Apixaban (Eliquis), dabigatran (Pradaxa) and rivaroxaban (Xarelto) vary in their degrees of renal excretion, half-lives, metabolism and bioavailability (see Table 1).
All three NOACs have hepatic and renal contraindications, and as a minimum, patients will require assessment of liver and kidney function prior to their initiation and assessment of kidney function every year (see Tables 2 and 3).1-5
Table 1. NOAC metabolism and elimination
| NOAC property||Apixaban1,4||Dabigatran2,4||Rivaroxaban3-5|
|Half-lifea||12 hours||12–17 hours||5–13 hours|
|Metabolism and bioavailability||Metabolised by CYP3A4/5 (major)|
Metabolised by CYP1A2, 2C8, 2C9, 2C19 and 2J2 (minor)
Substrate of P-gp, BCRP
Bioavailability of 50% (10 mg; no food interaction)
|Not metabolised by the CYP system |
Substrate of P-gp (dabigatran etexilate)
Prodrug dabigatran etexilate is converted to active dabigatran after oral administration, with bioavailability of 6.5% (no food interaction)
|Metabolised by CYP3A4, CYP2J2 and CYP-independent mechanisms|
Substrate of P-gp, BCRP
Oral bioavailability of 80–100% (10 mg), but 66% with 20 mg tablet under fasting conditions
15 mg and 20 mg tablets should be taken with food
Table 1 abbreviations: BCRP, breast cancer resistance protein; CYP, cytochrome P450; NOAC, non-vitamin K antagonist oral anticoagulant; P-gp, P-glycoprotein.
a Half-life is prolonged if renal function is impaired.
Table 2. NOAC use in hepatic impairment
|Contraindicated||Hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including severe hepatic impairment (Child-Pugh C)||Hepatic impairment or liver disease expected to have any impact on survival |
Manufacturer also contraindicates use if liver enzymes > 2 x ULN
|Significant hepatic disease (including Child-Pugh B and C), which is associated with coagulopathy leading to a clinically relevant bleeding risk|
|Monitoring||Perform liver function tests before starting a NOAC, and investigate if results are abnormal
Table 2 abbreviations: NOAC, non-vitamin K antagonist oral anticoagulant; ULN, upper limit of normal.
Table 3. NOAC use in renal impairment
|Contraindicated||CrCl < 25 mL/min||CrCl < 30 mL/min||Undergoing dialysis|
CrCl < 15 mL/min
|Monitoring||Assess renal function before starting a NOAC
Check renal function at least every year and whenever a clinical circumstance or medication change
Monitor more frequently in patients with impaired renal function
Table 3 abbreviations: NOAC, non-vitamin K antagonist oral anticoagulant; CrCl, creatinine clearance.