Xolair

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 

Xolair 75 mg powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains 75 mg of omalizumab*. 

 

After reconstitution one vial contains 125 mg/ml of omalizumab (75 mg in 0.6 ml). 

 

*Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology in 

a Chinese hamster ovary (CHO) mammalian cell line. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Powder and solvent for solution for injection. 

 

Powder: white to off-white lyophilisate 

Solvent: clear and colourless solution 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

Allergic asthma 

 

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

 

Xolair treatment should only be considered for patients with convincing IgE (immunoglobulin E) 

mediated asthma (see section 4.2). 

 

Adults and adolescents (12 years of age and older) 
Xolair 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 high-

dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist. 

 

Children (6 to <12 years of age) 
Xolair 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 beta2-

agonist. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Xolair is indicated as an add-on therapy with intranasal corticosteroids (INC) for the treatment of 

adults (18 years and above) with severe CRSwNP for whom therapy with INC does not provide 

adequate disease control. 

 



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4.2 Posology and method of administration 
 

Xolair treatment should be initiated by physicians experienced in the diagnosis and treatment of severe 

persistent asthma or chronic rhinosinusitis with nasal polyps (CRSwNP). 

 

Posology 

 

Dosing for allergic asthma and CRSwNP follows the same dosing principles. The appropriate dose 

and frequency of Xolair for these conditions is determined by baseline IgE (IU/ml), measured before 

the start of treatment, and body weight (kg). Prior to administration of the initial dose, patients should 

have their IgE level determined by any commercial serum total IgE assay for their dose assignment. 

Based on these measurements, 75 to 600 mg of Xolair in 1 to 4 injections may be needed for each 

administration. 

 

Allergic asthma patients with baseline IgE lower than 76 IU/ml were less likely to experience benefit 

(see section 5.1). Prescribing physicians should ensure that adult and adolescent patients with IgE 

below 76 IU/ml and children (6 to < 12 years of age) with IgE below 200 IU/ml have unequivocal in 

vitro reactivity (RAST) to a perennial allergen before starting therapy. 

 

See Table 1 for a conversion chart and Tables 2 and 3 for the dose determination charts. 

 

Patients whose baseline IgE levels or body weight in kilograms are outside the limits of the dose table 

should not be given Xolair. 

 

The maximum recommended dose is 600 mg omalizumab every two weeks. 

 

Table 1 Conversion from dose to number of vials, number of injections and total injection 

volume for each administration 

 

Dose (mg) Number of vials Number of injections Total injection volume (ml) 

 75 mg a 150 mg b   

75 1c 0 1 0.6 

150 0 1 1 1.2 

225 1c 1 2 1.8 

300 0 2 2 2.4 

375 1c 2 3 3.0 

450 0 3 3 3.6 

525 1c 3 4 4.2 

600 0 4 4 4.8 
a 0.6 ml = maximum delivered volume per vial (Xolair 75 mg). 
b 1.2 ml = maximum delivered volume per vial (Xolair 150 mg). 

c or use 0.6 ml from a 150 mg vial. 

 



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Table 2 ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 4 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20-

25* 

>25-  

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90-  

125 

>125-  

150 

30-100 75 75 75 150 150 150 150 150 300 300 

>100-200 150 150 150 300 300 300 300 300 450 600 

>200-300 150 150 225 300 300 450 450 450 600  

>300-400 225 225 300 450 450 450 600 600   

>400-500 225 300 450 450 600 600     

>500-600 300 300 450 600 600      

>600-700 300  450 600       

>700-800           

>800-900     ADMINISTRATION EVERY 2 WEEKS 

SEE TABLE 3 

 

>900-

1000 

     

>1000-

1100 

          

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 



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Table 3 ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 2 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20-

25* 

>25- 

30* 

>30- 

40 

>40- 

50 

>50-  

60 

>60- 

70 

>70- 

80 

>80- 

90 

>90-  

125 

>125- 

150 

30-100 ADMINISTRATION EVERY 

4 WEEKS 

SEE TABLE 2 

     

>100-200      

>200-300          375 

>300-400         450 525 

>400-500       375 375 525 600 

>500-600      375 450 450 600  

>600-700  225   375 450 450 525   

>700-800 225 225 300 375 450 450 525 600   

>800-900 225 225 300 375 450 525 600    

>900-

1000 

225 300 375 450 525 600     

>1000-

1100 

225 300 375 450 600      

>1100-

1200 

300 300 450 525 600 Insufficient data to recommend a dose 

>1200-

1300 

300 375 450 525       

>1300-

1500 

300 375 525 600       

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 

  



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Treatment duration, monitoring and dose adjustments 

Allergic asthma 

Xolair is intended for long-term treatment. Clinical trials have demonstrated that it takes at least 

12-16 weeks for Xolair treatment to show effectiveness. At 16 weeks after commencing Xolair 

therapy patients should be assessed by their physician for treatment effectiveness before further 

injections are administered. The decision to continue Xolair following the 16-week timepoint, or on 

subsequent occasions, should be based on whether a marked improvement in overall asthma control is 

seen (see section 5.1, Physician’s overall assessment of treatment effectiveness). 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical trials for CRSwNP, changes in nasal polyps score (NPS) and nasal congestion score (NCS) 

were observed at 4 weeks. The need for continued therapy should be periodically reassessed based 

upon the patient’s disease severity and level of symptom control. 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

Discontinuation of Xolair treatment 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 one 

year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment 

cannot be used as a guide for dose determination. Dose determination after treatment interruptions 

lasting less than one 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 Xolair 

has been interrupted for one year or more. 

 

Doses should be adjusted for significant changes in body weight (see Tables 2 and 3). 

 

Special populations 

Elderly (65 years of age and older) 

There are limited data available on the use of Xolair in patients older than 65 years but there is no 

evidence that elderly patients require a different dose from younger adult patients. 

 

Renal or hepatic impairment 

There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics 

of Xolair. Because omalizumab clearance at clinical doses is dominated by the reticular endothelial 

system (RES) it is unlikely to be altered by renal or hepatic impairment. While no particular dose 

adjustment is recommended for these patients, Xolair should be administered with caution (see 

section 4.4). 

 

Paediatric population 

In allergic asthma, the safety and efficacy of Xolair in patients below the age of 6 years have not been 

established. No data are available. 

 

In CRSwNP, the safety and efficacy of Xolair in patients below the age of 18 years have not been 

established. 

 

Method of administration 

 

For subcutaneous administration only. Xolair must not be administered by the intravenous or 

intramuscular route. 

 

Doses of more than 150 mg (Table 1) should be divided across two or more injection sites. 

 

There is limited experience with self-administration of Xolair powder and solvent for solution for 

injection. Therefore, treatment with this formulation is intended to be administered by a healthcare 

provider only. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6 and 

also information for the healthcare professional section of the package leaflet. 



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4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 
 

Traceability 

 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

General 

 

Xolair is not indicated for the treatment of acute asthma exacerbations, acute bronchospasm or status 

asthmaticus. 

 

Xolair has not been studied in patients with hyperimmunoglobulin E syndrome or allergic 

bronchopulmonary aspergillosis or for the prevention of anaphylactic reactions, including those 

provoked by food allergy, atopic dermatitis, or allergic rhinitis. Xolair is not indicated for the 

treatment of these conditions. 

 

Xolair therapy has not been studied in patients with autoimmune diseases, immune complex-mediated 

conditions, or pre-existing renal or hepatic impairment (see section 4.2). Caution should be exercised 

when administering Xolair in these patient populations. 

 

Abrupt discontinuation of systemic or inhaled corticosteroids after initiation of Xolair therapy in 

allergic asthma or CRSwNP is not recommended. Decreases in corticosteroids should be performed 

under the direct supervision of a physician and may need to be performed gradually. 

 

Immune system disorders 

 

Allergic reactions type I 

Type I local or systemic allergic reactions, including anaphylaxis and anaphylactic shock, may occur 

when taking omalizumab, even after a long duration of treatment. However, most of these reactions 

occurred within 2 hours after the first and subsequent injections of Xolair but some started beyond 

2 hours and even beyond 24 hours after the injection. The majority of anaphylactic reactions occurred 

within the first 3 doses of Xolair. A history of anaphylaxis unrelated to omalizumab may be a risk 

factor for anaphylaxis following Xolair administration. Therefore medicinal products for the treatment 

of anaphylactic reactions should always be available for immediate use following administration of 

Xolair. If an anaphylactic or other serious allergic reaction occurs, administration of Xolair must be 

discontinued immediately, and appropriate therapy initiated. Patients should be informed that such 

reactions are possible, and prompt medical attention should be sought if allergic reactions occur. 

 

Antibodies to omalizumab have been detected in a low number of patients in clinical trials (see 

section 4.8). The clinical relevance of anti-Xolair antibodies is not well understood. 

 

Serum sickness 

Serum sickness and serum sickness-like reactions, which are delayed allergic type III reactions, have 

been seen in patients treated with humanised monoclonal antibodies including omalizumab. The 

suggested pathophysiologic mechanism includes immune-complex formation and deposition due to 

development of antibodies against omalizumab. The onset has typically been 1-5 days after 

administration of the first or subsequent injections, also after long duration of treatment. Symptoms 

suggestive of serum sickness include arthritis/arthralgias, rash (urticaria or other forms), fever and 

lymphadenopathy. Antihistamines and corticosteroids may be useful for preventing or treating this 

disorder, and patients should be advised to report any suspected symptoms. 

 



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Churg-Strauss syndrome and hypereosinophilic syndrome 

Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or allergic 

eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), both of which are usually treated 

with systemic corticosteroids. 

 

In rare cases, patients on therapy with anti-asthma medicinal products, including omalizumab, may 

present or develop systemic eosinophilia and vasculitis. These events are commonly associated with 

the reduction of oral corticosteroid therapy. 

 

In these patients, physicians should be alert to the development of marked eosinophilia, vasculitic 

rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac complications, and/or 

neuropathy. 

 

Discontinuation of omalizumab should be considered in all severe cases with the above mentioned 

immune system disorders. 

 

Parasitic (helminth) infections 

 

IgE may be involved in the immunological response to some helminth infections. In patients at chronic 

high risk of helminth infection, a placebo-controlled trial showed a slight increase in infection rate 

with omalizumab, although the course, severity, and response to treatment of infection were unaltered. 

The helminth infection rate in the overall clinical programme, which was not designed to detect such 

infections, was less than 1 in 1,000 patients. However, caution may be warranted in patients at high 

risk of helminth infection, in particular when travelling to areas where helminthic infections are 

endemic. If patients do not respond to recommended anti-helminth treatment, discontinuation of 

Xolair should be considered. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Since IgE may be involved in the immunological response to some helminth infections, Xolair may 

indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic 

infections (see section 4.4). 

 

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 Xolair. There is no pharmacological reason 

to expect that commonly prescribed medicinal products used in the treatment of asthma or CRSwNP 

will interact with omalizumab. 

 

Allergic asthma 

 

In clinical studies Xolair 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 Xolair was altered with these other 

commonly used anti-asthma medicinal products. Limited data are available on the use of Xolair in 

combination with specific immunotherapy (hypo-sensitisation therapy). In a clinical trial where Xolair 

was co-administered with immunotherapy, the safety and efficacy of Xolair in combination with 

specific immunotherapy were found to be no different to that of Xolair alone. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

In clinical studies Xolair was used in conjunction with intranasal mometasone spray as per protocol. 

Other commonly used concomitant medicinal products included other intranasal corticosteroids, 

bronchodilators, antihistamines, leukotriene receptor antagonists, adrenergics/sympathomimetics and 

local nasal anaesthetics. There was no indication that the safety of Xolair was altered by the 

concomitant use of these other commonly used medicinal products. 

 



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4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) based on 

pregnancy registry and post-marketing spontaneous reports, indicates no malformative or 

foeto/neonatal toxicity. A prospective pregnancy registry study (EXPECT) in 250 pregnant women 

with asthma exposed to Xolair showed the prevalence of major congenital anomalies was similar 

(8.1% vs. 8.9%) between EXPECT and disease-matched (moderate and severe asthma) patients. The 

interpretation of data may be impacted due to methodological limitations of the study, including small 

sample size and non-randomised design. 

 

Omalizumab crosses the placental barrier. However, animal studies do not indicate either direct or 

indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

 

Omalizumab has been associated with age-dependent decreases in blood platelets in non-human 

primates, with a greater relative sensitivity in juvenile animals (see section 5.3). 

 

If clinically needed, the use of Xolair may be considered during pregnancy. 

 

Breast-feeding 

 

Immunoglobulins G (IgGs) are present in human milk and therefore it is expected that omalizumab 

will be present in human milk. Available data in non-human primates have shown excretion of 

omalizumab into milk (see section 5.3). 

 

The EXPECT study, with 154 infants who had been exposed to Xolair during pregnancy and through 

breast-feeding did not indicate adverse effects on the breast-fed infant. The interpretation of data may 

be impacted due to methodological limitations of the study, including small sample size and non-

randomised design. 

 

Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability. 

No effects on the breast-fed newborns/infants are anticipated. Consequently, if clinically needed, the 

use of Xolair may be considered during breast-feeding. 

 

Fertility 

 

There are no human fertility data for omalizumab. In specifically-designed non-clinical fertility studies 

in non-human primates, including mating studies, no impairment of male or female fertility was 

observed following repeated dosing with omalizumab at dose levels up to 75 mg/kg. Furthermore, no 

genotoxic effects were observed in a separate non-clinical genotoxicity study. 

 

4.7 Effects on ability to drive and use machines 
 

Xolair has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Summary of the safety profile 

During allergic asthma clinical trials in adult and adolescent patients 12 years of age and older, the 

most commonly reported adverse reactions were headaches and injection site reactions, including 

injection site pain, swelling, erythema and pruritus. In clinical trials in children 6 to <12 years of age, 

the most commonly reported adverse reactions were headache, pyrexia and upper abdominal pain. 

Most of the reactions were mild or moderate in severity. In clinical trials in patients ≥18 years of age 



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in CRSwNP, the most commonly reported adverse reactions were headache, dizziness, arthralgia, 

abdominal pain upper and injection site reactions. 

 

Tabulated list of adverse reactions 

Table 4 lists the adverse reactions recorded in clinical studies in the total allergic asthma and CRSwNP 

safety population treated with Xolair by MedDRA system organ class and frequency. Within each 

frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency 

categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to 

<1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Reactions reported in the post-

marketing setting are listed with frequency not known (cannot be estimated from the available data). 

 

Table 4 Adverse reactions in allergic asthma and CRSwNP 

 

Infections and infestations 

Uncommon Pharyngitis 

Rare Parasitic infection 

Blood and lymphatic system disorders 

Not known Idiopathic thrombocytopenia, including severe cases 

Immune system disorders 

Rare Anaphylactic reaction, other serious allergic conditions, anti-

omalizumab antibody development 

Not known Serum sickness, may include fever and lymphadenopathy 

Nervous system disorders 

Common Headache* 

Uncommon Syncope, paraesthesia, somnolence, dizziness# 

Vascular disorders 

Uncommon Postural hypotension, flushing 

Respiratory, thoracic and mediastinal disorders 

Uncommon Allergic bronchospasm, coughing 

Rare Laryngoedema 

Not known Allergic granulomatous vasculitis (i.e. Churg-Strauss syndrome) 

Gastrointestinal disorders 

Common Abdominal pain upper**,# 

Uncommon Dyspeptic signs and symptoms, diarrhoea, nausea 

Skin and subcutaneous tissue disorders 

Uncommon Photosensitivity, urticaria, rash, pruritus 

Rare Angioedema 

Not known Alopecia 

Musculoskeletal and connective tissue disorders 

Common Athralgia† 

Rare Systemic lupus erythematosus (SLE) 

Not known Myalgia, joint swelling 

General disorders and administration site conditions 

Very common Pyrexia** 

Common Injection site reactions such as swelling, erythema, pain, pruritus 

Uncommon Influenza-like illness, swelling arms, weight increase, fatigue 

*: Very common in children 6 to <12 years of age 

**: In children 6 to <12 years of age 
#: Common in nasal polyp trials 

†: Unknown in allergic asthma trials 

 

  



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Description of selected adverse reactions 

 

Immune system disorders 

For further information, see section 4.4. 

 

Anaphylaxis 

Anaphylactic reactions were rare in clinical trials. However, post-marketing data following a 

cumulative search in the safety database retrieved a total of 898 anaphylaxis cases. Based on an 

estimated exposure of 566,923 patient treatment years, this results in a reporting rate of approximately 

0.20%. 

 

Arterial thromboembolic events (ATE) 

In controlled clinical trials and during interim analyses of an observational study, a numerical 

imbalance of ATE was observed. The definition of the composite endpoint ATE included stroke, 

transient ischaemic attack, myocardial infarction, unstable angina, and cardiovascular death (including 

death from unknown cause). In the final analysis of the observational study, the rate of ATE per 1,000 

patient years was 7.52 (115/15,286 patient years) for Xolair-treated patients and 5.12 (51/9,963 patient 

years) for control patients. In a multivariate analysis controlling for available baseline cardiovascular 

risk factors, the hazard ratio was 1.32 (95% confidence interval 0.91-1.91). In a separate analysis of 

pooled clinical trials, which included all randomised double-blind, placebo-controlled clinical trials 

lasting 8 or more weeks, the rate of ATE per 1,000 patient years was 2.69 (5/1,856 patient years) for 

Xolair-treated patients and 2.38 (4/1,680 patient years) for placebo patients (rate ratio 1.13, 95% 

confidence interval 0.24-5.71). 

 

Platelets 

In clinical trials few patients had platelet counts below the lower limit of the normal laboratory range. 

None of these changes were associated with bleeding episodes or a decrease in haemoglobin. No 

pattern of persistent decrease in platelet counts, as observed in non-human primates (see section 5.3), 

has been reported in humans (patients above 6 years of age), even though isolated cases of idiopathic 

thrombocytopenia, including severe cases, have been reported in the post-marketing setting. 

 

Parasitic infections 

In patients at chronic high risk of helminth infection, a placebo-controlled trial showed a slight 

numerical increase in infection rate with omalizumab that was not statistically significant. The course, 

severity, and response to treatment of infections were unaltered (see section 4.4). 

 

Systemic lupus erythematosus 

Clinical trial and post-marketing cases of systemic lupus erythematosus (SLE) have been reported in 

patients with moderate to severe asthma and CSU. The pathogenesis of SLE is not well understood. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Maximum tolerated dose of Xolair has not been determined. Single intravenous doses up to 4,000 mg 

have been administered to patients without evidence of dose-limiting toxicities. The highest 

cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not 

result in any untoward acute effects. 

 

If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. 

