Omalizumab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Xolair: 75 mg/0.5 mL (0.5 mL); 150 mg/mL (1 mL)

Solution Reconstituted, Subcutaneous [preservative free]:

Xolair: 150 mg (1 ea)

Pharmacology

Mechanism of Action

Asthma: Omalizumab is an IgG monoclonal antibody (recombinant DNA derived) which inhibits IgE binding to the high-affinity IgE receptor on mast cells and basophils. By decreasing bound IgE, the activation and release of mediators in the allergic response (early and late phase) is limited. Serum free IgE levels and the number of high-affinity IgE receptors are decreased. Long-term treatment in patients with allergic asthma showed a decrease in asthma exacerbations and corticosteroid usage.

Chronic idiopathic urticaria: Omalizumab binds to IgE and lowers free IgE levels. Subsequently, IgE receptors (FcεRI) on cells down-regulate. The mechanism by which these effects of omalizumab result in an improvement of chronic idiopathic urticaria symptoms is unknown.

Pharmacokinetics/Pharmacodynamics

Absorption

Slow following SubQ injection

Distribution

V_d: 78 ± 32 mL/kg

Metabolism

Degradation of IgG and omalizumab:IgE complexes by reticuloendothelial system and endothelial cells in the liver

Excretion

Primarily via hepatic degradation; intact IgG may be secreted in bile

Onset of Action

Response to therapy: ~12 to 16 weeks (87% of patients had measurable response in 12 weeks)

Time to Peak

7-8 days

Half-Life Elimination

26 days (asthma patients); 24 days (chronic idiopathic urticaria patients)

Use: Labeled Indications

Asthma: Treatment of moderate to severe persistent asthma in adults and patients 6 years and older who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.

Guideline recommendations:

The 2007 National Asthma Education and Prevention Program asthma guidelines recommend use be considered as adjunctive therapy in patients with severe persistent asthma who have allergies and in patients with severe persistent asthma that is inadequately controlled with a combination of a high-dose inhaled corticosteroid and a long-acting beta₂-agonist (NAEPP 2007).

The Global Initiative for Asthma suggests use be considered as adjunctive therapy in patients with moderate or severe allergic asthma that is uncontrolled with a combination of a medium- to high-dose inhaled corticosteroid and a long-acting beta₂-agonist (GINA 2018).

Chronic idiopathic urticaria: Treatment of chronic idiopathic urticaria in adults and adolescents 12 years and older who remain symptomatic despite H₁ antihistamine treatment.

Contraindications

Severe hypersensitivity reaction to omalizumab or any component of the formulation

Dosage and Administration

Dosing: Adult

Asthma: SubQ: Dose and frequency based on body weight and pretreatment total IgE serum levels. Dosing should be adjusted during therapy for significant changes in body weight. Dosing should not be adjusted based on total IgE levels taken during treatment or <1 year following interruption of therapy. If therapy has been interrupted for ≥1 year, total IgE levels may be re-evaluated for dosage determination.

Pretreatment serum IgE ≥30 to 100 units/mL:

30 to 90 kg: 150 mg every 4 weeks

>90 to 150 kg: 300 mg every 4 weeks

Pretreatment serum IgE >100 to 200 units/mL:

30 to 90 kg: 300 mg every 4 weeks

>90 to 150 kg: 225 mg every 2 weeks

Pretreatment serum IgE >200 to 300 units/mL:

30 to 60 kg: 300 mg every 4 weeks

>60 to 90 kg: 225 mg every 2 weeks

>90 to 150 kg: 300 mg every 2 weeks

Pretreatment serum IgE >300 to 400 units/mL:

30 to 70 kg: 225 mg every 2 weeks

>70 to 90 kg: 300 mg every 2 weeks

>90 kg: Do not administer dose

Pretreatment serum IgE >400 to 500 units/mL:

30 to 70 kg: 300 mg every 2 weeks

>70 to 90 kg: 375 mg every 2 weeks

>90 kg: Do not administer dose

Pretreatment serum IgE >500 to 600 units/mL:

30 to 60 kg: 300 mg every 2 weeks

>60 to 70 kg: 375 mg every 2 weeks

>70 kg: Do not administer dose

Pretreatment serum IgE >600 to 700 units/mL:

30 to 60 kg: 375 mg every 2 weeks

>60 kg: Do not administer dose

Chronic idiopathic urticaria: SubQ: 150 or 300 mg every 4 weeks. Dosing is not dependent on serum IgE (free or total) level or body weight.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Omalizumab prefilled syringes and reconstituted lyophilized powder are different concentrations; use extra precaution during product selection and during dose volume calculations.

