Drug Interaction Report

Tigecycline does not significantly affect the pharmacokinetics of digoxin, and vice versa. In healthy subjects, coadministration of tigecycline (100 mg followed by 50 mg every 12 hours) and digoxin (0.5 mg followed by 0.25 mg orally every 24 hours) resulted in a 13% decrease in the peak plasma concentration (Cmax) of digoxin. There was no change in the steady-state pharmacodynamic effects of digoxin as indicated by ECG interval measurements, and the systemic exposure (AUC) and clearance of digoxin were also not altered. Digoxin did not affect the pharmacokinetics of tigecycline. No dosage adjustment of either drug is necessary during coadministration.

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.