Medical treatment should be sought and instituted appropriately. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


12 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for 

obstructive airway diseases, ATC code: R03DX05 

 

Omalizumab is a recombinant DNA-derived humanised monoclonal antibody that selectively binds to 

human immunoglobulin E (IgE). The antibody is an IgG1 kappa that contains human framework 

regions with the complementary-determining regions of a murine parent antibody that binds to IgE. 

 

Mechanism of action 

 

Omalizumab binds to IgE and prevents binding of IgE to FcRI (high-affinity IgE receptor) on 

basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the 

allergic cascade. Treatment of atopic subjects with omalizumab resulted in a marked down-regulation 

of FcRI receptors on basophils. Treatment with Xolair inhibits IgE-mediated inflammation, as 

evidenced by reduced blood and tissue eosinophils and reduced inflammatory mediators, including IL-

4, IL-5, and IL-13 by innate, adaptive and non-immune cells. 

 

Pharmacodynamic effects 

 

Allergic asthma 

The in vitro histamine release from basophils isolated from Xolair-treated subjects was reduced by 

approximately 90% following stimulation with an allergen compared to pre-treatment values. 

 

In clinical studies in allergic asthma patients, serum free IgE levels were reduced in a dose-dependent 

manner within one hour following the first dose and maintained between doses. One year after 

discontinuation of Xolair dosing, the IgE levels had returned to pre-treatment levels with no observed 

rebound in IgE levels after washout of the medicinal product. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical studies in patients with CRSwNP, Xolair treatment led to a reduction in serum free IgE 

(approx. 95%) and an increase in serum total IgE levels, to a similar extent as observed in patients 

with allergic asthma. Total IgE levels in serum increased due to the formation of omalizumab-IgE 

complexes that have a slower elimination rate compared with free IgE. 

 

Clinical efficacy and safety 

 

Allergic asthma 

Adults and adolescents ≥12 years of age 

The efficacy and safety of Xolair were demonstrated in a 28-week double-blind placebo-controlled 

study (study 1) involving 419 severe allergic asthmatics, ages 12-79 years, who had reduced lung 

function (FEV1 40-80% predicted) and poor asthma symptom control despite receiving high dose 

inhaled corticosteroids and a long-acting beta2-agonist. Eligible patients had experienced multiple 

asthma exacerbations requiring systemic corticosteroid treatment or had been hospitalised or attended 

an emergency room due to a severe asthma exacerbation in the past year despite continuous treatment 

with high-dose inhaled corticosteroids and a long-acting beta2-agonist. Subcutaneous Xolair or 

placebo were administered as add-on therapy to >1,000 micrograms beclomethasone dipropionate (or 

equivalent) plus a long-acting beta2-agonist. Oral corticosteroid, theophylline and leukotriene-

modifier maintenance therapies were allowed (22%, 27%, and 35% of patients, respectively). 

 



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The rate of asthma exacerbations requiring treatment with bursts of systemic corticosteroids was the 

primary endpoint. Omalizumab reduced the rate of asthma exacerbations by 19% (p = 0.153). Further 

evaluations which did show statistical significance (p<0.05) in favour of Xolair included reductions in 

severe exacerbations (where patient’s lung function was reduced to below 60% of personal best and 

requiring systemic corticosteroids) and asthma-related emergency visits (comprised of 

hospitalisations, emergency room, and unscheduled doctor visits), and improvements in Physician’s 

overall assessment of treatment effectiveness, Asthma-related Quality of Life (AQL), asthma 

symptoms and lung function. 

 

In a subgroup analysis, patients with pre-treatment total IgE ≥76 IU/ml were more likely to experience 

clinically meaningful benefit to Xolair. In these patients in study 1 Xolair reduced the rate of asthma 

exacerbations by 40% (p = 0.002). In addition more patients had clinically meaningful responses in the 

total IgE ≥76 IU/ml population across the Xolair severe asthma programme. Table 5 includes results in 

the study 1 population. 

 

Table 5 Results of study 1 

 

 Whole study 1 population 

 Xolair 

N=209 

Placebo 

N=210 

Asthma exacerbations   

Rate per 28-week period 0.74 0.92 

% reduction, p-value for rate ratio 19.4%, p = 0.153 

Severe asthma exacerbations   

Rate per 28-week period 0.24 0.48 

% reduction, p-value for rate ratio 50.1%, p = 0.002 

Emergency visits   

Rate per 28-week period 0.24 0.43 

% reduction, p-value for rate ratio 43.9%, p = 0.038 

Physician’s overall assessment   

% responders* 60.5% 42.8% 

p-value** <0.001 

AQL improvement   

% of patients ≥0.5 improvement 60.8% 47.8% 

p-value 0.008 

* marked improvement or complete control 

** p-value for overall distribution of assessment 

 

Study 2 assessed the efficacy and safety of Xolair in a population of 312 severe allergic asthmatics 

which matched the population in study 1. Treatment with Xolair in this open label study led to a 61% 

reduction in clinically significant asthma exacerbation rate compared to current asthma therapy alone. 

 

Four additional large placebo-controlled supportive studies of 28 to 52 weeks duration in 1,722 adults 

and adolescents (studies 3, 4, 5, 6) assessed the efficacy and safety of Xolair in patients with severe 

persistent asthma. Most patients were inadequately controlled but were receiving less concomitant 

asthma therapy than patients in studies 1 or 2. Studies 3-5 used exacerbation as primary endpoint, 

whereas study 6 primarily evaluated inhaled corticosteroid sparing. 

 

In studies 3, 4 and 5 patients treated with Xolair had respective reductions in asthma exacerbation 

rates of 37.5% (p = 0.027), 40.3% (p<0.001) and 57.6% (p<0.001) compared to placebo. 

 

In study 6, significantly more severe allergic asthma patients on Xolair were able to reduce their 

fluticasone dose to 500 micrograms/day without deterioration of asthma control (60.3%) compared to 

the placebo group (45.8%, p<0.05). 

 



14 

Quality of life scores were measured using the Juniper Asthma-related Quality of Life Questionnaire. 

For all six studies there was a statistically significant improvement from baseline in quality of life 

scores for Xolair patients versus the placebo or control group. 

 

Physician’s overall assessment of treatment effectiveness: 

Physician’s overall assessment was performed in five of the above studies as a broad measure of 

asthma control performed by the treating physician. The physician was able to take into account PEF 

(peak expiratory flow), day and night time symptoms, rescue medication use, spirometry and 

exacerbations. In all five studies a significantly greater proportion of Xolair treated patients were 

judged to have achieved either a marked improvement or complete control of their asthma compared 

to placebo patients. 

 

Children 6 to <12 years of age 

The primary support for safety and efficacy of Xolair in the group aged 6 to <12 years comes from one 

randomised, double-blind, placebo-controlled, multi-centre trial (study 7). 

 

Study 7 was a placebo-controlled trial which included a specific subgroup (n=235) of patients as 

defined in the present indication, who were treated with high-dose inhaled corticosteroids 

(≥500 µg/day fluticasone equivalent) plus long-acting beta agonist. 

 

A clinically significant exacerbation was defined as a worsening of asthma symptoms as judged 

clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least 

3 days and/or treatment with rescue systemic (oral or intravenous) corticosteroids for at least 3 days. 

 

In the specific subgroup of patients on high dose inhaled corticosteroids, the omalizumab group had a 

statistically significantly lower rate of clinically significant asthma exacerbations than the placebo 

group. At 24 weeks, the difference in rates between treatment groups represented a 34% (rate ratio 

0.662, p = 0.047) decrease relative to placebo for omalizumab patients. In the second double-blind 28-

week treatment period the difference in rates between treatment groups represented a 63% (rate ratio 

0.37, p<0.001) decrease relative to placebo for omalizumab patients. 

 

During the 52-week double-blind treatment period (including the 24-week fixed-dose steroid phase 

and the 28-week steroid adjustment phase) the difference in rates between treatment groups 

represented a 50% (rate ratio 0.504, p<0.001) relative decrease in exacerbations for omalizumab 

patients. 

 

The omalizumab group showed greater decreases in beta-agonist rescue medication use than the 

placebo group at the end of the 52-week treatment period, although the difference between treatment 

groups was not statistically significant. For the global evaluation of treatment effectiveness at the end 

of the 52-week double-blind treatment period in the subgroup of severe patients on high-dose inhaled 

corticosteroids plus long-acting beta agonists, the proportion of patients rated as having ‘excellent’ 

treatment effectiveness was higher, and the proportions having ‘moderate’ or ‘poor’ treatment 

effectiveness lower in the omalizumab group compared to the placebo group; the difference between 

groups was statistically significant (p<0.001), while there were no differences between the 

omalizumab and placebo groups for patients’ subjective Quality of Life ratings. 

 

  



15 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

The safety and efficacy of Xolair were evaluated in two randomised, double-blind, placebo-controlled 

trials in patients with CRSwNP (Table 7). Patients received Xolair or placebo subcutaneously every 2 

or 4 weeks (see section 4.2). All patients received background intranasal mometasone therapy 

throughout the study. Prior sino-nasal surgery or prior systemic corticosteroid usage were not required 

for inclusion in the studies. Patients received Xolair or placebo for 24 weeks followed by a 4-week 

follow-up period. Demographics and baseline characteristics, including allergic comorbidities, are 

described in Table 6. 

 

Table 6 Demographics and baseline characteristics of nasal polyp studies 

 
Parameter Nasal polyp study 1 

N=138 

Nasal polyp study 2 

N=127 

Mean age (years) (SD) 51.0 (13.2) 50.1 (11.9) 

% Male 63.8 65.4 

Patients with systemic 

corticosteroid use in the 

previous year (%) 

18.8 26.0 

Bilateral endoscopic nasal 

polyp score (NPS): mean (SD), 

range 0-8 

6.2 (1.0) 6.3 (0.9) 

Nasal congestion score (NCS): 

mean (SD), range 0-3 

2.4 (0.6) 2.3 (0.7) 

Sense of smell score: mean 

(SD), range 0-3 

2.7 (0.7) 2.7 (0.7) 

SNOT-22 total score: mean 

(SD) range 0-110 

60.1 (17.7) 59.5 (19.3) 

Blood eosinophils (cells/µl): 

mean (SD) 

346.1 (284.1) 334.6 (187.6) 

Total IgE IU/ml: mean (SD) 160.9 (139.6) 190.2 (200.5) 

Asthma (%) 53.6 60.6 

 Mild (%) 37.8 32.5 

 Moderate (%) 58.1 58.4 

 Severe (%) 4.1 9.1 

Aspirin exacerbated respiratory 

disease (%) 

19.6 35.4 

Allergic rhinitis 43.5 42.5 

SD = standard deviation; SNOT-22 = Sino-Nasal Outcome Test 22 Questionnaire; IgE = 

Immunoglobulin E; IU = international units. For NPS, NCS, and SNOT-22 higher scores indicate 

greater disease severity. 

 

  



16 

The co-primary endpoints were bilateral nasal polyps score (NPS) and average daily nasal congestion 

score (NCS) at Week 24. In both nasal polyp studies 1 and 2, patients who received Xolair had 

statistically significant greater improvements from baseline at Week 24 in NPS and weekly average 

NCS than patients who received placebo. Results from nasal polyp studies 1 and 2 are shown in 

Table 7. 

 

Table 7 Change from baseline at Week 24 in clinical scores from nasal polyp study 1, nasal 
polyp study 2, and pooled data 

 

 Nasal polyp 

study 1 

Nasal polyp 

study 2 

Nasal polyp 

pooled results 

 Placebo Xolair Placebo Xolair Placebo Xolair 

N 66 72 65 62 131 134 

Nasal polyp score    

Baseline mean 6.32 6.19 6.09 6.44 6.21 6.31 

LS mean change at 

Week 24 

0.06 -1.08 -0.31 -0.90 -0.13 -0.99 

Difference (95%) 

CI  

-1.14 (-1.59, -0.69) 

 

-0.59 (-1.05, -0.12) 

 

-0.86 (-1.18, -0.54) 

p-value <0.0001 0.0140 <0.0001 

7-day average of 

daily nasal 

congestion score 

   

Baseline mean 2.46 2.40 2.29 2.26 2.38 2.34 

LS mean change at 

Week 24 

-0.35 -0.89 -0.20 -0.70 -0.28 -0.80 

Difference (95%) 

CI 

-0.55 (-0.84, -0.25) 

 

-0.50 (-0.80, -0.19) 

 

-0.52 (-0.73, -0.31) 

p-value 0.0004 0.0017 <0.0001 

TNSS    

Baseline mean 9.33 8.56 8.73 8.37 9.03 8.47 

LS mean change at 

Week 24 

-1.06 -2.97 -0.44 -2.53 -0.77 -2.75 

Difference (95%) -1.91 (-2.85, -0.96) -2.09 (-3.00, -1.18)  -1.98 (-2.63, -1.33) 

p-value 0.0001 <0.0001 <0.0001 

SNOT-22    

Baseline mean 60.26 59.82 59.80 59.21 60.03 59.54 

LS mean change at 

Week 24 

-8.58 -24.70 -6.55 -21.59 -7.73 -23.10 

Difference (95%) -16.12 (-21.86, -10.38) -15.04 (-21.26, -8.82) -15.36 (-19.57, -11.16) 

p-value <0.0001 <0.0001 <0.0001 

(MID = 8.9)    

UPSIT    

Baseline mean 13.56 12.78 13.27 12.87 13.41 12.82 

LS mean change at 

Week 24 

0.63 4.44 0.44 4.31 0.54 4.38 

Difference (95%) 3.81 (1.38, 6.24) 3.86 (1.57, 6.15) 3.84 (2.17, 5.51) 

p-value 0.0024 0.0011 <0.0001 

LS=least-square; CI = confidence interval; TNSS = Total nasal symptom score; SNOT-22 = Sino-

Nasal Outcome Test 22 Questionnaire; UPSIT = University of Pennsylvania Smell Identification 

Test; MID = minimal important difference. 



17 

 

Figure 1 Mean change from baseline in nasal congestion score and mean change from 

baseline in nasal polyp score by treatment group in nasal polyp study 1 and study 2 

 

 
 

In a pre-specified pooled analysis of rescue treatment (systemic corticosteroids for 3 consecutive 

days or nasal polypectomy) during the 24-week treatment period, the proportion of patients requiring 

rescue treatment was lower in Xolair compared to placebo (2.3% versus 6.2%, respectively). The 

odds-ratio of having taken rescue treatment in Xolair compared to placebo was 0.38 (95% CI: 0.10, 

1.49). There were no sino-nasal surgeries reported in either study. 

 

5.2 Pharmacokinetic properties 
 

The pharmacokinetics of omalizumab have been studied in adult and adolescent patients with allergic 

asthma as well as in adult patients with CRSwNP. The general pharmacokinetic characteristics of 

omalizumab are similar in these patient populations. 

 

Absorption 

 

After subcutaneous administration, omalizumab is absorbed with an average absolute bioavailability 

of 62%. Following a single subcutaneous dose in adult and adolescent patients with asthma, 

omalizumab was absorbed slowly, reaching peak serum concentrations after an average of 7-8 days. 

The pharmacokinetics of omalizumab are linear at doses greater than 0.5 mg/kg. Following multiple 

doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady 

state were up to 6-fold of those after the first dose. 

 

Administration of Xolair manufactured as a lyophilised or liquid formulation resulted in similar serum 

concentration-time profiles of omalizumab. 

 

Distribution 

 

In vitro, omalizumab forms complexes of limited size with IgE. Precipitating complexes and 

complexes larger than one million Daltons in molecular weight are not observed in vitro or in vivo. 

The apparent volume of distribution in patients following subcutaneous administration was 

78 ± 32 ml/kg. 

 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Secondary 

efficacy analysis 

Secondary 

efficacy analysis 

Primary efficacy 

analysis 

Primary efficacy 

analysis 

Baseline 24 20 16 12 8 4 4 8 12 16 20 24 

Week Week 

Baseline 
M

ea
n
 c

h
an

g
e 

fr
o
m

 b
as

el
in

e 
in

 N
as

al
 C

o
n
g
es

ti
o
n
 S

co
re

 

M
ea

n
 c

h
an

g
e 

fr
o
m

 b
as

el
in

e 
in

 N
as

al
 P

o
ly

p
 S

co
re

 

0.25 0.25 

0.00 0.00 

-0.25 -0.25 

-0.50 -0.50 

-0.75 -0.75 

-1.00 -1.00 

-1.25 -1.25 



18 

Elimination 

 

Clearance of omalizumab involves IgG clearance processes as well as clearance via specific binding 

and complex formation with its target ligand, IgE. Liver elimination of IgG includes degradation in the 

reticuloendothelial system and endothelial cells. Intact IgG is also excreted in bile. In asthma patients 

the omalizumab serum elimination half-life averaged 26 days, with apparent clearance averaging 

2.4  1.1 ml/kg/day. In addition, doubling of body weight approximately doubled apparent clearance. 

 

Characteristics in patient populations 

 
Age, Race/Ethnicity, Gender, Body Mass Index 

The population pharmacokinetics of Xolair were analysed to evaluate the effects of demographic 

characteristics. Analyses of these limited data suggest that no dose adjustments are necessary for age 

(6-76 years for patients with allergic asthma; 18 to 75 years for patients with CRSwNP), 

race/ethnicity, gender or Body Mass Index (see section 4.2). 

 

Renal and hepatic impairment 

There are no pharmacokinetic or pharmacodynamic data in patients with renal or hepatic impairment 

(see sections 4.2 and 4.4). 

 

5.3 Preclinical safety data 
 

The safety of omalizumab has been studied in the cynomolgus monkey, since omalizumab binds to 

cynomolgus and human IgE with similar affinity. Antibodies to omalizumab were detected in some 

monkeys following repeated subcutaneous or intravenous administration. However, no apparent 

toxicity, such as immune complex-mediated disease or complement-dependent cytotoxicity, was seen. 

There was no evidence of an anaphylactic response due to mast-cell degranulation in cynomolgus 

monkeys. 

 

Chronic administration of omalizumab at dose levels of up to 250 mg/kg (at least 14 times the highest 

recommended clinical dose in mg/kg according to the recommended dosing table) was well tolerated 

in non-human primates (both adult and juvenile animals), with the exception of a dose-related and age-

dependent decrease in blood platelets, with a greater sensitivity in juvenile animals. The serum 

concentration required to attain a 50% drop in platelets from baseline in adult cynomolgus monkeys 

was roughly 4- to 20-fold higher than anticipated maximum clinical serum concentrations. In addition, 

acute haemorrhage and inflammation were observed at injection sites in cynomolgus monkeys. 

 

Formal carcinogenicity studies have not been conducted with omalizumab. 

 

In reproduction studies in cynomolgus monkeys, subcutaneous doses up to 75 mg/kg per week (at least 

8 times the highest recommended clinical dose in mg/kg over a 4-week period) did not elicit maternal 

toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and did not 

elicit adverse effects on foetal or neonatal growth when administered throughout late gestation, 

delivery and nursing. 

