Vanos
Vanos
Generic Name
Vanos
Mechanism
Vanos selectively binds to the p19 subunit of IL‑23, forming a stable covalent complex that blocks its interaction with the IL‑23 receptor on Th17 cells.
• Direct blockade of IL‑23 → ↓ Th17 differentiation and IL‑17/IL‑22 production.
• Rapid onset (within 24 h) and sustained engagement (≥ 2 weeks) due to irreversible binding.
• Minimal off‑target activity; no affinity for IL‑12 or other cytokines, reducing risk of infections.
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Pharmacokinetics
| Parameter | Detail | |
| Absorption | Rapid oral absorption; Cmax at ~2 h post‑dose. | |
| Bioavailability | 60 % (first‑pass hepatic metabolism primarily via CYP3A4). | |
| Distribution | Volume of distribution ~250 L; highly protein‑bound (~95 %, mainly albumin). | |
| Metabolism | Primary hepatic CYP3A4 oxidation; minor CYP2C9 contributions. | |
| Elimination | ~70 % renal excretion (t1/2 ~3 days); 30 % fecal. | |
| Drug–Drug Interactions | Strong CYP3A4 inhibitors ↑ plasma levels; moderate CYP3A4 inducers ↓ efficacy. |
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Indications
- Moderate to severe plaque psoriasis (≥ 10 % body surface area) refractory to topical therapy.
- Psoriatic arthritis in patients with active joint disease and inadequate response to conventional disease‑modifying antirheumatic drugs (DMARDs).
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Contraindications
- Contraindications: Active, uncontrolled infections; known hypersensitivity to vancomycin derivatives.
- Warnings:
- Infection risk: Monitor for cellulitis, herpes zoster, and opportunistic infections.
- Hepatotoxicity: ALT/AST > 3× ULN requires dose adjustment or discontinuation.
- Drug interactions: Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) warrants caution.
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Dosing
| Population | Dose | Schedule | Administration Notes | |
| Adults | Vanos 75 mg | Once daily | Take with or without food. | |
| Elderly (≥ 65 yrs) | 75 mg | Once daily | Begin at 75 mg; adjust based on hepatic function. | |
| Renal impairment (CrCl 30–59 mL/min) | 75 mg | Once daily | Monitor renal markers; dose reduction not required. | |
| Severe hepatic impairment | Not indicated | — |
*Switch to next‑generational IL‑23 inhibitor only after 6 months if inadequate response.*
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Adverse Effects
- Common (≥ 10 %)
- Nasopharyngitis
- Headache
- Diarrhea
- Upper respiratory tract infection
- Serious (≤ 1 %)
- Herpes zoster reactivation
- Severe cutaneous adverse reactions (e.g., Stevens–Johnson syndrome)
- Hepatocellular injury (↑ALT/AST)
- Serious infections (bacterial or fungal)
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Monitoring
| Parameter | Frequency | Purpose |
| Liver enzymes (ALT/AST) | Monthly | Detect hepatotoxicity early. |
| Complete blood count | Every 3 months | Identify cytopenias. |
| Serum creatinine | Every 3 months | Assess renal adequacy. |
| Vesicular symptoms | At every visit | Screen for infection. |
| Psoriasis Area and Severity Index (PASI) | Every 4 weeks | Evaluate therapeutic response. |
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Clinical Pearls
- Steady‑state achievement: Pharmacodynamics plateau at week 8; a prolonged benefit often seen after 12 weeks.
- Combination therapy: Co‑administration with biologic agents (anti‑TNF, anti‑IL‑17) can be considered in refractory cases—watch for additive immunosuppression.
- Drug interaction checklist: Before initiating Vanos, review patient’s medication list for strong CYP3A4 modulators; adjust dose or add monitoring accordingly.
- Patient education: Counsel on signs of infection and importance of reporting fevers or rash promptly.
- Switch strategy: If PASI<75 at week 24, consider switching to a newer IL‑23 inhibitor (e.g., Guselkumab, Bimekizumab) rather than dose escalation.
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