Omalizumab

One vial contains Omalizumab 150 mg.

Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell line.

After reconstitution, 1 vial contains Omalizumab 125 mg/mL (150 mg in 1.2 mL).

Omalizumab also contains the following excipients: Sucrose, L-histidine, L-histidine hydrochloride monohydrate, polysorbate 20 and water for injections.

Omalizumab is indicated in adults, adolescents and children (6 to <12 years).

Omalizumab treatment should only be considered for patients with convincing IgE (immunoglobulin E) mediated asthma.

Adults and Adolescents (≥12 Years): Omalizumab is indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and who have reduced lung function (FEV₁ <80%) as well as frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily highdose inhaled corticosteroids, plus a long-acting inhaled β₂-agonist.

Children (6 to <12 Years): Omalizumab is indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily high-dose inhaled corticosteroids, plus a long-acting inhaled β₂-agonist.

Chronic spontaneous urticaria (CSU): Omalizumab is indicated as add-on therapy for the treatment of chronic spontaneous urticaria in adult and adolescent (>12 years old) patients with inadequate response to H₁ antihistamine treatment.

Omalizumab injection is used to treat moderate to severe persistent allergic asthma. It is used when a patient's asthma has not been controlled sufficiently on other asthma medicines. Omalizumab will not relieve an asthma attack that has already started.

Omalizumab injection is also used to treat chronic idiopathic urticaria (CIU) in patients who continue to have hives that are not controlled by an antihistamine.

Omalizumab is a medicine called an IgE blocker. IgE is short for immunoglobulin E. IgE is a substance that occurs naturally in the body in small amounts. This substance plays an important role in allergic asthma. When people with allergic asthma breathe in a year-round allergen, such as cat or dog dander, their bodies make more IgE. This may cause a series of reactions in your body that can lead to asthma attacks and symptoms. Omalizumab works by helping to block IgE.

Omalizumab is to be given only by or under the direct supervision of your doctor.

Allergic Asthma: The appropriate dose and dosing frequency of Omalizumab is determined by baseline immunoglobulin E (IgE) (IU/mL), measured before the start of treatment and body weight (kg). Prior to initial dosing, patients should have their IgE level determined by any commercial serum total IgE assay for their dose assignment. Based on these measurements, Omalizumab 75-600 mg in 1-4 injections may be needed for each administration. See Table 4 for a conversion chart and Tables 5 and 6 for the dose determination charts in children (6 to <12 years) and in adults and adolescents (≥12 years). For doses of Omalizumab 225, 375 or 525 mg can be used in combination with Omalizumab 75 mg.

Patients whose baseline IgE levels or body weight in kg are outside the limits of the dosing table should not be given Omalizumab.

Treatment Duration, Monitoring and Dose Adjustments: In clinical trials, there were reductions in asthma exacerbation events and rescue medication use with improvements in symptom scores during the first 16 weeks of treatment. At least 12 weeks of treatment is required to adequately assess whether or not a patient is responding to Omalizumab.

Omalizumab is intended for long-term treatment. Discontinuation generally results in a return to elevated free IgE levels and associated symptoms.

Total IgE levels are elevated during treatment and remain elevated for up to 1 year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Omalizumab treatment cannot be used as a guide for dose determination. Dose determination after treatment interruptions lasting <1 year should be based on serum IgE levels obtained at the initial dose determination. Total serum IgE levels may be re-tested for dose determination if treatment with Omalizumab has been interrupted for ≥1 year.

Doses should be adjusted for significant changes in body weight.

Chronic Spontaneous Urticaria (CSU): Recommended Dose: 300 mg by SC injection every 4 weeks. Some patients may achieve control of their symptoms with a dose of 150 mg every 4 weeks.

Special Populations: Renal or Hepatic Impairment: There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics of Omalizumab. Because Omalizumab clearance at clinical doses is dominated by IgG clearance process including degradation in the reticular endothelial system (RES), it is unlikely to be altered by renal or hepatic impairment. While no particular dose adjustment is recommended, Omalizumab should be administered with caution in these patients.