 

Omalizumab is excreted in breast milk in cynomolgus monkeys. Milk levels of omalizumab were 

0.15% of the maternal serum concentration. 

 

 



19 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Powder 

 

Sucrose 

L-histidine 

L-histidine hydrochloride monohydrate 

Polysorbate 20 

 

Solvent 

 

Water for injections 

 

6.2 Incompatibilities 
 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

6.3 Shelf life 
 

4 years. 

 

After reconstitution 

 

The chemical and physical stability of the reconstituted medicinal product have been demonstrated for 

8 hours at 2°C to 8°C and for 4 hours at 30°C. 

 

From a microbiological point of view, the medicinal product should be used immediately after 

reconstitution. If not used immediately, in-use storage times and conditions prior to use are the 

responsibility of the user and would normally not be longer than 8 hours at 2°C to 8°C or 2 hours at 

25°C. 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 
 

Powder vial: Clear, colourless type I glass vial with a butyl rubber stopper and grey flip-off seal. 

 

Solvent ampoule: Clear, colourless type I glass ampoule containing 2 ml water for injections. 

 

Pack containing one vial of powder for solution for injection and one ampoule of water for injections. 

 

  



20 

6.6 Special precautions for disposal and other handling 
 

Xolair 75 mg powder for solution for injection is supplied in a single-use vial. 

 

From a microbiological point of view, the medicinal product should be used immediately after 

reconstitution (see section 6.3). 

 

The lyophilised medicinal product takes 15-20 minutes to dissolve, although in some cases it may take 

longer. The fully reconstituted medicinal product will appear clear to slightly opalescent, colourless to 

pale brownish-yellow and may have a few small bubbles or foam around the edge of the vial. Because 

of the viscosity of the reconstituted medicinal product care must be taken to withdraw all of the 

medicinal product from the vial before expelling any air or excess solution from the syringe in order to 

obtain the 0.6 ml. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 25 October 2005 

Date of latest renewal: 22 June 2015 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


21 

1. NAME OF THE MEDICINAL PRODUCT 
 

 

Xolair 150 mg powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains 150 mg of omalizumab*. 

 

After reconstitution one vial contains 125 mg/ml of omalizumab (150 mg in 1.2 ml). 

 

*Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology in 

a Chinese hamster ovary (CHO) mammalian cell line. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Powder and solvent for solution for injection. 

 

Powder: white to off-white lyophilisate 

Solvent: clear and colourless solution 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Allergic asthma 

 

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

 

Xolair treatment should only be considered for patients with convincing IgE (immunoglobulin E) 

mediated asthma (see section 4.2). 

 

Adults and adolescents (12 years of age and older) 

Xolair 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 high-

dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist. 

 

Children (6 to <12 years of age) 

Xolair 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 beta2-

agonist. 

 

  



22 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Xolair is indicated as an add-on therapy with intranasal corticosteroids (INC) for the treatment of 

adults (18 years and above) with severe CRSwNP for whom therapy with INC does not provide 

adequate disease control. 

 

Chronic spontaneous urticaria (CSU) 

 

Xolair is indicated as add-on therapy for the treatment of chronic spontaneous urticaria in adult and 

adolescent (12 years and above) patients with inadequate response to H1 antihistamine treatment. 

 

4.2 Posology and method of administration 
 

Xolair treatment should be initiated by physicians experienced in the diagnosis and treatment of severe 

persistent asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) or chronic spontaneous 

urticaria. 

 

Posology 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

Dosing for allergic asthma and CRSwNP follows the same dosing principles. The appropriate dose 

and frequency of Xolair for these conditions is determined by baseline IgE (IU/ml), measured before 

the start of treatment, and body weight (kg). Prior to administration of the initial dose, patients should 

have their IgE level determined by any commercial serum total IgE assay for their dose assignment. 

Based on these measurements, 75 to 600 mg of Xolair in 1 to 4 injections may be needed for each 

administration. 

 

Allergic asthma patients with baseline IgE lower than 76 IU/ml were less likely to experience benefit 

(see section 5.1). Prescribing physicians should ensure that adult and adolescent patients with IgE 

below 76 IU/ml and children (6 to < 12 years of age) with IgE below 200 IU/ml have unequivocal in 

vitro reactivity (RAST) to a perennial allergen before starting therapy. 

 

See Table 1 for a conversion chart and Tables 2 and 3 for the dose determination charts. 

 

Patients whose baseline IgE levels or body weight in kilograms are outside the limits of the dose table 

should not be given Xolair. 

 

The maximum recommended dose is 600 mg omalizumab every two weeks. 

 

  



23 

Table 1 Conversion from dose to number of vials, number of injections and total injection 

volume for each administration 

 

Dose (mg) Number of vials Number of injections Total injection volume (ml) 

 75 mg a 150 mg b   

75 1c 0 1 0.6 

150 0 1 1 1.2 

225 1c 1 2 1.8 

300 0 2 2 2.4 

375 1c 2 3 3.0 

450 0 3 3 3.6 

525 1c 3 4 4.2 

600 0 4 4 4.8 
a 0.6 ml = maximum delivered volume per vial (Xolair 75 mg). 
b 1.2 ml = maximum delivered volume per vial (Xolair 150 mg). 

c or use 0.6 ml from a 150 mg vial. 

 

Table 2 ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 4 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20- 

25* 

>25- 

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90-  

125 

>125-  

150 

30-100 75 75 75 150 150 150 150 150 300 300 

>100-200 150 150 150 300 300 300 300 300 450 600 

>200-300 150 150 225 300 300 450 450 450 600  

>300-400 225 225 300 450 450 450 600 600   

>400-500 225 300 450 450 600 600     

>500-600 300 300 450 600 600      

>600-700 300  450 600       

>700-800           

>800-900     ADMINISTRATION EVERY 2 WEEKS 

SEE TABLE 3 

 

>900-

1000 

     

>1000-

1100 

          

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 



24 

Table 3 ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 2 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20- 

25* 

>25- 

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90- 

125 

>125-

150 

30-100 ADMINISTRATION EVERY 4 WEEKS 

SEE TABLE 2 

     

>100-200      

>200-300          375 

>300-400         450 525 

>400-500       375 375 525 600 

>500-600      375 450 450 600  

>600-700  225   375 450 450 525   

>700-800 225 225 300 375 450 450 525 600   

>800-900 225 225 300 375 450 525 600    

>900-

1000 

225 300 375 450 525 600     

>1000-

1100 

225 300 375 450 600      

>1100-

1200 

300 300 450 525 600 Insufficient data to recommend a dose 

>1200-

1300 

300 375 450 525       

>1300-

1500 

300 375 525 600       

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 

  



25 

Treatment duration, monitoring and dose adjustments 

Allergic asthma 

Xolair is intended for long-term treatment. Clinical trials have demonstrated that it takes at least 

12-16 weeks for Xolair treatment to show effectiveness. At 16 weeks after commencing Xolair 

therapy patients should be assessed by their physician for treatment effectiveness before further 

injections are administered. The decision to continue Xolair following the 16-week timepoint, or on 

subsequent occasions, should be based on whether a marked improvement in overall asthma control is 

seen (see section 5.1, Physician’s overall assessment of treatment effectiveness). 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical trials for CRSwNP, changes in nasal polyps score (NPS) and nasal congestion score (NCS) 

were observed at 4 weeks. The need for continued therapy should be periodically reassessed based 

upon the patient’s disease severity and level of symptom control. 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

Discontinuation of Xolair treatment 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 one 

year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment 

cannot be used as a guide for dose determination. Dose determination after treatment interruptions 

lasting less than one 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 Xolair 

has been interrupted for one year or more. 

 

Doses should be adjusted for significant changes in body weight (see Tables 2 and 3). 

 

Chronic spontaneous urticaria (CSU) 

The recommended dose is 300 mg by subcutaneous injection every four weeks. 

 

Prescribers are advised to periodically reassess the need for continued therapy. 

 

Clinical trial experience of long-term treatment beyond 6 months in this indication is limited. 

 

Special populations 

Elderly (65 years of age and older) 

There are limited data available on the use of Xolair in patients older than 65 years but there is no 

evidence that elderly patients require a different dose from younger adult patients. 

 

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 the reticular 

endothelial system (RES) it is unlikely to be altered by renal or hepatic impairment. While no 

particular dose adjustment is recommended for these patients, Xolair should be administered with 

caution (see section 4.4). 

 

Paediatric population 

In allergic asthma, the safety and efficacy of Xolair in patients below the age of 6 years have not been 

established. No data are available. 

 

In CRSwNP, the safety and efficacy of Xolair in patients below the age of 18 years have not been 

established. 

 

In CSU, the safety and efficacy of Xolair in patients below the age of 12 years have not been 

established. 

 



26 

Method of administration 

 

For subcutaneous administration only. Xolair must not be administered by the intravenous or 

intramuscular route. 

 

Doses of more than 150 mg (Table 1) should be divided across two or more injection sites. 

 

There is limited experience with self-administration of Xolair powder and solvent for solution for 

injection. Therefore, treatment with this formulation is intended to be administered by a healthcare 

provider only. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6 and 

also information for the healthcare professional section of the package leaflet. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 
 

Traceability 

 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

General 

 

Xolair is not indicated for the treatment of acute asthma exacerbations, acute bronchospasm or status 

asthmaticus. 

 

Xolair has not been studied in patients with hyperimmunoglobulin E syndrome or allergic 

bronchopulmonary aspergillosis or for the prevention of anaphylactic reactions, including those 

provoked by food allergy, atopic dermatitis, or allergic rhinitis. Xolair is not indicated for the 

treatment of these conditions. 

 

Xolair therapy has not been studied in patients with autoimmune diseases, immune complex-mediated 

conditions, or pre-existing renal or hepatic impairment (see section 4.2). Caution should be exercised 

when administering Xolair in these patient populations. 

 

Abrupt discontinuation of systemic or inhaled corticosteroids after initiation of Xolair therapy in 

allergic asthma or CRSwNP is not recommended. Decreases in corticosteroids should be performed 

under the direct supervision of a physician and may need to be performed gradually. 

 

Immune system disorders 

 

Allergic reactions type I 

Type I local or systemic allergic reactions, including anaphylaxis and anaphylactic shock, may occur 

when taking omalizumab, even after a long duration of treatment. However, most of these reactions 

occurred within 2 hours after the first and subsequent injections of Xolair but some started beyond 

2 hours and even beyond 24 hours after the injection. The majority of anaphylactic reactions occurred 

within the first 3 doses of Xolair. A history of anaphylaxis unrelated to omalizumab may be a risk 

factor for anaphylaxis following Xolair administration. Therefore medicinal products for the treatment 

of anaphylactic reactions should always be available for immediate use following administration of 

Xolair. If an anaphylactic or other serious allergic reaction occurs, administration of Xolair must be 

discontinued immediately, and appropriate therapy initiated. Patients should be informed that such 

reactions are possible, and prompt medical attention should be sought if allergic reactions occur. 

 



27 

Antibodies to omalizumab have been detected in a low number of patients in clinical trials (see 

section 4.8). The clinical relevance of anti-Xolair antibodies is not well understood. 

 

Serum sickness 

Serum sickness and serum sickness-like reactions, which are delayed allergic type III reactions, have 

been seen in patients treated with humanised monoclonal antibodies including omalizumab. The 

suggested pathophysiologic mechanism includes immune-complex formation and deposition due to 

development of antibodies against omalizumab. The onset has typically been 1-5 days after 

administration of the first or subsequent injections, also after long duration of treatment. Symptoms 

suggestive of serum sickness include arthritis/arthralgias, rash (urticaria or other forms), fever and 

lymphadenopathy. Antihistamines and corticosteroids may be useful for preventing or treating this 

disorder, and patients should be advised to report any suspected symptoms. 

 

Churg-Strauss syndrome and hypereosinophilic syndrome 

Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or allergic 

eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), both of which are usually treated 

with systemic corticosteroids. 

 

In rare cases, patients on therapy with anti-asthma medicinal products, including omalizumab, may 

present or develop systemic eosinophilia and vasculitis. These events are commonly associated with 

the reduction of oral corticosteroid therapy. 

 

In these patients, physicians should be alert to the development of marked eosinophilia, vasculitic 

rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac complications, and/or 

neuropathy. 

 

Discontinuation of omalizumab should be considered in all severe cases with the above mentioned 

immune system disorders. 

 

Parasitic (helminth) infections 

 

IgE may be involved in the immunological response to some helminth infections. In patients at chronic 

high risk of helminth infection, a placebo-controlled trial in allergic patients showed a slight increase 

in infection rate with omalizumab, although the course, severity, and response to treatment of infection 

were unaltered. The helminth infection rate in the overall clinical programme, which was not designed 

to detect such infections, was less than 1 in 1,000 patients. However, caution may be warranted in 

patients at high risk of helminth infection, in particular when travelling to areas where helminthic 

infections are endemic. If patients do not respond to recommended anti-helminth treatment, 

discontinuation of Xolair should be considered. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Since IgE may be involved in the immunological response to some helmith infections, Xolair may 

indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic 

infections (see section 4.4). 

 

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 Xolair. There is no pharmacological reason 

to expect that commonly prescribed medicinal products used in the treatment of asthma, CRSwNP or 

CSU will interact with omalizumab. 

 



28 

Allergic asthma 

 

In clinical studies Xolair 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 Xolair was altered with these other 

commonly used anti-asthma medicinal products. Limited data are available on the use of Xolair in 

combination with specific immunotherapy (hypo-sensitisation therapy). In a clinical trial where Xolair 

was co-administered with immunotherapy, the safety and efficacy of Xolair in combination with 

specific immunotherapy were found to be no different to that of Xolair alone. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

In clinical studies Xolair was used in conjunction with intranasal mometasone spray as per protocol. 

Other commonly used concomitant medicinal products included other intranasal corticosteroids, 

bronchodilators, antihistamines, leukotriene receptor antagonists, adrenergics/sympathomimetics and 

local nasal anaesthetics. There was no indication that the safety of Xolair was altered by the 

concomitant use of these other commonly used medicinal products. 

 

Chronic spontaneous urticaria (CSU) 

 

In clinical studies in CSU, Xolair 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 (see section 5.2). 

 

Paediatric population 

 

Clinical studies in CSU included some patients aged 12 to 17 years taking Xolair in conjunction with 

antihistamines (anti-H1, anti-H2) and LTRAs. No studies have been performed in children under 

12 years. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) based on 

pregnancy registry and post-marketing spontaneous reports, indicates no malformative or 

foeto/neonatal toxicity. A prospective pregnancy registry study (EXPECT) in 250 pregnant women 

with asthma exposed to Xolair showed the prevalence of major congenital anomalies was similar 

(8.1% vs. 8.9%) between EXPECT and disease-matched (moderate and severe asthma) patients. The 

interpretation of data may be impacted due to methodological limitations of the study, including small 

sample size and non-randomised design. 

 

Omalizumab crosses the placental barrier. However, animal studies do not indicate either direct or 

indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

 

Omalizumab has been associated with age-dependent decreases in blood platelets in non-human 

primates, with a greater relative sensitivity in juvenile animals (see section 5.3). 

 

If clinically needed, the use of Xolair may be considered during pregnancy. 

 

  



29 

Breast-feeding 

 

Immunoglobulins G (IgGs) are present in human milk and therefore it is expected that omalizumab 

will be present in human milk. Available data in non-human primates have shown excretion of 

omalizumab into milk (see section 5.3). 

 

The EXPECT study, with 154 infants who had been exposed to Xolair during pregnancy and through 

breast-feeding did not indicate adverse effects on the breast-fed infant. The interpretation of data may 

be impacted due to methodological limitations of the study, including small sample size and non-

randomised design. 

 

Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability. 

No effects on the breast-fed newborns/infants are anticipated. Consequently, if clinically needed, the 

use of Xolair may be considered during breast-feeding. 

 

Fertility 

 

There are no human fertility data for omalizumab. In specifically-designed non-clinical fertility 

studies, in non-human primates including mating studies, no impairment of male or female fertility 

was observed following repeated dosing with omalizumab at dose levels up to 75 mg/kg. Furthermore, 

no genotoxic effects were observed in a separate non-clinical genotoxicity study. 

 

4.7 Effects on ability to drive and use machines 
 

Xolair has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Summary of safety profile 

During allergic asthma clinical trials in adult and adolescent patients 12 years of age and older, the 

most commonly reported adverse reactions were headaches and injection site reactions, including 

injection site pain, swelling, erythema and pruritus. In clinical trials in children 6 to <12 years of age, 

the most commonly reported adverse reactions were headache, pyrexia and upper abdominal pain. 

Most of the reactions were mild or moderate in severity. In clinical trials in patients ≥18 years of age 

in CRSwNP, the most commonly reported adverse reactions were headache, dizziness, arthralgia, 

abdominal pain upper and injection site reactions. 

 

Tabulated list of adverse reactions 

Table 4 lists the adverse reactions recorded in clinical studies in the total allergic asthma and CRSwNP 

safety population treated with Xolair by MedDRA system organ class and frequency. Within each 

frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency 

categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to 

<1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Reactions reported in the post-

marketing setting are listed with frequency not known (cannot be estimated from the available data). 

 

  



30 

Table 4 Adverse reactions in allergic asthma and CRSwNP 

 

Infections and infestations 

Uncommon Pharyngitis 

Rare Parasitic infection 

Blood and lymphatic system disorders 

Not known Idiopathic thrombocytopenia, including severe cases 

Immune system disorders 

Rare Anaphylactic reaction, other serious allergic conditions, anti-

omalizumab antibody development 

Not known Serum sickness, may include fever and lymphadenopathy 

Nervous system disorders 

Common Headache* 

Uncommon Syncope, paraesthesia, somnolence, dizziness# 

Vascular disorders 

Uncommon Postural hypotension, flushing 

Respiratory, thoracic and mediastinal disorders 

Uncommon Allergic bronchospasm, coughing 

Rare Laryngoedema 

Not known Allergic granulomatous vasculitis (i.e. Churg-Strauss syndrome) 

Gastrointestinal disorders 

Common Abdominal pain upper**,# 

Uncommon Dyspeptic signs and symptoms, diarrhoea, nausea 

Skin and subcutaneous tissue disorders 

Uncommon Photosensitivity, urticaria, rash, pruritus 

Rare Angioedema 

Not known Alopecia 

Musculoskeletal and connective tissue disorders 

Common Athralgia† 
Rare Systemic lupus erythematosus (SLE) 

Not known Myalgia, joint swelling 

General disorders and administration site conditions 

Very common Pyrexia** 

Common Injection site reactions such as swelling, erythema, pain, pruritus 

Uncommon Influenza-like illness, swelling arms, weight increase, fatigue 

*: Very common in children 6 to <12 years of age 

**: In children 6 to <12 years of age 
#: Common in nasal polyp trials 

†: Unknown in allergic asthma trials 

 

  



31 

Chronic spontaneous urticaria (CSU) 

 

Summary of safety profile 

The safety and tolerability of omalizumab were investigated with doses of 75 mg, 150 mg and 300 mg 

every four weeks in 975 CSU patients, 242 of whom received placebo. Overall, 733 patients were 

treated with omalizumab for up to 12 weeks and 490 patients for up to 24 weeks. Of those, 

412 patients were treated for up to 12 weeks and 333 patients were treated for up to 24 weeks at the 

300 mg dose. 

