Generic Name

Omalizumab

Mechanism

• IgE sequestration: Binds circulating free IgE with high affinity, forming stable immune complexes.
• Blockade of FcεRI expression: Reduces surface expression of the high‑affinity IgE receptor (FcεRI) on mast cells and basophils, decreasing their activation potential.
• Depletion of IgE‑sensitized effector cells: By lowering available IgE, downstream signaling pathways (e.g., phospholipase C, calcium mobilization) are dampened, curtailing mediator release.

Pharmacokinetics

• Absorption & bioavailability: Subcutaneous administration; ~100 % bioavailability at therapeutic doses.
• Distribution: 48 % into the interstitial fluid; 50 % bound to Fc receptors.
• Metabolism: Proteolytic catabolism into peptides and amino acids; not processed by CYP enzymes.
• Elimination & half‑life: T₁/₂ ≈ 26 days (dose‑dependent, longer at lower IgE concentrations).
• Special populations: No dose adjustment required for age, sex, mild‑moderate renal impairment, or mild hepatic impairment.

Indications

• Moderate‑to‑severe persistent allergic asthma (not adequately controlled by inhaled corticosteroids + controller therapy).
• Chronic spontaneous urticaria (CSU) refractory to H₁‑antihistamines.
• Other indications (as off‑label: allergic rhinitis, atopic dermatitis; clinical trials ongoing for chronic rhinosinusitis with nasal polyposis).

Contraindications

• Contraindicated in patients with a history of immediate hypersensitivity to omalizumab or any of its excipients.
• Warnings:
• Anaphylaxis: Rare but serious; monitor for 30 min post‑injection.
• Glomerulonephritis, thyroid disease, systemic lupus erythematosus: monitor for signs of organ involvement.
• Potential for respiratory syncytial virus (RSV) infection: counsel on hygiene measures.

Dosing

• Asthma:
• Weight 20–56 kg: 150 mg Q2‑4 weeks.
• Weight 56–70 kg: 225 mg Q2‑4 weeks.
• Weight > 70 kg: 300 mg Q2‑4 weeks.
• Doses adjusted per baseline serum IgE (30–700 IU/mL).
• Chronic spontaneous urticaria: 300 mg Q4 weeks.
• Route: Subcutaneous injection into thigh, abdomen, or upper arm; alternate sites each visit.

Adverse Effects

• Common (≥10 %):
• Injection‑site reactions (erythema, pain).
• Headache, fatigue, upper‑respiratory‑tract infections.
• Serious (≤1 %):
• Anaphylaxis, severe respiratory or cardiovascular reactions.
• Progressive multifocal leukoencephalopathy (rare).
• Cases of glomerulonephritis and thyroiditis have been reported.

Monitoring

• Clinical response: Asthma control score, peak expiratory flow, symptom diary.
• Serum IgE: Re‑measure every 6–12 months to adjust dosing.
• Adverse event surveillance:
• Post‑dose observation for ≥30 min.
• Educate patients on anaphylaxis recognition and epinephrine use.
• Laboratory tests: Baseline CBC, CMP; renal and hepatic panels as clinically indicated.

Clinical Pearls

• Dose recalculations: Because the product vial does not contain a fixed potency, each pre‑filled syringe must be weighed and the exact amount of omalizumab calculated to ensure accurate dosing.
• IgE‑dependent dosing: For patients with very low IgE (700 IU/mL), the drug is not indicated; consider alternative biologics.
• Treatment duration: A minimum of 6 months is recommended before assessing full therapeutic benefit, particularly for CSU.
• Injection‑site technique: Use a 20 mm needle for subcutaneous delivery; avoid intramuscular injection to reduce risk of systemic reactions.
• Drug interactions: Minimal drug–drug interactions; no routine monitoring of other medications is required, simplifying polypharmacy management.

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• Key takeaways: Omalizumab is a targeted immunotherapy offering significant benefit in allergic asthma and chronic spontaneous urticaria. Proper dosing relies on weight and serum IgE, with vigilant monitoring for anaphylaxis and other rare systemic reactions.