Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

The following interactions have been reported between MPA and other medicinal products: 
Aciclovir and ganciclovir
The potential for myelosuppression in patients receiving both Myfortic and aciclovir or ganciclovir has not been studied. Increased levels of mycophenolic acid glucuronide (MPAG) and aciclovir/ganciclovir may be expected when aciclovir/ganciclovir and Myfortic are administered concomitantly, possibly as a result of competition for the tubular secretion pathway.
The changes in MPAG pharmacokinetics are unlikely to be of clinical significance in patients with adequate renal function. In the presence of renal impairment, the potential exists for increases in plasma MPAG and aciclovir/ganciclovir concentrations; dose recommendations for aciclovir/ganciclovir should be followed and patients carefully observed.

Gastroprotective agents:
Magnesium and aluminium containing antacids:
MPA AUC and Cmax have been shown to decrease by approximately 37% and 25%, respectively, when a single dose of magnesium-aluminium containing antacids is given concomitantly with Myfortic. Magnesium aluminium-containing antacids may be used intermittently for the treatment of occasional dyspepsia. However, the chronic, daily use of magnesium-aluminium containing antacids with Myfortic is not recommended due to the potential for decreased mycophenolic acid exposure and reduced efficacy.


Proton pump inhibitors:
In healthy volunteers, no changes in the pharmacokinetics of MPA were observed following concomitant administration of Myfortic and pantoprazole given at 40 mg twice daily during the four previous days. No data are available with other proton pump inhibitors given at high doses.


MYF API March23 V3                                                                             REF UK SmPC March23 Oral contraceptives
Interaction studies between MMF and oral contraceptives indicate no interaction. Given the metabolic profile of MPA, no interactions would be expected for Myfortic and oral contraceptives.

Cholestyramine and drugs that bind bile acids
Caution should be used when co-administering drugs or therapies that may bind bile acids, for example bile acid sequestrates or oral activated charcoal, because of the potential to decrease MPA exposure and thus reduce the efficacy of Myfortic.

Ciclosporin
When studied in stable renal transplant patients, ciclosporin pharmacokinetics were unaffected by steady state dosing of Myfortic. When co-administered with mycophenolate mofetil, ciclosporin is known to decrease the exposure of MPA. When co-administered with Myfortic, ciclosporin may decrease the concentration of MPA as well (by approximately 20%, extrapolated from mycophenolate mofetil data), but the exact extent of this decrease is unknown because such an interaction has not been studied. However, as efficacy studies were conducted in combination with ciclosporin, this interaction does not modify the recommended posology of Myfortic. In case of interruption or discontinuation of ciclosporin, Myfortic dosage should be re-evaluated depending on the immunosuppressive regimen.

Tacrolimus
In a calcineurin cross-over study in stable renal transplant patients, steady-state Myfortic pharmacokinetics were measured during both Neoral and tacrolimus treatment. Mean MPA AUC was 19% higher (90% CI: -3, +47), whereas mean MPAG AUC was about 30% lower (90% CI: 16, 42) on tacrolimus compared to Neoral treatment. In addition, MPA AUC intra- subject variability was doubled when switching from Neoral to tacrolimus. Clinicians should note this increase both in MPA AUC and variability, and adjustments to Myfortic dosing should be dictated by the clinical situation. Close clinical monitoring should be performed when a switch from one calcineurin inhibitor to another is planned.

Live attenuated vaccines
Live vaccines should not be given to patients with an impaired immune response. The antibody response to other vaccines may be diminished.