Drug Interaction Report

MONITOR: Coadministration with inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may reduce the bioavailability of mycophenolic acid (MPA) from the administration of mycophenolate mofetil. The exact mechanism of interaction has not been established, but may involve a decrease in MPA solubility at higher gastric pH levels. When single doses of proton pump inhibitors were given to healthy volunteers and multiple doses to transplant patients receiving mycophenolate mofetil, MPA peak plasma concentration (Cmax) was reduced by 30% to 70% and systemic exposure (AUC) by 25% to 35%. The clinical significance is unknown. The interaction does not appear to occur when mycophenolic acid itself is administered. In 12 healthy volunteers, the pharmacokinetics of MPA were observed to be similar when a single 720 mg dose of mycophenolic acid was administered alone and following concomitant administration with pantoprazole, which was administered at a dosage of 40 mg twice daily for 4 days.

MANAGEMENT: Because clinical relevance of this interaction has not been established, PPIs or PCABs should be used with caution in transplant patients receiving mycophenolate mofetil.

ADJUST DOSING INTERVAL: Coadministration with antacids may decrease the oral bioavailability of mycophenolic acid. The exact mechanism of interaction is unknown but may involve chelation with polyvalent ions in antacids or enhanced drug solubility induced by an increase in gastric pH, or both. The interaction has been reported with magnesium/aluminum-containing antacids.

MANAGEMENT: Patients treated with oral mycophenolic acid who require an antacid or antacid-containing preparation (e.g., didanosine buffered tablets or pediatric oral solution) should separate the administration times of the medications by at least two hours.