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Pharmacology · mTOR inhibitors

Sirolimus !

A transplant drug (rapamycin) that blocks the mTOR growth switch in T cells. It raises cholesterol, slows wound healing and is avoided after liver transplants.

Updated 2026-11-01

  • Class: mTOR inhibitors
  • Enzyme: mTOR (mechanistic target of rapamycin), through FKBP12
  • ATC code: L04AH01

Also called: rapamycin

The figure shows rapamycin (sirolimus) holding together human FKBP12 and the FRB domain of mTOR: the drug works as molecular glue between the two proteins.

Target in 3D: mTOR (mechanistic target of rapamycin), through FKBP12. PDB structure 1FAP (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Sirolimus binds FKBP12; the complex binds mTOR and inhibits its activation. mTOR normally relays signals from IL-2 and other growth factors to the cell-cycle machinery. Without it, T cells cannot progress from the G1 to the S phase and do not proliferate, even though cytokine production is not blocked as it is with calcineurin inhibitors.

  1. Binds FKBP12 inside the T cell
  2. The complex binds and blocks mTOR
  3. IL-2 signals no longer reach the cell cycle
  4. T cells stall in G1 and do not proliferate

Pharmacokinetics

Absorption
Taken by mouth; levels vary and are measured
Metabolism
By CYP3A4 in the gut and liver; also a P-glycoprotein substrate
Half-life
Long, so dose changes take a week or two to reach a new steady state

Indications

  • Prevention of kidney transplant rejection
  • Lymphangioleiomyomatosis

Adverse effects

Common

  • Peripheral oedema
  • High triglycerides and cholesterol
  • Hypertension
  • Mouth ulcers (stomatitis)
  • Diarrhoea, nausea and abdominal pain
  • Anaemia and low platelets

Contraindications

  • Hypersensitivity to sirolimus

Key interactions

Strong CYP3A4 or P-glycoprotein inhibitors (azole antifungals, clarithromycin) and grapefruit
Large rise in sirolimus levels.
Strong CYP3A4 inducers (rifampicin)
Large fall in sirolimus levels.
Ciclosporin
Raises sirolimus levels; sirolimus is taken some hours after ciclosporin.
Live vaccines
Avoided during treatment.

What is monitored

  • Sirolimus trough levels
  • Lipids
  • Urine protein
  • Creatinine
  • Blood counts
  • Wound healing and lung symptoms

Administration and safety

  • Oral tablets or solution once a day, consistently with or without food, and some hours after ciclosporin.
  • The oral solution is diluted only with water or orange juice in a glass or plastic cup, never with grapefruit juice, and taken at once.
  • Caregivers avoid skin and eye contact with the oral solution.

Nursing care

  • Take trough levels as scheduled; dose changes need time to show in levels.
  • Inspect surgical wounds and report poor healing or fluid collections.
  • Check lipid results and teach diet and activity measures.
  • Ask about cough or breathlessness.
  • Teach sun protection, infection signs and effective contraception.

Pregnancy and breastfeeding

Can harm a fetus; highly effective contraception is used during treatment and for 12 weeks after the last dose.

Test yourself

Think of the answer, then tap the question to see it.

How does sirolimus differ from tacrolimus even though both bind FKBP12?

The sirolimus-FKBP12 complex inhibits mTOR, blocking the response to IL-2 and cell-cycle progression; the tacrolimus complex inhibits calcineurin and blocks IL-2 production.

Why is sirolimus avoided early after liver transplantation?

Used with tacrolimus or ciclosporin in new liver recipients, it was associated with hepatic artery thrombosis, graft loss and excess mortality.

Which juice must never be used to dilute sirolimus oral solution, and why?

Grapefruit juice, because it inhibits CYP3A4 and raises sirolimus levels.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Sirolimus: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - SIROLIMUS solution (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); THE STRUCTURE OF THE IMMUNOPHILIN-IMMUNOSUPPRESSANT FKBP12-RAPAMYCIN COMPLEX INTERACTING WITH HUMAN FRAP (RCSB Protein Data Bank, 1997).

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Representative model, for educational purposes only.