Drug Interaction Report

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase plasma digoxin concentrations and half-life. The exact mechanism is unknown, but may be related to reduced renal clearance of digoxin. Data have been conflicting. The interaction has been reported with indomethacin and ibuprofen, but data for other NSAIDs are not available.

MANAGEMENT: Patients who require concomitant therapy should be monitored for altered pharmacologic effects of digoxin and for increased plasma levels. The digoxin dosage may require adjustment. Patients should be advised to notify their physician if they experience nausea, anorexia, visual changes, slow pulse, or irregular heartbeats.

ADJUST DOSE: In-vivo studies have demonstrated that the absorption of bromfenac is greatly reduced if the drug is taken within three and one-half hours following a high fat meal. The concomitant administration of a high fat meal has led to a 75% reduction in peak plasma concentrations and a 60% reduction in total area under the curve. The mechanism has not been described.

MANAGEMENT: An increased dosage of bromfenac (from 25 to 50 mg) may be needed if a high fat meal is consumed. The clinician may want to warn the patient about subtherapeutic analgesic effects if high fat meals are regularly consumed.

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.