QIVIGY
QIVIGY
Generic Name
QIVIGY
Mechanism
QIVIGY is a purified, intravenous immunoglobulin (IVIG) preparation derived from pooled human plasma. Its multifaceted pharmacologic actions include:
• Neutralization of pathogenic antibodies (e.g., auto‑antibody, allo‑antibody) through Fc‑γ receptor blocking and Fc‑fragment competition.
• Modulation of FcγR‑mediated phagocytosis and dampening of pro‑inflammatory cytokine release (IL‑6, TNF‑α, IFN‑γ).
• Complement system regulation – competing for binding sites, preventing terminal complement activation.
• Immune modulation – induction of regulatory T‑cells, down‑regulation of B‑cell activation, and up‑regulation of anti‑inflammatory IgG subclasses (IgG2, IgG4).
• Enhancement of antibody clearance by saturating FcRn-mediated recycling pathways, thereby reducing circulating auto‑antibodies.
These actions collectively afford therapeutic benefit in immune‑deficiency states, autoimmune disorders, and acute immune‑mediated conditions.
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Pharmacokinetics
| Parameter | Typical Value (IVIG) | Notes |
| Volume of distribution | 0.4–0.6 L/kg | Reflects intravascular & interstitial distribution |
| Half‑life | 21–35 days | Lengthened by neonatal Fc receptor (FcRn) recycling |
| Clearance | 0.01–0.02 mL/min/kg | Reduced in distributive shock or high‑volume preparations |
| Steady‑state Concentration | ~10–20 µg/mL | Achieved with repeated dosing |
| Impact of disease | Autoimmune states may increase clearance | Requires dose adjustment |
| Age & Weight effect | Children may need higher mg/kg dosing | Growth & lean body mass considerations |
*Formulation Note*: QIVIGY is available as 10 % and 20 % solutions. Higher concentration formulations reduce infusion volume but require slower infusion rates to mitigate reaction risk.
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Indications
- Primary immunodeficiency (PID) – replacement therapy in Common Variable Immunodeficiency (CVID) and X‑linked Agammaglobulinemia.
- Secondary immunodeficiency – e.g., after rituximab, stem cell transplant, or long‑term chemotherapy.
- Autoimmune conditions
- Immune thrombocytopenic purpura (ITP) – first‑line or rescue therapy.
- Chronic inflammatory demyelinating polyneuropathy (CIDP).
- Guillain‑Barré syndrome (GBS) – within 4–8 weeks of onset.
- Kawasaki disease – acute phase (<10 days).
- Systemic lupus erythematosus (SLE) with refractory or severe manifestations (off‑label).
- Goodpasture syndrome and anti‑GBM disease (often combined with plasmapheresis).
- Infectious disease prophylaxis – HIV or viral hepatitis treatment rescue.
- Adjunct to other immunotherapies (e.g., post‑transplant with anti‑thymocyte globulin).
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Contraindications
| Category | Details |
| Absolute Contraindications | Known IgA deficiency with anti‑IgA antibodies (risk of anaphylaxis). |
| Relative Contraindications | Renal insufficiency (creatinine > 2 mg/dL), uncontrolled hypertension, high‑dose platelet consumption, pregnancy (Category B). |
| Warnings | Thromboembolic events in patients with pre‑existing risk, aseptic meningitis, hemolysis in glucose‑6‑phosphate dehydrogenase (G6PD) deficiency, allergy to human plasma proteins, hypersensitivity to gel or stabilizer components. |
| Precautions | Monitor glucose in diabetics (contains dextrose). Adequate hydration to preserve renal function. |
*Clinical note:* Use low‑IgA or IgA‑deficient IVIG preparations if IgA allergy suspected.
