Which combination is described as causing a clinically significant interaction?

• A. Warfarin, Ramipril
• B. Digoxin, Amiodarone
• C. Clarithromycin, Ramipril
• D. Amitriptyline, Metformin

Answer: (B)

Digoxin has a narrow therapeutic index, so small increases in its blood levels can lead to toxicity. Amiodarone strongly inhibits P-glycoprotein, a transporter that helps clear digoxin from the gut and kidneys. When these two are taken together, digoxin levels rise significantly, increasing the risk of serious toxicity such as bradycardia, heart block, nausea, confusion, visual disturbances, and other arrhythmias. This interaction is well recognized and clinically important, especially in older patients or those with reduced renal function, since amiodarone’s effect on digoxin clearance can persist for a long time. To manage this, clinicians commonly reduce the digoxin dose and monitor serum digoxin concentrations and electrolytes (potassium and magnesium) because electrolyte disturbances can worsen toxicity. The other combinations do not produce such a clear, high-risk interaction, so this pairing stands out as the clinically significant one.