Refrat Drug Interactions

Acyclovir: Higher MPAG and acyclovir plasma concentrations were observed when mycophenolate mofetil was administered with acyclovir than when the drugs administered alone. Because MPAG plasma concentrations are increased in the presence of renal impairment, as are acyclovir concentrations, the potential exists for mycophenolate and acyclovir, to complete for tubular secretion, further increasing the concentrations of both drugs.
Antacids with magnesium and aluminium hydroxides: Absorption of mycophenolate mofetil was decreased when the drug was administered with antacids.
Cholestyramine: Following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects pretreated with 4 g t.i.d. of cholestyramine for 4 days, there was a 40% reduction in the AUC of MPA. Caution should be used during concomitant administration or with drugs that interfere with enterohepatic circulation.
Cyclosporin A: Cyclosporin A pharmacokinetics were unaffected by mycophenolate mofetil.
Ganciclovir: Based on the results of a single dose administration study of recommended doses of oral mycophenolate and i.v. ganciclovir and the known effects of renal impairment on the pharmacokinetics of mycophenolate mofetil and ganciclovir, it is anticipated that coadministration of these agents (which compete for mechanisms of renal tubular secretion) will result in increases in MPAG and ganciclovir concentration. No substantial alteration of MPA pharmacokinetics is anticipated and a mycophenolate mofetil dose adjustment is not required. In patients with renal impairment in which mycophenolate mofetil and ganciclovir, are coadministered, the patient should be monitored carefully.
Oral contraceptives: The pharmacokinetics of oral contraceptives were unaffected by coadministration of mycophenolate mofetil. Study of coadministration of mycophenolate mofetil and combined oral contraceptives showed no clinically relevant influence of mycophenolate mofetil on serum levels of progesterone, LH and FSH, thus indicating no influence of mycophenolate mofetil on the ovulation-suppressing action of the oral contraceptives.
Trimethoprim/sulphamethoxazole: No effect on the bioavailability of MPA was observed.
Tacrolimus: In renal transplant patients: Stable renal transplant patients receiving cyclosporin and mycophenolate mofetil (1 g twice daily) showed about a 30% increase in MPA plasma AUC and about a 20% decrease in MPAG plasma AUC when cyclosporin was replaced with tacrolimus. MPA C_max was not affected, while MPAG C_max was reduced by approximately 20%. The mechanism of this finding is not well understood. Increased biliary secretion of MPAG accompanied with increased enterohepatic recirculation of MPA may be partly responsible for the finding, since the elevation of MPA concentrations associated with tacrolimus administration was more pronounced in later portions of the concentration - time profile (4-12 hours after dosing). For patients on tacrolimus, the dose of mycophenolate mofetil should not exceed 1 g twice a day. Patients should be carefully observed and managed appropriately. In another study in renal transplant patients, it was shown that the tacrolimus concentration did not appear to be altered by mycophenolate mofetil.
Other interactions: Coadministration of Probenecid with mycophenolate mofetil in monkeys raises the plasma AUC of MPAG 3- fold. Thus, other drugs known to undergo renal tubular secretion may compete with MPAG and thereby raise plasma concentrations of MPAG or the other drug undergoing tubular secretion.
Live vaccines: Live vaccines should not be given to patients with an impaired immune response. The antibody response to other vaccines may be administered.