Introduction
Hizentra (immune globulin subcutaneous, human - 20% solution) is a human-derived immunoglobulin G (IgG) preparation used for antibody replacement therapy in patients with primary immunodeficiency disorders. It is a sterile, preservative-free liquid formulation administered subcutaneously, providing an alternative to intravenous immunoglobulin therapy with the advantage of home-based administration and more stable IgG levels.
Mechanism of Action
Hizentra contains a broad spectrum of IgG antibodies that mirror the natural antibody distribution found in healthy human plasma. It works by providing passive immunity through neutralizing pathogens, opsonizing microorganisms for phagocytosis, and modulating immune responses through Fc receptor binding and complement activation. The subcutaneous administration provides sustained IgG levels with reduced peak-trough fluctuations compared to intravenous administration.
Indications
- Primary immunodeficiency (PI) disorders in adults and pediatric patients 2 years and older
- Chronic inflammatory demyelinating polyneuropathy (CIDP) in adults for maintenance therapy to prevent relapse
Dosage and Administration
Primary Immunodeficiency:- Initial dose: 100-200 mg/kg body weight weekly
- May be divided into multiple infusion sites
- Adjust dose based on clinical response and trough IgG levels
- Maximum infusion rate: 35 mL/h per site (adults); 25 mL/h per site (pediatrics)
- Maximum volume per site: 25 mL (adults); 15 mL (pediatrics)
- 0.2-2.0 g/kg body weight every 2-4 weeks
- Individualize based on clinical response
- Subcutaneous infusion only
- Use infusion pump with appropriate administration sets
- Rotate infusion sites (abdomen, thighs, upper arms, lateral hip)
- Pre-warm to room temperature before administration
- Renal impairment: Use with caution
- Hepatic impairment: No specific recommendations
- Elderly: Individualize based on renal function
- Pediatrics: Approved for children ≥2 years
Pharmacokinetics
Absorption: Bioavailability approximately 65-70% following subcutaneous administration Distribution: Distributes primarily in vascular and extravascular spaces Metabolism: Catabolized through proteolytic pathways similar to endogenous IgG Elimination: Half-life approximately 30-40 days Steady State: Achieved after approximately 4-6 weeks of weekly dosingContraindications
- History of anaphylactic or severe systemic reaction to human immune globulin
- Selective IgA deficiency with known antibodies against IgA
- Hyperprolinemia (contains L-proline as stabilizer)
Warnings and Precautions
Thrombotic Events: May increase risk of thrombosis; use caution in patients with cardiovascular risk factors Renal Dysfunction: Monitor renal function; acute renal failure reported with immune globulin products Aseptic Meningitis Syndrome: May occur, especially with high doses or rapid rate Hemolytic Anemia: Monitor for hemolysis and hemolytic anemia Transmissible Infectious Agents: Theoretical risk of transmitting infectious agents despite manufacturing processes Hyperproteinemia: May occur, monitor serum viscosity in patients at risk Inflammatory Responses: Local reactions common; monitor for systemic inflammatory responsesDrug Interactions
- Live virus vaccines: May diminish vaccine efficacy (delay vaccination for 3 months post-infusion)
- Other immunoglobulin products: Avoid concurrent administration
- Blood products: Monitor for volume overload when administered closely together
Adverse Effects
Most Common (≥5%):- Local reactions: swelling, redness, itching, pain at infusion site (47%)
- Headache (15%)
- Fatigue (7%)
- Nausea (5%)
- Diarrhea (5%)
- Fever (5%)
- Anaphylaxis (<0.1%)
- Thrombotic events (rare)
- Aseptic meningitis syndrome
- Acute renal failure
- Hemolytic anemia
- Transfusion-related acute lung injury (TRALI)
Monitoring Parameters
- Trough IgG levels (target >500 mg/dL for PI)
- Renal function (BUN, creatinine) at baseline and periodically
- Complete blood count with reticulocyte count
- Liver function tests
- Vital signs during and after infusion
- Signs of hemolysis (hemoglobin, haptoglobin, LDH)
- Local infusion site reactions
- Signs of aseptic meningitis
- Thrombotic events monitoring in high-risk patients
Patient Education
- Report any signs of allergic reaction immediately (hives, swelling, difficulty breathing)
- Understand proper infusion technique and site rotation
- Recognize and report local reactions
- Maintain infusion diary including sites used and reactions
- Be aware of potential delayed hemolytic reactions
- Report severe headaches, neck stiffness, or visual changes
- Understand importance of regular monitoring appointments
- Proper storage: refrigerate at 2-8°C; do not freeze
- Allow product to reach room temperature before administration
- Never administer intravenously
References
1. Hizentra® [package insert]. CSL Behring LLC; 2021. 2. Orange JS, et al. J Clin Immunol. 2012;32(6):1180-1192. 3. Berger M, et al. Clin Exp Immunol. 2013;172(3):500-506. 4. FDA Approved Drug Products: Hizentra (immune globulin subcutaneous, human - 20% solution) 5. Bonilla FA, et al. J Allergy Clin Immunol. 2015;136(5):1186-1205. 6. CIDP guidelines: Joint Task Force of the EFNS and the PNS. J Peripher Nerv Syst. 2010;15(1):1-9. 7. Clinical trials: NCT00278989, NCT01057927, NCT01423721
Note: This information is for educational purposes only and should not replace professional medical advice. Always consult with healthcare providers for specific medical guidance.