[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Calcineurin inhibitors](https://durgical.com/en/pharmacology/classes/calcineurin-inhibitors/) › Tacrolimus

[Pharmacology](https://durgical.com/en/pharmacology/) · [Calcineurin inhibitors](https://durgical.com/en/pharmacology/classes/calcineurin-inhibitors/)

# Tacrolimus

The most used anti-rejection drug after transplants. It blocks T-cell activation; its level is measured, and it can cause diabetes, tremor and kidney harm.

Updated 2026-11-01

- Class: [Calcineurin inhibitors](https://durgical.com/en/pharmacology/classes/calcineurin-inhibitors/)
- Enzyme: Calcineurin, through FKBP12
- ATC code: L04AD02
- WHO Model List of Essential Medicines

Also called: FK506

✂**Calcineurin, through FKBP12**Tacrolimus

ⓘ The figure shows tacrolimus (FK506) bound to human FKBP12, its immunophilin. Calcineurin, which the complex then blocks, is not in this crystal.

**Target in 3D:** Calcineurin, through FKBP12. PDB structure 1FKF (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1FKF) · Drag to rotate · pinch to zoom

## Mechanism of action

Tacrolimus is a macrolide that binds FKBP12 inside T cells. The tacrolimus-FKBP12 complex inhibits calcineurin, so NFAT is not dephosphorylated and cannot enter the nucleus. IL-2 and other cytokine genes stay off and T-cell activation is blocked.

- Binds FKBP12 inside the T cell
- The complex blocks calcineurin
- NFAT cannot enter the nucleus: no IL-2
- T-cell activation and rejection are prevented

## Pharmacokinetics

**Absorption**
Oral absorption is incomplete and variable; also given intravenously

**Distribution**
Concentrates in red blood cells, so whole blood is measured

**Metabolism**
Extensively by CYP3A4 in the liver and gut

**Elimination**
Almost entirely in the faeces, as metabolites

**Half-life**
Long and variable; roughly 2 days in healthy volunteers

## Indications

- Prevention of rejection of kidney, liver and heart transplants
- Fistulising Crohn disease, sometimes, off label [Crohn disease →](https://durgical.com/en/conditions/crohn-disease/)

## Adverse effects

### Common

- Tremor and headache
- Hypertension
- Hyperkalaemia and low magnesium
- Diarrhoea and nausea
- Hyperglycaemia

### Serious (rare, important)

- New-onset diabetes after transplant
- Nephrotoxicity
- Neurotoxicity: seizures, delirium, posterior reversible encephalopathy syndrome
- Serious infections and malignancy, including lymphoma
- QT prolongation
- Thrombotic microangiopathy, pure red cell aplasia, myocardial hypertrophy

## Contraindications

- Hypersensitivity to tacrolimus
- Intravenous form: hypersensitivity to polyoxyl 60 hydrogenated castor oil

## Key interactions

**Strong CYP3A4 inhibitors (ritonavir, azole antifungals, clarithromycin) and grapefruit**
Large rise in tacrolimus levels and toxicity.

**CYP3A4 inducers (rifampicin, carbamazepine, phenytoin)**
Lower tacrolimus levels: risk of rejection.

**Ciclosporin**
Not used together; one is stopped well before the other starts.

**Sirolimus**
Higher risk of thrombotic microangiopathy.

**Drugs that prolong the QT interval or raise potassium**
Additive QT prolongation or hyperkalaemia.

## What is monitored

- Tacrolimus trough whole-blood levels
- Creatinine
- Glucose
- Potassium and magnesium
- Blood pressure
- Neurological symptoms

## Administration and safety

- Oral capsules or intravenous infusion; intravenous use is reserved for patients who cannot take it by mouth.
- Look-alike risk: immediate-release and extended-release tacrolimus are not interchangeable; substitution errors have caused rejection and toxicity.
- The intravenous form contains a castor oil derivative that can cause anaphylaxis; the patient is observed closely.

## Nursing care

- Draw trough levels before the dose and record the exact timing.
- Check that the patient receives the same product each time: immediate-release and extended-release forms are not interchangeable.
- Monitor glucose, potassium and creatinine.
- Ask about tremor, headache, confusion or seizures.
- Teach to avoid grapefruit and to report new medicines; avoid live vaccines.

## Pregnancy and breastfeeding

May be continued after transplantation when the benefit outweighs the risk; it crosses the placenta and newborns are watched for high potassium and kidney problems.

## Memory aid

TACROlimus: Tremor, Anti-rejection, Creatinine up, Raised glucose, Off-limits for grapefruit.

## Test yourself

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

## What is FKBP12, and why does it matter for tacrolimus?

An immunophilin in T cells; tacrolimus must bind it first, and the tacrolimus-FKBP12 complex is what inhibits calcineurin.

## Why is glucose checked in a kidney transplant patient on tacrolimus?

Tacrolimus can cause new-onset diabetes after transplantation.

## Why must immediate-release and extended-release tacrolimus never be swapped?

They are not interchangeable; substitution errors have led to wrong levels, with graft rejection or toxicity.

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

## Related drugs

- [Ciclosporin](https://durgical.com/en/pharmacology/ciclosporin/)
- [Sirolimus](https://durgical.com/en/pharmacology/sirolimus/)
- [Mycophenolate mofetil](https://durgical.com/en/pharmacology/mycophenolate-mofetil/)

## Related conditions

- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)

[← Back to the class: Calcineurin inhibitors](https://durgical.com/en/pharmacology/classes/calcineurin-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: [Tacrolimus: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a601117.html) (MedlinePlus (U.S. National Library of Medicine), 2023); [DailyMed - TACROLIMUS capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=54fcc518-21d9-44a8-9e2c-87ebc2b3e2e6) (DailyMed (U.S. National Library of Medicine), 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L04AD02) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [ATOMIC STRUCTURE OF FKBP-FK506, AN IMMUNOPHILIN-IMMUNOSUPPRESSANT COMPLEX](https://www.rcsb.org/structure/1FKF) (RCSB Protein Data Bank, 1991).

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Representative model, for educational purposes only.

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