Hizentra
Hizentra
Generic Name
Hizentra
Mechanism
Hizentra delivers IgG antibodies that:
• Neutralize pathogens through opsonization and complement activation.
• Modulate the immune system by:
• Saturating Fc receptors and inhibiting auto‑antibody production.
• Suppressing pro‑inflammatory cytokines and stabilizing neutrophil functions.
• Provide passive immunity against common bacterial and viral infections, especially when endogenous IgG production is deficient.
The subcutaneous route allows steady, delayed absorption compared to IVIG, yielding a more stable serum IgG level with a lower peak‑trough fluctuation.
Pharmacokinetics
| Parameter | Typical Value (IgG) |
| Absorption | Subcutaneous depot → rapid absorption (~50–60 % of dose by 48 h). |
| Bioavailability | ~73 % relative to IVIG. |
| Distribution | Volume of distribution similar to plasma volume (~4–6 L). |
| Half‑life | ~21–28 days; dependent on individual IgG turnover. |
| Metabolism | Proteolytic digestion in the reticulo‑endothelial system; no liver metabolism. |
| Elimination | Predominantly via proteolytic catabolism; renal excretion minimal. |
Key point: SCIG results in less pronounced antibody peaks, reducing infusion‑related adverse events.
Indications
- Primary immunodeficiency (PID) requiring Ig replacement (e.g., CVID, X‑linked agammaglobulinemia).
- Immune thrombocytopenic purpura (ITP) refractory to conventional therapy.
- Graft‑versus‑host disease (GVHD) in certain contexts.
- Other immune‑mediated disorders: Kawasaki disease, idiopathic thrombocytopenic purpura, and some autoimmune diseases (evidence varies).
Contraindications
- Hypersensitivity to human immunoglobulin or excipients (e.g., gelatin, sucrose).
- Known IgA deficiency with anti‑IgA antibodies.
- Severe renal failure – dosing adjustments may be required.
- Uncorrected hypocalcemia – calcium supplementation can reduce serum calcium during infusion.
- Pregnancy & lactation: generally considered safe but should be used only if benefits outweigh risks.
Warnings:
• Thromboembolic events: monitor in patients with a history of thrombosis or hypercoagulability.
• Fluid overload: especially in pediatric or heart‑failure patients; adjust infusion rate.
• Infusion‑related reactions (fever, chills, headache): usually mild, treat with pre‑medication or rate adjustment.
Dosing
| Condition | Initial Dose | Maintenance Dose | Frequency | Location & Training |
| PID | 0.4 mL/kg SC (≈0.15–0.5 g/kg) | 0.4–0.6 mL/kg SC weekly | SC | Home or clinic; training on SC technique and recognition of local reaction. |
| ITP | 0.9 mL/kg SC (≈0.25–0.3 g/kg) | 0.3–0.6 mL/kg SC every 2–4 weeks | SC | Same as PID. |
• Volume per injection: ≤ 0.5 mL to minimize local irritation.
• Injection sites: abdomen, thigh, upper arm (avoid same site for 48 h).
• Pre‑medication: antihistamines and/or acetaminophen can be administered for prior mild reactions.
• Infusion rate: start at 0.5 mL/min, increase by 25 % increments as tolerated.
*Note: All dosing should be individualized based on serum IgG trough levels (target 400–800 mg/dL) and clinical response.*
Adverse Effects
- Local Reactions
- Pain, erythema, induration, rash, edema (≤ 50 % of patients) – transient.
- Systemic Reactions
- Fever, headache, myalgia, arthralgia (≤ 20 %).
- Hypotension, anaphylaxis (rare, < 0.1 %).
- Serious Events
- Thromboembolic phenomena (deep vein thrombosis, pulmonary embolism).
- Renal dysfunction especially in patients with pre‑existing CKD.
- Hemolysis in patients with G6PD deficiency (rare).
*Patients should be screened for risk factors (e.g., prior thromboembolic events, renal impairment) before initiation.*
Monitoring
| Parameter | Frequency | Target/Notes |
| Serum IgG trough level | 3–4 weeks after dose, before the next infusion | 400–800 mg/dL for PID; ≥600 mg/dL for ITP |
| Renal function (CrCl, BUN, electrolytes) | ↑ baseline, each 3–4 weeks, and at clinical suspicion | Adjust dose if CrCl 30 mmHg BP change |
| Adverse event log | at each visit | Record local/systemic reactions |
Clinical Pearls
- Subcutaneous vs. Intravenous: SCIG offers more stable IgG levels, reduced infusion time (≈10 min vs. 3–6 h for IVIG), and lower incidence of systemic reactions.
- Injection Site Management: Rotate sites, rotate arms each week; consider using a pre‑infusion mild corticosteroid for patients with chronic local reactions.
- Dose Adjustment in Pregnancy: For women who conceive while on Hizentra, continue therapy at the same dose but monitor IgG trough levels and inform obstetric care of the benefits/risks.
- Chemo‑induced Thrombocytopenia: In ITP patients on chemotherapy, a higher prophylactic IgG dose (0.6 mL/kg) may be needed, but balance against thrombosis risk.
- Switching from IVIG to SCIG: Typically requires a transitional period of 2–4 weeks with overlapping infusions to maintain trough levels.
- Infusion Rate Titration: For patients with hypersensitivity, start at 0.3 mL/kg over 30 min, increase by 0.1 mL/kg every 30 min as tolerated.
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