Administration: For SC administration only. Do not administer by the IV or IM route.

See also:
What is the most important information I should know about Omalizumab?

Some people using Omalizumab have had a severe, life-threatening allergic reaction to this medication, either right after the injection or hours later. Allergic reaction may occur even after using the medication regularly for a year or longer.

Get emergency medical help if you have any of these signs of an allergic reaction: wheezing, tightness in your chest, trouble breathing; hives or skin rash; feeling anxious or light-headed, fainting; warmth or tingling under your skin; or swelling of your face, lips, tongue, or throat.

Asthma is often treated with a combination of different drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

If you also use a steroid medication, do not stop using the steroid suddenly or you may have unpleasant withdrawal symptoms. Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks.

Your symptoms may not improve right away once you start receiving Omalizumab. For best results, keep receiving the medication as directed. Talk with your doctor if your symptoms do not improve after a few weeks of treatment.

Use Omalizumab regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Using this medication may increase your risk of certain types of cancers of the breast, skin, prostate, or salivary gland. Talk to your doctor about your individual risk.

Omalizumab is injected under the skin. A healthcare provider will give you this injection. Omalizumab is usually given every 2 or 4 weeks.

Before you start treatment with Omalizumab, your doctor may perform an allergy skin test or blood test to make sure this medicine is right for you.

You will be watched closely for a short time after receiving Omalizumab, to make sure you do not have an allergic reaction to the medication.

Your condition may be treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

If you also use a steroid medicine, do not stop using it suddenly or you may have unpleasant withdrawal symptoms. Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks.

While using Omalizumab, you may need frequent medical tests, such as allergy tests and lung function tests. Your stools may also need to be checked for parasites, especially if you travel.

Your condition may not improve right away. For best results, keep receiving the medication as directed. Talk with your doctor if your symptoms do not improve after a few weeks of treatment.

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 beta antihistamine treatment.

See also:
What other drugs will affect Omalizumab?

Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of Omalizumab; thus, there is little potential for drug-drug interactions. Medicinal product or vaccine interaction studies have not been performed with Omalizumab. There is no pharmacological reason to expect that commonly prescribed medicinal products used in the treatment of asthma will interact with Omalizumab.

Allergic Asthma: In clinical studies Omalizumab was commonly used in conjunction with inhaled and oral corticosteroids, inhaled short-acting 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 anti-asthma medicinal products. Limited data are available on the use of Omalizumab in combination with specific immunotherapy (hypo-sensitisation therapy). In a clinical trial where Omalizumab was co-administered with immunotherapy, the safety and efficacy of Omalizumab in combination with specific immunotherapy were found to be no different to that of Omalizumab alone.

Omalizumab may indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic infections.

Chronic Spontaneous Urticaria (CSU): In clinical studies in CSU, Omalizumab was used in conjunction with antihistamines (anti-H₁, anti-H₂) and leukotriene receptor antagonists (LTRAs). There was no evidence that the safety of Omalizumab was altered when used with these medicinal products relative to its known safety profile in allergic asthma. In addition, a population pharmacokinetic analysis showed no relevant effect of H₂ antihistamines and LTRAs on Omalizumab pharmacokinetics.

Paediatric Population: Clinical studies in CSU included some patients aged 12-17 years taking Omalizumab in conjunction with antihistamines (anti-H₁, anti-H₂) and LTRAs. No studies have been performed in children <12 years.

Incompatibilities: This medicinal product must not be mixed with other medicinal products except those mentioned in Dosage & Administration.

See also:
What are the possible side effects of Omalizumab?

