CellCept Drug Interactions

DNA Polymerase Inhibitors (acyclovir, ganciclovir): Acyclovir: Higher MPAG (the phenolic glucuronide of MPA) and acyclovir plasma concentrations were observed when mycophenolate mofetil was administered with acyclovir than when the drugs were 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 or its prodrugs e.g. valacyclovir to compete for tubular secretion, further increasing the concentrations of both drugs.
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 MMF (see Pharmacology: Pharmacokinetics under Actions and Precautions) 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 MMF dose adjustment is not required. In patients with renal impairment in whom MMF and ganciclovir or its prodrugs valganciclovir are co-administered, patients should be monitored carefully.
Antacids and proton pump inhibitors (PPIs): Decreased mycophenolic acid (MPA) exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole were administered with Mycophenolate mofetil (CellCept). When comparing rates of transplant rejection or rates of graft loss between Mycophenolate mofetil (CellCept) patients taking PPIs vs. Mycophenolate mofetil (CellCept) patients not taking PPIs, no significant differences were seen. These data support extrapolation of this finding to all antacids because the reduction in exposure when Mycophenolate mofetil (CellCept) was co-administered with magnesium and aluminium hydroxides is considerably lower than when Mycophenolate mofetil (CellCept) was co-administered with PPIs.
Sequestrants: Cholestyramine: Following single-dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects pretreated with 4 g three times daily of cholestyramine for 4 days, there was a 40% reduction in the AUC of MPA. Caution should be used during concomitant administration of drugs that interfere with enterohepatic circulation (see Precautions).
Sevelamer: Concomitant administration of sevelamer and Mycophenolate mofetil (CellCept) in adults and pediatric patients decreased the MPA C_max and AUC_0-12 by 30% and 25%, respectively (see Interactions under Precautions).
Immunosuppressants: Ciclosporin A: Ciclosporin A (CsA) pharmacokinetics were unaffected by mycophenolate mofetil. However, CsA interferes with MPA enterohepatic recycling, resulting in reduced MPA exposures by 30-50% in renal transplant patients treated with Mycophenolate mofetil (CellCept) and CsA compared with patients receiving sirolimus or belatacept and similar doses of Mycophenolate mofetil (CellCept). Conversely, changes of MPA exposure should be expected when switching patients from CsA to one of the immunosuppressants which do not interfere with MPA's enterohepatic cycle (see Precautions).
Tacrolimus: Exposure to tacrolimus concomitantly administered with Mycophenolate mofetil (CellCept) had no effect on the AUC or C_max of MPA in liver transplant recipients. A similar finding was observed in a recent study in kidney transplant recipients.
In renal transplant patients it was shown that the tacrolimus concentration did not appear to be altered by Mycophenolate mofetil (CellCept).
However, in hepatic transplant patients, there was an increase of approximately 20% in tacrolimus AUC when multiple doses of Mycophenolate mofetil (CellCept) (1.5 g twice daily) were administered to patients taking tacrolimus.
Antibiotics: Rifampicin: After correction for dose a 70% decrease in MPA exposure (AUC_0-12) has been observed with concomitant rifampicin administration in a single heart-lung transplant patient. It is therefore recommended to monitor MPA exposure levels and to adjust Mycophenolate mofetil (CellCept) doses accordingly to maintain clinical efficacy when the drugs are administered concomitantly.
Antibiotics eliminating β-glucuronidase-producing bacteria in the intestine (e.g. aminoglycoside, cephalosporin, fluoroquinolone, and penicillin classes of antibiotics) may interfere with MPAG/MPA enterohepatic recirculation thus leading to reduced systemic MPA exposure (see Interactions under Precautions).
Information concerning the following antibiotics is available: Ciprofloxacin or amoxicillin plus clavulanic acid: Reductions in pre-dose (trough) MPA concentrations of 54% have been reported in renal transplant recipients in the days immediately following commencement of oral ciprofloxacin or amoxicillin plus clavulanic acid. Effects tended to diminish with continued antibiotic use and cease after discontinuation. The change in pre-dose level may not accurately represent changes in overall MPA exposure, therefore clinical relevance of these observations is unclear.
Norfloxacin and metronidazole: Norfloxacin in combination with metronidazole reduced the MPA AUC_0-48 by 30% following a single dose of Mycophenolate mofetil (CellCept). No such effect on the systemic exposure of MPA with either of these antibiotics occurred when they were administered separately.
Trimethoprim/sulphamethoxazole: No effect on the systemic exposure of MPA (AUC, C_max) was seen with the combination trimethoprim/sulfamethoxazole.
Oral contraceptives: A study of coadministration of Mycophenolate mofetil (CellCept) (1 g twice daily) and combined oral contraceptives containing ethinylestradiol (0.02-0.04 mg) and levonorgestrel (0.05-0.20 mg), desogestrel (0.15 mg) or gestodene (0.05-0.10 mg) conducted in 18 women with psoriasis over 3 menstrual cycles showed no clinically relevant influence of Mycophenolate mofetil (CellCept) on serum levels of progesterone, LH and FSH, thus indicating no influence of Mycophenolate mofetil (CellCept) on the ovulation-suppressing action of the oral contraceptives. The pharmacokinetics of oral contraceptives were not affected to a clinically relevant degree by coadministration of Mycophenolate mofetil (CellCept) (see Females and Males of Reproductive Potential under Use in Pregnancy & Lactation).
Other interactions: Concomitant administration of drugs inhibiting glucuronidation of MPA may increase MPA exposure (e.g., increase of MPA AUC_0-∞ by 35% was observed with concomitant administration of isavuconazole). Caution is therefore recommended when administering these drugs concomitantly with Mycophenolate mofetil (CellCept).
Concomitant administration of telmisartan and Mycophenolate mofetil (CellCept) resulted in an approximately 30% decrease of mycophenolic acid (MPA) concentrations. Telmisartan changes MPA's elimination by enhancing PPAR gamma (peroxisome proliferator-activated receptor gamma) expression which in turn results in an enhanced UGT1A9 expression and activity, enhancing glucuronidation. When comparing rates of transplant rejection, rates of graft loss or adverse event profiles between Mycophenolate mofetil (CellCept) patients with and without concomitant telmisartan medication, no clinical consequences of the pharmacokinetic DDI were seen.
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 diminished (see Precautions).