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Pharmacology · 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
  • Enzyme: Calcineurin, through FKBP12
  • ATC code: L04AD02
  • WHO Model List of Essential Medicines

Also called: FK506

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

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.

  1. Binds FKBP12 inside the T cell
  2. The complex blocks calcineurin
  3. NFAT cannot enter the nucleus: no IL-2
  4. 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 →

Adverse effects

Common

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

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.

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.

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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: Tacrolimus: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); DailyMed - TACROLIMUS capsule (DailyMed (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); ATOMIC STRUCTURE OF FKBP-FK506, AN IMMUNOPHILIN-IMMUNOSUPPRESSANT COMPLEX (RCSB Protein Data Bank, 1991).

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Representative model, for educational purposes only.