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
Elective surgery
Consult with the patient’s relevant specialist at the earliest opportunity when planning for surgery so that a management plan can be made (see Further information)
Emergency surgery
Consult with the patient’s relevant specialist before next dose due to discuss management (see Further information)
Post-operative advice)
If stopped pre-operatively sirolimus should not be re-started until adequate wound healing has taken place – consult with the patient’s specialist to ensure a management plan is in place.
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
Antiemetics
The UK and US manufacturers state that metoclopramide might increase sirolimus concentrations. The clinical relevance of this remains unclear. Monitor for adverse effects if metoclopramide is used concomitantly with sirolimus
Antimicrobials
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)
PPIs can cause hypomagnesaemia, which might be additive with the magnesium-lowering effects of sirolimus. Consider monitoring magnesium concentrations before and during treatment if a PPI is used long-term with sirolimus.
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs should be avoided due to the risk of adverse interactions (including nephrotoxicity).
Further information
Infection risk
Sirolimus is associated with an increased incidence of infections and impaired wound healing in both renal and liver transplant recipients immediately after transplantation, which is probably further complicated by the use of corticosteroids in these groups of patients.
Prescribing guidance
Sirolimus
The 500 microgram (mcg) tablet is not bioequivalent to the 1mg and 2mg tablets. Multiples of 500mcg tablets should not be used as a substitute for other tablet strengths..
Plasma level monitoring
Sirolimus whole blood trough concentrations should be monitored. Close monitoring is required if there is concomitant treatment with potent inducers or inhibitors of sirolimus metabolism. Contact specialists for advice where necessary.
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
Fisher A, Seguel JM, de la Torre AN et al. Effect of Sirolimus on Infection Incidence in Liver Transplant Recipients. Liver Transplantation. 2004; 10(2):193-198
Grim S, Slover CM, Sankary H et al. Risk Factors for Wound Healing Complications in Sirolimus-Treated Renal Transplant Recipients. Transplantation Proceedings. 2006; 38(10):3520-3
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 12th March 2019]
Sirolimus. 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 – Rapamune® (sirolimus) 2mg coated tablets. Pfizer Limited. Accessed via www.medicines.org.uk 04/08/2019 [date of revision of the text June 2019]
Troppmann C, Pierce JL, Ghandi MM et al. Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: a matched-pair pilot study. Transplantation. 2003; 76(2):426-9