Generic Name

Cinryze

Mechanism

• Passive antibody replacement: Provides exogenous IgG that compensates for deficiencies in the patient’s own immunoglobulin pool.
• Neutralization of pathogens: IgG binds to bacteria, viruses, and toxins, marking them for clearance or directly neutralizing virulence factors.
• Immune modulation:
• Inhibits Fc receptor–mediated phagocytosis.
• Suppresses complement activation and cytokine release.
• Enhances anti‑idiotypic antibody production, stabilizing autoantibody titers.
• Protection against IgE‑mediated reactions in chronic idiopathic urticaria and some allergic diseases.

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Pharmacokinetics

• Absorption: Rapid plasma entry via IV infusion.
• Distribution: Distributed primarily within extravascular fluid compartments; mean volume of distribution ≈ 3 L.
• Half‑life: 21–28 days (depends on dose, patient IgG turnover, and infusion rate).
• Metabolism & Excretion: Manually processed by the reticuloendothelial system; excreted in normal renal function with minimal reliance on kidneys.
• Drug interactions: No clinically significant interactions with the most common antibiotics or β‑blockers. Avoid concurrent large‑volume infusions that may dilute serum IgG concentration.

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Indications

• Primary immunodeficiency disorders (PID): congenital, inherited, or acquired IgG deficiencies needing long‑term replacement.
• Secondary humoral deficiency (e.g., after splenectomy, chemo‑therapy).
• Chronic idiopathic urticaria: for patients who respond to IVIG but are intolerant of antihistamines.
• Certain autoimmune conditions (e.g., idiopathic thrombocytopenic purpura) when other therapies fail.
• Allergy prophylaxis: peri‑anaphylactic or for selected patients with severe drug hypersensitivity.

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Contraindications

• Contraindications
• Known IgA deficiency with anti‑IgA antibodies → risk of anaphylaxis.
• Severe albuminuria or end‑stage renal disease (high‑dose IVIG may worsen fluid overload).
• Warnings
• Thromboembolic events: Monitor for venous thrombosis, especially in patients with hypercoagulable states.
• Renal dysfunction: Amino‑acid content may precipitate acute kidney injury; review baseline serum creatinine.
• Infusion reactions: Hypotension, rash, chills, or fever usually transient.
• Immunologic complications: Rare cases of aseptic meningitis or immune complex deposition.

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Dosing

• Infusion Rate: Start low (≈ 0.5 mL/min) and titrate to 1–4 mL/min per body‑weight pad, monitor for reactions.
• Premedication: Acetaminophen + antihistamine routinely; steroids only if history of severe reactions.
• Monitoring During Infusion: Blood pressure, heart rate, oxygen saturation; record any flushing or fever.

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•

Monitoring

• Serum IgG trough levels: maintain ≥ 6 g/L in most adults; target 10–12 g/L for severe PIDs.
• Renal function: Serum creatinine, BUN, urine output.
• Complete blood count (CBC): Monitor for hemolysis or thrombocytopenia.
• Coagulation profile: PT/INR, aPTT in patients with thrombotic risk.
• Clinical response: Frequency of infections, urticaria flares, or bleeding episodes.
• Allergy testing if infusion reactions occur.

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Clinical Pearls

• Dose adjustment by body weight: Many students forget that even in severe deficiency, the recommended dose is ≤ 0.6 g/kg; exceeding this increases renal load without extra benefit.
• Premedication with acetaminophen/antihistamine is *always* advised even for first infusion to blunt mild reactions.
• Infusion rate escalation should not exceed 4 mL/kg/h in the first 2 hours; this limit is critical for older patients with cardiac issues.
• For IgA‑deficient patients, use a two‑step infusion: begin at 1 mL/h, monitor for 1 h, then double the rate if tolerated.
• Track serum IgG every 4–6 weeks during the first year; at steady state later can space to 8–12 weeks; this provides early detection of dose failure.
• Avoid high‑dose use (~20 g) without a clear indication; the marginal clinical benefit does not outweigh the risk of renal injury.
• Patients on anticoagulation need pre‑infusion assessment of coagulation parameters; consider temporary cessation or bridging therapy.
• Educate patients on early signs of renal dysfunction (diminished urine, swelling, oliguria), as timely interruption can prevent irreversible damage.

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• Key Takeaway:

Cinryze is a reliable, weight‑based IVIG therapy. Master its dosing algorithm, vigilant monitor for renal and thrombotic risks, and educate patients on early signs of adverse events for optimal clinical outcomes.