Xolair - Drug Monograph

Introduction

Xolair (omalizumab) is a recombinant 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, offering targeted therapy for patients who remain symptomatic despite conventional treatments.

Mechanism of Action

Xolair inhibits IgE-mediated inflammation by binding to the FcεRI binding site on free IgE, preventing IgE from attaching to mast cells and basophils. This action reduces the release of inflammatory mediators (histamine, leukotrienes, prostaglandins) that cause bronchoconstriction and inflammation in allergic asthma. Xolair also downregulates FcεRI receptors on basophils and mast cells over time.

Indications

• Moderate to severe persistent asthma in patients ≥6 years with positive skin test or in vitro reactivity to a perennial aeroallergen and inadequate control with inhaled corticosteroids
• Chronic spontaneous urticaria in patients ≥12 years who remain symptomatic despite H1-antihistamine treatment
• Chronic rhinosinusitis with nasal polyps in adults (add-on therapy)
• Food allergy risk reduction in certain patients (recently approved)

Dosage and Administration

• Dosing based on body weight and pretreatment IgE levels (30-700 IU/mL)
• Administered subcutaneously every 2 or 4 weeks
• Typical dose range: 150-375 mg every 2-4 weeks

• Fixed doses of 150 mg or 300 mg every 4 weeks
• Administered subcutaneously

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: No specific recommendations
• Elderly: Use with caution due to increased infection risk
• Pediatrics: Approved for asthma ≥6 years, urticaria ≥12 years

Pharmacokinetics

• Absorption: Bioavailability ~62% following subcutaneous administration
• Distribution: Volume of distribution ~78 mL/kg; limited tissue distribution
• Metabolism: Cleared via IgG clearance pathways (proteolytic degradation)
• Elimination: Half-life ~26 days; clearance increases with body weight
• No significant organ-based metabolism

Contraindications

• History of severe hypersensitivity reaction to omalizumab or any component
• Acute bronchospasm or status asthmaticus
• Patients with IgE levels >700 IU/mL or body weight outside recommended ranges for asthma indication

Warnings and Precautions

Additional precautions:

• Malignancy: Potential increased risk of malignant neoplasms
• Parasitic infections: May be at increased risk for helminth infections
• Fever, arthralgia, and rash: Some patients experience serum sickness-like reactions
• Cardiovascular events: Monitor patients with pre-existing cardiac disease
• Corticosteroid reduction: Reduce corticosteroids gradually under medical supervision

Drug Interactions

• No formal drug interaction studies conducted
• Theoretical interactions with other monoclonal antibodies
• Live vaccines: Avoid administration during treatment
• Cyclosporine: Potential increased risk of immune effects
• Warfarin: Monitor INR due to potential protein-binding interactions

Adverse Effects

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

• Anaphylaxis (0.2%)
• Malignancy (0.5%)
• Thrombocytopenia
• Arthralgia/myalgia syndrome
• Alopecia
• Eosinophilic conditions

Monitoring Parameters

• Serum IgE levels
• Asthma control assessment
• Complete blood count
• Cardiac assessment if indicated

• Asthma symptoms and control
• Injection site reactions
• Signs of anaphylaxis for 2 hours post-injection
• CBC periodically (monitor for thrombocytopenia)
• Parasitic infection screening in endemic areas
• Malignancy surveillance

• Pulmonary function tests
• Quality of life assessments
• Corticosteroid requirement reduction

Patient Education

• Understand anaphylaxis signs: hives, itching, swelling, breathing difficulty, chest tightness
• Remain under observation for 2 hours after initial injections, 30 minutes thereafter
• Report any injection site reactions, fever, joint pain, or unusual bleeding/bruising
• Do not discontinue other asthma medications without medical guidance
• Carry emergency epinephrine if prescribed
• Inform all healthcare providers about Xolair treatment
• Report any new lumps or growths to physician
• Keep scheduled appointments for regular monitoring

References

1. US Food and Drug Administration. Xolair prescribing information. 2023. 2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2023. 3. Casale TB, et al. Omalizumab effectiveness by biomarker status in patients with asthma: A meta-analysis. J Allergy Clin Immunol Pract. 2019;7(3):893-901. 4. Kaplan AP, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132(1):101-109. 5. Normansell R, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;(1):CD003559. 6. Bachert C, et al. Efficacy and safety of omalizumab in nasal polyposis: Two randomized phase III trials. J Allergy Clin Immunol. 2020;146(3):595-605. 7. Tonacci A, et al. Omalizumab for the treatment of chronic idiopathic urticaria: A meta-analysis. Expert Opin Biol Ther. 2017;17(12):1467-1474.