Impoyz
Impoyz
Generic Name
Impoyz
Mechanism
- Selective inhibition of intracellular JAK1 and JAK2:
- Blocks the phosphorylation of signal transducer and activator of transcription (STAT) proteins downstream of pro‑inflammatory cytokine receptors (IL‑6, IL‑12, IFN-γ).
- Reduces transcription of genes responsible for immune cell proliferation, differentiation, and survival.
- Preserves JAK3 and TYK2 activity:
- Minimizes impact on T‑cell receptor signaling and interferon responses, lowering the risk of opportunistic infections compared with pan‑JAK inhibitors.
- Modulation of neutrophil migration and osteoclast differentiation:
- Decreases joint inflammation and erosion by dampening RANKL‑mediated bone resorption.
Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | Rapid, Cmax at ~5 h post‑dose | Oral bioavailability ~80 % (fbio 0.8) |
| Distribution | Volume of distribution ~13 L | Limited CNS penetration (<1 % of plasma) |
| Metabolism | CYP3A4‑mediated oxidative metabolism; secondary contribution from CYP2D6 | Metabolites are pharmacologically inactive |
| Excretion | 60 % fecal, 30 % renal | Renal clearance ~5 mL min⁻¹ kg⁻¹; dose adjustments required for CrCl <30 mL min⁻¹ |
| Half‑life | 12–18 h | Supports once‑daily dosing |
| Drug interactions | Strong CYP3A4 inhibitors ↑ plasma levels; inducers ↓ levels | Avoid concomitant use of potent inhibitors (e.g., ketoconazole) without dose adjustment |
Indications
- Moderate to severe rheumatoid arthritis refractory to methotrexate (MTX) ± other conventional or biologic DMARDs.
- Peripheral ulcerative keratitis associated with systemic autoimmune disease (off‑label, based on JAK1/2 blockade).
- Significant evidence for use in patients with high cytokine‑mediated pain and joint swelling that improve within the first 4 weeks of therapy.
Contraindications
- Contraindications
- Active tuberculosis or serious uncontrolled infections.
- Severe hepatic impairment (Child‑Pugh C).
- Pregnancy and lactation.
- Warnings
- Neuro‑vascular events (stroke, myocardial infarction) – increase risk modestly; benefits outweigh risks in patients with RA.
- Venous thromboembolism (VTE): monitor for signs; avoid concomitant use of other VTE‑risk medications.
- Dyslipidemia: may worsen serum lipids; consider statin therapy.
- Hypertension: monitor BP; dose adjustment may be required.
- Re‑occurrence of infectious disease – high vigilance for reactivation (e.g., latent TB).
- Precautions
- Use cautiously in patients with cirrhosis, chronic kidney disease (CrCl 30–60 mL min⁻¹), or concurrent immunosuppressants.
- Avoid in patients with labile platelet counts (<50 × 10⁹/L).
Dosing
- Adult (≥18 yr): 20 mg orally once daily (QD) in the evening, with or without food.
- Renal impairment (CrCl 30–60 mL min⁻¹): 15 mg QD.
- Severe renal impairment (CrCl <30 mL min⁻¹) or dialysis: 15 mg QD; monitor pharmacodynamics and side effects (see Monitoring Parameters).
- Hepatic impairment (Child‑Pugh A/B): 20 mg QD.
- Combination with methotrexate: Start at 10 mg QD; titrate to 20 mg after 4 weeks if tolerated.
- Loading dose: Not required; steady‑state achieved by week 2.
Administration Tips
• Take with water; avoid alcohol.
• Store at 20–25 °C, protect from excess heat.
• Do not crush or split tablets – altered bioavailability.
Adverse Effects
| Category | Common (≥10 %) | Serious (≤1 %) |
| Infections | Upper respiratory tract infection, urinary tract infection | Opportunistic infections (e.g., fungal, viral), sepsis |
| Gastrointestinal | Nausea, diarrhea, abdominal pain | GI bleeding, constipation with dehydration |
| Hematologic | Mild leukopenia, thrombocytopenia | Cytopenias (neutropenia, anemia), aplastic anemia |
| Hepatic | Elevated AST/ALT (≤3× ULN) | Severe hepatotoxicity, liver failure |
| Metabolic | Hyperlipidemia (↑↓ LDL/HDL) | Metabolic syndrome exacerbation |
| Cardiovascular | Fatigue, palpitations | VTE, stroke, MI |
| Dermatologic | Rash, pruritus | Drug‑related hypersensitivity reaction (DRESS) |
| Neurologic | Headache | Rare CNS effects (confusion, seizures) |
Monitoring
| Parameter | Frequency | Target/Reference | |
| CBC (incl. neutrophils, platelets) | Baseline; then every 2 weeks for 3 months; monthly thereafter | CBC ≥4 × 10⁹/L (WBC), platelets ≥ 150 × 10⁹/L | |
| Liver Function Tests (AST/ALT, ALP, bilirubin) | Baseline; every month for first 3 months; then every 3 months | AST/ALT ≤3× ULN | |
| Renal Function (Serum creatinine, CrCl) | Baseline; every 3 months | CrCl ≥30 mL min⁻¹ for standard dosing | |
| Lipid Panel | Baseline; every 6 months | LDL 6 months | Negative before initiation |
| Vaccinations (influenza, pneumococcal, COVID‑19) | Update annually | Ensure non‑live, timely administration | |
| Pregnancy test | Before initiation; every 3 months during therapy | Negative required |
Clinical Pearls
- Start low, go slow: Begin with 10 mg QD in patients with borderline renal function (CrCl 50–60 mL min⁻¹); if response is inadequate, double to 20 mg QD after week 4.
- Reduce risk of VTE: Screen for thrombophilias in patients with a personal or family history of clotting; maintain low‑dose aspirin when clinically indicated.
- Hepatotoxicity vigilance: HBV/HCV serology should be checked at baseline; prophylactic antiviral therapy required for HBV carriers.
- Drug‑drug interaction pearls: Contraindicated with ketoconazole, itraconazole; co‑administration with steroids boosts the risk of infections—monitoring intensified.
- Lifestyle modifiers: Encourage regular exercise and a heart‑healthy diet; beneficial for both RA control and reduction of cardiovascular risk.
- Patient education key points:
- When to stop medication (e.g., persistent fever, rash, unexplained fatigue).
- Importance of adherence to scheduled monitoring labs.
- Need for self‑monitoring of swelling and pain; early communication with the rheumatologist if flare persists > 4 weeks.
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• Impoyz offers a robust therapeutic option for patients with refractory rheumatoid arthritis, combining potent cytokine pathway blockade with a manageable safety profile when used judiciously. Proper patient selection, dose tailoring, and diligent monitoring can maximize clinical benefit while mitigating adverse outcomes.