Asthma: Dose and frequency based on body weight and pretreatment total IgE serum concentrations. Dosing should be adjusted during therapy for significant changes in body weight. Dosing should not be adjusted based on total IgE concentrations taken during treatment or if there is an interruption of therapy <1 year in duration as total IgE concentrations are elevated during treatment and remain elevated for up to 1 year after discontinuation of treatment. If therapy has been interrupted for ≥1 year, total IgE levels may be reevaluated for dosage determination.

Children ≥6 to <12 years: SubQ:

Pretreatment serum IgE ≥30 to 100 units/mL:

20 to 40 kg: 75 mg every 4 weeks

>40 to 90 kg: 150 mg every 4 weeks

>90 to 150 kg: 300 mg every 4 weeks

Pretreatment serum IgE >100 to 200 units/mL:

20 to 40 kg: 150 mg every 4 weeks

>40 to 90 kg: 300 mg every 4 weeks

>90 to 125 kg: 225 mg every 2 weeks

>125 to 150 kg: 300 mg every 2 weeks

Pretreatment serum IgE >200 to 300 units/mL:

20 to 30 kg: 150 mg every 4 weeks

>30 to 40 kg: 225 mg every 4 weeks

>40 to 60 kg: 300 mg every 4 weeks

>60 to 90 kg: 225 mg every 2 weeks

>90 to 125 kg: 300 mg every 2 weeks

>125 to 150 kg: 375 mg every 2 weeks

Pretreatment serum IgE >300 to 400 units/mL:

20 to 30 kg: 225 mg every 4 weeks

>30 to 40 kg: 300 mg every 4 weeks

>40 to 70 kg: 225 mg every 2 weeks

>70 to 90 kg: 300 mg every 2 weeks

>90 kg: Do not administer dose

Pretreatment serum IgE >400 to 500 units/mL:

20 to 25 kg: 225 mg every 4 weeks

>25 to 30 kg: 300 mg every 4 weeks

>30 to 50 kg: 225 mg every 2 weeks

>50 to 70 kg: 300 mg every 2 weeks

>70 to 90 kg: 375 mg every 2 weeks

>90 kg: Do not administer dose

Pretreatment serum IgE >500 to 600 units/mL:

20 to 30 kg: 300 mg every 4 weeks

>30 to 40 kg: 225 mg every 2 weeks

>40 to 60 kg: 300 mg every 2 weeks

>60 to 70 kg: 375 mg every 2 weeks

>70 kg: Do not administer dose

Pretreatment serum IgE >600 to 700 units/mL:

20 to 25 kg: 300 mg every 4 weeks

>25 to 40 kg: 225 mg every 2 weeks

>40 to 50 kg: 300 mg every 2 weeks

>50 to 60 kg: 375 mg every 2 weeks

>60 kg: Do not administer dose

Pretreatment serum IgE >700 to 900 units/mL:

20 to 30 kg: 225 mg every 2 weeks

>30 to 40 kg: 300 mg every 2 weeks

>40 to 50 kg: 375 mg every 2 weeks

>50 kg: Do not administer dose

Pretreatment serum IgE >900 to 1,100 units/mL:

20 to 25 kg: 225 mg every 2 weeks

>25 to 30 kg: 300 mg every 2 weeks

>30 to 40 kg: 375 mg every 2 weeks

>40 kg: Do not administer dose

Pretreatment serum IgE >1,100 to 1,200 units/mL:

