Is it safe to take sulfate ferrous (iron supplement), folic acid, and vitamin B12 with Eliquis (apixaban)?

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Safety of Iron, Folic Acid, and Vitamin B12 with Eliquis (Apixaban)

Yes, ferrous sulfate (iron), folic acid, and vitamin B12 supplements are safe to take with Eliquis (apixaban) and are not contraindicated. There are no clinically significant drug interactions between these nutritional supplements and apixaban that would increase bleeding risk or reduce anticoagulant efficacy.

Evidence Supporting Safety

No Direct Interactions Identified

  • A comprehensive survey of 791 patients taking apixaban found that dietary supplements were commonly used (20.2% took supplements daily), but iron, folic acid, and B12 were not identified among products with potentially serious apixaban interactions 1.
  • The primary concern with apixaban relates to antiplatelet agents (aspirin, NSAIDs) and certain herbal supplements, not standard vitamin supplementation 1.

Mechanism of Non-Interaction

  • Apixaban is a direct factor Xa inhibitor that works through selective enzyme inhibition, not through vitamin K-dependent pathways 2, 3.
  • Iron, folic acid, and B12 do not affect factor Xa activity, platelet function, or the cytochrome P450 metabolism of apixaban 2.
  • These supplements do not alter the pharmacokinetics or pharmacodynamics of direct oral anticoagulants 4.

Clinical Context for Combined Use

Common Clinical Scenario

  • Patients on anticoagulation frequently require treatment for anemia or vitamin deficiencies, making concurrent supplementation medically necessary 5.
  • B vitamins (including folic acid and B12) are commonly prescribed for hyperhomocysteinemia in cardiovascular disease patients who may also be on anticoagulation 6.

Important Safety Considerations

  • Always check B12 levels before starting folic acid supplementation to avoid masking pernicious anemia while allowing irreversible neurological damage to progress 6, 5.
  • For patients with confirmed B12 deficiency requiring treatment, oral B12 (1000-2000 mcg daily) or intramuscular administration can be safely combined with apixaban 5.
  • Iron supplementation (50-100 mg elemental iron once daily) does not interact with apixaban and can be used concurrently when treating iron deficiency anemia 5.

Monitoring Recommendations

  • No additional anticoagulation monitoring is required when adding these supplements to apixaban therapy 3, 4.
  • Monitor hemoglobin and vitamin levels according to standard protocols for deficiency treatment, not for anticoagulation concerns 5.
  • Continue routine assessment for bleeding complications as appropriate for any patient on anticoagulation, regardless of supplement use 3.

Critical Pitfall to Avoid

  • Do not confuse these safe supplements with NSAIDs or antiplatelet agents, which do significantly increase bleeding risk when combined with apixaban 1. Aspirin was taken by 14.7% of apixaban patients in one study, and 64.7% of those also consumed other potentially interacting products 1.

References

Research

Apixaban: a new player in the anticoagulant class.

Current drug targets, 2012

Guideline

Management of Simultaneous Vitamin B12 and Iron Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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