Use of Omalizumab has been associated with:

• Anaphylaxis
• Malignancies

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions From Clinical Studies In Adult And Adolescent Patients 12 Years Of Age And Older With Asthma

The data described below reflect Omalizumab exposure for 2076 adult and adolescent patients ages 12 and older, including 1687 patients exposed for six months and 555 exposed for one year or more, in either placebo-controlled or other controlled asthma studies. The mean age of patients receiving Omalizumab was 42 years, with 134 patients 65 years of age or older; 60% were women, and 85% Caucasian. Patients received Omalizumab 150 to 375 mg every 2 or 4 weeks or, for patients assigned to control groups, standard therapy with or without a placebo.

The adverse events most frequently resulting in clinical intervention (e.g., discontinuation of Omalizumab, or the need for concomitant medication to treat an adverse event) were injection site reaction (45%), viral infections (23%), upper respiratory tract infection (20%), sinusitis (16%), headache (15%), and pharyngitis (11%). These events were observed at similar rates in Omalizumab-treated patients and control patients.

Table 5 shows adverse reactions from four placebo-controlled asthma trials that occurred ≥ 1% and more frequently in adult and adolescent patients 12 years of age and older receiving Omalizumab than in those receiving placebo. Adverse events were classified using preferred terms from the International Medical Nomenclature (IMN) dictionary. Injection site reactions were recorded separately from the reporting of other adverse events.

Table 5: Adverse Reactions ≥ 1% More Frequent in Omalizumab-Treated Adult or Adolescent Patients 12 years of Age and Older in Four Placebo-controlled Asthma Trials

There were no differences in the incidence of adverse reactions based on age (among patients under 65), gender or race.

Anaphylaxis Case Control Study

A retrospective case-control study investigated risk factors for anaphylaxis to Omalizumab among patients treated with Omalizumab for asthma. Cases with an adjudicated history of anaphylaxis to Omalizumab were compared to controls with no such history. The study found that a self-reported history of anaphylaxis to foods, medications or other causes was more common among patients with Omalizumab anaphylaxis (57% of 30 cases) compared to controls (23% of 88 controls) [OR 8.1, 95% CI 2.7 to 24.3]. Because this is a case control study, the study cannot provide the incidence of anaphylaxis among Omalizumab users. From other sources, anaphylaxis to Omalizumab was observed in 0.1% of patients in clinical trials and at least 0.2% of patients based upon postmarketing reports.

Injection Site Reactions

In adults and adolescents, injection site reactions of any severity occurred at a rate of 45% in Omalizumab-treated patients compared with 43% in placebo-treated patients. The types of injection site reactions included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.

Severe injection site reactions occurred more frequently in Omalizumab-treated patients compared with patients in the placebo group (12% versus 9%).

The majority of injection site reactions occurred within 1 hour-post injection, lasted less than 8 days, and generally decreased in frequency at subsequent dosing visits.

Adverse Reactions From Clinical Studies In Pediatric Patients 6 To < 12 Years Of Age With Asthma

The data described below reflect Omalizumab exposure for 926 patients 6 to < 12 years of age, including 583 patients exposed for six months and 292 exposed for one year or more, in either placebo-controlled or other controlled asthma studies. The mean age of pediatric patients receiving Omalizumab was 8.8 years; 69% were male, and 64% were Caucasian. Pediatric patients received Omalizumab 75 mg to 375 mg every 2 or 4 weeks or, for patients assigned to control groups, standard therapy with or without a placebo. No cases of malignancy were reported in patients treated with Omalizumab in these trials.

The most common adverse reactions occurring at ≥ 3% in the pediatric patients receiving Omalizumab and more frequently than in patients treated with placebo were nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.

The adverse events most frequently resulting in clinical intervention (e.g., discontinuation of Omalizumab, or the need for concomitant medication to treat an adverse event) were bronchitis (0.2%), headache (0.2%) and urticaria (0.2%). These events were observed at similar rates in Omalizumab-treated patients and control patients.