 

Tabulated list of adverse reactions 

A separate table (Table 5) shows the adverse reactions for the CSU indication resulting from 

differences in dosages and treatment populations (with significantly different risk factors, 

comorbidities, co-medications and ages [e.g. asthma trials included children from 6-12 years of age]). 

 

Table 5 lists the adverse reactions (events occurring in ≥1% of patients in any treatment group and 

≥2% more frequently in any omalizumab treatment group than with placebo (after medical review)) 

reported with 300 mg in the three pooled phase III studies. The adverse reactions presented are divided 

into two groups: those identified in the 12-week and the 24-week treatment periods. 

 

The adverse reactions are listed by MedDRA system organ class. Within each system organ class, the 

adverse reactions are ranked by frequency, with the most frequent reactions listed first. The 

corresponding frequency category for each adverse reaction is based on the following convention: 

very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 

to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from the available data). 

 

Table 5 Adverse reactions from the pooled CSU safety database (day 1 to week 24) at 

300 mg omalizumab 

 

12-Week 
Omalizumab studies 1, 2 and 3 Pooled Frequency category 

Placebo N=242 300 mg N=412  

Infections and infestations 

Sinusitis 5 (2.1%) 20 (4.9%) Common 

Nervous system disorders 

Headache 7 (2.9%) 25 (6.1%) Common 

Musculoskeletal and connective tissue disorders 

Arthralgia 1 (0.4%) 12 (2.9%) Common 

General disorder and administration site conditions 
Injection site reaction* 2 (0.8%) 11 (2.7%) Common 

24-Week 
Omalizumab studies 1 and 3 Pooled Frequency category 

Placebo N=163 300 mg N=333  

Infections and infestations 
Upper respiratory tract 

infection 
5 (3.1%) 19 (5.7%) Common 

* Despite not showing a 2% difference to placebo, injection site reactions were included as all cases 

were assessed causally related to study treatment. 

 

  



32 

Description of selected adverse reactions 

 

Immune system disorders 

For further information, see section 4.4. 

 

Anaphylaxis 

Anaphylactic reactions were rare in clinical trials. However, post-marketing data following a 

cumulative search in the safety database retrieved a total of 898 anaphylaxis cases. Based on an 

estimated exposure of 566,923 patient treatment years, this results in a reporting rate of approximately 

0.20%. 

 

Arterial thromboembolic events (ATE) 

In controlled clinical trials and during interim analyses of an observational study, a numerical 

imbalance of ATE was observed. The definition of the composite endpoint ATE included stroke, 

transient ischaemic attack, myocardial infarction, unstable angina, and cardiovascular death (including 

death from unknown cause). In the final analysis of the observational study, the rate of ATE per 1,000 

patient years was 7.52 (115/15,286 patient years) for Xolair-treated patients and 5.12 (51/9,963 patient 

years) for control patients. In a multivariate analysis controlling for available baseline cardiovascular 

risk factors, the hazard ratio was 1.32 (95% confidence interval 0.91-1.91). In a separate analysis of 

pooled clinical trials, which included all randomised double-blind, placebo-controlled clinical trials 

lasting 8 or more weeks, the rate of ATE per 1,000 patient years was 2.69 (5/1,856 patient years) for 

Xolair-treated patients and 2.38 (4/1,680 patient years) for placebo patients (rate ratio 1.13, 95% 

confidence interval 0.24-5.71). 

 

Platelets 

In clinical trials few patients had platelet counts below the lower limit of the normal laboratory range. 

None of these changes were associated with bleeding episodes or a decrease in haemoglobin. No 

pattern of persistent decrease in platelet counts, as observed in non-human primates (see section 5.3), 

has been reported in humans (patients above 6 years of age), even though isolated cases of idiopathic 

thrombocytopenia, including severe cases, have been reported in the post-marketing setting. 

 

Parasitic infections 

In allergic patients at chronic high risk of helminth infection, a placebo-controlled trial showed a slight 

numerical increase in infection rate with omalizumab that was not statistically significant. The course, 

severity, and response to treatment of infections were unaltered (see section 4.4). 

 

Systemic lupus erythematosus 

Clinical trial and post-marketing cases of systemic lupus erythematosus (SLE) have been reported in 

patients with moderate to severe asthma and CSU. The pathogenesis of SLE is not well understood. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Maximum tolerated dose of Xolair has not been determined. Single intravenous doses up to 4,000 mg 

have been administered to patients without evidence of dose-limiting toxicities. The highest 

cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not 

result in any untoward acute effects. 

 

If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. 

Medical treatment should be sought and instituted appropriately. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


33 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for 

obstructive airway diseases, ATC code: R03DX05 

 

Omalizumab is a recombinant DNA-derived humanised monoclonal antibody that selectively binds to 

human immunoglobulin E (IgE). The antibody is an IgG1 kappa that contains human framework 

regions with the complementary-determining regions of a murine parent antibody that binds to IgE. 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Mechanism of action 

Omalizumab binds to IgE and prevents binding of IgE to FcRI (high-affinity IgE receptor) on 

basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the 

allergic cascade. Treatment of atopic subjects with omalizumab resulted in a marked down-regulation 

of FcRI receptors on basophils. Treatment with Xolair inhibits IgE-mediated inflammation, as 

evidenced by reduced blood and tissue eosinophils and reduced inflammatory mediators, including 

IL-4, IL-5, and IL-13 by innate, adaptive and non-immune cells. 

 

Pharmacodynamic effects 

Allergic asthma 

The in vitro histamine release from basophils isolated from Xolair-treated subjects was reduced by 

approximately 90% following stimulation with an allergen compared to pre-treatment values. 

 

In clinical studies in allergic asthma patients, serum free IgE levels were reduced in a dose-dependent 

manner within one hour following the first dose and maintained between doses. One year after 

discontinuation of Xolair dosing, the IgE levels had returned to pre-treatment levels with no observed 

rebound in IgE levels after washout of the medicinal product. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical studies in patients with CRSwNP, Xolair treatment led to a reduction in serum free IgE 

(approx. 95%) and an increase in serum total IgE levels, to a similar extent as observed in patients 

with allergic asthma. Total IgE levels in serum increased due to the formation of omalizumab-IgE 

complexes that have a slower elimination rate compared with free IgE. 

 

Chronic spontaneous urticaria (CSU) 

 

Mechanism of action 

Omalizumab binds to IgE and lowers free IgE levels. Subsequently, IgE receptors (FcεRI) on cells 

down-regulate. It is not entirely understood how this results in an improvement of CSU symptoms. 

 

Pharmacodynamic effect 

In clinical studies in CSU patients, maximum suppression of free IgE was observed 3 days after the 

first subcutaneous dose. After repeated dosing once every 4 weeks, pre-dose serum free IgE levels 

remained stable between 12 and 24 weeks of treatment. After discontinuation of Xolair, free IgE levels 

increased towards pre-treatment levels over a 16-week treatment-free follow-up period. 

 



34 

Clinical efficacy and safety 

 

Allergic asthma 

Adults and adolescents ≥12 years of age 

The efficacy and safety of Xolair were demonstrated in a 28-week double-blind placebo-controlled 

study (study 1) involving 419 severe allergic asthmatics, ages 12-79 years, who had reduced lung 

function (FEV1 40-80% predicted) and poor asthma symptom control despite receiving high dose 

inhaled corticosteroids and a long-acting beta2-agonist. Eligible patients had experienced multiple 

asthma exacerbations requiring systemic corticosteroid treatment or had been hospitalised or attended 

an emergency room due to a severe asthma exacerbation in the past year despite continuous treatment 

with high-dose inhaled corticosteroids and a long-acting beta2-agonist. Subcutaneous Xolair or 

placebo were administered as add-on therapy to >1,000 micrograms beclomethasone dipropionate (or 

equivalent) plus a long-acting beta2-agonist. Oral corticosteroid, theophylline and leukotriene-

modifier maintenance therapies were allowed (22%, 27%, and 35% of patients, respectively). 

 

The rate of asthma exacerbations requiring treatment with bursts of systemic corticosteroids was the 

primary endpoint. Omalizumab reduced the rate of asthma exacerbations by 19% (p = 0.153). Further 

evaluations which did show statistical significance (p<0.05) in favour of Xolair included reductions in 

severe exacerbations (where patient’s lung function was reduced to below 60% of personal best and 

requiring systemic corticosteroids) and asthma-related emergency visits (comprised of 

hospitalisations, emergency room, and unscheduled doctor visits), and improvements in Physician’s 

overall assessment of treatment effectiveness, Asthma-related Quality of Life (AQL), asthma 

symptoms and lung function. 

 

In a subgroup analysis, patients with pre-treatment total IgE ≥76 IU/ml were more likely to experience 

clinically meaningful benefit to Xolair. In these patients in study 1 Xolair reduced the rate of asthma 

exacerbations by 40% (p = 0.002). In addition more patients had clinically meaningful responses in the 

total IgE ≥76 IU/ml population across the Xolair severe asthma programme. Table 6 includes results in 

the study 1 population. 

 

Table 6 Results of study 1 

 

 Whole study 1 

population 

 Xolair 

N=209 

Placebo 

N=210 

Asthma exacerbations   

Rate per 28-week period 0.74 0.92 

% reduction, p-value for rate ratio 19.4%, p = 0.153 

Severe asthma exacerbations   

Rate per 28-week period 0.24 0.48 

% reduction, p-value for rate ratio 50.1%, p = 0.002 

Emergency visits   

Rate per 28-week period 0.24 0.43 

% reduction, p-value for rate ratio 43.9%, p = 0.038 

Physician’s overall assessment   

% responders* 60.5% 42.8% 

p-value** <0.001 

AQL improvement   

% of patients ≥0.5 improvement 60.8% 47.8% 

p-value 0.008 

* marked improvement or complete control 

** p-value for overall distribution of assessment 

 

Study 2 assessed the efficacy and safety of Xolair in a population of 312 severe allergic asthmatics 

which matched the population in study 1. Treatment with Xolair in this open label study led to a 61% 

reduction in clinically significant asthma exacerbation rate compared to current asthma therapy alone. 



35 

 

Four additional large placebo-controlled supportive studies of 28 to 52 weeks duration in 1,722 adults 

and adolescents (studies 3, 4, 5, 6) assessed the efficacy and safety of Xolair in patients with severe 

persistent asthma. Most patients were inadequately controlled but were receiving less concomitant 

asthma therapy than patients in studies 1 or 2. Studies 3-5 used exacerbation as primary endpoint, 

whereas study 6 primarily evaluated inhaled corticosteroid sparing. 

 

In studies 3, 4 and 5 patients treated with Xolair had respective reductions in asthma exacerbation 

rates of 37.5% (p = 0.027), 40.3% (p<0.001) and 57.6% (p<0.001) compared to placebo. 

 

In study 6, significantly more severe allergic asthma patients on Xolair were able to reduce their 

fluticasone dose to 500 micrograms/day without deterioration of asthma control (60.3%) compared to 

the placebo group (45.8%, p<0.05). 

 

Quality of life scores were measured using the Juniper Asthma-related Quality of Life Questionnaire. 

For all six studies there was a statistically significant improvement from baseline in quality of life 

scores for Xolair patients versus the placebo or control group. 

 

Physician’s overall assessment of treatment effectiveness: 

Physician’s overall assessment was performed in five of the above studies as a broad measure of 

asthma control performed by the treating physician. The physician was able to take into account PEF 

(peak expiratory flow), day and night time symptoms, rescue medication use, spirometry and 

exacerbations. In all five studies a significantly greater proportion of Xolair treated patients were 

judged to have achieved either a marked improvement or complete control of their asthma compared 

to placebo patients. 

 

Children 6 to <12 years of age 

The primary support for safety and efficacy of Xolair in the group aged 6 to <12 years comes from one 

randomised, double-blind, placebo-controlled, multi-centre trial (study 7). 

 

Study 7 was a placebo-controlled trial which included a specific subgroup (n=235) of patients as 

defined in the present indication, who were treated with high-dose inhaled corticosteroids 

(≥500 µg/day fluticasone equivalent) plus long-acting beta agonist. 

 

A clinically significant exacerbation was defined as a worsening of asthma symptoms as judged 

clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least 

3 days and/or treatment with rescue systemic (oral or intravenous) corticosteroids for at least 3 days. 

 

In the specific subgroup of patients on high dose inhaled corticosteroids, the omalizumab group had a 

statistically significantly lower rate of clinically significant asthma exacerbations than the placebo 

group. At 24 weeks, the difference in rates between treatment groups represented a 34% (rate ratio 

0.662, p = 0.047) decrease relative to placebo for omalizumab patients. In the second double-blind 28-

week treatment period the difference in rates between treatment groups represented a 63% (rate ratio 

0.37, p<0.001) decrease relative to placebo for omalizumab patients. 

 

During the 52-week double-blind treatment period (including the 24-week fixed-dose steroid phase 

and the 28-week steroid adjustment phase) the difference in rates between treatment groups 

represented a 50% (rate ratio 0.504, p<0.001) relative decrease in exacerbations for omalizumab 

patients. 

 



36 

The omalizumab group showed greater decreases in beta-agonist rescue medication use than the 

placebo group at the end of the 52-week treatment period, although the difference between treatment 

groups was not statistically significant. For the global evaluation of treatment effectiveness at the end 

of the 52-week double-blind treatment period in the subgroup of severe patients on high-dose inhaled 

corticosteroids plus long-acting beta agonists, the proportion of patients rated as having ‘excellent’ 

treatment effectiveness was higher, and the proportions having ‘moderate’ or ‘poor’ treatment 

effectiveness lower in the omalizumab group compared to the placebo group; the difference between 

groups was statistically significant (p<0.001), while there were no differences between the 

omalizumab and placebo groups for patients’ subjective Quality of Life ratings. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

The safety and efficacy of Xolair were evaluated in two randomised, double-blind, placebo-controlled 

trials in patients with CRSwNP (Table 8). Patients received Xolair or placebo subcutaneously every 2 

or 4 weeks (see section 4.2). All patients received background intranasal mometasone therapy 

throughout the study. Prior sino-nasal surgery or prior systemic corticosteroid usage were not required 

for inclusion in the studies. Patients received Xolair or placebo for 24 weeks followed by a 4-week 

follow-up period. Demographics and baseline characteristics, including allergic comorbidities, are 

described in Table 7. 

 

Table 7 Demographics and baseline characteristics of nasal polyp studies 

 
Parameter Nasal polyp study 1 

N=138 

Nasal polyp study 2 

N=127 

Mean age (years) (SD) 51.0 (13.2) 50.1 (11.9) 

% Male 63.8 65.4 

Patients with systemic 

corticosteroid use in the 

previous year (%) 

18.8 26.0 

Bilateral endoscopic nasal 

polyp score (NPS): mean (SD), 

range 0-8 

6.2 (1.0) 6.3 (0.9) 

Nasal congestion score (NCS): 

mean (SD), range 0-3 

2.4 (0.6) 2.3 (0.7) 

Sense of smell score: mean 

(SD), range 0-3 

2.7 (0.7) 2.7 (0.7) 

SNOT-22 total score: mean 

(SD) range 0-110 

60.1 (17.7) 59.5 (19.3) 

Blood eosinophils (cells/µl): 

mean (SD) 

346.1 (284.1) 334.6 (187.6) 

Total IgE IU/ml: mean (SD) 160.9 (139.6) 190.2 (200.5) 

Asthma (%) 53.6 60.6 

 Mild (%) 37.8 32.5 

 Moderate (%) 58.1 58.4 

 Severe (%) 4.1 9.1 

Aspirin exacerbated respiratory 

disease (%) 

19.6 35.4 

Allergic rhinitis 43.5 42.5 

SD = standard deviation; SNOT-22 = Sino-Nasal Outcome Test 22 Questionnaire; IgE = 

Immunoglobulin E; IU = international units. For NPS, NCS, and SNOT-22 higher scores indicate 

greater disease severity. 

 

  



37 

The co-primary endpoints were bilateral nasal polyps score (NPS) and average daily nasal congestion 

score (NCS) at Week 24. In both nasal polyp studies 1 and 2, patients who received Xolair had 

statistically significant greater improvements from baseline at Week 24 in NPS and weekly average 

NCS than patients who received placebo. Results from nasal polyp studies 1 and 2 are shown in 

Table 8. 

 

Table 8 Change from baseline at Week 24 in clinical scores from nasal polyp study 1, nasal 
polyp study 2, and pooled data 

 

 Nasal polyp 

study 1 

Nasal polyp 

study 2 

Nasal polyp 

pooled results 

 Placebo Xolair Placebo Xolair Placebo Xolair 

N 66 72 65 62 131 134 

Nasal polyp score    

Baseline mean 6.32 6.19 6.09 6.44 6.21 6.31 

LS mean change at 

Week 24 

0.06 -1.08 -0.31 -0.90 -0.13 -0.99 

Difference (95%) 

CI  

-1.14 (-1.59, -0.69) 

 

-0.59 (-1.05, -0.12) 

 

-0.86 (-1.18, -0.54) 

p-value <0.0001 0.0140 <0.0001 

7-day average of 

daily nasal 

congestion score 

   

Baseline mean 2.46 2.40 2.29 2.26 2.38 2.34 

LS mean change at 

Week 24 

-0.35 -0.89 -0.20 -0.70 -0.28 -0.80 

Difference (95%) 

CI 

-0.55 (-0.84, -0.25) 

 

-0.50 (-0.80, -0.19) 

 

-0.52 (-0.73, -0.31) 

p-value 0.0004 0.0017 <0.0001 

TNSS    

Baseline mean 9.33 8.56 8.73 8.37 9.03 8.47 

LS mean change at 

Week 24 

-1.06 -2.97 -0.44 -2.53 -0.77 -2.75 

Difference (95%) -1.91 (-2.85, -0.96) -2.09 (-3.00, -1.18)  -1.98 (-2.63, -1.33) 

p-value 0.0001 <0.0001 <0.0001 

SNOT-22    

Baseline mean 60.26 59.82 59.80 59.21 60.03 59.54 

LS mean change at 

Week 24 

-8.58 -24.70 -6.55 -21.59 -7.73 -23.10 

Difference (95%) -16.12 (-21.86, -10.38) -15.04 (-21.26, -8.82) -15.36 (-19.57, -11.16) 

p-value <0.0001 <0.0001 <0.0001 

(MID = 8.9)    

UPSIT    

Baseline mean 13.56 12.78 13.27 12.87 13.41 12.82 

LS mean change at 

Week 24 

0.63 4.44 0.44 4.31 0.54 4.38 

Difference (95%) 3.81 (1.38, 6.24) 3.86 (1.57, 6.15) 3.84 (2.17, 5.51) 

p-value 0.0024 0.0011 <0.0001 

LS=least-square; CI = confidence interval; TNSS = Total nasal symptom score; SNOT-22 = Sino-

Nasal Outcome Test 22 Questionnaire; UPSIT = University of Pennsylvania Smell Identification 

Test; MID = minimal important difference. 



