What are the indications, dosing regimen, monitoring requirements, and contraindications for oral tofacitinib tablets?

Tofacitinib Tablets: Clinical Overview

Approved Indications

Tofacitinib is FDA-approved for rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), ulcerative colitis (UC), and polyarticular course juvenile idiopathic arthritis (pcJIA). 1

• RA and PsA: For moderate to severe active disease in adults who have inadequate response or intolerance to one or more DMARDs 2, 1
• Ankylosing Spondylitis: For active disease 1
• Ulcerative Colitis: For moderate to severe active disease 2, 1
• pcJIA: For active disease in patients ≥2 years of age 1

---

Dosing Regimens

Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

The standard dose is 5 mg twice daily (immediate release) or 11 mg once daily (extended release). 2, 1

• Can be used as monotherapy or in combination with non-biologic DMARDs 1
• Efficacy is comparable to TNF inhibitors when combined with methotrexate 3

Ulcerative Colitis

Induction therapy requires 10 mg twice daily (or 22 mg XR once daily) for 8 weeks, with possible extension to 16 weeks maximum if needed. 2, 1

• Maintenance therapy: 5 mg twice daily (or 11 mg XR once daily) 2, 1
• For loss of response during maintenance, may increase to 10 mg twice daily for the shortest duration possible, with careful risk-benefit assessment 1

Dose Adjustments for Organ Impairment

For moderate to severe renal impairment (CrCl <60 mL/min) or moderate hepatic impairment, reduce to 5 mg once daily. 2, 1

• Severe hepatic impairment (Child-Pugh C): Tofacitinib is not recommended 2
• For UC patients with renal/hepatic impairment, specific dose reductions apply for both induction and maintenance phases 1

Drug Interactions Requiring Dose Adjustment

When combined with potent CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 plus potent CYP2C19 inhibitors, reduce dose to 5 mg once daily. 2, 1

• Rifampicin increases tofacitinib metabolism, potentially requiring dose increase 2
• Tofacitinib is metabolized via CYP3A4 with 30% renal excretion 2

---

Contraindications and High-Risk Populations

Absolute Contraindications

Do not initiate tofacitinib if absolute lymphocyte count <500 cells/mm³, absolute neutrophil count <1000 cells/mm³, or hemoglobin <9 g/dL. 1

• Active serious infections: Including localized infections, latent or active tuberculosis, and opportunistic infections 2, 1
• Pregnancy and lactation: Tofacitinib is teratogenic in animal studies; contraception required for both male and female patients; breastfeeding is contraindicated 2

Special Caution Required (Use Only if No Alternative)

In patients ≥65 years with cardiovascular risk factors, tofacitinib should be used only if no other treatment alternative exists, per EMA guidance. 2

• This population showed higher rates of serious infections, MACE, and malignancies compared to TNF inhibitors 2
• The 10 mg twice daily dose carries several-fold higher infection risk in elderly patients compared to 5 mg twice daily 2

History of Venous Thromboembolism

Patients with prior VTE require careful risk-benefit evaluation before initiating tofacitinib. 2

• The 10 mg twice daily dose increases pulmonary embolism risk five-fold compared to TNF inhibitors 4, 5
• Patients with recurrent VTE on anticoagulation may have counteracted risk 2

Malignancy History

Use requires shared decision-making considering timing of past malignancy; most trials excluded patients with malignancy within 5 years. 2

• Lung and breast cancers are the most common nonhematologic malignancies reported 5
• Lymphoma, including EBV-associated cases, has been reported 5

---

Monitoring Requirements

Pre-Treatment Mandatory Screening

Before initiating tofacitinib, obtain: complete blood count with differential, comprehensive metabolic panel, lipid profile, tuberculosis screening, hepatitis B and C screening, and pregnancy test if applicable. 6

• Screen for latent tuberculosis and treat before starting therapy 4
• Consider zoster vaccination before initiation, especially in patients >70 years or >50 years at high risk 4, 5
• Live vaccines are contraindicated once tofacitinib is started 4, 1

Ongoing Laboratory Monitoring

Monitor CBC with differential, comprehensive metabolic panel at 4-8 weeks, then every 3 months; lipid profile annually. 6

Thresholds for Dose Interruption or Discontinuation

Discontinue immediately if:

• Lymphocyte count <500 cells/mm³ 6, 5
• Absolute neutrophil count <500 cells/mm³ 6, 5
• Hemoglobin decreases ≥2 g/dL or falls <8.0 g/dL 6, 5

Hold therapy during active serious infection until resolved. 4, 1

Lipid Monitoring

Dose-related elevations in total cholesterol, LDL, HDL, and triglycerides occur and require monitoring. 5

• Liver enzyme elevations >3× upper limit of normal have been recorded 5
• Serum creatinine increases occur in a dose-dependent manner 5

---

Critical Safety Warnings and Common Pitfalls

Serious Infections

Herpes zoster occurs at significantly higher rates with tofacitinib compared to TNF inhibitors and the general RA population, though infections remain clinically manageable. 5, 3

• Most common serious infections: cellulitis, urinary tract infection, pneumonia, herpes zoster 5
• Tuberculosis reactivation can occur; baseline screening is mandatory 6, 5

Cardiovascular and Thrombotic Events

The 10 mg twice daily dose should be avoided in patients at increased risk of pulmonary embolism per EMA guidance. 4, 5

• Increased MACE and cancer risk compared to TNF inhibitors in RA patients >50 years with cardiovascular risk factors 4

Drug Combination Pitfalls

Do not combine tofacitinib with other potent immunosuppressants, biologics for inflammatory diseases, or IL-6 inhibitors. 4

• Can be used with methotrexate and corticosteroids 4
• Combining with other systemic immunosuppressants increases infection and malignancy risk 6

Hematologic Monitoring Pitfall

Lymphopenia after 3 months correlates with increased incidence of treated and serious infections; do not skip monitoring. 5

Gastrointestinal Perforation Risk

Use with caution in patients at increased risk for gastrointestinal perforation. 1

---

Special Populations

Pregnancy and Fertility

Use only if potential benefit justifies fetal risk; pregnancy test required before initiation in all patients of childbearing potential. 4

• Recommend 4-week gap after last dose if pregnancy is contemplated 2
• Limited UC data showed healthy newborns with no increased congenital malformations 2

Renal Impairment

For CrCl <30 mL/min, reduce to 5 mg once daily for RA/PsA/AS; specific UC dosing adjustments apply. 2, 1

Hepatic Impairment

For moderate hepatic impairment, reduce to 5 mg once daily; avoid in severe hepatic impairment. 2, 1