What are the indications, dosing, and precautions for Tofacitinib (Xeljanz)?

Tofacitinib (Xeljanz): Indications, Dosing, and Precautions

Tofacitinib is FDA-approved for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis, with specific dosing regimens and critical safety monitoring requirements that must be followed to minimize serious risks including infections, thrombosis, and malignancies. 1

FDA-Approved Indications

Rheumatoid Arthritis

• XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily 1
• Can be used as monotherapy or in combination with methotrexate and other non-biologic DMARDs 1

Psoriatic Arthritis

• XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily in combination with non-biologic DMARDs 1
• Demonstrated superiority to placebo with 50% ACR20 response at 3 months for the 5 mg dose and 61% for the 10 mg dose 2

Ankylosing Spondylitis

• XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily 1

Ulcerative Colitis

• Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks, with possible extension to 16 weeks maximum if needed 1
• Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily 1
• For loss of response during maintenance, may increase to 10 mg twice daily for shortest duration possible 1
• Recommended as first-line option alongside biologics for moderate-to-severe UC when conventional therapy has failed 3

Polyarticular Course Juvenile Idiopathic Arthritis

• Weight-based dosing: 3.2 mg twice daily (10-20 kg), 4 mg twice daily (20-40 kg), or 5 mg twice daily (≥40 kg) 1

Off-Label Use: Psoriasis

• Not FDA-approved but can be considered at 5 mg or 10 mg twice daily 3
• The 10 mg twice daily dose shows greater efficacy but carries higher risk of infections and cytopenias 3

Critical Pre-Treatment Requirements

Absolute Contraindications to Initiation

Do not initiate tofacitinib if: 1, 3

• Lymphocyte count <500 cells/mm³
• Absolute neutrophil count (ANC) <1000 cells/mm³
• Hemoglobin <9 g/dL
• Active serious infection present 1

Mandatory Screening

• Tuberculosis testing with IGRA or tuberculin skin test before starting therapy 1
• Treat latent TB for at least 1 month prior to tofacitinib initiation 4
• Zoster vaccination (Shingrix) as 2-dose series separated by 2-6 months in patients ≥18 years before starting therapy 3, 4
• Baseline CBC with differential, comprehensive metabolic panel, and lipid profile 4

Dosage Adjustments for Specific Populations

Renal Impairment

• Moderate to severe renal impairment (CrCl <50 mL/min): Reduce to 5 mg once daily for all indications except UC 1, 3
• For UC patients with moderate/severe renal impairment: Induction 10 mg once daily; maintenance 5 mg once daily 1
• Administer after dialysis on dialysis days; no supplemental doses needed 1

Hepatic Impairment

• Moderate hepatic impairment: Reduce to 5 mg once daily 1, 3
• Severe hepatic impairment: Not recommended 3, 1

Drug Interactions

• With potent CYP3A4 inhibitors (ketoconazole) OR moderate CYP3A4 + potent CYP2C19 inhibitors (fluconazole): Reduce to 5 mg once daily 3, 1

FDA Black Box Warnings

Tofacitinib carries four critical black box warnings: 3

1. Serious infections including tuberculosis, invasive fungal infections, bacterial, viral, and opportunistic pathogens
2. Increased mortality (particularly in patients ≥65 years with cardiovascular risk factors)
3. Thrombosis including venous thromboembolism and pulmonary embolism
4. Malignancies including lymphoma and increased EBV-mediated post-transplant lymphoproliferative disorder

Age-Related Precautions

• Patients ≥65 years have significantly higher serious infection rates and should only receive tofacitinib if no alternative exists 4

Mandatory Monitoring Schedule

During Treatment

• CBC with differential at 4-8 weeks, then every 3 months 4, 1
• Liver enzymes at 4 weeks, then every 3 months 4, 1
• Lipid panel at 4-12 weeks, then annually 4, 1
• Renal function every 3 months 5

Criteria for Dose Interruption or Discontinuation

Discontinue tofacitinib if: 3, 1

• Lymphocyte count <500 cells/mm³ (confirmed by repeat testing)
• ANC <500 cells/mm³ (confirmed by repeat testing)
• Hemoglobin decreases ≥2 g/dL or is <8.0 g/dL (confirmed by repeat testing)

Hold tofacitinib temporarily if: 3

• ANC persistently 500-1000 cells/mm³ until ANC ≥1000 cells/mm³
• Hemoglobin abnormalities until values normalize

Combination Therapy Restrictions

Permitted Combinations

• Can be used with methotrexate 3

Prohibited Combinations

• Do not combine with potent immunosuppressants (azathioprine, cyclosporine) 3
• Do not combine with biologics used for psoriasis or other inflammatory conditions 3
• Do not combine with tocilizumab or other immunomodulators if using for COVID-19 3
• Insufficient evidence for combination with other systemic agents or phototherapy 3

Infection Management

Active Infections

• Avoid tofacitinib during any active serious infection 3, 1
• Urinary tract infections are the most common serious infections with tofacitinib 5
• Herpes zoster occurs at elevated rates; clinically manageable but requires vigilance 6, 7

Vaccination Considerations

• Live vaccines must be avoided during tofacitinib therapy 3, 1
• Complete all indicated vaccinations, particularly Shingrix, before starting treatment 3

Special Populations

Pregnancy

• Use only if potential benefit justifies potential risk to fetus 3

Lactation

• Advise not to breastfeed 1

Thromboembolism Risk Mitigation

• Patients hospitalized with COVID-19 receiving tofacitinib must receive at least prophylactic anticoagulation 3
• The 10 mg twice daily dose in RA patients was associated with increased VTE and PE risk 3
• Consider thromboembolism risk factors before initiating therapy, particularly in UC patients requiring higher induction doses 8

Common Pitfalls to Avoid

• Do not attribute new symptoms solely to known tofacitinib effects without excluding serious pathology (e.g., hematuria requires full workup, not just monitoring creatinine changes) 5
• Do not continue full-dose tofacitinib in declining renal function without dose adjustment 5
• Do not overlook malignancy screening, particularly in older patients; lung and breast cancer are most common non-hematologic malignancies 5
• Do not assume seborrhea or other dermatologic findings are drug-related without ruling out infections (particularly herpes zoster) or independent inflammatory conditions 9