Atajec Drug Interactions

Aciclovir: Higher aciclovir plasma concentrations were observed when mycophenolate mofetil was administered with aciclovir in comparison to the administration of aciclovir alone. The changes in MPAG (the phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8%) were minimal and are not considered clinically significant. Because MPAG plasma concentrations are increased in the presence of renal impairment, as are aciclovir concentrations, the potential exists for mycophenolate mofetil and aciclovir, or its prodrugs, e.g. valaciclovir, to compete for tubular secretion and further increases in concentrations of both substances may occur.
Antacids and proton pump inhibitors (PPIs): Decreased MPA exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole were administered with mycophenolate mofetil. When comparing rates of transplant rejection or rates of graft loss between mycophenolate mofetil patients taking PPIs vs. mycophenolate mofetil 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 was co-administered with magnesium and aluminium hydroxides is considerably less than when mycophenolate mofetil was co-administered with PPIs.
Cholestyramine: Following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects pre-treated with 4 g TID of cholestyramine for 4 days, there was a 40% reduction in the AUC of MPA. Caution should be used during concomitant administration because of the potential to reduce efficacy of mycophenolate mofetil.
Medicinal products that interfere with enterohepatic circulation: Caution should be used with medicinal products that interfere with enterohepatic circulation because of their potential to reduce the efficacy of mycophenolate mofetil.
Ciclosporin A: Ciclosporin A (CsA) pharmacokinetics are unaffected by mycophenolate mofetil.
In contrast, if concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30% should be expected. CsA interferes with MPA enterohepatic recycling, resulting in reduced MPA exposures by 30-50% in renal transplant patients treated with mycophenolate mofetil and CsA compared with patients receiving sirolimus or belatacept and similar doses of mycophenolate mofetil. Conversely, changes of MPA exposure should be expected when switching patients from CsA to one of the immunosuppressants which does not interfere with MPA's enterohepatic cycle.
Telmisartan: Concomitant administration of telmisartan and mycophenolate mofetil resulted in an approximately 30% decrease of 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. When comparing rates of transplant rejection, rates of graft loss or adverse event profiles between mycophenolate mofetil patients with and without concomitant telmisartan medication, no clinical consequences of the pharmacokinetic drug-drug interaction were seen.
Ganciclovir: Based on the results of a single dose administration study of recommended doses of oral mycophenolate mofetil and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics of mycophenolate mofetil and ganciclovir, it is anticipated that co-administration 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 mycophenolate mofetil dose adjustment is not required.
In patients with renal impairment in whom mycophenolate mofetil and ganciclovir or its prodrugs, e.g. valganciclovir are co-administered, the dose recommendations for ganciclovir should be observed and patients should be monitored carefully.
Oral contraceptives: The pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by co-administration of mycophenolate mofetil.
Rifampicin: In patients not also taking ciclosporin, concomitant administration of mycophenolate mofetil and rifampicin resulted in a decrease in MPA exposure (AUC_(1-12h)) of 18% to 70%. It is recommended to monitor MPA exposure levels and to adjust mycophenolate mofetil doses accordingly to maintain clinical efficacy when rifampicin is administered concomitantly.
Sevelamer: Decrease in MPA C_max and (AUC_(1-12h)) by 30% and 25%, respectively, were observed when mycophenolate mofetil was concomitantly administered with sevelamer without any clinical consequences (i.e. graft rejection). It is recommended, however, to administer mycophenolate mofetil at least one hour before or three hours after sevelamer intake to minimize the impact on the absorption of MPA. There are no data on mycophenolate mofetil with phosphate binders other than sevelamer.
Trimethoprim/sulfamethoxazole: No effect on the bioavailability of MPA was observed.
Norfloxacin and metronidazole: In healthy volunteers, no significant interaction was observed when mycophenolate mofetil was concomitantly administered with norfloxacin or metronidazole separately. However, norfloxacin and metronidazole combined reduced the MPA exposure by approximately 30% following a single dose of mycophenolate mofetil.
Ciprofloxacin and amoxicillin plus clavulanic acid: Reductions in pre-dose (rough) MPA concentrations of about 50% have been reported in renal transplant recipients in the days immediately following commencement of oral ciprofloxacin or amoxicillin plus clavulanic acid. This effect tended to diminish with continued antibiotic use and to cease within a few days of antibiotic discontinuation. The change in pre-dose level may not accurately represent changes in overall MPA exposure.
Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.
Tacrolimus: In hepatic transplant patients initiated on mycophenolate mofetil and tacrolimus, the AUC and C_max of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by co-administration with tacrolimus. In contrast, there was an increase of approximately 20% in tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g BID) were administered to hepatic transplant patients taking tacrolimus.
However, in renal transplant patients, tacrolimus concentration did not appear to be altered by mycophenolate mofetil.
Other interactions: Co-administration of probenecid with mycophenolate mofetil in monkeys raises plasma AUC of MPAG by 3-fold. Thus, other substances known to undergo renal tubular secretion may compete with MPAG, and thereby raise plasma concentrations of MPAG or the other substance 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.
Paediatric population: Interaction studies have only been performed in adults.