38 

 

Figure 1 Mean change from baseline in nasal congestion score and mean change from 

baseline in nasal polyp score by treatment group in nasal polyp study 1 and study 2 

 

 
 

In a pre-specified pooled analysis of rescue treatment (systemic corticosteroids for 3 consecutive 

days or nasal polypectomy) during the 24-week treatment period, the proportion of patients requiring 

rescue treatment was lower in Xolair compared to placebo (2.3% versus 6.2%, respectively). The 

odds-ratio of having taken rescue treatment in Xolair compared to placebo was 0.38 (95% CI: 0.10, 

1.49). There were no sino-nasal surgeries reported in either study. 
 

Chronic spontaneous urticaria (CSU) 

 

The efficacy and safety of Xolair were demonstrated in two randomised, placebo-controlled phase III 

studies (study 1 and 2) in patients with CSU who remained symptomatic despite H1 antihistamine 

therapy at the approved dose. A third study (study 3) primarily evaluated the safety of Xolair in 

patients with CSU who remained symptomatic despite treatment with H1 antihistamines at up to four 

times the approved dose and H2 antihistamine and/or LTRA treatment. The three studies enrolled 

975 patients aged between 12 and 75 years (mean age 42.3 years; 39 patients 12-17 years, 54 patients 

≥65 years; 259 males and 716 females). All patients were required to have inadequate symptom 

control, as assessed by a weekly urticaria activity score (UAS7, range 0-42) of ≥16, and a weekly itch 

severity score (which is a component of the UAS7; range 0-21) of ≥8 for the 7 days prior to 

randomisation, despite having used an antihistamine for at least 2 weeks beforehand. 

 

In studies 1 and 2, patients had a mean weekly itch severity score of between 13.7 and 14.5 at baseline 

and a mean UAS7 score of 29.5 and 31.7 respectively. Patients in safety study 3 had a mean weekly 

itch severity score of 13.8 and a mean UAS7 score of 31.2 at baseline. Across all three studies, 

patients reported receiving on average 4 to 6 medications (including H1 antihistamines) for CSU 

symptoms prior to study enrollment. Patients received Xolair at 75 mg, 150 mg or 300 mg or placebo 

by subcutaneous injection every 4 weeks for 24 and 12 weeks in studies 1 and 2, respectively, and 

300 mg or placebo by subcutaneous injection every 4 weeks for 24 weeks in study 3. All studies had a 

16-week treatment-free follow-up period. 

 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Secondary 

efficacy analysis 

Secondary 

efficacy analysis 

Primary efficacy 

analysis 

Primary efficacy 

analysis 

Baseline 24 20 16 12 8 4 4 8 12 16 20 24 

Week Week 

Baseline 
M

ea
n
 c

h
an

g
e 

fr
o
m

 b
as

el
in

e 
in

 N
as

al
 C

o
n
g
es

ti
o
n
 S

co
re

 

M
ea

n
 c

h
an

g
e 

fr
o
m

 b
as

el
in

e 
in

 N
as

al
 P

o
ly

p
 S

co
re

 

0.25 0.25 

0.00 0.00 

-0.25 -0.25 

-0.50 -0.50 

-0.75 -0.75 

-1.00 -1.00 

-1.25 -1.25 



39 

The primary endpoint was the change from baseline to week 12 in weekly itch severity score. 

Omalizumab at 300 mg reduced the weekly itch severity score by 8.55 to 9.77 (p <0.0001) compared 

to a reduction of 3.63 to 5.14 for placebo (see Table 9). Statistically significant results were further 

observed in the responder rates for UAS7≤6 (at week 12) which were higher for the 300 mg treatment 

groups, ranging from 52-66% (p<0.0001) compared to 11-19% for the placebo groups, and complete 

response (UAS7=0) was achieved by 34-44% (p<0.0001) of patients treated with 300 mg compared to 

5-9% of patients in the placebo groups. Patients in the 300 mg treatment groups achieved the highest 

mean proportion of angioedema-free days from week 4 to week 12, (91.0-96.1%; p<0.001) compared 

to the placebo groups (88.1-89.2%). Mean change from baseline to week 12 in the overall DLQI for 

the 300 mg treatment groups was greater (p<0.001) than for placebo showing an improvement ranging 

from 9.7-10.3 points compared to 5.1-6.1 points for the corresponding placebo groups. 

 

Table 9 Change from baseline to week 12 in weekly itch severity score, studies 1, 2 and 3 

(mITT population*) 

 

 

Placebo 

Omalizumab 

300 mg 

Study 1   

 N 80 81 

 Mean (SD) −3.63 (5.22) −9.40 (5.73) 

 Difference in LS means vs. placebo1 - −5.80 

 95% CI for difference - −7.49,−4.10 

 P-value vs. placebo2 - <0.0001 

Study 2   

 N 79 79 

 Mean (SD) −5.14 (5.58) −9.77 (5.95) 

 Difference in LS means vs. placebo1 - −4.81 

 95% CI for difference - −6.49,−3.13 

 P-value vs. placebo2 - <0.0001 

Study 3   

 N 83 252 

 Mean (SD) −4.01 (5.87) −8.55 (6.01) 

 Difference in LS means vs. placebo1 - -4.52 

 95% CI for difference - −5.97, −3.08 

 P-value vs. placebo2 - <0.0001 

*Modified intent-to-treat (mITT) population: included all patients who were randomised and received 

at least one dose of study medication. 

BOCF (Baseline Observation Carried Forward) was used to impute missing data. 
1 The LS mean was estimated using an ANCOVA model. The strata were baseline weekly itch severity 

score (<13 vs. ≥13) and baseline weight (<80 kg vs. ≥80 kg). 
2 p-value is derived from ANCOVA t-test. 

 

Figure 2 shows the mean weekly itch severity score over time in study 1. The mean weekly itch 

severity scores significantly decreased with a maximum effect around week 12 that was sustained over 

the 24-week treatment period. The results were similar in study 3. 

 

In all three studies the mean weekly itch severity score increased gradually during the 16-week 

treatment-free follow-up period, consistent with symptom re-occurrence. Mean values at the end of the 

follow-up period were similar to the placebo group, but lower than respective mean baseline values. 

 



40 

Figure 2 Mean weekly itch severity score over time, study 1 (mITT population) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BOCF=baseline observation carried forward; mITT=modified intention-to-treat population 

 

Efficacy after 24 weeks of treatment 

The magnitude of the efficacy outcomes observed at week 24 of treatment was comparable to that 

observed at week 12: 

For 300 mg, in studies 1 and 3, the mean decrease from baseline in weekly itch severity score was 9.8 

and 8.6, the proportion of patients with UAS7≤6 was 61.7% and 55.6%, and the proportion of patients 

with complete response (UAS7=0) was 48.1% and 42.5%, respectively, (all p<0.0001, when compared 

to placebo). 

 

There is limited clinical experience in re-treatment of patients with omalizumab. 

 

Clinical trial data on adolescents (12 to 17 years) included a total of 39 patients, of whom 11 received 

the 300 mg dose. Results for the 300 mg are available for 9 patients at week 12 and 6 patients at 

week 24, and show a similar magnitude of response to omalizumab treatment compared to the adult 

population. Mean change from baseline in weekly itch severity score showed a reduction of 8.25 at 

week 12 and of 8.95 at week 24. The responder rates were: 33% at week 12 and 67% at week 24 for 

UAS7=0, and 56% at week 12 and 67% at week 24 for UAS7≤6. 

 

5.2 Pharmacokinetic properties 
 

The pharmacokinetics of omalizumab have been studied in adult and adolescent patients with allergic 

asthma as well as in adult patients with CRSwNP, and adult and adolescent patients with CSU. The 

general pharmacokinetic characteristics of omalizumab are similar in these patient populations. 

 

Absorption 

 

After subcutaneous administration, omalizumab is absorbed with an average absolute bioavailability 

of 62%. Following a single subcutaneous dose in adult and adolescent patients with asthma or CSU, 

omalizumab was absorbed slowly, reaching peak serum concentrations after an average of 6-8 days. In 

patients with asthma, following multiple doses of omalizumab, areas under the serum concentration-

time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after the first dose. 

 

0

5

10

15

0 4 8 12 16 20 24 28 32 36 40

      

Week 12 

Primary 

Endpoint Omalizumab 300 mg 

Placebo 
M

ea
n

 w
ee

k
ly

 i
tc

h
 s

ev
er

it
y

 s
co

re
 

Week 

Omalizumab or placebo administered 



41 

The pharmacokinetics of omalizumab are linear at doses greater than 0.5 mg/kg. Following doses of 

75 mg, 150 mg or 300 mg every 4 weeks in patients with CSU, trough serum concentrations of 

omalizumab increased proportionally with the dose level. 

 

Administration of Xolair manufactured as a lyophilised or liquid formulation resulted in similar serum 

concentration-time profiles of omalizumab. 

 

Distribution 

 

In vitro, omalizumab forms complexes of limited size with IgE. Precipitating complexes and 

complexes larger than one million Daltons in molecular weight are not observed in vitro or in vivo. 

Based on population pharmacokinetics, distribution of omalizumab was similar in patients with 

allergic asthma and patients with CSU. The apparent volume of distribution in patients with asthma 

following subcutaneous administration was 78 ± 32 ml/kg. 

 

Elimination 

 

Clearance of omalizumab involves IgG clearance processes as well as clearance via specific binding 

and complex formation with its target ligand, IgE. Liver elimination of IgG includes degradation in the 

reticuloendothelial system and endothelial cells. Intact IgG is also excreted in bile. In asthma patients 

the omalizumab serum elimination half-life averaged 26 days, with apparent clearance averaging 

2.4  1.1 ml/kg/day. Doubling of body weight approximately doubled apparent clearance. In CSU 

patients, based on population pharmacokinetic simulations, omalizumab serum elimination half-life at 

steady state averaged 24 days and apparent clearance at steady state for a patient of 80 kg weight was 

3.0 ml/kg/day. 

 

Characteristics in patient populations 

 

Age, Race/Ethnicity, Gender, Body Mass Index 

Patients with allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

The population pharmacokinetics of omalizumab were analysed to evaluate the effects of demographic 

characteristics. Analyses of these limited data suggest that no dose adjustments are necessary for age 

(6-76 years for patients with allergic asthma; 18 to 75 years for patients with CRSwNP), 

race/ethnicity, gender or body mass index (see section 4.2). 

 

Patients with CSU 

The effects of demographic characteristics and other factors on omalizumab exposure were evaluated 

based on population pharmacokinetics. In addition, covariate effects were evaluated by analysing the 

relationship between omalizumab concentrations and clinical responses. These analyses suggest that 

no dose adjustments are necessary in patients with CSU for age (12-75 years), race/ethnicity, gender, 

body weight, body mass index, baseline IgE, anti-FcRI autoantibodies or concomitant use of H2 

antihistamines or LTRAs. 

 

Renal and hepatic impairment 

There are no pharmacokinetic or pharmacodynamic data in allergic asthma or CSU patients with renal 

or hepatic impairment (see sections 4.2 and 4.4). 

 

5.3 Preclinical safety data 
 

The safety of omalizumab has been studied in the cynomolgus monkey, since omalizumab binds to 

cynomolgus and human IgE with similar affinity. Antibodies to omalizumab were detected in some 

monkeys following repeated subcutaneous or intravenous administration. However, no apparent 

toxicity, such as immune complex-mediated disease or complement-dependent cytotoxicity, was seen. 

There was no evidence of an anaphylactic response due to mast-cell degranulation in cynomolgus 

monkeys. 

 



42 

Chronic administration of omalizumab at dose levels of up to 250 mg/kg (at least 14 times the highest 

recommended clinical dose in mg/kg according to the recommended dosing table) was well tolerated 

in non-human primates (both adult and juvenile animals), with the exception of a dose-related and age-

dependent decrease in blood platelets, with a greater sensitivity in juvenile animals. The serum 

concentration required to attain a 50% drop in platelets from baseline in adult cynomolgus monkeys 

was roughly 4- to 20-fold higher than anticipated maximum clinical serum concentrations. In addition, 

acute haemorrhage and inflammation were observed at injection sites in cynomolgus monkeys. 

 

Formal carcinogenicity studies have not been conducted with omalizumab. 

 

In reproduction studies in cynomolgus monkeys, subcutaneous doses up to 75 mg/kg per week (at least 

8 times the highest recommended clinical dose in mg/kg over a 4-week period) did not elicit maternal 

toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and did not 

elicit adverse effects on foetal or neonatal growth when administered throughout late gestation, 

delivery and nursing. 

 

Omalizumab is excreted in breast milk in cynomolgus monkeys. Milk levels of omalizumab were 

0.15% of the maternal serum concentration. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Powder 

 

Sucrose 

L-histidine 

L-histidine hydrochloride monohydrate 

Polysorbate 20 

 

Solvent 

 

Water for injections 

 

6.2 Incompatibilities 
 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

6.3 Shelf life 
 

4 years. 

 

After reconstitution 

 

The chemical and physical stability of the reconstituted medicinal product have been demonstrated for 

8 hours at 2°C to 8°C and for 4 hours at 30°C. 

 

From a microbiological point of view, the medicinal product should be used immediately after 

reconstitution. If not used immediately, in-use storage times and conditions prior to use are the 

responsibility of the user and would normally not be longer than 8 hours at 2°C to 8°C or 2 hours at 

25°C. 

 

  



43 

6.4 Special precautions for storage 
 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 
 

Powder vial: Clear, colourless type I glass vial with a butyl rubber stopper and blue flip-off seal. 

 

Solvent ampoule: Clear, colourless type I glass ampoule containing 2 ml water for injections. 

 

Pack containing 1 vial of powder and 1 ampoule of water for injections, and multipacks containing 

4 (4 x 1) vials of powder and 4 (4 x 1) ampoules of water for injections or 10 (10 x 1) vials of powder 

and 10 (10 x 1) ampoules of water for injections. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

Xolair 150 mg powder for solution for injection is supplied in a single-use vial. 

 

From a microbiological point of view, the medicinal product should be used immediately after 

reconstitution (see section 6.3). 

 

The lyophilised medicinal product takes 15-20 minutes to dissolve, although in some cases it may take 

longer. The fully reconstituted medicinal product will appear clear to slightly opalescent, colourless to 

pale brownish-yellow and may have a few small bubbles or foam around the edge of the vial. Because 

of the viscosity of the reconstituted medicinal product care must be taken to withdraw all of the 

medicinal product from the vial before expelling any air or excess solution from the syringe in order to 

obtain the 1.2 ml. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/002 

EU/1/05/319/003 

EU/1/05/319/004 

 

 

  



44 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 25 October 2005 

Date of latest renewal: 22 June 2015 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


45 

1. NAME OF THE MEDICINAL PRODUCT 
 

Xolair 75 mg solution for injection in pre-filled syringe 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each pre-filled syringe of 0.5 ml solution contains 75 mg of omalizumab*. 

 

*Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology in 

a Chinese hamster ovary (CHO) mammalian cell line. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for injection in pre-filled syringe (injection). 

 

Clear to slightly opalescent, colourless to pale brownish-yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Allergic asthma 

 

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

 

Xolair treatment should only be considered for patients with convincing IgE (immunoglobulin E) 

mediated asthma (see section 4.2). 

 

Adults and adolescents (12 years of age and older) 

Xolair 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 high-

dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist. 

 

Children (6 to <12 years of age) 

Xolair 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 beta2-

agonist. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Xolair is indicated as an add-on therapy with intranasal corticosteroids (INC) for the treatment of 

adults (18 years and above) with severe CRSwNP for whom therapy with INC does not provide 

adequate disease control. 

 

  



46 

4.2 Posology and method of administration 
 

Xolair treatment should be initiated by physicians experienced in the diagnosis and treatment of severe 

persistent asthma or chronic rhinosinusitis with nasal polyps (CRSwNP). 

 

Posology 

 

Dosing for allergic asthma and CRSwNP follows the same dosing principles. The appropriate dose 

and frequency of Xolair for these conditions is determined by baseline IgE (IU/ml), measured before 

the start of treatment, and body weight (kg). Prior to administration of the initial dose, patients should 

have their IgE level determined by any commercial serum total IgE assay for their dose assignment. 

Based on these measurements, 75 to 600 mg of Xolair in 1 to 4 injections may be needed for each 

administration. 

 

Allergic asthma patients with baseline IgE lower than 76 IU/ml were less likely to experience benefit 

(see section 5.1). Prescribing physicians should ensure that adult and adolescent patients with IgE 

below 76 IU/ml and children (6 to < 12 years of age) with IgE below 200 IU/ml have unequivocal in 

vitro reactivity (RAST) to a perennial allergen before starting therapy. 

 

See Table 1 for a conversion chart and Tables 2 and 3 for the dose determination charts. 

 

Patients whose baseline IgE levels or body weight in kilograms are outside the limits of the dose table 

should not be given Xolair. 

 

The maximum recommended dose is 600 mg omalizumab every two weeks. 

