Tacrolimus
A calcineurin inhibitor from Streptomyces bacteria that prevents transplant rejection; as an ointment it treats atopic dermatitis.
Also called FK506 (research code name).
Drug card
- How it works
- Blocking calcineurin so T cells cannot switch on interleukin-2
- Used for
- Preventing rejection of kidney, liver and heart transplants
- Moderate to severe atopic dermatitis (ointment)
- Known for
- Kidney damage (nephrotoxicity)
- New diabetes after transplant
- Tremor, headache and tingling
- Its name
- -rolimus means a macrolide immunosuppressant
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does tacrolimus work?
Tacrolimus, a macrolide, binds FKBP-12 inside T cells; with calcium and calmodulin the complex inhibits the phosphatase activity of calcineurin, so NFAT is not dephosphorylated and interleukin-2 and other cytokines are not made. It is more potent than ciclosporin.
Like other calcineurin inhibitors: Inside T cells ciclosporin binds cyclophilin and tacrolimus binds FKBP-12, and each drug-protein complex blocks calcineurin, the calcium- and calmodulin-dependent phosphatase that activates the transcription factor NFAT. NFAT then cannot enter the nucleus, so the T cell does not make interleukin-2 and other cytokines and is not activated, which prevents graft rejection.
Uses
What is tacrolimus used for?
- Preventing rejection of kidney, liver and heart transplants
- Moderate to severe atopic dermatitis (ointment)
Side effects
Side effects of tacrolimus
- Kidney damage (nephrotoxicity)Known forSerious
- New diabetes after transplantKnown forSerious
- Tremor, headache and tinglingKnown for
- Seizures and brain swelling (PRES)Serious
- High potassium (hyperkalemia)Serious
- High blood pressure
- QT prolongationSerious
- Serious infections, such as CMV and BK virusSerious
- JC virus brain infection (PML)Serious
- Lymphoma and other cancersSerious
- Skin cancerSerious
- Anemia, including pure red cell aplasiaSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Trough blood levels are monitored, and immediate- and extended-release products are not interchangeable.
- Strong CYP3A4 inhibitors such as clarithromycin, azoles and ritonavir, and grapefruit, raise levels sharply; rifampicin lowers them.
- Potassium, glucose and kidney function are checked; other drugs that raise potassium or prolong the QT interval need care.
- It is not given together with ciclosporin, and live vaccines are avoided.
Good to know: More potent than ciclosporin; in trials it caused more new-onset diabetes and tremor, but less hyperlipidemia.
Remember it
A way to remember it
No calcineurin, no NFAT, no interleukin-2
Calcineurin removes a phosphate from NFAT so it can enter the nucleus and switch on the interleukin-2 gene; with calcineurin blocked, T cells never get the interleukin-2 signal to activate and multiply.
Written for biofideX
Its name
-rolimus means macrolide immunosuppressant
Tacrolimus binds FKBP-12 and blocks calcineurin; sirolimus and everolimus also bind FKBP-12 but block mTOR. Ciclosporin, the other calcineurin inhibitor, lacks the stem.
- Every drug name stem
Its class
Calcineurin inhibitors
Other calcineurin inhibitors with a card:
Easily mixed up with antiproliferative immunosuppressants and glucocorticoids.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Tacrolimus capsules: label (DailyMed)
- Tacrolimus extended-release capsules: label (DailyMed)
- Tacrolimus ointment: label (DailyMed)
- Tacrolimus (NCI Thesaurus)
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Targeted therapy and the immune system
Tacrolimus is one of 13 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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