Drug Interaction Report

MONITOR: Coadministration with green tea may decrease the plasma concentrations of digoxin. The mechanism of interaction has not been established, but may involve induction of P-glycoprotein (P-gp)-mediated efflux of digoxin in the intestine by one or more of the catechins in green tea, or inhibition of one or more transporters involved in the intestinal uptake of digoxin that have yet to be identified. In a study consisting of 16 healthy volunteers, administration of a single 0.5 mg dose of digoxin following pretreatment with green tea extract for 13 days decreased digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) by 26% and 33%, respectively, compared to administration of digoxin alone. The green tea used in the study was a commercially available 630 mg formulation of green tea extract containing 300 mg of catechins. It is not known whether, and to what extent, the data from this study may be applicable to other preparations and products of green tea, since the compositions, amounts, and bioavailabilities of catechins may vary substantially.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. If green tea products are consumed regularly, digoxin levels may need to be checked more frequently and the dosage adjusted accordingly. Patients should be advised to notify their physician if they experience a worsening of their heart symptoms. Due to differences in phytochemical content and potency of commercial herbal products in general, the pharmacokinetic effects of green tea may vary depending on the specific preparation.

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.