Drug Interactions between digoxin and Zartan

ADJUST DOSING INTERVAL: Oral products containing zinc such as mineral supplements and multivitamins may interfere with the gastrointestinal absorption of cephalexin, ceftibuten or cephradine. In one pharmacokinetic study (n=12), concurrent administration of zinc sulfate (250 mg, single oral dose) and cephalexin (500 mg, single oral dose) decreased cephalexin maximum concentration (Cmax) and systemic exposure (AUC; 0-inf) by 31.05% and 27.4%, respectively. However, in the same study, when zinc sulfate was administered 3 hours after the cephalexin dose, no significant alteration in cephalexin pharmacokinetics were observed.

MANAGEMENT: Oral medications or mineral supplements that contain zinc are recommended to be administered at least 3 hours after the cephalexin, ceftibuten or cephradine dose.

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.