Which interaction is most important to consider when a patient is on theophylline and digoxin and drinks grapefruit juice?

• A. Theophylline is predicted to increase the risk of digoxin toxicity when given with digoxin
• B. Grapefruit juice has no effect on theophylline
• C. Grapefruit juice reduces digoxin levels
• D. Theophylline decreases digoxin toxicity risk

Answer: (A)

Digoxin has a narrow therapeutic window, and interactions that raise its level or amplify its cardiac effects can push a patient into toxicity. When grapefruit juice is consumed, it can increase digoxin exposure by inhibiting intestinal P-glycoprotein, leading to higher absorption and higher serum levels. Theophylline, used with digoxin, can also raise the risk of digoxin toxicity because their combined effects on the heart and on electrolyte balance can predispose to arrhythmias and other toxic effects. In this scenario, the interaction that matters most is the potential for theophylline to increase the risk of digoxin toxicity when both drugs are present, with grapefruit juice further magnifying digoxin exposure. Clinically, this means monitoring for signs of digoxin toxicity (nausea, vomiting, confusion, visual changes, or arrhythmias), checking digoxin levels if indicated, and being cautious with grapefruit juice and theophylline dosing or use.