 

Table 1 Conversion from dose to number of syringes, number of injections and total 

injection volume for each administration 

 

Dose (mg) Number of syringes Number of injections Total injection volume (ml) 

 75 mg  150 mg    

75 1 0 1 0.5 

150 0 1 1 1.0 

225 1 1 2 1.5 

300 0 2 2 2.0 

375 1 2 3 2.5 

450 0 3 3 3.0 

525 1 3 4 3.5 

600 0 4 4 4.0 

 



47 

Table 2 ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 4 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20- 

25* 

>25-  

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90-  

125 

>125-  

150 

30-100 75 75 75 150 150 150 150 150 300 300 

>100-200 150 150 150 300 300 300 300 300 450 600 

>200-300 150 150 225 300 300 450 450 450 600  

>300-400 225 225 300 450 450 450 600 600   

>400-500 225 300 450 450 600 600     

>500-600 300 300 450 600 600      

>600-700 300  450 600       

>700-800           

>800-900     ADMINISTRATION EVERY 2 WEEKS 

SEE TABLE 3 

 

>900-

1000 

     

>1000-

1100 

          

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 



48 

Table 3 ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 2 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20-

25* 

>25-  

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90-  

125 

>125-  

150 

30-100 ADMINISTRATION EVERY 4 WEEKS 

SEE TABLE 2 

     

>100-200      

>200-300          375 

>300-400         450 525 

>400-500       375 375 525 600 

>500-600      375 450 450 600  

>600-700  225   375 450 450 525   

>700-800 225 225 300 375 450 450 525 600   

>800-900 225 225 300 375 450 525 600    

>900-

1000 

225 300 375 450 525 600     

>1000-

1100 

225 300 375 450 600      

>1100-

1200 

300 300 450 525 600 Insufficient data to recommend a dose 

>1200-

1300 

300 375 450 525       

>1300-

1500 

300 375 525 600       

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 

  



49 

Treatment duration, monitoring and dose adjustments 

Allergic asthma 

Xolair is intended for long-term treatment. Clinical trials have demonstrated that it takes at least 

12-16 weeks for Xolair treatment to show effectiveness. At 16 weeks after commencing Xolair 

therapy patients should be assessed by their physician for treatment effectiveness before further 

injections are administered. The decision to continue Xolair following the 16-week timepoint, or on 

subsequent occasions, should be based on whether a marked improvement in overall asthma control is 

seen (see section 5.1, Physician’s overall assessment of treatment effectiveness). 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical trials for CRSwNP, changes in nasal polyps score (NPS) and nasal congestion score (NCS) 

were observed at 4 weeks. The need for continued therapy should be periodically reassessed based 

upon the patient’s disease severity and level of symptom control. 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

Discontinuation of Xolair treatment 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 one 

year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment 

cannot be used as a guide for dose determination. Dose determination after treatment interruptions 

lasting less than one 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 Xolair 

has been interrupted for one year or more. 

 

Doses should be adjusted for significant changes in body weight (see Tables 2 and 3). 

 

Special populations 

Elderly (65 years of age and older) 

There are limited data available on the use of Xolair in patients older than 65 years but there is no 

evidence that elderly patients require a different dose from younger adult patients. 

 

Renal or hepatic impairment 

There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics 

of Xolair. Because omalizumab clearance at clinical doses is dominated by the reticular endothelial 

system (RES) it is unlikely to be altered by renal or hepatic impairment. While no particular dose 

adjustment is recommended for these patients, Xolair should be administered with caution (see 

section 4.4). 

 

Paediatric population 

In allergic asthma, the safety and efficacy of Xolair in patients below the age of 6 years have not been 

established. No data are available. 

 

In CRSwNP, the safety and efficacy of Xolair in patients below the age of 18 years have not been 

established. 

 

Method of administration 

 

For subcutaneous administration only. Xolair must not be administered by the intravenous or 

intramuscular route. 

 

Doses of more than 150 mg (Table 1) should be divided across two or more injection sites. 

 

Patients with no known history of anaphylaxis may self-inject Xolair or be injected by a caregiver 

from the 4th dose onwards if a physician determines that this is appropriate (see section 4.4). The 

patient or the caregiver must have been trained in the correct injection technique and the recognition of 

the early signs and symptoms of serious allergic reactions. 

 



50 

Patients or caregivers should be instructed to inject the full amount of Xolair according to the 

instructions provided in the package leaflet. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 
 

Traceability 

 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

General 

 

Xolair is not indicated for the treatment of acute asthma exacerbations, acute bronchospasm or status 

asthmaticus. 

 

Xolair has not been studied in patients with hyperimmunoglobulin E syndrome or allergic 

bronchopulmonary aspergillosis or for the prevention of anaphylactic reactions, including those 

provoked by food allergy, atopic dermatitis, or allergic rhinitis. Xolair is not indicated for the 

treatment of these conditions. 

 

Xolair therapy has not been studied in patients with autoimmune diseases, immune complex-mediated 

conditions, or pre-existing renal or hepatic impairment (see section 4.2). Caution should be exercised 

when administering Xolair in these patient populations. 

 

Abrupt discontinuation of systemic or inhaled corticosteroids after initiation of Xolair therapy in 

allergic asthma or CRSwNP is not recommended. Decreases in corticosteroids should be performed 

under the direct supervision of a physician and may need to be performed gradually. 

 

Immune system disorders 

 

Allergic reactions type I 

Type I local or systemic allergic reactions, including anaphylaxis and anaphylactic shock, may occur 

when taking omalizumab, even after a long duration of treatment. However, most of these reactions 

occurred within 2 hours after the first and subsequent injections of Xolair but some started beyond 

2 hours and even beyond 24 hours after the injection. The majority of anaphylactic reactions occurred 

within the first 3 doses of Xolair. Therefore, the first 3 doses must be administered either by or under 

the supervision of a healthcare professional. A history of anaphylaxis unrelated to omalizumab may be 

a risk factor for anaphylaxis following Xolair administration. Therefore for patients with a known 

history of anaphylaxis, Xolair must be administered by a health care professional, who should always 

have medicinal products for the treatment of anaphylactic reactions available for immediate use 

following administration of Xolair. If an anaphylactic or other serious allergic reaction occurs, 

administration of Xolair must be discontinued immediately, and appropriate therapy initiated. Patients 

should be informed that such reactions are possible, and prompt medical attention should be sought if 

allergic reactions occur. 

 

Antibodies to omalizumab have been detected in a low number of patients in clinical trials (see 

section 4.8). The clinical relevance of anti-Xolair antibodies is not well understood. 

 



51 

Serum sickness 

Serum sickness and serum sickness-like reactions, which are delayed allergic type III reactions, have 

been seen in patients treated with humanised monoclonal antibodies including omalizumab. The 

suggested pathophysiologic mechanism includes immune-complex formation and deposition due to 

development of antibodies against omalizumab. The onset has typically been 1-5 days after 

administration of the first or subsequent injections, also after long duration of treatment. Symptoms 

suggestive of serum sickness include arthritis/arthralgias, rash (urticaria or other forms), fever and 

lymphadenopathy. Antihistamines and corticosteroids may be useful for preventing or treating this 

disorder, and patients should be advised to report any suspected symptoms. 

 

Churg-Strauss syndrome and hypereosinophilic syndrome 

Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or allergic 

eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), both of which are usually treated 

with systemic corticosteroids. 

 

In rare cases, patients on therapy with anti-asthma medicinal products, including omalizumab, may 

present or develop systemic eosinophilia and vasculitis. These events are commonly associated with 

the reduction of oral corticosteroid therapy. 

 

In these patients, physicians should be alert to the development of marked eosinophilia, vasculitic 

rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac complications, and/or 

neuropathy. 

 

Discontinuation of omalizumab should be considered in all severe cases with the above mentioned 

immune system disorders. 

 

Parasitic (helminth) infections 

 

IgE may be involved in the immunological response to some helminth infections. In patients at chronic 

high risk of helminth infection, a placebo-controlled trial showed a slight increase in infection rate 

with omalizumab, although the course, severity, and response to treatment of infection were unaltered. 

The helminth infection rate in the overall clinical programme, which was not designed to detect such 

infections, was less than 1 in 1,000 patients. However, caution may be warranted in patients at high 

risk of helminth infection, in particular when travelling to areas where helminthic infections are 

endemic. If patients do not respond to recommended anti-helminth treatment, discontinuation of 

Xolair should be considered. 

 

Latex-sensitive individuals 

 

The removable needle cap of this pre-filled syringe contains a derivative of natural rubber latex. No 

natural rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of 

Xolair solution for injection in pre-filled syringe in latex-sensitive individuals has not been studied and 

thus there is a potential risk for hypersensitivity reactions which cannot be completely ruled out. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Since IgE may be involved in the immunological response to some helminth infections, Xolair may 

indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic 

infections (see section 4.4). 

 

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 Xolair. There is no pharmacological reason 

to expect that commonly prescribed medicinal products used in the treatment of asthma or CRSwNP 

will interact with omalizumab. 

 



52 

Allergic asthma 

 

In clinical studies Xolair 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 Xolair was altered with these other 

commonly used anti-asthma medicinal products. Limited data are available on the use of Xolair in 

combination with specific immunotherapy (hypo-sensitisation therapy). In a clinical trial where Xolair 

was co-administered with immunotherapy, the safety and efficacy of Xolair in combination with 

specific immunotherapy were found to be no different to that of Xolair alone. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

In clinical studies Xolair was used in conjunction with intranasal mometasone spray as per protocol. 

Other commonly used concomitant medicinal products included other intranasal corticosteroids, 

bronchodilators, antihistamines, leukotriene receptor antagonists, adrenergics/sympathomimetics and 

local nasal anaesthetics. There was no indication that the safety of Xolair was altered by the 

concomitant use of these other commonly used medicinal products. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) based on 

pregnancy registry and post-marketing spontaneous reports, indicates no malformative or 

foeto/neonatal toxicity. A prospective pregnancy registry study (EXPECT) in 250 pregnant women 

with asthma exposed to Xolair showed the prevalence of major congenital anomalies was similar 

(8.1% vs. 8.9%) between EXPECT and disease-matched (moderate and severe asthma) patients. The 

interpretation of data may be impacted due to methodological limitations of the study, including small 

sample size and non-randomised design. 

 

Omalizumab crosses the placental barrier. However, animal studies do not indicate either direct or 

indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

 

Omalizumab has been associated with age-dependent decreases in blood platelets in non-human 

primates, with a greater relative sensitivity in juvenile animals (see section 5.3). 

 

If clinically needed, the use of Xolair may be considered during pregnancy. 

 

Breast-feeding 

 

Immunoglobulins G (IgGs) are present in human milk and therefore it is expected that omalizumab 

will be present in human milk. Available data in non-human primates have shown excretion of 

omalizumab into milk (see section 5.3). 

 

The EXPECT study, with 154 infants who had been exposed to Xolair during pregnancy and through 

breast-feeding did not indicate adverse effects on the breast-fed infant. The interpretation of data may 

be impacted due to methodological limitations of the study, including small sample size and non-

randomised design. 

 

Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability. 

No effects on the breast-fed newborns/infants are anticipated. Consequently, if clinically needed, the 

use of Xolair may be considered during breast-feeding. 

 



53 

Fertility 

 

There are no human fertility data for omalizumab. In specifically-designed non-clinical fertility 

studies, in non-human primates including mating studies, no impairment of male or female fertility 

was observed following repeated dosing with omalizumab at dose levels up to 75 mg/kg. Furthermore, 

no genotoxic effects were observed in a separate non-clinical genotoxicity study. 

 

4.7 Effects on ability to drive and use machines 
 

Xolair has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 
 

Summary of the safety profile 

During allergic asthma clinical trials in adult and adolescent patients 12 years of age and older, the 

most commonly reported adverse reactions were headaches and injection site reactions, including 

injection site pain, swelling, erythema and pruritus. In clinical trials in children 6 to <12 years of age, 

the most commonly reported adverse reactions were headache, pyrexia and upper abdominal pain. 

Most of the reactions were mild or moderate in severity. In clinical trials in patients ≥18 years of age 

in CRSwNP, the most commonly reported adverse reactions were headache, dizziness, arthralgia, 

abdominal pain upper and injection site reactions. 

 

Tabulated list of adverse reactions 

Table 4 lists the adverse reactions recorded in clinical studies in the total allergic asthma and CRSwNP 

safety population treated with Xolair by MedDRA system organ class and frequency. Within each 

frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency 

categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to 

<1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Reactions reported in the post-

marketing setting are listed with frequency not known (cannot be estimated from the available data). 

 

  



54 

Table 4 Adverse reactions in allergic asthma and CRSwNP 

 

Infections and infestations 

Uncommon Pharyngitis 

Rare Parasitic infection 

Blood and lymphatic system disorders 

Not known Idiopathic thrombocytopenia, including severe cases 

Immune system disorders 

Rare Anaphylactic reaction, other serious allergic conditions, anti-

omalizumab antibody development 

Not known Serum sickness, may include fever and lymphadenopathy 

Nervous system disorders 

Common Headache* 

Uncommon Syncope, paraesthesia, somnolence, dizziness# 

Vascular disorders 

Uncommon Postural hypotension, flushing 

Respiratory, thoracic and mediastinal disorders 

Uncommon Allergic bronchospasm, coughing 

Rare Laryngoedema 

Not known Allergic granulomatous vasculitis (i.e. Churg-Strauss syndrome) 

Gastrointestinal disorders 

Common Abdominal pain upper**,# 

Uncommon Dyspeptic signs and symptoms, diarrhoea, nausea 

Skin and subcutaneous tissue disorders 

Uncommon Photosensitivity, urticaria, rash, pruritus 

Rare Angioedema 

Not known Alopecia 

Musculoskeletal and connective tissue disorders 

Common Athralgia† 
Rare Systemic lupus erythematosus (SLE) 

Not known Myalgia, joint swelling 

General disorders and administration site conditions 

Very common Pyrexia** 

Common Injection site reactions such as swelling, erythema, pain, pruritus 

Uncommon Influenza-like illness, swelling arms, weight increase, fatigue 

*: Very common in children 6 to <12 years of age 

**: In children 6 to <12 years of age 
#: Common in nasal polyp trials 

†: Unknown in allergic asthma trials 

 

Description of selected adverse reactions 

 

Immune system disorders 

For further information, see section 4.4. 

 

Anaphylaxis 

Anaphylactic reactions were rare in clinical trials. However, post-marketing data following a 

cumulative search in the safety database retrieved a total of 898 anaphylaxis cases. Based on an 

estimated exposure of 566,923 patient treatment years, this results in a reporting rate of approximately 

0.20%. 

 



55 

Arterial thromboembolic events (ATE) 

In controlled clinical trials and during interim analyses of an observational study, a numerical 

imbalance of ATE was observed. The definition of the composite endpoint ATE included stroke, 

transient ischaemic attack, myocardial infarction, unstable angina, and cardiovascular death (including 

death from unknown cause). In the final analysis of the observational study, the rate of ATE per 1,000 

patient years was 7.52 (115/15,286 patient years) for Xolair-treated patients and 5.12 (51/9,963 patient 

years) for control patients. In a multivariate analysis controlling for available baseline cardiovascular 

risk factors, the hazard ratio was 1.32 (95% confidence interval 0.91-1.91). In a separate analysis of 

pooled clinical trials, which included all randomised double-blind, placebo-controlled clinical trials 

lasting 8 or more weeks, the rate of ATE per 1,000 patient years was 2.69 (5/1,856 patient years) for 

Xolair-treated patients and 2.38 (4/1,680 patient years) for placebo patients (rate ratio 1.13, 95% 

confidence interval 0.24-5.71). 

 

Platelets 

In clinical trials few patients had platelet counts below the lower limit of the normal laboratory range. 

None of these changes were associated with bleeding episodes or a decrease in haemoglobin. No 

pattern of persistent decrease in platelet counts, as observed in non-human primates (see section 5.3), 

has been reported in humans (patients above 6 years of age), even though isolated cases of idiopathic 

thrombocytopenia, including severe cases, have been reported in the post-marketing setting. 

 

Parasitic infections 

In patients at chronic high risk of helminth infection, a placebo-controlled trial showed a slight 

numerical increase in infection rate with omalizumab that was not statistically significant. The course, 

severity, and response to treatment of infections were unaltered (see section 4.4). 

 

Systemic lupus erythematosus 

Clinical trial and post-marketing cases of systemic lupus erythematosus (SLE) have been reported in 

patients with moderate to severe asthma and CSU. The pathogenesis of SLE is not well understood. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Maximum tolerated dose of Xolair has not been determined. Single intravenous doses up to 4,000 mg 

have been administered to patients without evidence of dose-limiting toxicities. The highest 

cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not 

result in any untoward acute effects. 

 

If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. 

Medical treatment should be sought and instituted appropriately. 

 

 

  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


56 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for 

obstructive airway diseases, ATC code: R03DX05 

 

Omalizumab is a recombinant DNA-derived humanised monoclonal antibody that selectively binds to 

human immunoglobulin E (IgE). The antibody is an IgG1 kappa that contains human framework 

regions with the complementary-determining regions of a murine parent antibody that binds to IgE. 

 

Mechanism of action 

 

Omalizumab binds to IgE and prevents binding of IgE to FcRI (high-affinity IgE receptor) on 

basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the 

allergic cascade. Treatment of atopic subjects with omalizumab resulted in a marked down-regulation 

of FcRI receptors on basophils. Treatment with Xolair inhibits IgE-mediated inflammation, as 

evidenced by reduced blood and tissue eosinophils and reduced inflammatory mediators, including IL-

4, IL-5, and IL-13 by innate, adaptive and non-immune cells. 

 

Pharmacodynamic effects 

 

Allergic asthma 

The in vitro histamine release from basophils isolated from Xolair-treated subjects was reduced by 

approximately 90% following stimulation with an allergen compared to pre-treatment values. 

 

In clinical studies in allergic asthma patients, serum free IgE levels were reduced in a dose-dependent 

manner within one hour following the first dose and maintained between doses. One year after 

discontinuation of Xolair dosing, the IgE levels had returned to pre-treatment levels with no observed 

rebound in IgE levels after washout of the medicinal product. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical studies in patients with CRSwNP, Xolair treatment led to a reduction in serum free IgE 

(approx. 95%) and an increase in serum total IgE levels, to a similar extent as observed in patients 

with allergic asthma. Total IgE levels in serum increased due to the formation of omalizumab-IgE 

complexes that have a slower elimination rate compared with free IgE. 

 

Clinical efficacy and safety 

 

Allergic asthma 
Adults and adolescents ≥12 years of age 

The efficacy and safety of Xolair were demonstrated in a 28-week double-blind placebo-controlled 

study (study 1) involving 419 severe allergic asthmatics, ages 12-79 years, who had reduced lung 

function (FEV1 40-80% predicted) and poor asthma symptom control despite receiving high dose 

inhaled corticosteroids and a long-acting beta2-agonist. Eligible patients had experienced multiple 

asthma exacerbations requiring systemic corticosteroid treatment or had been hospitalised or attended 

an emergency room due to a severe asthma exacerbation in the past year despite continuous treatment 

with high-dose inhaled corticosteroids and a long-acting beta2-agonist. Subcutaneous Xolair or 

placebo were administered as add-on therapy to >1,000 micrograms beclomethasone dipropionate (or 

equivalent) plus a long-acting beta2-agonist. Oral corticosteroid, theophylline and leukotriene-

modifier maintenance therapies were allowed (22%, 27%, and 35% of patients, respectively). 

