Contraindicated/not recommended conditions for use of oral anticoagulants with reference to published pharmacology data [29, 35–39]
| Rivaroxaban (Xarelto; Bayer HealthCare/Janssen Pharmaceuticals) | Apixaban (Eliquis; Bristol-Myers Squibb/Pfizer) | Edoxaban (Lixiana; Daiichi Sankyo) | Dabigatran etexilate (Pradaxa; Boehringer Ingelheim) | Warfarin (generic) |
| Age <18 years CrCl <15 mL·min−1 | Age <18 years CrCl <15 mL·min−1 | To be confirmed (not yet licensed for any indication in Europe) | Age <18 years CrCl <30 mL·min−1 | Hypersensitivity to warfarin or excipients Haemorrhagic stroke |
| Hypersensitivity to the active substance or excipients Clinically significant active bleeding or lesions at risk of clinically significant bleeding Concomitant strong inhibitors of both CYP3A4 and P-gp Concomitant dronedarone Hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child–Pugh B or C Malignant neoplasms at high risk of bleeding Pregnancy or breast feeding | Hepatic disease associated with coagulopathy and clinically relevant bleeding risk Severe hepatic impairment or dialysis Elevated liver enzymes (ALT/AST >2 × ULN) or total bilirubin ≥1.5 × ULN Hypersensitivity to active substance or excipients Clinically significant active bleeding Concomitant strong inhibitors of both CYP3A4 and P-gp Increased bleeding risk for other reasons Pregnancy or breast feeding | Hypersensitivity to the active substance or any of the excipients Clinically significant active bleeding or a lesion or condition at significant risk of major bleeding Hepatic impairment or liver disease expected to impact survival Concomitant treatment with other anticoagulants (except when switching) or systemic ketoconazole, cyclosporine, itraconazole, tacrolimus or dronedarone Pregnancy or breast feeding | Clinically significant bleeding Use within 72 h of surgery with risk of severe bleeding Use within 48 h post-partum Pregnancy or breast feeding Drugs where interactions lead to a significantly increased risk of bleeding (multiple) |
CrCl: creatinine clearance; CYP3A4: cytochrome P450 3A4; P-gp: P-glycoprotein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal.