in case of prior treatment with a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor and weak or moderate CYP3A4 inhibitor or with a P-glycoprotein inducer or strong CYP3A4 inducer.