Drug Interaction Report

MONITOR CLOSELY: Tetracyclines may increase serum levels of orally administered digoxin by preventing specific bacteria, present in the lower intestine, from inactivating digoxin. About 10% of the population use this mechanism to metabolize digoxin. When digoxin was administered with tetracycline in a pharmacokinetic study done in adults, the digoxin serum concentration increased by 100%. Currently there is no data demonstrating the effects of other tetracyclines on digoxin levels. The risk of an interaction may be less with digoxin solution in capsules because absorption occurs in the upper GI tract.

MANAGEMENT: Close clinical monitoring of digoxin serum concentration as well as signs or symptoms of digoxin toxicity are recommended when antibiotic therapy is initiated or discontinued. It is advisable to obtain a baseline digoxin level prior to initiating concomitant therapy. Some authorities recommend reducing the digoxin dose by around 30% to 50% or modifying the dosing frequency, followed by additional monitoring. Patients should be advised to notify their physicians if they experience nausea, anorexia, fatigue, visual changes, slow pulse, and/or irregular heartbeats.

GENERALLY AVOID: The oral bioavailability of quinolone and tetracycline antibiotics may be reduced by concurrent administration of preparations containing polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc. Therapeutic failure may result. The proposed mechanism is chelation of quinolone and tetracycline antibiotics by di- and trivalent cations, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. Reduced gastrointestinal absorption of the cations should also be considered.

MANAGEMENT: Concomitant administration of oral quinolone and tetracycline antibiotics with preparations containing aluminum, calcium, iron, magnesium, and/or zinc salts should generally be avoided. Otherwise, the times of administration should be staggered by as much as possible to minimize the potential for interaction. Quinolones should typically be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation preparations, depending on the quinolone and formulation. Likewise, tetracyclines and polyvalent cation preparations should typically be administered 2 to 4 hours apart. The prescribing information for the antibiotic should be consulted for more specific dosing recommendations.

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.