Adverse Reactions From Clinical Studies In Patients With Chronic Idiopathic Urticaria (CIU)

The safety of Omalizumab for the treatment of CIU was assessed in three placebo-controlled, multiple-dose clinical trials of 12 weeks' (CIU Trial 2) and 24 weeks' duration (CIU Trials 1 and 3). In CIU Trials 1 and 2, patients received Omalizumab 75, 150, or 300 mg or placebo every 4 weeks in addition to their baseline level of H1 antihistamine therapy throughout the treatment period. In CIU Trial 3 patients were randomized to Omalizumab 300 mg or placebo every 4 weeks in addition to their baseline level of H1 antihistamine therapy. The data described below reflect Omalizumab exposure for 733 patients enrolled and receiving at least one dose of Omalizumab in the three clinical trials, including 684 patients exposed for 12 weeks and 427 exposed for 24 weeks. The mean age of patients receiving Omalizumab 300 mg was 43 years, 75% were women, and 89% were white. The demographic profiles for patients receiving Omalizumab 150 mg and 75 mg were similar.

Table 6 shows adverse reactions that occurred in ≥ 2% of patients receiving Omalizumab (150 or 300 mg) and more frequently than those receiving placebo. Adverse reactions are pooled from Trial 2 and the first 12 weeks of Trials 1 and 3.

Table 6: Adverse Reactions Occurring in ≥ 2% in Omalizumab-Treated Patients and More Frequently than in Patients Treated with Placebo (Day 1 to Week 12) in CIU Trials

Additional reactions reported during the 24 week treatment period in Trials 1 and 3 [ ≥ 2% of patients receiving Omalizumab (150 or 300 mg) and more frequently than those receiving placebo] included: toothache, fungal infection, urinary tract infection, myalgia, pain in extremity, musculoskeletal pain, peripheral edema, pyrexia, migraine, sinus headache, anxiety, oropharyngeal pain, asthma, urticaria, and alopecia.

Injection Site Reactions

Injection site reactions of any severity occurred during the studies in more Omalizumab-treated patients [11 patients (2.7%) at 300 mg, 1 patient (0.6%) at 150 mg] compared with 2 placebo-treated patients (0.8%). The types of injection site reactions included: swelling, erythema, pain, bruising, itching, bleeding and urticaria. None of the events resulted in study discontinuation or treatment interruption.

Cardiovascular And Cerebrovascular Events From Clinical Studies In Patients With Asthma

A 5-year observational cohort study was conducted in patients ≥ 12 years of age with moderate to severe persistent asthma and a positive skin test reaction to a perennial aeroallergen to evaluate the long term safety of Omalizumab, including the risk of malignancy. A total of 5007 Omalizumab-treated and 2829 non-Xolairtreated patients enrolled in the study. Similar percentages of patients in both cohorts were current (5%) or former smokers (29%). Patients had a mean age of 45 years and were followed for a mean of 3.7 years. More Omalizumab-treated patients were diagnosed with severe asthma (50%) compared to the non-Omalizumab-treated patients (23%) and 44% of patients prematurely discontinued the study. Additionally, 88% of patients in the Omalizumab-treated cohort had been previously exposed to Omalizumab for a mean of 8 months.

A higher incidence rate (per 1000 patient-years) of overall cardiovascular and cerebrovascular serious adverse events (SAEs) was observed in Omalizumab-treated patients (13.4) compared to non-Omalizumab-treated patients (8.1). Increases in rates were observed for transient ischemic attack (0.7 versus 0.1), myocardial infarction (2.1 versus 0.8), pulmonary hypertension (0.5 versus 0), pulmonary embolism/venous thrombosis (3.2 versus 1.5), and unstable angina (2.2 versus 1.4), while the rates observed for ischemic stroke and cardiovascular death were similar among both study cohorts. The results suggest a potential increased risk of serious cardiovascular and cerebrovascular events in patients treated with Omalizumab. However, the observational study design, the inclusion of patients previously exposed to Omalizumab (88%), baseline imbalances in cardiovascular risk factors between the treatment groups, an inability to adjust for unmeasured risk factors, and the high study discontinuation rate limit the ability to quantify the magnitude of the risk.