20 to 30 kg: 300 mg every 2 weeks

>30 kg: Do not administer dose

Pretreatment serum IgE >1,200 to 1,300 units/mL:

20 to 25 kg: 300 mg every 2 weeks

>25 to 30 kg: 375 mg every 2 weeks

>30 kg: Do not administer dose

Children ≥12 years and Adolescents: SubQ:

Pretreatment serum IgE ≥30 to 100 units/mL:

30 to 90 kg: 150 mg every 4 weeks

>90 to 150 kg: 300 mg every 4 weeks

Pretreatment serum IgE >100 to 200 units/mL:

30 to 90 kg: 300 mg every 4 weeks

>90 to 150 kg: 225 mg every 2 weeks

Pretreatment serum IgE >200 to 300 units/mL:

30 to 60 kg: 300 mg every 4 weeks

>60 to 90 kg: 225 mg every 2 weeks

>90 to 150 kg: 300 mg every 2 weeks

Pretreatment serum IgE >300 to 400 units/mL:

30 to 70 kg: 225 mg every 2 weeks

>70 to 90 kg: 300 mg every 2 weeks

>90 kg: Do not administer dose

Pretreatment serum IgE >400 to 500 units/mL:

30 to 70 kg: 300 mg every 2 weeks

>70 to 90 kg: 375 mg every 2 weeks

>90 kg: Do not administer dose

Pretreatment serum IgE >500 to 600 units/mL:

30 to 60 kg: 300 mg every 2 weeks

>60 to 70 kg: 375 mg every 2 weeks

>70 kg: Do not administer dose

Pretreatment serum IgE >600 to 700 units/mL:

30 to 60 kg: 375 mg every 2 weeks

>60 kg: Do not administer dose

Chronic idiopathic urticaria: Children ≥12 years and Adolescents: SubQ: 150 or 300 mg every 4 weeks. Dosing is not dependent on serum IgE (free or total) level or body weight.

Dosing: Adjustment for Toxicity

Severe hypersensitivity reaction or anaphylaxis: Discontinue treatment.

Fever, arthralgia, and rash: Discontinue treatment if this constellation of symptoms occurs.

Reconstitution

SubQ: Vial: Reconstitute using SWFI only; add SWFI 1.4 mL to upright vial using a 1-inch, 18-gauge needle on a 3 mL syringe and swirl gently for ~1 minute to evenly wet the powder; do not shake. Then gently swirl the upright vial for 5 to 10 seconds approximately every 5 minutes until dissolved; generally takes 15 to 20 minutes to dissolve completely. If it takes >20 minutes to dissolve completely, continue to swirl the upright vial for 5 to 10 seconds every 5 minutes until no gel-like particles are visible in the solution; do not use if contents are not completely dissolved after 40 minutes. After reconstitution, solution is somewhat viscous and will appear clear or slightly opalescent. It is acceptable if there are a few small bubbles or foam around edge of vial. Invert the vial for 15 seconds so the solution drains toward the stopper. Remove all of the solution by inserting a new 3 mL syringe with a 1-inch, 18-gauge needle into the inverted vial. Replace the 18-gauge needle with a 25-gauge needle for subcutaneous injection and expel any air or bubbles. Vial contains overfill; expel excess solution to obtain the resulting dose of 150 mg/1.2 mL or 75 mg/0.6 mL. Note: Vial contains 202.5 mg including overfill (ISMP 2019). Concentrations following reconstitution of the vial differ from concentrations of prefilled syringes.

Administration

SubQ: For SubQ injection only; doses >150 mg should be divided over more than one injection site (eg, 225 mg or 300 mg administered as two injections, 375 mg administered as three injections); each injection site should be separated by ≥1 inch. Do not inject into moles, scars, bruises, tender areas, or broken skin. Injections may take 5 to 10 seconds to administer (solution is slightly viscous). Administer only under direct medical supervision and observe patient for 2 hours after the first 3 injections and 30 minutes after subsequent injections (Lieberman 2015) or in accordance with individual institution policies and procedures.

Lyophilized powder (vial): Recommended injection sites include the upper arm, stomach, or the front and middle of the thighs.

