Drug Interactions between digoxin and ticagrelor

MONITOR: Coadministration with ticagrelor may increase the plasma concentrations of digoxin. The proposed mechanism is reduced clearance of digoxin due to inhibition of P-glycoprotein-mediated renal tubular secretion by ticagrelor. In study subjects, administration of digoxin in combination with ticagrelor increased the mean digoxin peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 75%, 28% and 30%, respectively, with individual increases in the latter of up to twofold. Digoxin had no significant effect on the Cmax and AUC of ticagrelor or its active metabolite.

MONITOR: Ventricular pauses and bradycardia, mostly asymptomatic, have been observed in clinical studies with ticagrelor. Theoretically, the risk of symptomatic bradycardia may be increased during concomitant use of other agents known to induce bradycardia such as digoxin. However, in PLATO, a large, randomized, double-blind efficacy and safety comparison study with clopidogrel in patients with acute coronary syndromes, no evidence of clinically significant adverse interactions was observed during concomitant administration with one or more drugs known to induce bradycardia including beta-blockers (96%), the calcium channel blockers diltiazem and verapamil (33%), and digoxin (4%).

MANAGEMENT: Caution is advised if digoxin must be used in combination with ticagrelor. Pharmacologic response and serum digoxin levels should be monitored more closely whenever ticagrelor is added to or withdrawn from therapy, and the digoxin dosage adjusted as necessary. Patients should be advised to notify their doctor if they experience potential signs and symptoms of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.