Xeljanz
Xeljanz
Generic Name
Xeljanz
Mechanism
Tofacitinib selectively inhibits JAK1 and, to a lesser extent, JAK3, blocking downstream signaling of cytokine receptors involved in lymphocyte activation.
• Key Steps
1. Blocks JAK1/JAK3 → ↓STAT phosphorylation
2. ↓STAT → ↓ transcription of inflammatory mediators (IL‑2, IL‑4, IFN‑γ, TNF‑α, etc.)
3. Suppresses aberrant immune responses in rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease.
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Pharmacokinetics
- Absorption: Rapid, peak plasma concentrations in 0.5–2 h; bioavailability 79% (food reduces exposure by ~1/3).
- Distribution: ~152 L total body volume; highly protein‑bound (~87%).
- Metabolism: Primarily via CYP3A4/5; minor CYP2D6 and CYP2C9 pathways.
- Elimination: Urine (≈66% unchanged) and feces; mean elimination half‑life ≈ 12 h in healthy adults.
- Drug‑Drug Interactions: Strong inhibitors/inducers of CYP3A4 (e.g., ketoconazole, rifampin) can markedly alter systemic exposure.
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Indications
- Rheumatoid Arthritis (RA) – erosive, active disease uncontrolled by ≥1 conventional DMARD (methotrexate optional).
- Active, Moderately to Severely Involved Inflammatory Bowel Disease (IBD) – ulcerative colitis (excluding severe cases).
- Axial Spondyloarthritis (axSpA) – ankylosing spondylitis plus non‑radiographic axSpA.
- Psoriatic Arthritis (PsA) – active disease with or without plaque psoriasis.
- Moderate to Severe Plaque Psoriasis – as adjunct to topical therapy in adults.
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Contraindications
- Contraindications
- Active serious infections (TB, fungal, viral hepatitis, etc.).
- Known malignancy or lymphoma.
- Severe hepatic or renal impairment (eGFR < 30 mL/min).
- Warnings
- Reactivation of latent TB and profound immunosuppression → screen *before* initiation and monitor.
- Opportunistic infections (e.g., fungal, opportunistic viral infections).
- Thromboembolic events: risk for DVT/PE ↑ in elderly and patients with cardiovascular risk factors.
- Gastrointestinal perforation risk in patients on NSAIDs or steroids.
- Pregnancy: Category B; potential teratogenicity – avoid in pregnancy unless essential.
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Dosing
| Indication | Loading Dose | Maintenance Dose | Frequency | Notes |
| RA | 10 mg BID (week 0‑1) | 5 mg BID | BID | Once tapered to 2.5 mg BID if appropriate. |
| IBD | 10 mg BID (first 4 weeks) | 5 mg BID | BID | Weight‑adjusted dosing (≥75 kg: 10 mg BID, 50–74 kg: 5 mg BID). |
| axSpA | 10 mg BID (first 2 weeks) | 5 mg BID | BID | Weight‑adjusted as above. |
| PsA | 10 mg BID (first 4 weeks) | 5 mg BID | BID | Weight‑adjusted as above. |
| Plaque Psoriasis | 10 mg BID (first 4 weeks) | 5 mg BID | BID | Weight‑adjusted as above. |
• Administration: Oral tablets, with or without food; avoid simultaneously with grapefruit or high‑fat meals.
• Titration: Adjust based on clinical response and tolerability; typically reduce to 2.5 mg BID after disease control.
• Resumption: Re‑initiate at 1/2 the previous dose after drug holidays.
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Adverse Effects
- Common
- Headache, nausea, diarrhea, dysgeusia (taste changes).
- Upper respiratory tract infections, nasopharyngitis.
- Mildly elevated liver enzymes.
- Serious
- Serious infections: TB, PJP pneumonia, HSV, bacterial sepsis.
- Cytopenias: neutropenia, anemia, thrombocytopenia.
- Venous thromboembolism, pulmonary embolism, myocardial infarction.
- Dyslipidemia: ↑ LDL, triglycerides.
- Cutaneous malignancies (non‑melanoma skin cancers).
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Monitoring
| Parameter | Frequency | Rationale |
| Baseline CBC, LFTs, Lipid Panel, Creatinine | Prior to initiation | Detect pre‑existing cytopenias, hepatic dysfunction, lipid derangements. |
| TB Screening (IGRA/QFT‑TB) + Hepatitis B/C serology | Baseline + prior to dose increase | Identify latent infections. |
| CBC & LFTs | Every 3–6 months | Monitor for bone marrow suppression or hepatic toxicity. |
| Lipid Panel | Every 3–6 months | Adjust statin therapy if needed. |
| Pregnancy tests | In females of childbearing potential | Avoid teratogenic risk. |
| Screen for VTE | Clinical signs; consider D-dimer if symptomatic | Early detection of thrombotic events. |
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Clinical Pearls
- Weight‑Based Dosing: Use the 10 mg BID (≥75 kg) vs. 5 mg BID (50–74 kg) scheme for inflammatory diseases – reduces clinical failures in overweight patients.
- Drug‑Drug Interaction Check: Tofacitinib therapy can increase systemic exposure of drugs metabolized by CYP3A4; adjust concomitant therapy accordingly (e.g., avoid high‑dose statins).
- Infection Vigilance: Conduct a thorough history of TB exposure; treat latent TB before starting Xeljanz.
- Statin Liaisons: Because of dyslipidemia, concurrently prescribe statins only if lipid goals unachievable; dosages of statins should be used cautiously due to possible CYP3A4 interactions.
- Concomitant NSAIDs: Use NSAIDs sparingly; they can increase GI perforation risk; consider gastroprotective agents.
- Patient Education: Reinforce the importance of early infection reporting and adherence to scheduled monitoring labs.
- Pregnancy & Lactation: Counsel patients regarding the need for effective contraception and discontinuation in detected pregnancy.
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• *This drug card provides a succinct yet comprehensive snapshot of Xeljanz for professionals seeking quick, evidence‑based insights.*