Omalizumab

Indications

Omalizumab is used for: Severe allergic asthma, Chronic Idiopathic Urticaria, Nasal Polyps

Adult Dose

Subcutaneous Allergic Asthma, Poorly controlled, moderate to severe asthma Indicated for moderate-to-severe persistent asthma in patients with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids Adult: 150-375 mg SC q2-4Weekly Determine precise dose and frequency by total IgE level and body weight measured before starting therapy and then periodically as follows. Adult: Doses (mg) and dosing frequency are based on pre-treatment serum IgE levels (IU/mL) and body wt (kg) as follows: >30-100 IU/mL: 150 mg (30-90 kg); 300 mg (>90-150 kg). >100-200 IU/mL: 300 mg (30-90 kg). >200-300 IU/mL: 300 mg (30-60 kg). All doses to be taken every 4 wk. >100-200 IU/mL: 225 mg (>90-150 kg). >200-300 IU/mL: 225 mg (>60-90 kg); 300 mg (>90-150 kg). >300-400 IU/mL: 225 mg (30-70 kg); 300 mg (>70-90 kg). >400-500 IU/mL: 300 mg (30-70 kg); 375 mg (>70-90 kg). >500-600 IU/mL: 300 mg (30-60 kg); 375 mg (>60-70 kg). > 600?700 IU/mL: 375 mg (30-60 kg). All doses to be taken every 2 wk. Doses no more than 150 mg should be admin at 1 inj site. Chronic idiopathic urticaria Indicated for chronic idiopathic urticaria (CIU) in patients who remain symptomatic despite H1 antihistamine treatment Adult: 150 or 300 mg every 4 wk. Dosing in CIU patients is not dependent on serum IgE level or body weight Nasal Polyps Indicated for add-on maintenance treatment of nasal polyps in adults aged ?18 years with inadequate response to nasal corticosteroids 75-600 mg SC every 2-4weeks Determine precise dose and frequency by total IgE level and body weight measured before starting therapy and then periodically.

Child Dose

Subcutaneous Allergic Asthma Indicated for moderate-to-severe persistent asthma in patients with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids <6 years: Safety and efficacy not established 6 to <12 years: 75-375 mg SC q2-4Weekly Children >12 yr: 150-375 mg SC q2-4Weekly Determine precise dose and frequency by total IgE level and body weight measured before starting therapy and then periodically Chronic Idiopathic Urticaria Indicated for chronic idiopathic urticaria (CIU) in patients who remain symptomatic despite H1 antihistamine treatment <12 years: Safety and efficacy not established >12 years: 150-300 mg SC every 4weeks Dosing in CIU patients is not dependent on serum IgE level or body weight

Renal Dose

Administration

Reconstitution: Add sterile water for inj 1.4 mL to upright vial and gently swirl for 5-10 seconds every 5 min until dissolved to produce approx 150 mg/1.2 mL soln. It may take >20 min to dissolve completely. Do not use if powd dissolves w/in 40 min. SC Administration Administer by subcutaneous injection The injection may take 5-10 seconds to administer because the solution is slightly viscous Do not administer >150 mg (contents of 1 vial) per injection site Divide doses >150 mg among 2 or more injection sites

Contra Indications

Previous severe hypersensitivity reaction, acute bronchospasm, status asthmaticus.

Precautions

Anaphylaxis (eg, bronchospasm, hypotension, syncope, urticaria, angioedema of throat or tongue) reported. Anaphylaxis has occurred as early as after first dose, but also has occurred beyond 1 year after beginning regularly administered treatment. Initiate therapy in a healthcare setting and closely observe patients for an appropriate period after administration. Be prepared to manage anaphylaxis that can be life-threatening. Inform patients of the signs and symptoms of anaphylaxis and instruct to seek immediate medical care should symptoms occur. Arthritis/arthralgia, rash, fever, and lymphadenopathy reported. Not intended for treatment of acute asthma exacerbations, acute bronchospasm or status asthmaticus. Patient at risk of parasitic infections. May increase risk of malignancy. Renal and hepatic impairment. Elevated serum total IgE levels may persist for up to 1 yr following discontinuation; do not use serum total IgE levels obtained <1 year following discontinuation to reassess dosing regimen for asthma or nasal polyps.

Pregnancy-Lactation

Pregnancy Exposure during pregnancy showed no increase in rate of major birth defects or miscarriage; Increased rate of low birth weight among registry infants compared to infants in the other cohorts reported, despite average gestational age at birth; however, women taking the drug during pregnancy also had more severe asthma, which makes it difficult to determine whether ow birth weight is due to drug or disease severity Monoclonal antibodies, such as omalizumab, are transported across placenta in a linear fashion as pregnancy progresses; potential effects on fetus are likely to be greater during second and third trimesters of pregnancy In women with poorly or moderately controlled asthma, evidence demonstrates that there is increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate; level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control Human IgG antibodies are known to cross placental barrier; therefore, drug may be transmitted from mother to developing fetus Lactation Majority of infants (80.9%, 186/230) in pregnancy exposure registry were breastfed; events categorized as “infections and infestations” were not significantly increased in infants who were exposed through breastfeeding compared with infants who were not breastfed, or infants who were breastfed without exposure

Interactions

Cytochrome P-450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of omalizumab; thus, there is little potential for drug-drug interactions. No formal drug or vaccine interaction studies have been performed with Omalizumab. There is no pharmacological reason to expect that commonly prescribed medications used in the treatment of asthma will interact with omalizumab. In clinical studies, Omalizumab was commonly used in conjunction with inhaled and oral corticosteroids, inhaled short- and long-acting beta-agonists, leukotriene modifiers, theophyllines and oral antihistamines. There was no indication that the safety of Omalizumab was altered with these other commonly used asthma medications. Limited data are available on the use of Xolair in combination with specific immunotherapy (hyposensitisation therapy). Omalizumab may indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic infections. Incompatibilities: Omalizumab should not be mixed with any medication or diluents other than water for injections.

Adverse Effects

Side effects of Omalizumab : >10% Asthma (aged >12 yr) Injection site reactions (45%) CIU Headache (12%) 1-10% Asthma (aged >12 yr) Arthralgia (8%) Pain (7%) Leg pain (4%) Dizziness (3%) Fatigue (3%) Earache (2%) Pruritus (2%) Dermatitis (2%) Arm pain (2%) Fracture (2%) CIU Nasopharyngitis (9.1%) Arthralgia (2.9%) Viral upper respiratory tract infection (2.3%) Nausea (1.1%) Cough (1.1%) Sinusitis (1.1%) Upper respiratory tract infection (1.1%) Nasal polyps Headache (8.1%) Injection site reactions (5.2%) Upper abdominal pain (3%) Arthralgia (3%) Dizziness (3%) Potentially Fatal: Anaphylactic reactions including bronchospasm, hypotension, syncope, dyspnoea and/or angioedema of the throat or tongue.

Mechanism of Action

Omalizumab is an IgG monoclonal antibody (recombinant DNA-derived) which inhibits IgE binding to the high-affinity IgE receptor on mast cells and basophils.