Tofacitinib

Generic Name: Tofacitinib

Brand Names: Xeljanz

Tofacitinib is a JAK inhibitor for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and other conditions.

RheumatologicGastrointestinalJAK Inhibitor

Drug Class

JAK Inhibitor (Janus Kinase Inhibitor)

Pregnancy

Based on animal data, may cause fetal harm. Females of reproductive potential should use effective contraception during treatment and for 6 weeks after the last dose. No adequate human data; avoid use in pregnancy unless no suitable alternative exists.

Available Forms

Tablet (immediate-release): 5 mg, Tablet (immediate-release): 10 mg, Tablet (extended-release): 11 mg, Oral solution: 1 mg/mL

What It's Used For

Dosage Quick Reference

These are general dosage guidelines. Your doctor will determine the appropriate dose for your specific situation.

Condition	Starting Dose	Maintenance Dose
Rheumatoid Arthritis	5 mg twice daily or 11 mg XR once daily	5 mg twice daily or 11 mg XR once daily
Psoriatic Arthritis	5 mg twice daily or 11 mg XR once daily	5 mg twice daily or 11 mg XR once daily
Ulcerative Colitis (induction)	10 mg twice daily for 8 weeks	5 mg or 10 mg twice daily (maintenance)

Side Effects

Common Side Effects:

Upper respiratory tract infections
Nasopharyngitis
Diarrhea
Headache
Elevated cholesterol
Hypertension

Serious Side Effects:

Serious infections (opportunistic, TB)
Malignancies (lymphoma, lung cancer, NMSC)
Major cardiovascular events
Thrombosis (VTE, PE)
GI perforations
Laboratory abnormalities (lymphopenia, neutropenia, anemia)

Drug Interactions

Strong CYP3A4 inhibitors (ketoconazole, itraconazole) — Significantly increase tofacitinib exposure. Reduce tofacitinib dose to 5 mg once daily (immediate-release) when co-administered.
Moderate CYP3A4 inhibitors combined with strong CYP2C19 inhibitors (fluconazole) — Increase tofacitinib levels. Reduce dose accordingly.
Strong CYP3A4 inducers (rifampin) — Substantially decrease tofacitinib plasma levels, potentially reducing efficacy. Avoid concurrent use.
Immunosuppressants (azathioprine, cyclosporine, tacrolimus) — Risk of additive immunosuppression. Avoid concurrent use with biologic DMARDs or potent immunosuppressants.
Live vaccines — Avoid administration of live vaccines during and immediately prior to tofacitinib therapy due to immunosuppression.

Additional Information

Tofacitinib is a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, and polyarticular course juvenile idiopathic arthritis. It represents an oral alternative to biologic therapies.

Mechanism of Action

Tofacitinib inhibits Janus kinase enzymes:

JAK1 and JAK3 inhibition: Primary targets of tofacitinib
JAK2 inhibition: Also inhibited to some degree
Blocks cytokine signaling: Prevents signal transduction from type I and type II cytokine receptors
Reduces inflammation: Interrupts signaling of multiple inflammatory cytokines (IL-2, IL-6, IL-7, IL-15, IL-21, IFNs)
Oral administration: Convenience over injectable biologics

Available Formulations

Immediate-release tablets: 5 mg, 10 mg
Extended-release tablets (XR): 11 mg, 22 mg
Oral solution: 1 mg/mL

Medical Uses

FDA-Approved Indications:

Rheumatoid arthritis (moderate to severe, inadequate response to methotrexate)
Psoriatic arthritis (inadequate response to methotrexate or other DMARDs)
Ulcerative colitis (moderate to severe, inadequate response to TNF blockers)
Ankylosing spondylitis (inadequate response to TNF blockers)
Polyarticular course juvenile idiopathic arthritis (age ≥2 years)

Dosing Guidelines

Rheumatoid Arthritis:

5 mg twice daily (IR) or 11 mg once daily (XR)
With or without methotrexate or other non-biologic DMARDs

Psoriatic Arthritis:

5 mg twice daily (IR) or 11 mg once daily (XR)
With or without non-biologic DMARDs

Ulcerative Colitis:

Induction: 10 mg twice daily (IR) or 22 mg once daily (XR) for at least 8 weeks
Maintenance: 5 mg twice daily (IR) or 11 mg once daily (XR)
Use lowest effective dose for maintenance

