Usage
- Medical Conditions: Omalizumab is prescribed for moderate to severe persistent allergic asthma, chronic idiopathic urticaria (CIU), chronic rhinosinusitis with nasal polyps (CRSwNP), and IgE-mediated food allergies. It’s used as an add-on therapy when standard treatments like inhaled corticosteroids (for asthma) or H1 antihistamines (for CIU) are insufficient.
- Pharmacological Classification: Monoclonal antibody (specifically, a humanized IgG1 kappa monoclonal antibody). It’s also classified as an anti-asthmatic, antihistamine, and immunomodulator.
- Mechanism of Action: Omalizumab targets immunoglobulin E (IgE). It binds to free IgE in the blood, preventing IgE from attaching to mast cells and basophils. This reduces the release of inflammatory mediators like histamine, thereby lessening allergic symptoms.
Alternate Names
- International Nonproprietary Name (INN): Omalizumab
- Brand Name: Xolair
How It Works
- Pharmacodynamics: By binding to free IgE, Omalizumab downregulates the high-affinity IgE receptor (FcεRI) on the surface of mast cells and basophils. This prevents IgE-mediated degranulation and the release of inflammatory mediators, thus controlling allergic reactions.
- Pharmacokinetics:
- Absorption: Administered subcutaneously; absorption is slow, reaching peak serum concentrations in about 7-8 days. Steady-state levels are achieved after multiple doses.
- Metabolism: As a large molecule, it is primarily broken down by the reticuloendothelial system (RES), similar to the breakdown of endogenous IgG.
- Elimination: Clearance is primarily through the RES system, with a small fraction of the dose excreted unchanged in urine and bile. The half-life is approximately 26 days.
- Mode of Action: Omalizumab specifically targets the Cε3 domain of IgE, the region responsible for binding to FcεRI. This selective binding prevents cross-linking of IgE on mast cells and basophils. It does not bind to IgE already attached to FcεRI or activate complement.
- Receptor Binding: Binds with high affinity to free IgE.
- Enzyme Inhibition/Neurotransmitter Modulation: Not applicable to omalizumab’s primary mechanism.
- Elimination Pathways: Primarily RES-mediated degradation; minimal renal or hepatic excretion.
Dosage
Omalizumab dosing is individualized and determined by the patient’s pre-treatment serum total IgE level (IU/mL) and body weight (kg). It’s administered subcutaneously every 2 or 4 weeks.
Standard Dosage
Adults (12 years and older): 75 mg to 600 mg, based on baseline IgE and body weight.
Children (6 to <12 years): 75 mg to 375 mg for asthma based on baseline IgE and body weight. Use is not recommended for other indications in this age group. For patients 1 year and older with IgE-mediated food allergy, the dose can be between 75 and 600 mg.
Special Cases:
- Elderly Patients: No specific dosage adjustment is typically required.
- Patients with Renal Impairment: No specific dosage adjustment is needed; however, caution is advised.
- Patients with Hepatic Dysfunction: No specific dosage adjustment is needed; however, caution is advised.
- Patients with Comorbid Conditions: Dosage should be carefully considered based on the specific comorbidity.
Clinical Use Cases
Omalizumab is not indicated for acute conditions such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. It is a maintenance medication for chronic allergic conditions.
Dosage Adjustments
Dose adjustments may be needed for significant changes in body weight. After treatment interruptions of less than one year, dosing restarts based on initial IgE levels. Interruptions lasting one year or more require IgE re-testing.
Side Effects
Common Side Effects:
Injection site reactions (pain, swelling, redness, itching), headache, upper respiratory tract infections, sinusitis, fatigue, arthralgia, dizziness.
Rare but Serious Side Effects:
Anaphylaxis (including anaphylactic shock), angioedema, serum sickness, thrombocytopenia, Churg-Strauss syndrome, hypersensitivity vasculitis, and malignancy.
Long-Term Effects:
Long-term effects are still being evaluated. Some studies suggest a potential increased risk of certain infections.
Contraindications
- Hypersensitivity to omalizumab or its components.
Drug Interactions
- There are limited clinically significant drug interactions. Concomitant use with other immunomodulators may increase the risk of infection.
- CYP450 Interactions: Not applicable.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Limited data available. Some studies suggest no major birth defects or miscarriage risk, but a possible increased risk of low birth weight.
- Breastfeeding: IgG antibodies are present in human milk, and it’s expected that omalizumab would also be present, though probably in small quantities. However, limited data suggest no adverse effects. Consult a neonatologist or breastfeeding specialist before using.
Drug Profile Summary
- Mechanism of Action: Inhibits IgE binding to mast cells and basophils, reducing allergic mediator release.
- Side Effects: Injection site reactions, headache, infections, anaphylaxis (rare).
- Contraindications: Hypersensitivity.
- Drug Interactions: Limited.
- Pregnancy & Breastfeeding: Limited data, discuss risks and benefits with patients.
- Dosage: Individualized based on IgE and body weight.
- Monitoring Parameters: IgE levels, body weight, and any signs of allergic reactions.
Popular Combinations
Omalizumab is often used in conjunction with inhaled corticosteroids for asthma control and H1-antihistamines for CIU. Specific combinations are determined based on individual patient needs.
Precautions
- Assess for hypersensitivity and monitor for signs of anaphylaxis, especially after the first three doses.
- Caution in patients with a history of anaphylaxis or malignancy.
- Do not abruptly discontinue systemic corticosteroids after initiating omalizumab.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Omalizumab?
A: The dosage is individualized based on the patient’s pretreatment serum total IgE (IU/mL) and body weight (kg). Ranges are 75-600 mg for adults and 75-375 mg for children (6-11 years for asthma) given subcutaneously every 2 or 4 weeks.
Q2: How is Omalizumab administered?
A: Subcutaneously.
Q3: What are the most common side effects?
A: Injection site reactions (pain, redness, swelling, itching), headache, upper respiratory tract infections.
Q4: Can Omalizumab be used during pregnancy?
A: Data is limited, and risks and benefits should be carefully discussed with the patient. Consider consulting with a maternal-fetal medicine specialist.
Q5: What should be done in case of a suspected anaphylactic reaction?
A: Immediately discontinue the drug and administer appropriate emergency treatment (e.g., epinephrine, antihistamines, corticosteroids).
Q6: How long does it take for Omalizumab to work?
A: Some patients experience improvement within days, while others may take several weeks or months.
Q7: Is Omalizumab effective for all types of urticaria?
A: It is primarily indicated for chronic idiopathic urticaria (CIU). Its efficacy in other types of urticaria is less established.
Q8: Can Omalizumab cure asthma or allergies?
A: No, it does not cure the underlying condition. It helps control symptoms and reduce exacerbations.
Q9: Does Omalizumab interact with other medications?
A: Limited clinically significant drug interactions are known. Concomitant use with other immunomodulators requires caution as there is the potential for an increased risk of infection.
Q10: How often are IgE levels monitored during Omalizumab therapy?
A: IgE levels are measured before treatment initiation to determine the initial dose. Subsequent monitoring is based on patient response and clinical need. IgE levels during treatment do not guide dose adjustments.
