A 63-year-old woman on ergocalciferol therapy asks which concomitant medication could cause a severe interaction. Which drug is most likely to cause a severe interaction with ergocalciferol?

• A. Warfarin
• B. Theophylline
• C. Digoxin
• D. Phenytoin

Answer: (C)

The key idea is how nutrient supplements can alter a drug’s effect, especially when calcium levels are involved. Ergocalciferol increases intestinal calcium absorption, which can raise serum calcium. Digoxin has a very narrow therapeutic window, and its toxicity is worsened by higher calcium levels. Hypercalcemia can enhance digoxin’s effects on the heart, increasing the risk of dangerous arrhythmias and other toxicity symptoms.

So, combining ergocalciferol with digoxin is most likely to produce a severe interaction because the vitamin D–induced rise in calcium can amplify digoxin toxicity.

Other drugs don’t have this same calcium-driven risk with ergocalciferol. Warfarin’s major interaction is with vitamin K, not calcium. Theophylline and phenytoin interact with many meds in other ways, but not in a particularly severe, calcium-mediated way with ergocalciferol.