Annals of Phlebology

Table. 2.

Table 2. Pharmacokinetics and drug interactions of DOACs

Anticoagulant Bioavaliability Renal excretion Half-life Potential drug interactions*
Dabigatran (Pradaxa) 3 to 7% bioavailable Over 80% cleared by the kidney 12 to 17 hours P-gp inhibitors can increase dabigatran effect
Unaffected by food Prolonged with kidney impairment and in older adults P-gp inducers can decrease dabigatran effectΔ
Capsule must be taken intact and requires gastric acidity for absorption Avoidance of some combinations or dose adjustment may be needed
Apixaban (Eliquis) 50% bioavailable
27% cleared by the kidney 12 hours Strong dual CYP3A4 and P-gp inhibitors can increase apixaban effect
Unaffected by food Prolonged in older adults Strong single CYP3A4 inhibitors (ie, without P-gp inhibition) can also increase apixaban effect
Strong CYP3A4 inducers and/or P-gp inducers can decrease apixaban effectΔ
Avoidance of some combinations or dose adjustment may be needed
Edoxaban (Lixiana) 62% bioavailable 50% cleared by the kidney 10 to 14 hours P-gp inhibitors can increase edoxaban effect
Unaffected by food Reduced efficacy in patients with nonvalvular atrial fibrillation and CrCl>95 ml/min Prolonged in renal impairment P-gp inducers can decrease edoxaban effect
Avoidance of some combinations or dose adjustment may be needed
Rivaroxaban (Xarelto) 10 mg dose:
- 80 to 100% bioavailable
- Unaffected by food
36% cleared by the kidney 5 to 9 hours Strong dual CYP3A4 and P-gp inhibitors can increase rivaroxaban effect§
20 mg dose:
- 66% bioavailable if taken when fasting; increased if taken with food
Prolonged to 11 to 13 hours in older adults Strong CYP3A4 inducers and/or P-gp inducers can decrease rivaroxaban effectΔ
Avoidance of some combinations or dose adjustment may be needed

DOACs: Direct oral anticoagulants include direct thrombin inhibitors (eg, dabigatran) and direct factor Xa inhibitors (eg, apixaban, edoxaban, rivaroxaban).

P-gp: P-glycoprotein drug efflux pump, CYP3A4: cytochrome p450 3A4 isoform.

*Examples of P-gp inhibitors that reduce metabolism of DOACs, leading to increased DOAC levels, include clarithromycin, ombitasvir- or ritonavir-containing combinations, and verapamil. Examples of P-gp inducers that increase DOAC metabolism, leading to lower DOAC levels, include phenytoin, rifampin, and St. John’s wort.

Examples of strong CYP3A4 inhibitors that reduce metabolism of some DOACs, leading to increased DOAC levels, include clarithromycin and ombitasvir- or ritonavir-containing combinations. Examples of strong CYP3A4 inducers that increase metabolism of some DOACs, leading to lower DOAC levels, include carbamazepine, phenytoin, and rifampin.

ΔIn patients with AF, combined use of levetiracetam or valproate with dabigatran, apixaban, or rivaroxaban was associated with an increased risk of ischemic stroke or systemic embolism. The mechanism of this interaction is unknown.

Blood levels of edoxaban were reduced and a higher rate of ischemic stroke was observed in patients with AF and CrCl >95 ml/min who were treated with edoxaban compared with those receiving warfarin.

§Drugs that either inhibit CYP3A4 or P-gp, as opposed to both, do not seem to significantly alter rivaroxaban.

Ann Phlebology 2022;20:9~14 https://doi.org/10.37923/phle.2022.20.1.9
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