DurgicalDurgical
EN
Open the app

Pharmacology · 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
  • Enzyme: Janus kinases, mainly JAK1 and JAK3
  • ATC code: L04AF01

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

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.

  1. Enters the cell and binds the JAK ATP site
  2. JAK1/JAK3 cannot phosphorylate STATs
  3. Cytokine genes stay off
  4. 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

Adverse effects

Common

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

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.

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)

← Back to the class: 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 (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - TOFACITINIB tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Altered Immunocompetence | Vaccines & Immunizations | CDC (Centers for Disease Control and Prevention (CDC), 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.