A pooled analysis of 25 randomized double-blind, placebo-controlled clinical trials of 8 to 52 weeks in duration was conducted to further evaluate the imbalance in cardiovascular and cerebrovascular SAEs noted in the above observational cohort study. A total of 3342 Xolairtreated patients and 2895 placebo-treated patients were included in the pooled analysis. The patients had a mean age of 38 years, and were followed for a mean duration of 6.8 months. No notable imbalances were observed in the rates of cardiovascular and cerebrovascular SAEs listed above. However, the results of the pooled analysis were based on a low number of events, slightly younger patients, and shorter duration of follow-up than the observational cohort study; therefore, the results are insufficient to confirm or reject the findings noted in the observational cohort study.

Immunogenicity

Antibodies to Omalizumab were detected in approximately 1/1723 ( < 0.1%) of patients treated with Omalizumab in the clinical studies evaluated for approval of asthma in patients 12 years of age and older. In three pediatric studies, antibodies to Omalizumab were detected in one patient out of 581 patients 6 to < 12 years of age treated with Omalizumab and evaluated for antibodies. There were no detectable antibodies in the patients treated in the phase 3 CIU clinical trials, but due to levels of Omalizumab at the time of anti-therapeutic antibody sampling and missing samples for some patients, antibodies to Omalizumab could only have been determined in 88% of the 733 patients treated in these clinical studies. The data reflect the percentage of patients whose test results were considered positive for antibodies to Omalizumab in ELISA assays and are highly dependent on the sensitivity and specificity of the assays. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Omalizumab with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Omalizumab in adult and adolescent patients 12 years of age and older. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Anaphylaxis: Based on spontaneous reports and an estimated exposure of about 57,300 patients from June 2003 through December 2006, the frequency of anaphylaxis attributed to Omalizumab use was estimated to be at least 0.2% of patients. Diagnostic criteria of anaphylaxis were skin or mucosal tissue involvement, and, either airway compromise, and/or reduced blood pressure with or without associated symptoms, and a temporal relationship to Omalizumab administration with no other identifiable cause. Signs and symptoms in these reported cases included bronchospasm, hypotension, syncope, urticaria, angioedema of the throat or tongue, dyspnea, cough, chest tightness, and/or cutaneous angioedema. Pulmonary involvement was reported in 89% of the cases. Hypotension or syncope was reported in 14% of cases. Fifteen percent of the reported cases resulted in hospitalization. A previous history of anaphylaxis unrelated to Omalizumab was reported in 24% of the cases.

Of the reported cases of anaphylaxis attributed to Omalizumab, 39% occurred with the first dose, 19% occurred with the second dose, 10% occurred with the third dose, and the rest after subsequent doses. One case occurred after 39 doses (after 19 months of continuous therapy, anaphylaxis occurred when treatment was restarted following a 3 month gap). The time to onset of anaphylaxis in these cases was up to 30 minutes in 35%, greater than 30 and up to 60 minutes in 16%, greater than 60 and up to 90 minutes in 2%, greater than 90 and up to 120 minutes in 6%, greater than 2 hours and up to 6 hours in 5%, greater than 6 hours and up to 12 hours in 14%, greater than 12 hours and up to 24 hours in 8%, and greater than 24 hours and up to 4 days in 5%. In 9% of cases the times to onset were unknown.

Twenty-three patients who experienced anaphylaxis were rechallenged with Omalizumab and 18 patients had a recurrence of similar symptoms of anaphylaxis. In addition, anaphylaxis occurred upon rechallenge with Omalizumab in 4 patients who previously experienced urticaria only.

Eosinophilic Conditions: Eosinophilic conditions have been reported.

Fever, Arthralgia, and Rash: A constellation of signs and symptoms including arthritis/arthralgia, rash (urticaria or other forms), fever and lymphadenopathy similar to serum sickness have been reported in post-approval use of Omalizumab.

Hematologic: Severe thrombocytopenia has been reported.

Skin: Hair loss has been reported.