Drug Interaction Report

MONITOR: Theoretically, coadministration of trospium chloride with other drugs that are eliminated by active tubular secretion may result in increased plasma concentrations of trospium and/or the coadministered drug(s). The mechanism is competitive inhibition of renal excretion. Drugs that are thought to undergo active tubular secretion include acyclovir/valacyclovir, cidofovir, cimetidine, digoxin, flecainide, ganciclovir/valganciclovir, metformin, midodrine, morphine, pancuronium, procainamide, quinidine, ranitidine, tenofovir, triamterene, and vancomycin.

MANAGEMENT: Patients receiving trospium chloride in combination with other drugs that undergo active tubular secretion should be monitored for excessive pharmacologic effects of one or both drugs, and the dosages of the drugs adjusted if necessary.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of trospium chloride. According to the product labeling, administration of trospium chloride with a high fat meal reduced the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 70% to 80% compared to administration while fasting.

MANAGEMENT: To ensure maximal oral absorption, trospium chloride should be administered at least 1 hour before meals or on an empty stomach. If trospium chloride is administered as a combination with xanomeline, the manufacturer recommends administering the capsules at least 1 hour before a meal or at least 2 hours after a meal. Capsules should be taken whole.

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.