B Vitamins and Eliquis (Apixaban): Safety Assessment
Direct Answer
B vitamins are safe to take with Eliquis (apixaban) as there are no known drug-drug interactions between these agents. The major European and American guidelines on anticoagulation do not identify B vitamins as interacting substances with apixaban or other direct oral anticoagulants 1.
Mechanism and Rationale
Why No Interaction Exists
Apixaban is metabolized primarily through CYP3A4 (approximately 25%) and eliminated renally (27%), with the remainder through direct biliary excretion 1. B vitamins do not affect these metabolic pathways 1.
The 2018 European Heart Rhythm Association guidelines extensively detail drug-drug interactions with apixaban, focusing on P-glycoprotein (P-gp) inhibitors/inducers and CYP3A4 modulators 1. B vitamins (including B6, B12, and folic acid) are not listed among substances requiring caution or dose adjustment.
B vitamins do not inhibit or induce P-gp, CYP3A4, or BCRP (breast cancer resistance protein)—the key transporters and enzymes that affect apixaban levels 1.
Clinical Context: B Vitamins and Thrombosis
Potential Benefit in Specific Populations
Folic acid combined with vitamin B12 has been shown to reduce homocysteine levels, which may decrease thrombosis recurrence risk in patients with hyperhomocysteinemia 2. In one study, patients receiving folic acid and B12 had a lower deep vein thrombosis recurrence rate (4.4% vs 28.9%) compared to those not receiving supplementation 2.
This effect is mediated through homocysteine reduction, not through direct interaction with anticoagulants 2. The mechanism involves preventing thrombosis formation rather than altering anticoagulant drug levels.
What Actually Matters: Substances to Avoid with Apixaban
High-Risk Interactions (Contraindicated)
Strong dual P-gp and CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) are contraindicated with apixaban 1.
Strong dual P-gp and CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) significantly reduce apixaban levels and should be avoided 1.
Moderate-Risk Interactions (Caution Required)
Moderate P-gp or CYP3A4 inhibitors (e.g., diltiazem, verapamil, clarithromycin) may increase apixaban exposure by approximately 40% 1. These require clinical monitoring but not necessarily dose adjustment for apixaban.
Dronedarone with apixaban requires caution due to combined P-gp and CYP3A4 inhibition 1.
Practical Recommendations
Safe Co-Administration
Patients taking apixaban can safely take B-complex vitamins, folic acid, vitamin B6, and vitamin B12 without dose adjustment of either agent 1.
No additional monitoring beyond standard apixaban surveillance (renal function annually, clinical bleeding assessment) is required when adding B vitamins 3, 4.
When B Vitamins May Be Particularly Appropriate
Consider B vitamin supplementation in patients with documented hyperhomocysteinemia who are at risk for recurrent thrombosis 2, as this addresses an independent thrombotic risk factor without interfering with anticoagulation.
Patients with nutritional deficiencies, malabsorption, or those on metformin (which depletes B12) can safely receive B vitamin supplementation while on apixaban 1.
Common Pitfall to Avoid
- Do not confuse vitamin B with vitamin K—vitamin K antagonists (warfarin) are affected by dietary vitamin K intake, but apixaban is not a vitamin K antagonist and is unaffected by vitamin K or other vitamin supplementation 1.