Prefilled syringe: Allow to warm to room temperature for 15 to 30 minutes; leave in carton to protect from light. Do not speed warming process in any way (eg, microwave, warm water). Recommended injection sites include the upper arm and the front and middle of the thighs.

Storage

Prefilled syringe: Store under refrigeration at 2°C to 8°C (36°F to 46°F) in the original carton. Protect from direct sunlight; do not freeze.

Vial: Prior to reconstitution, store under refrigeration at 2°C to 8°C (36°F to 46°F); product may be shipped at room temperature. Following reconstitution, protect from direct sunlight. May be stored for up to 8 hours if refrigerated or 4 hours if stored at room temperature ≤30°C (≤86°F).

Drug Interactions

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Test Interactions

Total IgE levels are elevated for up to 1 year following treatment. Total serum IgE may be retested after interruption of therapy for 1 year or more.

Adverse Reactions

Incidences reported in children and adults unless otherwise noted.

>10%:

Central nervous system: Headache (6% to 12%; children: ≥3%)

Local: Injection site reaction (asthma: 45%, severe 12%; chronic idiopathic urticaria: 3%; may include bleeding, bruising, burning, erythema, induration, inflammation, mass, pain, pruritus, stinging, swelling, warmth, urticaria)

1% to 10%:

Cardiovascular: Peripheral edema (≥2%)

Central nervous system: Pain (7%), dizziness (3%), fatigue (3%), anxiety (≥2%), migraine (≥2%)

Dermatologic: Alopecia (≥2%), urticaria (chronic idiopathic urticaria: ≥2%, asthma: <1%), dermatitis (2%), pruritus (2%)

Gastrointestinal: Upper abdominal pain (children: ≥3%), viral gastroenteritis (children: ≥3%), toothache (≥2%)

Genitourinary: Urinary tract infection (≥2%)

Infection: Fungal infection (≥2%)

Neuromuscular & skeletal: Arthralgia (3% to 8%), limb pain (2% to 4%), musculoskeletal pain (≥2%), myalgia (≥2%), bone fracture (2%)

Otic: Otitis media (children: ≥3%), otalgia (2%)

Respiratory: Nasopharyngitis (9%; children: ≥3%), sinusitis (5%), epistaxis (children: ≥3%), streptococcal pharyngitis (≥3%), upper respiratory tract infection (3%), asthma (≥2%), oropharyngeal pain (≥2%), sinus headache (≥2%), cough (2%), viral upper respiratory tract infection (≤2%)

Miscellaneous: Fever (≥2%)

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, antibody development, arthritis, bronchospasm, chest tightness, decreased serum immunoglobulins (free IgE), dyspnea, eosinophilia, eosinophilic granulomatosis with polyangiitis, hypotension, increased serum immunoglobulin (total IgE), lymphadenopathy, malignant neoplasm, pharyngeal edema, serum sickness, severe thrombocytopenia, skin rash, swollen tongue, syncope, vasculitis

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Cerebrovascular events, including transient ischemic attack and ischemic stroke, have been reported.
• Eosinophilia and vasculitis: In rare cases, patients may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss), a condition which is often treated with systemic corticosteroid therapy. Health care providers should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between omalizumab and these underlying conditions has not been established.
• Fever/arthralgia/rash: Reports of a constellation of symptoms including fever, arthritis or arthralgia, rash, and lymphadenopathy have been reported with postmarketing use (symptoms resemble those seen in patients experiencing serum sickness, although circulating immune complexes or a skin biopsy consistent with a Type III hypersensitivity reaction were not seen with these cases). Onset of symptoms generally occurred 1 to 5 days following the first or subsequent doses. Discontinue therapy in any patient reporting this constellation of signs/symptoms.
• Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Anaphylaxis, including delayed-onset anaphylaxis, has been reported following administration; anaphylaxis may present as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue. Anaphylaxis has occurred after the first dose and in some cases >1 year after initiation of regular treatment. Due to the risk, patients should be observed closely for an appropriate time period after administration and should receive treatment only under direct medical supervision. Healthcare providers should be prepared to administer appropriate therapy for managing potentially life-threatening anaphylaxis. Patients should be instructed on identifying signs/symptoms of anaphylaxis and to seek immediate care if they arise. In postmarketing reports, anaphylaxis usually occurred with the first or second dose and with a time to onset of ≤60 minutes; however, reactions have been reported with subsequent doses (after 39 doses) and with a time to onset of up to 4 days after administration. A case-control study showed that patients with a history of anaphylaxis to foods, medications, or other causes were at an increased risk of anaphylaxis. An epinephrine autoinjector should be prescribed for all patients receiving omalizumab (Lieberman 2015). Discontinue therapy following any severe reaction.
• Malignant neoplasms: Have been reported rarely with use in short-term studies; impact of long-term use is not known.

