[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [mTOR inhibitors](https://durgical.com/en/pharmacology/classes/mtor-inhibitors/) › Sirolimus

[Pharmacology](https://durgical.com/en/pharmacology/) · [mTOR inhibitors](https://durgical.com/en/pharmacology/classes/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](https://durgical.com/en/pharmacology/classes/mtor-inhibitors/)
- Enzyme: mTOR (mechanistic target of rapamycin), through FKBP12
- ATC code: L04AH01

Also called: rapamycin

✂**mTOR (mechanistic target of rapamycin), through FKBP12**Sirolimus

ⓘ 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](https://www.rcsb.org/structure/1FAP) · Drag to rotate · pinch to zoom

## 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.

- Binds FKBP12 inside the T cell
- The complex binds and blocks mTOR
- IL-2 signals no longer reach the cell cycle
- 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

### Serious (rare, important)

- Serious infections and lymphoma
- Impaired wound healing, lymphocele and wound dehiscence
- Excess mortality, graft loss and hepatic artery thrombosis in liver transplantation
- Bronchial anastomotic dehiscence in lung transplantation
- Interstitial pneumonitis
- Proteinuria; with calcineurin inhibitors, more risk of thrombotic microangiopathy

## 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.

## Memory aid

SiROlimus is RApamycin: it glues FKBP12 to mTOR, freezes the cell cycle in G1, and leaves fat in the blood and open wounds.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/sirolimus/)

## Related drugs

- [Tacrolimus](https://durgical.com/en/pharmacology/tacrolimus/)
- [Ciclosporin](https://durgical.com/en/pharmacology/ciclosporin/)
- [Everolimus](https://durgical.com/en/pharmacology/everolimus/)

[← Back to the class: mTOR inhibitors](https://durgical.com/en/pharmacology/classes/mtor-inhibitors/)

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](https://medlineplus.gov/druginfo/meds/a602026.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DailyMed - SIROLIMUS solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f9843d49-0e16-4427-9cea-9f66f32b97f7) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L04AH01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [THE STRUCTURE OF THE IMMUNOPHILIN-IMMUNOSUPPRESSANT FKBP12-RAPAMYCIN COMPLEX INTERACTING WITH HUMAN FRAP](https://www.rcsb.org/structure/1FAP) (RCSB Protein Data Bank, 1997).

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Representative model, for educational purposes only.

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