 



57 

The rate of asthma exacerbations requiring treatment with bursts of systemic corticosteroids was the 

primary endpoint. Omalizumab reduced the rate of asthma exacerbations by 19% (p = 0.153). Further 

evaluations which did show statistical significance (p<0.05) in favour of Xolair included reductions in 

severe exacerbations (where patient’s lung function was reduced to below 60% of personal best and 

requiring systemic corticosteroids) and asthma-related emergency visits (comprised of 

hospitalisations, emergency room, and unscheduled doctor visits), and improvements in Physician’s 

overall assessment of treatment effectiveness, Asthma-related Quality of Life (AQL), asthma 

symptoms and lung function. 

 

In a subgroup analysis, patients with pre-treatment total IgE ≥76 IU/ml were more likely to experience 

clinically meaningful benefit to Xolair. In these patients in study 1 Xolair reduced the rate of asthma 

exacerbations by 40% (p = 0.002). In addition more patients had clinically meaningful responses in the 

total IgE ≥76 IU/ml population across the Xolair severe asthma programme. Table 5 includes results in 

the study 1 population. 

 

Table 5 Results of study 1 

 

 Whole study 1 population 

 Xolair 

N=209 

Placebo 

N=210 

Asthma exacerbations   

Rate per 28-week period 0.74 0.92 

% reduction, p-value for rate ratio 19.4%, p = 0.153 

Severe asthma exacerbations   

Rate per 28-week period 0.24 0.48 

% reduction, p-value for rate ratio 50.1%, p = 0.002 

Emergency visits   

Rate per 28-week period 0.24 0.43 

% reduction, p-value for rate ratio 43.9%, p = 0.038 

Physician’s overall assessment   

% responders* 60.5% 42.8% 

p-value** <0.001 

AQL improvement   

% of patients ≥0.5 improvement 60.8% 47.8% 

p-value 0.008 

* marked improvement or complete control 

** p-value for overall distribution of assessment 

 

Study 2 assessed the efficacy and safety of Xolair in a population of 312 severe allergic asthmatics 

which matched the population in study 1. Treatment with Xolair in this open label study led to a 61% 

reduction in clinically significant asthma exacerbation rate compared to current asthma therapy alone. 

 

Four additional large placebo-controlled supportive studies of 28 to 52 weeks duration in 1,722 adults 

and adolescents (studies 3, 4, 5, 6) assessed the efficacy and safety of Xolair in patients with severe 

persistent asthma. Most patients were inadequately controlled but were receiving less concomitant 

asthma therapy than patients in studies 1 or 2. Studies 3-5 used exacerbation as primary endpoint, 

whereas study 6 primarily evaluated inhaled corticosteroid sparing. 

 

In studies 3, 4 and 5 patients treated with Xolair had respective reductions in asthma exacerbation 

rates of 37.5% (p = 0.027), 40.3% (p<0.001) and 57.6% (p<0.001) compared to placebo. 

 

In study 6, significantly more severe allergic asthma patients on Xolair were able to reduce their 

fluticasone dose to 500 micrograms/day without deterioration of asthma control (60.3%) compared to 

the placebo group (45.8%, p<0.05). 

 



58 

Quality of life scores were measured using the Juniper Asthma-related Quality of Life Questionnaire. 

For all six studies there was a statistically significant improvement from baseline in quality of life 

scores for Xolair patients versus the placebo or control group. 

 

Physician’s overall assessment of treatment effectiveness: 

Physician’s overall assessment was performed in five of the above studies as a broad measure of 

asthma control performed by the treating physician. The physician was able to take into account PEF 

(peak expiratory flow), day and night time symptoms, rescue medication use, spirometry and 

exacerbations. In all five studies a significantly greater proportion of Xolair treated patients were 

judged to have achieved either a marked improvement or complete control of their asthma compared 

to placebo patients. 

 

Children 6 to <12 years of age 

The primary support for safety and efficacy of Xolair in the group aged 6 to <12 years comes from one 

randomised, double-blind, placebo-controlled, multi-centre trial (study 7). 

 

Study 7 was a placebo-controlled trial which included a specific subgroup (n=235) of patients as 

defined in the present indication, who were treated with high-dose inhaled corticosteroids 

(≥500 µg/day fluticasone equivalent) plus long-acting beta agonist. 

 

A clinically significant exacerbation was defined as a worsening of asthma symptoms as judged 

clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least 

3 days and/or treatment with rescue systemic (oral or intravenous) corticosteroids for at least 3 days. 

 

In the specific subgroup of patients on high dose inhaled corticosteroids, the omalizumab group had a 

statistically significantly lower rate of clinically significant asthma exacerbations than the placebo 

group. At 24 weeks, the difference in rates between treatment groups represented a 34% (rate ratio 

0.662, p = 0.047) decrease relative to placebo for omalizumab patients. In the second double-blind 28-

week treatment period the difference in rates between treatment groups represented a 63% (rate ratio 

0.37, p<0.001) decrease relative to placebo for omalizumab patients. 

 

During the 52-week double-blind treatment period (including the 24-week fixed-dose steroid phase 

and the 28-week steroid adjustment phase) the difference in rates between treatment groups 

represented a 50% (rate ratio 0.504, p<0.001) relative decrease in exacerbations for omalizumab 

patients. 

 

The omalizumab group showed greater decreases in beta-agonist rescue medication use than the 

placebo group at the end of the 52-week treatment period, although the difference between treatment 

groups was not statistically significant. For the global evaluation of treatment effectiveness at the end 

of the 52-week double-blind treatment period in the subgroup of severe patients on high-dose inhaled 

corticosteroids plus long-acting beta agonists, the proportion of patients rated as having ‘excellent’ 

treatment effectiveness was higher, and the proportions having ‘moderate’ or ‘poor’ treatment 

effectiveness lower in the omalizumab group compared to the placebo group; the difference between 

groups was statistically significant (p<0.001), while there were no differences between the 

omalizumab and placebo groups for patients’ subjective Quality of Life ratings. 

 

  



59 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

The safety and efficacy of Xolair were evaluated in two randomised, double-blind, placebo-controlled 

trials in patients with CRSwNP (Table 7). Patients received Xolair or placebo subcutaneously every 2 

or 4 weeks (see section 4.2). All patients received background intranasal mometasone therapy 

throughout the study. Prior sino-nasal surgery or prior systemic corticosteroid usage were not required 

for inclusion in the studies. Patients received Xolair or placebo for 24 weeks followed by a 4-week 

follow-up period. Demographics and baseline characteristics, including allergic comorbidities, are 

described in Table 6. 

 

Table 6 Demographics and baseline characteristics of nasal polyp studies 

 
Parameter Nasal polyp study 1 

N=138 

Nasal polyp study 2 

N=127 

Mean age (years) (SD) 51.0 (13.2) 50.1 (11.9) 

% Male 63.8 65.4 

Patients with systemic 

corticosteroid use in the 

previous year (%) 

18.8 26.0 

Bilateral endoscopic nasal 

polyp score (NPS): mean (SD), 

range 0-8 

6.2 (1.0) 6.3 (0.9) 

Nasal congestion score (NCS): 

mean (SD), range 0-3 

2.4 (0.6) 2.3 (0.7) 

Sense of smell score: mean 

(SD), range 0-3 

2.7 (0.7) 2.7 (0.7) 

SNOT-22 total score: mean 

(SD) range 0-110 

60.1 (17.7) 59.5 (19.3) 

Blood eosinophils (cells/µl): 

mean (SD) 

346.1 (284.1) 334.6 (187.6) 

Total IgE IU/ml: mean (SD) 160.9 (139.6) 190.2 (200.5) 

Asthma (%) 53.6 60.6 

 Mild (%) 37.8 32.5 

 Moderate (%) 58.1 58.4 

 Severe (%) 4.1 9.1 

Aspirin exacerbated respiratory 

disease (%) 

19.6 35.4 

Allergic rhinitis 43.5 42.5 

SD = standard deviation; SNOT-22 = Sino-Nasal Outcome Test 22 Questionnaire; IgE = 

Immunoglobulin E; IU = international units. For NPS, NCS, and SNOT-22 higher scores indicate 

greater disease severity. 

 

  



60 

The co-primary endpoints were bilateral nasal polyps score (NPS) and average daily nasal congestion 

score (NCS) at Week 24. In both nasal polyp studies 1 and 2, patients who received Xolair had 

statistically significant greater improvements from baseline at Week 24 in NPS and weekly average 

NCS than patients who received placebo. Results from nasal polyp studies 1 and 2 are shown in 

Table 7. 

 

Table 7 Change from baseline at Week 24 in clinical scores from nasal polyp study 1, nasal 
polyp study 2, and pooled data 

 

 Nasal polyp 

study 1 

Nasal polyp 

study 2 

Nasal polyp 

pooled results 

 Placebo Xolair Placebo Xolair Placebo Xolair 

N 66 72 65 62 131 134 

Nasal polyp score    

Baseline mean 6.32 6.19 6.09 6.44 6.21 6.31 

LS mean change at 

Week 24 

0.06 -1.08 -0.31 -0.90 -0.13 -0.99 

Difference (95%) 

CI  

-1.14 (-1.59, -069) 

 

-0.59 (-1.05, -012) 

 

-0.86 (-1.18, -0.54) 

p-value <0.0001 0.0140 <0.0001 

7-day average of 

daily nasal 

congestion score 

   

Baseline mean 2.46 2.40 2.29 2.26 2.38 2.34 

LS mean change at 

Week 24 

-0.35 -0.89 -0.20 -0.70 -0.28 -0.80 

Difference (95%) 

CI 

-0.55 (-0.84, -0.25) 

 

-0.50 (-0.80, -0.19) 

 

-0.52 (-0.73, -0.31) 

p-value 0.0004 0.0017 <0.0001 

TNSS    

Baseline mean 9.33 8.56 8.73 8.37 9.03 8.47 

LS mean change at 

Week 24 

-1.06 -2.97 -0.44 -2.53 -0.77 -2.75 

Difference (95%) -1.91 (-2.85, -0.96) -2.09 (-3.00, -1.18)  -1.98 (-2.63, -1.33) 

p-value 0.0001 <0.0001 <0.0001 

SNOT-22    

Baseline mean 60.26 59.82 59.80 59.21 60.03 59.54 

LS mean change at 

Week 24 

-8.58 -24.70 -6.55 -21.59 -7.73 -23.10 

Difference (95%) -16.12 (-21.86, -10.38) -15.04 (-21.26, -8.82) -15.36 (-19.57, -11.16) 

p-value <0.0001 <0.0001 <0.0001 

(MID = 8.9)    

UPSIT    

Baseline mean 13.56 12.78 13.27 12.87 13.41 12.82 

LS mean change at 

Week 24 

0.63 4.44 0.44 4.31 0.54 4.38 

Difference (95%) 3.81 (1.38, 6.24) 3.86 (1.57, 6.15) 3.84 (2.17, 5.51) 

p-value 0.0024 0.0011 <0.0001 

LS=least-square; CI = confidence interval; TNSS = Total nasal symptom score; SNOT-22 = Sino-

Nasal Outcome Test 22 Questionnaire; UPSIT = University of Pennsylvania Smell Identification 

Test; MID = minimal important difference. 



61 

 

Figure 1 Mean change from baseline in nasal congestion score and mean change from 

baseline in nasal polyp score by treatment group in nasal polyp study 1 and study 2 

 

 
 

In a pre-specified pooled analysis of rescue treatment (systemic corticosteroids for 3 consecutive 

days or nasal polypectomy) during the 24-week treatment period, the proportion of patients requiring 

rescue treatment was lower in Xolair compared to placebo (2.3% versus 6.2%, respectively). The 

odds-ratio of having taken rescue treatment in Xolair compared to placebo was 0.38 (95% CI: 0.10, 

1.49). There were no sino-nasal surgeries reported in either study. 

 

5.2 Pharmacokinetic properties 
 

The pharmacokinetics of omalizumab have been studied in adult and adolescent patients with allergic 

asthma as well as in adult patients with CRSwNP. The general pharmacokinetic characteristics of 

omalizumab are similar in these patient populations. 

 

Absorption 

 

After subcutaneous administration, omalizumab is absorbed with an average absolute bioavailability 

of 62%. Following a single subcutaneous dose in adult and adolescent patients with asthma, 

omalizumab was absorbed slowly, reaching peak serum concentrations after an average of 7-8 days. 

The pharmacokinetics of omalizumab are linear at doses greater than 0.5 mg/kg. Following multiple 

doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady 

state were up to 6-fold of those after the first dose. 

 

Administration of Xolair manufactured as a lyophilised or liquid formulation resulted in similar serum 

concentration-time profiles of omalizumab. 

 

Distribution 

 

In vitro, omalizumab forms complexes of limited size with IgE. Precipitating complexes and 

complexes larger than one million Daltons in molecular weight are not observed in vitro or in vivo. 

The apparent volume of distribution in patients following subcutaneous administration was 

78 ± 32 ml/kg. 

 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Secondary 

efficacy analysis 

Secondary 

efficacy analysis 

Primary efficacy 

analysis 

Primary efficacy 

analysis 

Baseline 24 20 16 12 8 4 4 8 12 16 20 24 

Week Week 

Baseline 
M

ea
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0.25 0.25 

0.00 0.00 

-0.25 -0.25 

-0.50 -0.50 

-0.75 -0.75 

-1.00 -1.00 

-1.25 -1.25 



62 

Elimination 

 

Clearance of omalizumab involves IgG clearance processes as well as clearance via specific binding 

and complex formation with its target ligand, IgE. Liver elimination of IgG includes degradation in the 

reticuloendothelial system and endothelial cells. Intact IgG is also excreted in bile. In asthma patients 

the omalizumab serum elimination half-life averaged 26 days, with apparent clearance averaging 

2.4  1.1 ml/kg/day. In addition, doubling of body weight approximately doubled apparent clearance. 

 

Characteristics in patient populations 

 
Age, Race/Ethnicity, Gender, Body Mass Index 

The population pharmacokinetics of Xolair were analysed to evaluate the effects of demographic 

characteristics. Analyses of these limited data suggest that no dose adjustments are necessary for age 

(6-76 years for patients with allergic asthma; 18 to 75 years for patients with CRSwNP), 

race/ethnicity, gender or Body Mass Index (see section 4.2). 

 

Renal and hepatic impairment 

There are no pharmacokinetic or pharmacodynamic data in patients with renal or hepatic impairment 

(see sections 4.2 and 4.4). 

 

5.3 Preclinical safety data 
 

The safety of omalizumab has been studied in the cynomolgus monkey, since omalizumab binds to 

cynomolgus and human IgE with similar affinity. Antibodies to omalizumab were detected in some 

monkeys following repeated subcutaneous or intravenous administration. However, no apparent 

toxicity, such as immune complex-mediated disease or complement-dependent cytotoxicity, was seen. 

There was no evidence of an anaphylactic response due to mast-cell degranulation in cynomolgus 

monkeys. 

 

Chronic administration of omalizumab at dose levels of up to 250 mg/kg (at least 14 times the highest 

recommended clinical dose in mg/kg according to the recommended dosing table) was well tolerated 

in non-human primates (both adult and juvenile animals), with the exception of a dose-related and age-

dependent decrease in blood platelets, with a greater sensitivity in juvenile animals. The serum 

concentration required to attain a 50% drop in platelets from baseline in adult cynomolgus monkeys 

was roughly 4- to 20-fold higher than anticipated maximum clinical serum concentrations. In addition, 

acute haemorrhage and inflammation were observed at injection sites in cynomolgus monkeys. 

 

Formal carcinogenicity studies have not been conducted with omalizumab. 

 

In reproduction studies in cynomolgus monkeys, subcutaneous doses up to 75 mg/kg per week (at least 

8 times the highest recommended clinical dose in mg/kg over a 4-week period) did not elicit maternal 

toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and did not 

elicit adverse effects on foetal or neonatal growth when administered throughout late gestation, 

delivery and nursing. 

 

Omalizumab is excreted in breast milk in cynomolgus monkeys. Milk levels of omalizumab were 

0.15% of the maternal serum concentration. 

 

 



63 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

L-arginine hydrochloride 

L-histidine hydrochloride 

L-histidine 

Polysorbate 20 

Water for injections 

 

6.2 Incompatibilities 
 

This medicinal product must not be mixed with other medicinal products. 

 

6.3 Shelf life 
 

15 months. 

 

The shelf life includes potential temperature excursions. The product may be kept for a total of 4 hours 

at 25C. If necessary, the product may be returned to the refrigerator for later use, but this must not be 

done more than once. 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Store in the original package in order to protect from light. 

 

6.5 Nature and contents of container 
 

0.5 ml solution in a pre-filled syringe barrel (type I glass) with staked needle (stainless steel), (type I) 

plunger stopper and needle cap. 

 

Pack containing 1 pre-filled syringe, and multipacks containing 4 (4 x 1) or 10 (10 x 1) pre-filled 

syringes. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

Xolair 75 mg solution for injection is supplied in a single-use pre-filled syringe for individual use. The 

syringe should be taken out of the refrigerator 20 minutes before injecting to allow it to reach room 

temperature. 

 

Disposal instructions 

 

Dispose of the used syringe immediately in a sharps container. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 



64 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/005 

EU/1/05/319/006 

EU/1/05/319/007 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 25 October 2005 

Date of latest renewal: 22 June 2015 

 

 

10. DATE OF REVISION OF THE TEXT 
 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


65 

1. NAME OF THE MEDICINAL PRODUCT 
 

Xolair 150 mg solution for injection in pre-filled syringe 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each pre-filled syringe of 1 ml solution contains 150 mg of omalizumab*. 

 

*Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology in 

a Chinese hamster ovary (CHO) mammalian cell line. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for injection in pre-filled syringe (injection). 

 

Clear to slightly opalescent, colourless to pale brownish-yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Allergic asthma 

 

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

 

Xolair treatment should only be considered for patients with convincing IgE (immunoglobulin E) 

mediated asthma (see section 4.2). 

 

Adults and adolescents (12 years of age and older) 

Xolair 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 high-

dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist. 

 

Children (6 to <12 years of age) 

Xolair 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 beta2-

agonist. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Xolair is indicated as an add-on therapy with intranasal corticosteroids (INC) for the treatment of 

adults (18 years and above) with severe CRSwNP for whom therapy with INC does not provide 

adequate disease control. 

 

Chronic spontaneous urticaria (CSU) 

 

Xolair is indicated as add-on therapy for the treatment of chronic spontaneous urticaria in adult and 

adolescent (12 years and above) patients with inadequate response to H1 antihistamine treatment. 



66 

 

4.2 Posology and method of administration 
 

Xolair treatment should be initiated by physicians experienced in the diagnosis and treatment of severe 

persistent asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) or chronic spontaneous 

urticaria. 

 

Posology 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 
Dosing for allergic asthma and CRSwNP follows the same dosing principles. The appropriate dose 

and frequency of Xolair for these conditions is determined by baseline IgE (IU/ml), measured before 

the start of treatment, and body weight (kg). Prior to administration of the initial dose, patients should 

have their IgE level determined by any commercial serum total IgE assay for their dose assignment. 

