Omalizumab - Drug Monograph

Introduction

Omalizumab (brand name Xolair®) is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to immunoglobulin E (IgE). It represents a significant advancement in the treatment of allergic asthma and other IgE-mediated conditions by targeting the underlying immunological mechanisms rather than merely providing symptomatic relief. First approved by the FDA in 2003, omalizumab has since expanded its therapeutic applications through additional FDA approvals and clinical research.

Mechanism of Action

Omalizumab exerts its therapeutic effects through several immunomodulatory mechanisms:

• IgE neutralization: Binds to the FcεRI binding site on free IgE, preventing IgE from attaching to mast cells and basophils
• Receptor downregulation: Reduces the number of high-affinity IgE receptors (FcεRI) on inflammatory cells
• Inflammatory mediator inhibition: Decreases the release of histamine, leukotrienes, cytokines, and other inflammatory mediators
• Eosinophil reduction: Lowers tissue and blood eosinophil counts through indirect mechanisms

The drug does not bind to IgE already bound to receptors on mast cells and basophils, preventing cell activation and degranulation.

Indications

• Moderate to severe persistent asthma in patients 6 years and older with positive skin test or in vitro reactivity to a perennial aeroallergen, not adequately controlled with inhaled corticosteroids
• Chronic idiopathic urticaria (CIU) in patients 12 years and older who remain symptomatic despite H1-antihistamine treatment
• Nasal polyps in adults 18 years and older with inadequate response to nasal corticosteroids
• Food allergy risk reduction in certain patients (recent expanded approval)

• Allergic bronchopulmonary aspergillosis (ABPA)
• Atopic dermatitis
• Allergic rhinitis
• Mast cell activation disorders

Dosage and Administration

• Dosed based on body weight and baseline IgE levels (30-700 IU/mL)
• Administered subcutaneously every 2 or 4 weeks
• Initial dose: 150-375 mg depending on weight and IgE level

| Body Weight (kg) | IgE (IU/mL) | Dose (mg) | Frequency | |------------------|-------------|-----------|-----------| | 30-90 | 30-100 | 150 | Q4 weeks | | 30-90 | 101-200 | 300 | Q4 weeks | | >90-150 | 30-100 | 300 | Q4 weeks | | >90-150 | 101-200 | 225 | Q2 weeks |

• Administer by healthcare professional
• Rotate injection sites (arm, thigh)
• Observe patients for 2 hours after initial doses and 30 minutes after subsequent doses
• Do not abruptly discontinue systemic or inhaled corticosteroids

• Renal/hepatic impairment: No dosage adjustment required
• Elderly: Use with caution due to increased infection risk
• Pregnancy: Category B - use if clearly needed
• Pediatrics: Approved for children ≥6 years with asthma

Pharmacokinetics

• Bioavailability: 62% following subcutaneous administration
• Tmax: 7-8 days after subcutaneous injection

• Volume of distribution: 78 ± 32 mL/kg
• Does not readily cross blood-brain barrier

• Degraded via proteolytic enzymes throughout the body
• No hepatic metabolism via cytochrome P450 system

• Clearance: 2.4 ± 1.1 mL/kg/day
• Half-life: 26 days
• Elimination: IgG-like pathways including FcRn-mediated recycling

Contraindications

• Hypersensitivity to omalizumab or any component of the formulation
• Severe hypersensitivity reaction to previous omalizumab administration
• Acute bronchospasm or status asthmaticus

Warnings and Precautions

• Anaphylaxis: Occurred in 0.1-0.2% of patients, typically within 2 hours of administration
• Requires healthcare setting administration and post-injection observation

• Malignancy: Small increased risk observed in clinical trials (0.5% vs 0.2% placebo)
• Parasitic infection: Increased risk of helminth infections in endemic areas
• Fever, arthralgia, rash: May occur 1-5 days after injection
• Corticosteroid reduction: Monitor carefully during steroid tapering
• Eosinophilic conditions: Rare cases of eosinophilic pneumonia and vasculitis

Drug Interactions

• None identified with cytochrome P450 substrates
• Live vaccines: Theoretical risk - avoid administration during treatment

• Corticosteroids: Allows reduction but requires careful monitoring
• Other biologics: Limited data on combination therapy
• Immunosuppressants: Potential additive immunosuppressive effects

Adverse Effects

• Injection site reactions (45%): erythema, burning, urticaria
• Viral infections (23%)
• Upper respiratory tract infections (20%)
• Sinusitis (16%)
• Headache (15%)
• Pharyngitis (11%)

• Anaphylaxis (0.1-0.2%)
• Malignancy (0.5%)
• Thrombocytopenia
• Eosinophilic conditions
• Arthralgia/myalgia syndrome
• Cardiac and cerebrovascular events

Monitoring Parameters

• IgE levels (must be 30-700 IU/mL for asthma indication)
• Weight measurement
• Asthma control assessment (ACT score, symptom frequency)
• Pulmonary function tests (FEV1)
• Complete blood count with platelets

• Anaphylaxis signs for 2 hours post-injection (initial doses)
• Asthma symptoms and control
• Corticosteroid reduction effects
• Injection site reactions
• Malignancy screening per standard guidelines
• Parasitic infections in endemic areas
• Platelet counts if thrombocytopenia suspected

• At 16 weeks: Evaluate asthma control improvement
• Continue if response adequate; discontinue if no meaningful improvement

Patient Education

• Administration schedule and need for healthcare setting administration
• Anaphylaxis recognition: difficulty breathing, throat swelling, hives, dizziness
• Importance of post-injection observation period
• Do not stop controller medications unless directed by physician
• Report any unusual symptoms, especially fever, rash, or joint pain
• Carry epinephrine auto-injector if prescribed
• Inform all healthcare providers of omalizumab therapy
• Pregnancy planning: discuss with physician before conception
• Travel to areas with parasitic infections: take appropriate precautions

• Improvement may take several weeks to months
• Not a rescue medication - continue prescribed rescue inhalers
• Regular follow-up essential for monitoring safety and efficacy

References

1. FDA Prescribing Information: Xolair (omalizumab). Revised 2023. 2. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;(1):CD003559. 3. Saini SS, Bindslev-Jensen C, Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines. J Allergy Clin Immunol. 2015;136(1):109-114. 4. Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364(11):1005-1015. 5. Casale TB, Luskin AT, Busse W, et al. Omalizumab effectiveness by biomarker status in patients with asthma: Evidence from PROSPERO. J Allergy Clin Immunol. 2019;143(2):711-720. 6. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2023. 7. Tsabouri S, Tseretopoulou X, Priftis K, et al. Omalizumab for the treatment of inadequately controlled allergic rhinitis. Ann Allergy Asthma Immunol. 2014;113(6):624-629.