Xromi
Xromi
Generic Name
Xromi
Mechanism
Xromi competitively binds the adenosine triphosphate (ATP)‑binding cleft of the catalytic domains of JAK 1 and JAK 2, thereby preventing phosphorylation of signal‑transducer and activator of transcription (STAT) proteins.
• ↓ STAT nuclear translocation → ↓ pro‑inflammatory cytokine signaling (IL‑6, IFN‑γ, GM‑CSF)
• ↓ B‑cell proliferation and T‑cell activation
• ↓ immune‑mediated joint inflammation and cartilage degradation
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Rapid; oral bioavailability ~40% | Food reduces peak concentration (Cmin) by ~25% |
| Distribution | Vd ~ 50 L | Highly protein‑bound (~85%) to albumin & α‑1‑acid glycoprotein |
| Metabolism | Predominantly CYP3A4; minor CYP2D6 | Genotype‐linked variability (CYP3A4 poor metabolizers ↑ exposure) |
| Elimination | 90% via feces; 10% renal | Half‑life: 12–14 h (steady‑state ~5 days) |
| Drug interactions | Strong CYP3A4 or P‑gp inhibitors ↑ plasma levels (e.g., ketoconazole, clarithromycin); CYP3A4 inducers ↓ levels (e.g., rifampin) | Dose adjustment or avoidance recommended |
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Indications
- Moderate‑to‑severe rheumatoid arthritis in adults with inadequate response or intolerance to at least one disease‑modifying anti‑rhythmic drug (DMARD)
- *Off‑label* use reported for ankylosing spondylitis and psoriatic arthritis (case series only)
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Contraindications
| Contraindication / Warning | Key Points |
| Severe hepatic impairment (Child‑Pugh C) | Contraindicated; avoid in cirrhosis |
| Active tuberculosis or other serious infections | Screen prior to initiation; treat latent TB before starting |
| Uncontrolled malignancy | Caution: potential oncogenic risk; monitor closely |
| Pregnancy / lactation | Category D; avoid; prefer alternative DMARDs |
| Thromboembolic events | ↑ risk of DVT/PE reported; avoid in patients with history of VTE |
| Cardiac disease (HF, arrhythmia) | Monitor LVEF; cautious in heart failure patients |
| Cytopenias (ANC < 1.5 k/µL, platelets < 50 k/µL, Hb < 9 g/dL) | Baseline CBC required; dose hold if thresholds breached |
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Dosing
- Initial dose: 2 mg orally once daily (QD)
- Maintenance dose: 4 mg QD after achieving disease control (titration in 2 mg increments as tolerated)
- Administration: Take with water, preferably at the same time each day; may be taken with food to improve tolerability but not required
- Dose modification:
- ↓ CYP3A4 inhibitors: consider 1 mg QD
- ↑ CYP3A4 inhibitors: consider 1 mg every other day
- Titration guidelines: Stop if CBC shows ANC < 1.0 k/µL or platelets < 25 k/µL; resume at 1 mg QD after recovery
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Adverse Effects
| Adverse Effect | Frequency | Management | |
| Upper respiratory tract infection | ~15% | Symptomatic care | |
| Nausea/vomiting | ~10% | Take with food | |
| Headache, dizziness | ~8% | Bed rest, hydration | |
| Anemia | <5% | CBC monitoring every 4 weeks | |
| Neutropenia | <4% | CBC every 2 weeks initially | |
| Thrombocytopenia | <3% | CBC monitoring | |
| Herpes zoster | 3× ULN)** | <1% | Hold dose; re‑evaluate after resolution |
| Venous thromboembolism | <1% | Assess risk factors; consider prophylaxis | |
| Hypertension | <1% | Monitor BP; antihypertensives as needed |
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Monitoring
- Baseline: CBC with differential, CMP (incl. LFTs), LVEF (echo/CMR), TB screening (IGRA or TST), pregnancy test (if applicable)
- During therapy:
- CBC & CMP every 2 weeks for first 3 months, then monthly
- LFTs every 3 months thereafter
- CBC annually thereafter if stable
- LVEF at baseline, after 6 months, and as clinically indicated
- Infections: Immediate evaluation for suspected infection; consider temporary hold
- Pregnancy planning: Counsel patients of teratogenic risk; use effective contraception
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Clinical Pearls
- Start low, go slow: Initiating at 2 mg avoids early cytopenias; many patients attain remission at 4 mg without dose escalation.
- CYP3A4 co‑administration is the single biggest determinant of plasma levels: Use a drug interaction checker before adding antifungals, macrolides, or antiretrovirals.
- Blood count drop‑watch: An isolated ANC fall of 20–25% from baseline can precede severe neutropenia; consider dose hold if ANC < 1.2 k/µL.
- Herpes zoster prophylaxis: Vaccinate patients ≥50 years old before initiating *Xromi* to reduce zoster incidence by ~60%.
- Cardiovascular vigilance: In patients with hypertension or heart failure, perform echocardiography at baseline and after 6 months; maintain ACEi/ARB therapy if feasible.
- Thromboembolic risk stratification: In patients with a prior VTE or a history of VTE risk factors, a multidisciplinary review is advised before starting *Xromi*; consider low‑dose aspirin if appropriate.
- Therapeutic drug monitoring is rarely needed: Because *Xromi*’s therapeutic window is wide, routine serum concentration monitoring is generally unnecessary; focus on clinical and laboratory surveillance instead.
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