Issues for surgery
For suppression of transplant rejection – risk of rejection if omitted.
Risk of post-operative infection if continued (see Further information).
Advice in the perioperative period
Ensure that the patient is maintained on a specific manufacturer’s product (see Further information).
Elective surgery
Continue – the patient’s relevant specialist should be involved in the planning for surgery.
Emergency surgery
Continue – inform the patient’s relevant specialist at the earliest opportunity.
Post-operative advice
Restart treatment in the immediate post-operative period when next dose due. If the patient cannot take their usual oral medication post-operatively, their relevant specialist must be consulted for advice on an alternative medication, dose, route and frequency.
Monitor for signs of infection.
Monitor renal function and electrolytes. If renal function deteriorates post-operatively, the patient’s specialist should be consulted.
Due to the nature of these agents and the potential interactions that can occur, consult product literature prior to starting any medicines in the post-operative period.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
Corticosteroids
Surgical stress, corticosteroids and MMF may contribute to gastrointestinal ulcers, so consideration should be given to providing stress ulcer prophylaxis for transplanted patients.
Antimicrobials
Reductions in mycophenolic acid (MPA) exposure have been seen with a number of antibacterials; the effect appears to be additive. In some cases, this is due to antibacterials interfering with the enterohepatic circulation.
Reductions in trough MPA concentrations of about 50% have been reported in renal transplant recipients in the days immediately following commencement of oral ciprofloxacin or co-amoxiclav. 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.
In healthy volunteers, no significant interaction was observed when MMF 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 MMF. Close clinical monitoring should be performed during and shortly after antibiotic treatment if the combination is used. Note that the US manufacturers consider that the combination of metronidazole and norfloxacin should not be used with MMF.
Clarithromycin (due to inhibition of cytochrome P450 isoenzyme CYP3A4) and erythromycin are predicted to increase the concentration of sirolimus – manufacturer advises avoid. If concurrent use is unavoidable, increase the frequency of monitoring sirolimus concentrations and effects (e.g. on renal function), and adjust the sirolimus dose as needed. This combination should not be used without prior consultation with the patient’s relevant specialist.
Antacids and proton pump inhibitors (PPIs)
Decreased MPA exposure has been observed when PPIs have been administered with MMF; however, the available information is conflicting. When comparing rates of transplant rejection or rate of graft loss between MMF patients taking PPIs vs. MMF patients not taking PPIs, no significant differences were seen.
Mycophenolate has been associated with an increased incidence of digestive system adverse effects, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and perforation. Surgical stress and potential use of corticosteroids further increase this risk – see Corticosteroids. Single doses of PPI should not pose a problem but consider this interaction if there is a need to continue a PPI long-term post-operatively.
Antacids may reduce absorption of MMF; however, the reductions in peak plasma concentrations of MPA were considered unlikely to be clinically significant. UK licensed product information for MPA states that, although magnesium- or aluminium- containing antacids decrease MPA exposure and peak plasma concentration, they may be used intermittently for the treatment of occasional dyspepsia; chronic use of antacids is not recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs should be avoided due to the risk of adverse interactions (including nephrotoxicity).
Further information
Infection risk
Patients treated with immunosuppressants are at increased risk of opportunistic infections, fatal infections and sepsis. Patients should be monitored for neutropenia. Patients may not present with the typical signs and symptoms of infections (i.e. fever, leucocytosis). Microbiology advice may need to be sought when infections develop.
Prescribing guidance
MPA (as sodium salt) and MMF have different pharmacokinetic profiles. Unnecessary switching between manufacturer’s products should be avoided – ensure that the patient is maintained on the same brand.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 7th April 2019]
Brusich KT, Acan I. Anesthetic Considerations in Transplant Recipients for Nontransplant Surgery. Organ Donation and Transplantation – Current Status and Future Challenges. 2018. Accessed via www.intechopen.com 08/08/19
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 12th March 2019]
Mycophenolate. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 30th March 2019]
Summary of Product Characteristics – Cellcept® (mycophenolate mofetil) 500mg Film-Coated Tablets. Roche Products Limited. Accessed via www.medicines.org.uk 04/08/2019 [date of revision of the text March 2018]
Summary of Product Characteristics – Myfortic® (Mycophenolic acid as mycophenolate sodium) 360 mg gastro-resistant tablets. Novartis Pharmaceuticals UK Ltd. Accessed via www.medicines.org.uk 04/08/2019 [date of revision of the text August 2018]
Summary of Product Characteristics – Mycophenolate Mofetil 500 mg Film-coated Tablets. Mylan. Accessed via www.medicines.org.uk 04/08/2019 [date of revision of the text December 2017]