[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [JAK inhibitors](https://durgical.com/en/pharmacology/classes/jak-inhibitors/) › Tofacitinib

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

# Tofacitinib

An oral JAK inhibitor for rheumatoid arthritis, psoriatic arthritis, spondylitis and ulcerative colitis after a TNF blocker. Clots and shingles are watched for.

Updated 2026-11-01

- Class: [JAK inhibitors](https://durgical.com/en/pharmacology/classes/jak-inhibitors/)
- Enzyme: Janus kinases, mainly JAK1 and JAK3
- ATC code: L04AF01

✂**Janus kinases, mainly JAK1 and JAK3**Tofacitinib

ⓘ The figure shows the human JAK3 kinase domain with tofacitinib in its ATP site.

**Target in 3D:** Janus kinases, mainly JAK1 and JAK3. PDB structure 3LXK (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3LXK) · Drag to rotate · pinch to zoom

## Mechanism of action

Tofacitinib competes with ATP in the kinase domain of the Janus kinases, mainly JAK1 and JAK3, and to a lesser degree JAK2. Signalling of cytokines that use the common gamma chain (IL-2, IL-4, IL-7, IL-15, IL-21) and of IL-6 and interferons is reduced, so STAT proteins are not phosphorylated and lymphocyte activation and inflammation fall.

- Enters the cell and binds the JAK ATP site
- JAK1/JAK3 cannot phosphorylate STATs
- Cytokine genes stay off
- Lymphocyte activation and inflammation fall

## Pharmacokinetics

**Absorption**
Oral; immediate- and extended-release tablets and an oral solution

**Metabolism**
About 70% liver metabolism, mainly CYP3A4 with a minor role for CYP2C19

**Elimination**
About 30% excreted unchanged by the kidneys

## Indications

- Rheumatoid arthritis after inadequate response or intolerance to a TNF blocker [Rheumatoid arthritis →](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- Psoriatic arthritis [Psoriatic arthritis →](https://durgical.com/en/conditions/psoriatic-arthritis/)
- Ankylosing spondylitis [Ankylosing spondylitis →](https://durgical.com/en/conditions/ankylosing-spondylitis/)
- Ulcerative colitis [Ulcerative colitis →](https://durgical.com/en/conditions/ulcerative-colitis/)
- Polyarticular-course juvenile idiopathic arthritis [Juvenile idiopathic arthritis →](https://durgical.com/en/conditions/juvenile-idiopathic-arthritis/)

## Adverse effects

### Common

- Nasopharyngitis and upper respiratory infections
- Raised cholesterol and creatine kinase
- Headache, diarrhoea, rash
- Herpes zoster

### Serious (rare, important)

- Serious infections, including tuberculosis, opportunistic infections and herpes zoster
- Major cardiovascular events (heart attack, stroke, cardiovascular death)
- Venous and arterial thrombosis, including pulmonary embolism
- Lymphoma, lung cancer and skin cancer
- Higher all-cause mortality, including sudden cardiovascular death, than TNF blockers in rheumatoid arthritis
- Gastrointestinal perforation
- Low lymphocytes, neutrophils or haemoglobin

## Contraindications

- Active serious infection, including active tuberculosis
- Very low lymphocyte or neutrophil count or haemoglobin before starting

## Key interactions

**Strong CYP3A4 inhibitors (e.g. ketoconazole) and drugs that inhibit both CYP3A4 and CYP2C19 (e.g. fluconazole)**
Tofacitinib levels rise; its dose is adjusted.

**Strong CYP3A4 inducers (e.g. rifampicin)**
Levels fall and the effect can be lost.

**Biologic DMARDs and potent immunosuppressants (azathioprine, ciclosporin)**
Not recommended together: added immunosuppression.

**Live vaccines**
Avoided during treatment.

## What is monitored

- Latent TB test before and during treatment; viral hepatitis screening
- Lymphocytes, neutrophils and haemoglobin before starting and regularly
- Liver enzymes and lipids
- New abdominal pain (perforation) and signs of thrombosis

## Administration and safety

- Oral tablet (immediate- or extended-release) or oral solution; the product and form are checked against the prescription.
- Treatment is not started while lymphocytes, neutrophils or haemoglobin are very low.

## Nursing care

- Before starting, confirm the latent TB test, hepatitis screening, blood count and up-to-date vaccines.
- Ask about smoking, previous heart attack, stroke or blood clots.
- Teach the signs of a clot (painful swollen leg, sudden shortness of breath, chest pain) and of shingles (painful band-shaped rash).
- Live vaccines are avoided during treatment.

## Pregnancy and breastfeeding

Human data are limited; the treating team weighs benefits and risks.

## Memory aid

TOFAcitinib: Thrombosis, Opportunistic infections and zoster, Fat (lipids) up, Avoid live vaccines.

## Test yourself

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

## Which Janus kinases does tofacitinib mainly inhibit?

JAK1 and JAK3 (JAK2 to a lesser degree).

## Which laboratory values are checked before and during tofacitinib?

Lymphocytes, neutrophils, haemoglobin, liver enzymes and lipids, plus latent TB and viral hepatitis screening.

## Why is tofacitinib not combined with a TNF inhibitor?

Combining it with biologic DMARDs or potent immunosuppressants adds immunosuppression and is not recommended.

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

## Related drugs

- [Baricitinib](https://durgical.com/en/pharmacology/baricitinib/)
- [Ruxolitinib](https://durgical.com/en/pharmacology/ruxolitinib/)
- [Adalimumab](https://durgical.com/en/pharmacology/adalimumab/)

## Related conditions

- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Psoriatic arthritis](https://durgical.com/en/conditions/psoriatic-arthritis/)
- [Ankylosing spondylitis](https://durgical.com/en/conditions/ankylosing-spondylitis/)
- [Ulcerative colitis](https://durgical.com/en/conditions/ulcerative-colitis/)
- [Juvenile idiopathic arthritis](https://durgical.com/en/conditions/juvenile-idiopathic-arthritis/)

[← Back to the class: JAK inhibitors](https://durgical.com/en/pharmacology/classes/jak-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: [Tofacitinib: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a613025.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DailyMed - TOFACITINIB tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=10403307-e2f9-44d1-bc72-552fdba299d1) (DailyMed (U.S. National Library of Medicine), 2026); [Altered Immunocompetence | Vaccines & Immunizations | CDC](https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html) (Centers for Disease Control and Prevention (CDC), 2024); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L04AF01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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