Sirolimus

How it works

It binds the intracellular protein FKBP-12, and this complex inhibits the mammalian target of rapamycin (mTOR), arresting T-lymphocyte activation and proliferation in response to cytokine signalling.

Prescribing in practice

• Sirolimus is a substrate of CYP3A4 and P-glycoprotein, so strong inducers or inhibitors (and grapefruit juice) markedly alter exposure and require careful review of co-prescribing.
• Impaired wound healing and lymphocele are recognised, so it is generally avoided in the immediate post-operative period and around surgery.
• It can cause hyperlipidaemia, cytopenias, proteinuria and interstitial lung disease.

Monitoring

Monitor whole-blood trough drug concentrations together with renal function, full blood count and lipids, and remain alert for new respiratory symptoms.

Counselling the patient

• Take the dose consistently in relation to food and avoid grapefruit juice, which can raise drug levels.
• Report breathlessness, persistent cough, leg swelling or poor wound healing.
• Do not stop or change other medicines without checking for interactions, and avoid live vaccines.

Evidence & guidelines

Its use in transplantation and in lymphangioleiomyomatosis is supported by randomised controlled trials and established guideline recommendations.