Drug Interaction Report

In vitro studies have shown that mycophenolic acid in concentrations up to 100 mcg/mL decreases protein binding of theophylline from 53% to 45%. The clinical significance of this interaction is unknown. Decreased protein binding theoretically could lead to increased plasma theophylline concentrations. However, clinical toxicity has not been reported. It may be appropriate to monitor more closely patients receiving theophylline or other methylxanthine derivatives with mycophenolic acid products. Patients should be advised to contact their physician if they experience potential symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, and irregular heartbeat.

ADJUST DOSING INTERVAL: Administration of enteric coated mycophenolic acid with meals may alter its pharmacokinetics relative to administration in the fasting state. When mycophenolic acid 720 mg was administered with a high-fat meal, there was a 33% decrease in the peak plasma concentration (Cmax); a 3.5-hour increase in delay time for the rise of plasma mycophenolic acid; and a 5-hour delay in the time to reach peak plasma concentration (Tmax). However, no effect was observed on the systemic exposure of mycophenolic acid.

MANAGEMENT: To avoid variability in drug absorption between doses, enteric coated formulations of mycophenolic acid should be taken on an empty stomach, one hour before or two hours after food intake. The tablets should be swallowed whole and not crushed, chewed or divided in order to maintain the integrity of the enteric coating.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.