Ciclosporin × Digoxin

Ciclosporin inhibits P-glycoprotein and reduces digoxin clearance (ciclosporin SmPC). Digoxin is cleared by the kidneys, so ciclosporin nephrotoxicity can also keep it in the blood longer (both labels). The US Food and Drug Administration (FDA) ciclosporin label describes severe digitalis toxicity within days of starting ciclosporin. The size of the rise cannot be predicted: the FDA digoxin label calls it unclear.

Nausea, vomiting, loss of appetite, weakness, confusion. Visual changes: blurred vision, green-yellow colour changes, halos around lights. Rhythm disorders: ventricular premature beats, often as bigeminy, atrioventricular block, atrial tachycardia with block. Older age, low body weight, reduced kidney function and electrolyte disorders raise the risk of toxicity (digoxin label).

The combination is acceptable only with close monitoring. The ciclosporin SmPC requires close clinical observation to detect digoxin toxicity early, followed by a lower digoxin dose or stopping digoxin. The US Food and Drug Administration (FDA) ciclosporin label says serum digoxin concentrations should be monitored. Measure the digoxin concentration before ciclosporin is started, keep monitoring and reduce the digoxin dose as needed (FDA digoxin label). Draw the sample just before the next digoxin dose or at least 6 hours after the last one (FDA digoxin label). Ciclosporin requires frequent checks of kidney function and raises the risk of hyperkalaemia, so check creatinine and potassium regularly (ciclosporin SmPC). The digoxin SmPC already asks for periodic electrolyte and creatinine checks.