Is there an interaction between calcium supplements with vitamin K and Eliquis (apixaban)?

No Clinically Significant Interaction Between Calcium Supplements with Vitamin K and Eliquis

There is no clinically significant drug interaction between calcium supplements (with or without vitamin K) and Eliquis (apixaban), and these can be safely taken together. The available evidence from major guidelines and drug interaction reviews does not identify calcium or vitamin K supplementation as problematic when combined with apixaban 1.

Why This Combination is Safe

Apixaban's Mechanism Does Not Interact with Calcium or Vitamin K

• Apixaban is a direct Factor Xa inhibitor that works independently of the vitamin K pathway, unlike warfarin which is a vitamin K antagonist 2.
• The major drug interactions with apixaban involve CYP3A4 and P-glycoprotein (P-gp) inhibitors or inducers—calcium and vitamin K do not affect these pathways 1.
• Comprehensive guidelines on DOAC drug interactions specifically address CYP3A4 and P-gp modulators but do not list calcium or vitamin K supplements as concerning agents 1.

Evidence from Clinical Practice

• Large surveys of patients taking apixaban show that calcium and vitamin D supplements are among the most commonly used over-the-counter products (15% of patients), yet these are not flagged as having potentially serious interactions 3.
• A study examining drug-food interactions with DOACs found that patients should avoid St. John's wort but did not identify calcium or vitamin K as problematic 4.

Important Distinction: Vitamin K Matters Only for Warfarin

• Vitamin K supplementation is a significant concern only with warfarin (a vitamin K antagonist), where it can reduce anticoagulant effectiveness by counteracting warfarin's mechanism of action 1.
• The 2022 Circulation guidelines extensively discuss vitamin K interactions with warfarin but make no such warnings for apixaban or other DOACs 1.
• This is a critical point of confusion—vitamin K restrictions apply to warfarin patients, not to those taking apixaban 1, 2.

What You Actually Need to Avoid with Eliquis

High-Risk Medications to Avoid or Use with Caution

• NSAIDs (ibuprofen, naproxen): These significantly increase bleeding risk when combined with apixaban and should be avoided or used with extreme caution 1, 2.
• Aspirin: Increases bleeding risk, particularly in patients with higher kidney function (eGFR >80), and should only be used when specifically indicated 5.
• Strong dual CYP3A4 and P-gp inhibitors (e.g., ketoconazole, ritonavir): These are contraindicated as they can dangerously increase apixaban levels 1, 2.
• Strong dual CYP3A4 and P-gp inducers (e.g., rifampin, carbamazepine, St. John's wort): These should not be used as they reduce apixaban effectiveness 1, 4.

Safe Pain Relief Options

• Acetaminophen is the preferred analgesic for patients on apixaban, as it does not have antiplatelet effects and does not significantly interact with the medication 6.
• Limit acetaminophen to a maximum of 4 grams per day (some experts recommend 3 grams for chronic use) to prevent liver toxicity 6.

Special Considerations for Kidney Function

• Apixaban dosing may need adjustment based on kidney function and other patient characteristics (age ≥80 years, weight ≤60 kg, creatinine >1.5 mg/dL) 1.
• The standard dose is 5 mg twice daily, but 2.5 mg twice daily should be used if any 2 of the above criteria are present 1.
• Apixaban is contraindicated in severe kidney disease (CrCl <15 mL/min) per European guidelines, though FDA labeling differs slightly 1.

Common Pitfalls to Avoid

• Do not confuse warfarin restrictions with apixaban restrictions: Patients and providers often mistakenly apply vitamin K dietary restrictions from warfarin to apixaban—this is unnecessary 1, 2.
• Monitor for cumulative bleeding risk: While calcium/vitamin K supplements are safe, the combination of apixaban with multiple other products (especially NSAIDs, aspirin, or other antiplatelet agents) significantly increases bleeding risk 2, 3.
• Be aware of hidden NSAIDs: Many over-the-counter combination products contain NSAIDs—patients taking 33% of OTC products with potentially serious interactions often don't recognize the risk 3.

When to Seek Medical Attention

• Unusual bleeding or bruising while taking any combination of medications with apixaban requires immediate medical evaluation 6, 2.
• Before any surgical or dental procedures, inform healthcare providers about apixaban use, as temporary discontinuation may be needed 6, 2.
• Signs of excessive anticoagulation include easy bruising, prolonged bleeding from cuts, blood in urine or stool, or severe headaches 2.