Introduction
Xeljanz XR (tofacitinib citrate) is an extended-release formulation of the first Janus kinase (JAK) inhibitor approved by the US Food and Drug Administration. It represents a novel class of targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) used in the management of several chronic inflammatory conditions. This monograph provides comprehensive clinical information about Xeljanz XR for healthcare professionals.
Mechanism of Action
Tofacitinib functions as a selective inhibitor of Janus kinases (JAKs), specifically JAK1 and JAK3, with lesser inhibition of JAK2. JAKs are intracellular enzymes that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Through inhibition of JAKs, tofacitinib prevents the phosphorylation and activation of Signal Transducers and Activators of Transcription (STATs), thereby modulating the immune response by interfering with the JAK-STAT signaling pathway. This mechanism results in reduced production of inflammatory cytokines and inhibition of lymphocyte activation.
Indications
Xeljanz XR is FDA-approved for:
- Moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to methotrexate
- Active psoriatic arthritis in adults
- Moderately to severely active ulcerative colitis in adults
- Active ankylosing spondylitis in adults who have had an inadequate response or intolerance to TNF blockers
Dosage and Administration
Standard dosing:- Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis: 11 mg once daily
- Ulcerative colitis: 10 mg twice daily for at least 8 weeks, followed by 11 mg once daily as maintenance therapy
- Administer orally with or without food
- Swallow tablet whole; do not crush, split, or chew
- Missed dose: Take as soon as remembered unless close to next dose
- Renal impairment: Reduce dose in moderate to severe impairment
- Hepatic impairment: Reduce dose in moderate impairment; not recommended in severe impairment
- Elderly: Consider increased risk of infections and malignancies
- Pregnancy: Use only if potential benefit justifies potential risk (Category C)
Pharmacokinetics
Absorption: Bioavailability is 74%; median Tmax is 4 hours; high-fat meal does not affect AUC but increases Cmax by 27% Distribution: Volume of distribution is 87 L; 40% bound to plasma proteins Metabolism: Primarily hepatic via CYP3A4 (70%) and CYP2C19 (30%) Elimination: Half-life is approximately 3 hours; 70% excreted in urine (primarily as metabolites), 30% in feces Extended-release characteristics: Provides sustained plasma concentrations over 24 hoursContraindications
- Hypersensitivity to tofacitinib or any component of the formulation
- Concomitant use with biological DMARDs or potent immunosuppressants
- Active serious infections, including localized infections
- Severe hepatic impairment
Warnings and Precautions
Black Box Warnings:- Serious infections leading to hospitalization or death
- Increased risk of all-cause mortality, major adverse cardiovascular events, and malignancy
- Thrombosis: Increased risk of arterial and venous thrombosis
- Gastrointestinal perforations: Use with caution in patients at risk
- Laboratory abnormalities: Lymphopenia, neutropenia, anemia, liver enzyme elevations
- Lipid elevations: Increases in LDL and HDL cholesterol
- Reactivation of viral infections: Including hepatitis B and C
Drug Interactions
Strong CYP3A4 inhibitors: (e.g., ketoconazole, clarithromycin): Reduce Xeljanz XR dose Moderate CYP3A4 inhibitors and strong CYP3A4 inducers: (e.g., rifampin): May require dose adjustment Immunosuppressants: Increased risk of immunosuppression (contraindicated) Live vaccines: Avoid concurrent administrationAdverse Effects
Very common (>10%): Upper respiratory tract infections, headache, diarrhea Common (1-10%): Nasopharyngitis, hypertension, increased creatine phosphokinase, nausea, rash, herpes zoster Serious but less common: Serious infections, malignancies, thrombosis, gastrointestinal perforation, hepatic injuryMonitoring Parameters
Baseline:- CBC with differential
- Liver function tests
- Lipid profile
- Hepatitis B and C serology
- Tuberculosis screening
- Pregnancy test if applicable
- CBC monthly for first 3 months, then quarterly
- Liver enzymes periodically
- Lipid levels 4-8 weeks after initiation
- Signs/symptoms of infection
- Clinical response assessment
- Thrombosis symptoms
Patient Education
- Take exactly as prescribed; do not adjust dose without medical supervision
- Report any signs of infection immediately (fever, sweats, chills, cough, shortness of breath, blood in phlegm, weight loss, warm/red/painful skin sores)
- Inform all healthcare providers about Xeljanz XR use before any procedures
- Avoid live vaccines during treatment
- Report unusual bleeding, bruising, or thrombosis symptoms
- Notify provider if planning pregnancy or becoming pregnant
- Store at room temperature in original container
References
1. US Food and Drug Administration. Xeljanz XR prescribing information. 2023. 2. Smolen JS, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508-519. 3. Sandborn WJ, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376(18):1723-1736. 4. Winthrop KL, et al. Herpes zoster and tofacitinib: clinical outcomes and risk factors. Drug Saf. 2017;40(2):125-133. 5. Ytterberg SR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326. 6. Cohen SB, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017;76(7):1253-1262.
This information is intended for healthcare professionals and should not replace clinical judgment. Always consult the most current prescribing information and clinical guidelines.