Digoxin × Diltiazem

The transporter P-glycoprotein limits digoxin absorption in the gut and removes it through the kidneys and bile (FDA digoxin label). Diltiazem weakly inhibits this transporter (diltiazem label). In studies, blood digoxin levels rose by about 20%; two studies found a 46–50% rise in digoxin AUC and a third found no significant interaction (diltiazem labels in Spain and the US). The second mechanism does not depend on drug levels: both drugs slow conduction through the atrioventricular (AV) node, and together they can cause bradycardia and AV block up to complete heart block (FDA digoxin label).

Signs of digoxin toxicity: loss of appetite, nausea, vomiting, weakness, dizziness and color vision changes with a yellow-green tint. Cardiac effects are rhythm and conduction disorders: atrioventricular (AV) block of any degree, atrial tachycardia with block, ventricular premature beats, often as bigeminy, and ventricular tachycardia (FDA digoxin label). The combined effect of both drugs on the AV node can slow the pulse even without a rise in digoxin levels; the risk is higher in older patients and at high doses (diltiazem label).

Measure serum digoxin before starting diltiazem. Then reduce the digoxin dose by about 15–30% or give it less often, and keep monitoring levels (FDA digoxin label). Check digoxin levels when diltiazem is started, when its dose changes and when it is stopped, to avoid both over- and under-digitalization (diltiazem labels in Spain and the US). Take blood just before the next digoxin dose or at least 6 hours after the last one. Do not change the dose on a single level without the clinical picture (FDA digoxin label). Both drugs slow the pulse, so watch it closely in older patients and at high doses (diltiazem label).