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Dosing
| Indication | Typical Dose / Schedule | Modifications |
| PID replacement | 0.4 – 0.8 g/kg every 3–4 weeks (target trough IgG 5–12 g/L) | Weight‑based; larger volumes need slower infusion. |
| ITP (acute) | 1 – 2 g/kg total (0.5 – 1 g/kg × 2 infusions, 24 h apart). | Rapid response; monitor platelet count. |
| CIDP | 0.4 – 0.6 g/kg monthly (maintenance). | Often 0.8 – 1.2 g/kg initially for better response. |
| GBS | 0.4 – 0.6 g/kg daily for 5 days (total 2 – 3 g/kg). | Early administration critical. |
| Kawasaki disease | 2 g/kg single infusion | Often combined with high‑dose aspirin. |
| Off‑label IVIG for other autoimmune | 0.3 – 1.0 g/kg (often 0.5 – 1 g/kg) | Tailored to patient response. |
Infusion guidelines
1. Preparation – Dilute QIVIGY 1:1 with saline both for priming and the infusion line.
2. Infusion rate – Start at 0.5 mL/kg/hr; increase to a maximum of 10 mL/kg/hr after 30 min if tolerated.
3. Premedication – Antipyretic (acetaminophen) and antihistamine (diphenhydramine) are common; corticosteroids considered if severe reactions anticipated.
4. Monitoring – Vital signs every 15 min during first hour, then every 30 min.
5. Completion – Discontinue infusion if serious reaction occurs; treat accordingly.
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Adverse Effects
| Class | Examples | Frequency | Management |
| Infusion reactions | Fever, chills, headache, rigors, urticaria | 5–20 % | Slow infusion, premedication, steroids. |
| Aseptic meningitis | Neck pain, photophobia, meningismus | < 0.5 % | Stop infusion, NSAIDs or steroids; re‑infuse at lower rate. |
| Renal dysfunction | Elevated creatinine, proteinuria | 1–5 % | Ensure adequate hydration; avoid nephrotoxins. |
| Thromboembolism | DVT, PE, stroke | < 1 % | Use anticoagulation in high‑risk patients. |
| Hemolysis | Warm hemolytic anemia | Rare (< 0.1 %) | Check for G6PD; discontinue if severe. |
| Anaphylaxis (IgA‑deficient) | Angioedema, hypotension, bronchospasm | Rare | Immediate epinephrine, airway management. |
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Monitoring
| Parameter | Timing | Target/Notes |
| Serum IgG trough level | Every 4–6 weeks (PID) | 5–12 g/L |
| Platelet count | Baseline, Day 3, weekly | > 30 × 10¹²/L (ITP) |
| Renal function (CrCl & electrolytes) | Before each infusion | Normal/adjust dose |
| Vital signs (during infusion) | Every 15–30 min | Tachycardia > 140 bpm, BP change > 20 mmHg |
| Neurologic assessment | Daily (neuromuscular disease) | Muscle strength, sensation |
| Inflammatory markers (CRP, ESR) | Baseline, then as needed | Decrease by > 50 % |
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Clinical Pearls
- Use of low‑IgA IVIG: Preferred for patients with severe IgA deficiency or history of anaphylaxis to plasma products.
- Pre‑infusion hydration: Adequate IV fluids (1–2 L/infusion) reduce risk of renal insult and thrombosis.
- Dose–Response Relationship: In pediatric PID, weight‑normalized dose can be higher (up to 1 g/kg if serum IgG targets not met).
- Combination therapy: IVIG can synergize with steroids in ITP; check for interaction with antiplatelet agents.
- Timing for GBS & CIDP: Early initiation (≤ 8 weeks for GBS, within 12 months for CIDP) yields better outcomes.
- Infusion rate escalation: Limit to < 10 mL/kg/hr for hyperosmolar 20 % solutions; 10 % solutions may tolerate 20 – 30 mL/kg/hr safely.
- Drug–Drug Interactions: Monitor for cytochrome P450 modulation; although minimal, monitor with hepatotoxic agents.
- Aseptic meningitis prophylaxis: Short courses of NSAIDs pre‑infusion reduce incidence in high‑risk patients.
- Personalized medicine: Track anti‑IgG3 responses in Goodpasture syndrome; adjust treatment if renal function deteriorates.
Key Takeaway: QIVIGY remains a versatile, evidence‑based therapy for a spectrum of immune disorders—proper dosing, vigilant monitoring, and patient‑specific precautions are paramount for optimal outcomes.