Drug Interaction Report

MONITOR CLOSELY: Parathyroid hormone may alter the effects of digitalis glycosides. The inotropic effects of digitalis glycosides are affected by serum calcium levels. Since parathyroid hormone causes a transient increase in serum calcium, it can potentiate the risk of digitalis toxicity if hypercalcemia develops. On the other hand, digitalis efficacy may be reduced if hypocalcemia occurs. Severe cases of both hypercalcemia and hypocalcemia have been reported during treatment with parathyroid hormone. The risk of hypercalcemia is greatest when starting or increasing the dose of parathyroid hormone, whereas the risk of hypocalcemia is greatest when parathyroid hormone is withheld, missed, or abruptly discontinued.

MANAGEMENT: Serum calcium and digitalis levels should be closely monitored during parathyroid hormone therapy, and the digitalis dosage adjusted as necessary. Patients should be advised to seek medical attention if they experience signs of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeat.

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.