Drug Interaction Report

MONITOR: Rare cases of digoxin toxicity have been reported with concomitant use of tramadol. The mechanism of the interaction has not been described.

MANAGEMENT: If digoxin and tramadol are used together, the patient should be closely monitored for clinical or laboratory signs of digoxin toxicity. Patients should be advised to notify their physicians if they experience signs of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

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.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.