What are the potential drug interactions with cholecalciferol (Vitamin D3)?

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Last updated: June 22, 2025View editorial policy

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From the FDA Drug Label

Not recommended for children, pregnant or lactating women, or individuals with liver disease, and those taking thiazide diuretics may be at greater risk of toxicity.

  • Key Interactions:
    • Thiazide diuretics: may increase the risk of toxicity
  • Special Considerations:
    • Liver disease: not recommended
    • Pregnancy and lactation: not recommended
    • Children: not recommended 1

From the Research

Cholecalciferol (Vitamin D3) can interact with several medications, requiring careful monitoring and potential dosage adjustments, with the most significant interactions occurring with anticonvulsants, corticosteroids, and certain diuretics. The most significant interactions occur with anticonvulsants (phenytoin, phenobarbital, carbamazepine), which can increase vitamin D metabolism and reduce its effectiveness, as shown in a study where cholecalciferol enhanced the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock 2. Corticosteroids like prednisone can impair vitamin D absorption and metabolism, potentially requiring higher vitamin D supplementation. Cholestyramine, orlistat, and other fat-binding medications can decrease vitamin D absorption since it is fat-soluble. Certain diuretics interact differently - thiazide diuretics may increase calcium levels when taken with vitamin D (risking hypercalcemia), while loop diuretics like furosemide can increase calcium excretion. Digoxin's effects may be enhanced when combined with vitamin D, potentially causing cardiac arrhythmias due to increased calcium levels. Aluminum-containing antacids used long-term with vitamin D can raise aluminum blood levels, posing risks especially for kidney patients.

Some key points to consider when managing patients on cholecalciferol include:

  • Monitoring vitamin D and calcium levels regularly, especially in patients with kidney disease or those taking medications that interact with vitamin D
  • Adjusting vitamin D dosages as needed to avoid toxicity or deficiency
  • Being aware of the potential for increased calcium levels when combining vitamin D with thiazide diuretics
  • Considering alternative treatments for patients with severe vitamin D deficiency or those who are not responding to cholecalciferol supplementation, as seen in a study where high-dose cholecalciferol supplementation was effective in treating vitamin D deficiency in haemodialysis patients 3
  • Recognizing the potential benefits of cholecalciferol supplementation on biomarkers of inflammation and myocardial structure in hemodialysis patients without hyperparathyroidism, as shown in a study where cholecalciferol supplementation reduced systemic inflammation and left ventricular hypertrophy 4.

Overall, cholecalciferol supplementation requires careful consideration of potential drug interactions and monitoring of vitamin D and calcium levels to ensure safe and effective treatment. Patients taking these medications should consult healthcare providers about appropriate vitamin D dosing and may need more frequent monitoring of vitamin D and calcium levels, as supported by a study on the impact of cholecalciferol treatment on biomarkers of inflammation and myocardial structure in hemodialysis patients without hyperparathyroidism 4.

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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