Vitamin D Drug Interactions

A number of commonly prescribed drugs alter vitamin D metabolism or interact with its downstream effects. Some accelerate vitamin D catabolism (creating deficiency even on standard supplementation), some reduce absorption, and some create calcium-related risks when combined with vitamin D at higher doses.

Drugs that reduce vitamin D levels

• Anticonvulsants — phenytoin, phenobarbital, carbamazepine, primidone, oxcarbazepine induce CYP3A4/CYP24A1 and accelerate vitamin D catabolism. Patients on chronic anticonvulsants often need 2–4× standard doses; osteomalacia and osteoporosis rates are elevated. Newer anticonvulsants (levetiracetam, lamotrigine) have less impact.
• Glucocorticoids — chronic prednisone reduces calcium absorption, increases urinary calcium loss, and impairs osteoblast function. Standard practice: calcium 1,000–1,200 mg + vitamin D 800–1,000 IU/day, plus bisphosphonate for prolonged high-dose steroids.
• Rifampin — CYP3A4 induction; accelerates 25(OH)D degradation.
• Isoniazid — inhibits 1α-hydroxylase; may reduce calcitriol.
• Antiretrovirals — efavirenz reduces 25(OH)D; tenofovir causes renal phosphate wasting and can worsen bone mineral density.
• Cholestyramine, colestipol — bind fat-soluble vitamins; take vitamin D 4+ hours apart.
• Orlistat — reduces fat absorption; take vitamin D 2+ hours after orlistat.
• Mineral oil, olestra — reduce fat-soluble vitamin absorption.

Drugs where vitamin D can cause problems

• Thiazide diuretics (HCTZ, chlorthalidone, indapamide) — reduce urinary calcium; combined with high-dose vitamin D can cause hypercalcaemia. Use standard doses cautiously; monitor calcium if using both.
• Digoxin — hypercalcaemia potentiates digoxin toxicity. Avoid vitamin D overdose in patients on digoxin.
• Calcium channel blockers — verapamil in particular; hypercalcaemia can reduce efficacy.
• Lithium — vitamin D-induced hypercalcaemia can precipitate lithium toxicity.
• Aluminium-containing antacids — chronic vitamin D combined with aluminium antacid can increase aluminium absorption; potential toxicity in CKD.

Drugs that raise 25(OH)D

• Ketoconazole, itraconazole, voriconazole — inhibit CYP24A1 (vitamin D catabolism) and can transiently raise 25(OH)D.
• Thiazides (mild) — via reduced urinary calcium.

Diseases that require caution with vitamin D

• Granulomatous disease (sarcoidosis, tuberculosis, chronic berylliosis) — extra-renal 1α-hydroxylase converts 25(OH)D to calcitriol without regulation; standard doses of vitamin D can cause hypercalcaemia.
• Lymphoma — similar risk to granulomatous disease.
• Primary hyperparathyroidism — pre-existing hypercalcaemia; correcting associated vitamin D deficiency needs careful monitoring.
• Nephrolithiasis — calcium-based stones; high-dose vitamin D combined with calcium supplements can increase risk.
• Chronic kidney disease — see our CKD page.