Renal Impairment:

Moderate to severe: 5 mg once daily (IR formulations)

Important Safety Information

Boxed Warnings:

Serious infections (including tuberculosis, invasive fungal infections, viral reactivation)
Mortality (increased all-cause mortality including sudden cardiovascular death)
Malignancy (increased incidence of lymphoma and other malignancies)
Major adverse cardiovascular events (MACE)
Thrombosis (DVT, PE, arterial thrombosis)

Contraindications:

No absolute contraindications listed

Warnings and Precautions:

Screen for TB before starting
Do not initiate during active serious infection
Monitor lymphocytes, neutrophils, hemoglobin
Interrupt for serious infections, lymphocyte <500, ANC <1000, or Hgb <8

Drug Interactions

Strong CYP3A4 inhibitors (ketoconazole): Reduce tofacitinib dose by half
Strong CYP3A4 inducers (rifampin): May reduce efficacy; avoid
Moderate CYP3A4 inhibitors + CYP2C19 inhibitors (fluconazole): Reduce tofacitinib dose
Immunosuppressants (biologics, azathioprine, cyclosporine): Avoid combination
Live vaccines: Avoid

Special Populations

Hepatic Impairment:
- Mild: No adjustment
- Moderate: Reduce dose
- Severe: Not recommended
Renal Impairment: Reduce dose in moderate to severe impairment
Pregnancy: Based on animal data, may cause fetal harm
Lactation: Present in breast milk; not recommended
Elderly: Higher risk of adverse events; use with caution

Frequently Asked Questions

JAK (Janus kinase) inhibitors block specific enzymes inside immune cells that transmit signals driving inflammation. Tofacitinib primarily inhibits JAK1 and JAK3, reducing the production of inflammatory cytokines responsible for joint damage and gut inflammation in conditions such as rheumatoid arthritis and ulcerative colitis.

Your doctor will typically monitor a complete blood count (CBC), liver function tests, lipid panel, and renal function before starting and periodically during treatment. Lymphocyte counts and hemoglobin levels are particularly important because tofacitinib can cause lymphopenia and anemia.

Yes. Tofacitinib suppresses the immune system and can increase the risk of serious infections including tuberculosis, herpes zoster (shingles), and opportunistic infections. Your doctor will screen for latent tuberculosis before starting treatment and may recommend the shingles vaccine.

A large post-marketing safety study (ORAL Surveillance) found increased risks of major adverse cardiovascular events (MACE) and malignancies in RA patients aged 50 and older with at least one cardiovascular risk factor. The FDA now requires boxed warnings on all JAK inhibitors, and tofacitinib is recommended only after failure of a TNF inhibitor in many patients.

Yes. Tofacitinib is commonly used in combination with methotrexate for rheumatoid arthritis. However, it should not be combined with biologic DMARDs (such as adalimumab or etanercept) or other potent immunosuppressants such as azathioprine or cyclosporine.

Questions to Ask Your Doctor

Consider discussing these topics at your next appointment:

✓Am I a candidate for tofacitinib, or should I try a biologic therapy first?
✓What screening tests (TB, hepatitis) do I need before starting?
✓Should I get the shingles vaccine before beginning tofacitinib?
✓How will we monitor for cardiovascular risks and blood count changes?
✓What symptoms should prompt me to stop the medication and call your office?

Schedule an Appointment

Related Health Conditions

This medication is commonly used to treat or manage the following conditions:

Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory bowel disease causing ulcers and inflammation in the colon and rectum, driven by immune dysfunction, genetics, and environmental factors, leading to symptoms like diarrhea and abdominal pain.

Learn More

Lymphoma

Lymphoma is a cancer of lymphocytes in the immune system, leading to uncontrolled growth and tumor formation, with various types, causes, and associations to infections and toxins.

Learn More

Stroke

A stroke, caused by interrupted brain blood supply from blockage (ischemic) or bleeding (hemorrhagic), is a medical emergency requiring prompt treatment to minimize brain damage.

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Medical Disclaimer: This information is for educational purposes only and should not be considered medical advice. Always consult with your healthcare provider before starting, stopping, or changing any medication. Your doctor can provide personalized recommendations based on your specific health condition and medical history.