Observed Interactions Resulting in a Concomitant Use Not Recommended: Azathioprine: It is recommended that mycophenolic acid should not be administered concomitantly with azathioprine because such concomitant administration has not been studied (see Precautions).
Live Vaccines: Live vaccines should not be given to patients with an impaired immune response. The antibody response to other vaccines may be diminished (see Precautions).
Observed Interactions to be Considered: Aciclovir: Higher plasma concentrations of both MPAG (mycophenolic acid glucuronide) and aciclovir may occur in the presence of renal impairment. Therefore, the potential exists for these two drugs to compete for tubular secretion, resulting in a further increase in the concentration of both MPAG and aciclovir. In this situation patients should be carefully followed up.
Gastroprotective Agents: Antacids with Magnesium and Aluminum Hydroxides: The absorption of mycophenolate sodium was decreased when administered with antacids. Concomitant administration of mycophenolic acid and antacids containing magnesium and aluminum hydroxide results in a 37% decrease in MPA systemic exposure and a 25% decrease in MPA maximal concentration. Caution should be used when co-administering antacids (containing magnesium and aluminum hydroxide) with mycophenolic acid.
Proton Pump Inhibitors: In healthy volunteers, concomitant administration of MMF 1000 mg and pantoprazole 40 mg twice daily led to a 27% decrease in the MPA AUC and to a 57% decrease in the MPA Cmax. However, in the same study, no changes in the pharmacokinetics of MPA were observed following concomitant administration of mycophenolic acid and pantoprazole.
Ganciclovir: MPA and MPAG pharmacokinetics are unaffected by the addition of ganciclovir. The clearance of ganciclovir is unchanged in the setting of therapeutic MPA exposure. However, in patients with renal impairment in which mycophenolic acid and ganciclovir are coadministered the dose recommendations for ganciclovir should be observed and patients monitored carefully.
Tacrolimus: In a calcineurin cross-over study in stable renal transplant patients, steady state mycophenolic acid pharmacokinetics were measured during both Neoral and tacrolimus treatments. Mean MPA AUC was 19% higher and Cmax about 20% lower. Conversely mean MPAG AUC and Cmax were about 30% lower on tacrolimus treatment compared to Neoral treatment.
Ciclosporin A: When studied in stable renal transplant patients, ciclosporin A pharmacokinetics were unaffected by steady state dosing of mycophenolic acid.
Anticipated Interactions to be Considered: Cholestyramine and Drugs That Interfere with Enterohepatic Circulation: Due to its capacity to block the enteric circulation of drugs, cholestyramine may decrease the systemic exposure of MPA. Caution should be used when co-administering cholestyramine or drugs that interfere with enterohepatic circulation because of the potential to reduce the efficacy of mycophenolic acid.
Oral Contraceptives: Oral contraceptives undergo oxidative metabolism while mycophenolic acid is metabolized by glucuronidation. A clinically significant effect of oral contraceptives on mycophenolic acid pharmacokinetics is not anticipated. However, given that the long term effect of mycophenolic acid dosing on the pharmacokinetics of oral contraceptives is not known, it is possible that the efficacy of oral contraceptives may be adversely affected (see Use in Pregnancy & Lactation).