Disease-related concerns:

• Parasitic infections: Use with caution and monitor patients at high risk for parasitic (helminth) infections; risk of infection may be increased; appropriate duration of continued monitoring following therapy discontinuation has not been established.

Concurrent drug therapy issues:

• Corticosteroid therapy: Gradually taper systemic or inhaled corticosteroid therapy; do not discontinue corticosteroids abruptly following initiation of omalizumab therapy. The combined use of omalizumab and corticosteroids in patients with chronic idiopathic urticaria has not been evaluated.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Latex: Prefilled syringe: The needle cap may contain natural rubber latex.

Other warnings/precautions:

• Appropriate use: Therapy has not been shown to alleviate acute asthma exacerbations; do not use to treat acute bronchospasm, status asthmaticus, or other allergic conditions. Do not use to treat forms of urticaria other than chronic idiopathic urticaria.
• Dosing/IgE levels: Dosing for asthma is based on body weight and pretreatment total IgE serum levels. IgE levels remain elevated up to 1 year following treatment; therefore, levels taken during treatment or for up to 1 year following treatment cannot and should not be used as a dosage guide. Dosing in chronic idiopathic urticaria is not dependent on serum IgE (free or total) level or body weight.

Monitoring Parameters

Anaphylactic/hypersensitivity reactions (observe patients for 2 hours after the first 3 injections and 30 minutes after subsequent injections [Lieberman 2015] or in accordance with individual institution policies and procedures); baseline serum total IgE; FEV₁, peak flow, and/or other pulmonary function tests; monitor for signs of infection

Pregnancy

Pregnancy Considerations

Omalizumab is a humanized monoclonal antibody (IgG₁). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Information related to the use of omalizumab in pregnancy is available from case reports of women with severe asthma (Kupryś-Lipińska 2014) or chronic idiopathic urticaria (some also with asthma) (Cuervo-Pardo 2016; Ensina 2017; Ghazanfar 2015; González-Medina 2017). In addition, information from the Xolair Pregnancy Registry (EXPECT) is available. Based on data collected from 250 women between 2006 and 2018, the incidence of major congenital malformations was not increased when compared to pregnant females with asthma not treated with omalizumab. The risk of low birth weight infants was increased; however, more severe asthma in the females taking omalizumab may also have contributed.

Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low-birth-weight infants). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Optimal control of asthma prior to and during pregnancy is recommended (ACOG 90 2008; GINA 2018).

Patient Education

What is this drug used for?

• It is used to treat hives.
• It is used to treat asthma.
• Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.

Frequently reported side effects of this drug

• Headache
• Nausea
• Injection site irritation
• Loss of strength and energy
• Sore throat
• Stuffy nose
• Common cold symptoms
• Ear pain
• Painful extremities
• Abdominal pain (children)
• Vomiting (children)
• Nosebleed (children)

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes.
• DVT like edema, warmth, numbness, change in color, or pain in the extremities.
• Burning or numbness feeling
• Bone pain
• Chest pain
• Jaw pain
• Arm pain
• Passing out
• Shortness of breath
• Difficulty breathing
• Joint pain
• Joint rigidity
• Muscle pain
• Joint swelling
• Swollen glands
• Rash
• Coughing up blood
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.