Based on these measurements, 75 to 600 mg of Xolair in 1 to 4 injections may be needed for each 

administration. 

 

Allergic asthma patients with baseline IgE lower than 76 IU/ml were less likely to experience benefit 

(see section 5.1). Prescribing physicians should ensure that adult and adolescent patients with IgE 

below 76 IU/ml and children (6 to < 12 years of age) with IgE below 200 IU/ml have unequivocal in 

vitro reactivity (RAST) to a perennial allergen before starting therapy. 

 

See Table 1 for a conversion chart and Tables 2 and 3 for the dose determination charts. 

 

Patients whose baseline IgE levels or body weight in kilograms are outside the limits of the dose table 

should not be given Xolair. 

 

The maximum recommended dose is 600 mg omalizumab every two weeks. 

 

Table 1 Conversion from dose to number of syringes, number of injections and total 

injection volume for each administration 

 

Dose (mg) Number of syringes Number of injections Total injection volume (ml) 

 75 mg  150 mg    

75 1 0 1 0.5 

150 0 1 1 1.0 

225 1 1 2 1.5 

300 0 2 2 2.0 

375 1 2 3 2.5 

450 0 3 3 3.0 

525 1 3 4 3.5 

600 0 4 4 4.0 

 



67 

Table 2 ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 4 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20-

25* 

>25-  

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90-  

125 

>125-  

150 

30-100 75 75 75 150 150 150 150 150 300 300 

>100-200 150 150 150 300 300 300 300 300 450 600 

>200-300 150 150 225 300 300 450 450 450 600  

>300-400 225 225 300 450 450 450 600 600   

>400-500 225 300 450 450 600 600     

>500-600 300 300 450 600 600      

>600-700 300  450 600       

>700-800           

>800-900     ADMINISTRATION EVERY 2 WEEKS 

SEE TABLE 3 

 

>900-

1000 

     

>1000-

1100 

          

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 



68 

Table 3 ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) 

administered by subcutaneous injection every 2 weeks 

 

 Body weight (kg) 

Baseline 

IgE 

(IU/ml) 

20- 

25* 

>25-  

30* 

>30-  

40 

>40-  

50 

>50-  

60 

>60-  

70 

>70-  

80 

>80-  

90 

>90-  

125 

>125-  

150 

30-100 ADMINISTRATION EVERY 4 WEEKS 

SEE TABLE 2 

     

>100-200      

>200-300          375 

>300-400         450 525 

>400-500       375 375 525 600 

>500-600      375 450 450 600  

>600-700  225   375 450 450 525   

>700-800 225 225 300 375 450 450 525 600   

>800-900 225 225 300 375 450 525 600    

>900-

1000 

225 300 375 450 525 600     

>1000-

1100 

225 300 375 450 600      

>1100-

1200 

300 300 450 525 600 Insufficient data to recommend a dose 

>1200-

1300 

300 375 450 525       

>1300-

1500 

300 375 525 600       

*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP. 

 

  



69 

Treatment duration, monitoring and dose adjustments 

Allergic asthma 

Xolair is intended for long-term treatment. Clinical trials have demonstrated that it takes at least 

12-16 weeks for Xolair treatment to show effectiveness. At 16 weeks after commencing Xolair 

therapy patients should be assessed by their physician for treatment effectiveness before further 

injections are administered. The decision to continue Xolair following the 16-week timepoint, or on 

subsequent occasions, should be based on whether a marked improvement in overall asthma control is 

seen (see section 5.1, Physician’s overall assessment of treatment effectiveness). 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical trials for CRSwNP, changes in nasal polyps score (NPS) and nasal congestion score (NCS) 

were observed at 4 weeks. The need for continued therapy should be periodically reassessed based 

upon the patient’s disease severity and level of symptom control. 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

Discontinuation of Xolair treatment 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 one 

year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment 

cannot be used as a guide for dose determination. Dose determination after treatment interruptions 

lasting less than one 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 Xolair 

has been interrupted for one year or more. 

 

Doses should be adjusted for significant changes in body weight (see Tables 2 and 3). 

 

Chronic spontaneous urticaria (CSU) 

The recommended dose is 300 mg by subcutaneous injection every four weeks. 

 

Prescribers are advised to periodically reassess the need for continued therapy. 

 

Clinical trial experience of long-term treatment beyond 6 months in this indication is limited. 

 

Special populations 

Elderly (65 years of age and older) 

There are limited data available on the use of Xolair in patients older than 65 years but there is no 

evidence that elderly patients require a different dose from younger adult patients. 

 

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 the reticular 

endothelial system (RES) it is unlikely to be altered by renal or hepatic impairment. While no 

particular dose adjustment is recommended for these patients, Xolair should be administered with 

caution (see section 4.4). 

 

Paediatric population 

In allergic asthma, the safety and efficacy of Xolair in patients below the age of 6 years have not been 

established. No data are available. 

 

In CRSwNP, the safety and efficacy of Xolair in patients below the age of 18 years have not been 

established. 

 

In CSU, the safety and efficacy of Xolair in patients below the age of 12 years have not been 

established. 

 



70 

Method of administration 

 

For subcutaneous administration only. Xolair must not be administered by the intravenous or 

intramuscular route. 

 

Doses of more than 150 mg (Table 1) should be divided across two or more injection sites. 

 

Patients with no known history of anaphylaxis may self-inject Xolair or be injected by a caregiver 

from the 4th dose onwards if a physician determines that this is appropriate (see section 4.4). The 

patient or the caregiver must have been trained in the correct injection technique and the recognition of 

the early signs and symptoms of serious allergic reactions. 

 
Patients or caregivers should be instructed to inject the full amount of Xolair according to the 

instructions provided in the package leaflet. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 
 

Traceability 

 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

General 

 

Xolair is not indicated for the treatment of acute asthma exacerbations, acute bronchospasm or status 

asthmaticus. 

 

Xolair has not been studied in patients with hyperimmunoglobulin E syndrome or allergic 

bronchopulmonary aspergillosis or for the prevention of anaphylactic reactions, including those 

provoked by food allergy, atopic dermatitis, or allergic rhinitis. Xolair is not indicated for the 

treatment of these conditions. 

 

Xolair therapy has not been studied in patients with autoimmune diseases, immune complex-mediated 

conditions, or pre-existing renal or hepatic impairment (see section 4.2). Caution should be exercised 

when administering Xolair in these patient populations. 

 

Abrupt discontinuation of systemic or inhaled corticosteroids after initiation of Xolair therapy in 

allergic asthma or CRSwNP is not recommended. Decreases in corticosteroids should be performed 

under the direct supervision of a physician and may need to be performed gradually. 

 



71 

Immune system disorders 

 

Allergic reactions type I 

Type I local or systemic allergic reactions, including anaphylaxis and anaphylactic shock, may occur 

when taking omalizumab, even after a long duration of treatment. However, most of these reactions 

occurred within 2 hours after the first and subsequent injections of Xolair but some started beyond 

2 hours and even beyond 24 hours after the injection. The majority of anaphylactic reactions occurred 

within the first 3 doses of Xolair. Therefore, the first 3 doses must be administered either by or under 

the supervision of a healthcare professional. A history of anaphylaxis unrelated to omalizumab may be 

a risk factor for anaphylaxis following Xolair administration. Therefore for patients with a known 

history of anaphylaxis, Xolair must be administered by a health care professional, who should always 

have medicinal products for the treatment of anaphylactic reactions available for immediate use 

following administration of Xolair. If an anaphylactic or other serious allergic reaction occurs, 

administration of Xolair must be discontinued immediately, and appropriate therapy initiated. Patients 

should be informed that such reactions are possible, and prompt medical attention should be sought if 

allergic reactions occur. 

 

Antibodies to omalizumab have been detected in a low number of patients in clinical trials (see 

section 4.8). The clinical relevance of anti-Xolair antibodies is not well understood. 

 

Serum sickness 

Serum sickness and serum sickness-like reactions, which are delayed allergic type III reactions, have 

been seen in patients treated with humanised monoclonal antibodies including omalizumab. The 

suggested pathophysiologic mechanism includes immune-complex formation and deposition due to 

development of antibodies against omalizumab. The onset has typically been 1-5 days after 

administration of the first or subsequent injections, also after long duration of treatment. Symptoms 

suggestive of serum sickness include arthritis/arthralgias, rash (urticaria or other forms), fever and 

lymphadenopathy. Antihistamines and corticosteroids may be useful for preventing or treating this 

disorder, and patients should be advised to report any suspected symptoms. 

 

Churg-Strauss syndrome and hypereosinophilic syndrome 

Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or allergic 

eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), both of which are usually treated 

with systemic corticosteroids. 

 

In rare cases, patients on therapy with anti-asthma medicinal products, including omalizumab, may 

present or develop systemic eosinophilia and vasculitis. These events are commonly associated with 

the reduction of oral corticosteroid therapy. 

 

In these patients, physicians should be alert to the development of marked eosinophilia, vasculitic 

rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac complications, and/or 

neuropathy. 

 

Discontinuation of omalizumab should be considered in all severe cases with the above mentioned 

immune system disorders. 

 

Parasitic (helminth) infections 

 

IgE may be involved in the immunological response to some helminth infections. In patients at chronic 

high risk of helminth infection, a placebo-controlled trial in allergic patients showed a slight increase 

in infection rate with omalizumab, although the course, severity, and response to treatment of infection 

were unaltered. The helminth infection rate in the overall clinical programme, which was not designed 

to detect such infections, was less than 1 in 1,000 patients. However, caution may be warranted in 

patients at high risk of helminth infection, in particular when travelling to areas where helminthic 

infections are endemic. If patients do not respond to recommended anti-helminth treatment, 

discontinuation of Xolair should be considered. 

 



72 

Latex-sensitive individuals 

 

The removable needle cap of this pre-filled syringe contains a derivative of natural rubber latex. No 

natural rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of 

Xolair solution for injection in pre-filled syringe in latex-sensitive individuals has not been studied and 

thus there is a potential risk for hypersensitivity reactions which cannot be completely ruled out. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Since IgE may be involved in the immunological response to some helminth infections, Xolair may 

indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic 

infections (see section 4.4). 

 

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 Xolair. There is no pharmacological reason 

to expect that commonly prescribed medicinal products used in the treatment of asthma, CRSwNP or 

CSU will interact with omalizumab. 

 

Allergic asthma 

 

In clinical studies Xolair 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 Xolair was altered with these other 

commonly used anti-asthma medicinal products. Limited data are available on the use of Xolair in 

combination with specific immunotherapy (hypo-sensitisation therapy). In a clinical trial where Xolair 

was co-administered with immunotherapy, the safety and efficacy of Xolair in combination with 

specific immunotherapy were found to be no different to that of Xolair alone. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

In clinical studies Xolair was used in conjunction with intranasal mometasone spray as per protocol. 

Other commonly used concomitant medicinal products included other intranasal corticosteroids, 

bronchodilators antihistamines, leukotriene receptor antagonists, adrenergics/sympathomimetics and 

local nasal anesthetics. There was no indication that the safety of Xolair was altered by the 

concomitant use of these other commonly used medicinal products. 

 

Chronic spontaneous urticaria (CSU) 

 

In clinical studies in CSU, Xolair 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 (see section 5.2). 

 

Paediatric population 

Clinical studies in CSU included some patients aged 12 to 17 years taking Xolair in conjunction with 

antihistamines (anti-H1, anti-H2) and LTRAs. No studies have been performed in children under 

12 years. 

 



73 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) based on 

pregnancy registry and post-marketing spontaneous reports, indicates no malformative or 

foeto/neonatal toxicity. A prospective pregnancy registry study (EXPECT) in 250 pregnant women 

with asthma exposed to Xolair showed the prevalence of major congenital anomalies was similar 

(8.1% vs. 8.9%) between EXPECT and disease-matched (moderate and severe asthma) patients. The 

interpretation of data may be impacted due to methodological limitations of the study, including small 

sample size and non-randomised design. 

 

Omalizumab crosses the placental barrier. However, animal studies do not indicate either direct or 

indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

 

Omalizumab has been associated with age-dependent decreases in blood platelets in non-human 

primates, with a greater relative sensitivity in juvenile animals (see section 5.3). 

 

If clinically needed, the use of Xolair may be considered during pregnancy. 

 

Breast-feeding 

 

Immunoglobulins G (IgGs) are present in human milk and therefore it is expected that omalizumab 

will be present in human milk. Available data in non-human primates have shown excretion of 

omalizumab into milk (see section 5.3). 

 

The EXPECT study, with 154 infants who had been exposed to Xolair during pregnancy and through 

breast-feeding did not indicate adverse effects on the breast-fed infant. The interpretation of data may 

be impacted due to methodological limitations of the study, including small sample size and non-

randomised design. 

 

Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability. 

No effects on the breast-fed newborns/infants are anticipated. Consequently, if clinically needed, the 

use of Xolair may be considered during breast-feeding. 

 

Fertility 

 

There are no human fertility data for omalizumab. In specifically-designed non-clinical fertility 

studies, in non-human primates including mating studies, no impairment of male or female fertility 

was observed following repeated dosing with omalizumab at dose levels up to 75 mg/kg. Furthermore, 

no genotoxic effects were observed in a separate non-clinical genotoxicity study. 

 

4.7 Effects on ability to drive and use machines 
 

Xolair has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Summary of the safety profile 

 

During allergic asthma clinical trials in adult and adolescent patients 12 years of age and older, the 

most commonly reported adverse reactions were headaches and injection site reactions, including 

injection site pain, swelling, erythema and pruritus. In clinical trials in children 6 to <12 years of age, 

the most commonly reported adverse reactions were headache, pyrexia and upper abdominal pain. 

Most of the reactions were mild or moderate in severity. In clinical trials in patients ≥18 years of age 



74 

in CRSwNP, the most commonly reported adverse reactions were headache, dizziness, arthralgia, 

abdominal pain upper and injection site reactions. 

 

Tabulated list of adverse reactions 

 

Table 4 lists the adverse reactions recorded in clinical studies in the total allergic asthma and CRSwNP 

safety population treated with Xolair by MedDRA system organ class and frequency. Within each 

frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency 

categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to 

<1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Reactions reported in the post-

marketing setting are listed with frequency not known (cannot be estimated from the available data). 

 

Table 4 Adverse reactions in allergic asthma and CRSwNP 

 
Infections and infestations 

Uncommon Pharyngitis 

Rare Parasitic infection 

Blood and lymphatic system disorders 

Not known Idiopathic thrombocytopenia, including severe cases 

Immune system disorders 

Rare Anaphylactic reaction, other serious allergic conditions, anti-

omalizumab antibody development 

Not known Serum sickness, may include fever and lymphadenopathy 

Nervous system disorders 

Common Headache* 

Uncommon Syncope, paraesthesia, somnolence, dizziness# 

Vascular disorders 

Uncommon Postural hypotension, flushing 

Respiratory, thoracic and mediastinal disorders 

Uncommon Allergic bronchospasm, coughing 

Rare Laryngoedema 

Not known Allergic granulomatous vasculitis (i.e. Churg-Strauss syndrome) 

Gastrointestinal disorders 

Common Abdominal pain upper**,# 

Uncommon Dyspeptic signs and symptoms, diarrhoea, nausea 

Skin and subcutaneous tissue disorders 

Uncommon Photosensitivity, urticaria, rash, pruritus 

Rare Angioedema 

Not known Alopecia 

Musculoskeletal and connective tissue disorders 

Common Athralgia† 
Rare Systemic lupus erythematosus (SLE) 

Not known Myalgia, joint swelling 

General disorders and administration site conditions 

Very common Pyrexia** 

Common Injection site reactions such as swelling, erythema, pain, pruritus 

Uncommon Influenza-like illness, swelling arms, weight increase, fatigue 

*: Very common in children 6 to <12 years of age 

**: In children 6 to <12 years of age 
#: Common in nasal polyp trials 

†: Unknown in allergic asthma trials 

 

  



75 

Chronic spontaneous urticaria (CSU) 

 

Summary of the safety profile 

The safety and tolerability of omalizumab were investigated with doses of 75 mg, 150 mg and 300 mg 

every four weeks in 975 CSU patients, 242 of whom received placebo. Overall, 733 patients were 

treated with omalizumab for up to 12 weeks and 490 patients for up to 24 weeks. Of those, 

412 patients were treated for up to 12 weeks and 333 patients were treated for up to 24 weeks at the 

300 mg dose. 

 

Tabulated list of adverse reactions 

A separate table (Table 5) shows the adverse reactions for the CSU indication resulting from 

differences in dosages and treatment populations (with significantly different risk factors, 

comorbidities, co-medications and ages [e.g. asthma trials included children from 6-12 years of age]). 

 

Table 5 lists the adverse reactions (events occurring in ≥1% of patients in any treatment group and 

≥2% more frequently in any omalizumab treatment group than with placebo (after medical review)) 

reported with 300 mg in the three pooled phase III studies. The adverse reactions presented are divided 

into two groups: those identified in the 12-week and the 24-week treatment periods. 

 

The adverse reactions are listed by MedDRA system organ class. Within each system organ class, the 

adverse reactions are ranked by frequency, with the most frequent reactions listed first. The 

corresponding frequency category for each adverse reaction is based on the following convention: 

very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 

to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from the available data). 

 

Table 5 Adverse reactions from the pooled CSU safety database (day 1 to week 24) at 

300 mg omalizumab 

 

12-Week 
Omalizumab studies 1, 2 and 3 Pooled Frequency category 

Placebo N=242 300 mg N=412  

Infections and infestations 

Sinusitis 5 (2.1%) 20 (4.9%) Common 

Nervous system disorders 

Headache 7 (2.9%) 25 (6.1%) Common 

Musculoskeletal and connective tissue disorders 

Arthralgia 1 (0.4%) 12 (2.9%) Common 

General disorder and administration site conditions 
Injection site reaction* 2 (0.8%) 11 (2.7%) Common 

24-Week 
Omalizumab studies 1 and 3 Pooled Frequency category 

Placebo N=163 300 mg N=333  

Infections and infestations 
Upper respiratory tract 

infection 
5 (3.1%) 19 (5.7%) Common 

* Despite not showing a 2% difference to placebo, injection site reactions were included as all cases 

were assessed causally related to study treatment. 

 

  



76 

Description of selected adverse reactions 

 

Immune system disorders 

For further information, see section 4.4. 

 

Anaphylaxis 

Anaphylactic reactions were rare in clinical trials. However, post-marketing data following a 

cumulative search in the safety database retrieved a total of 898 anaphylaxis cases. Based on an 

estimated exposure of 566,923 patient treatment years, this results in a reporting rate of approximately 

0.20%. 

 

Arterial thromboembolic events (ATE) 

In controlled clinical trials and during interim analyses of an observational study, a numerical 

imbalance of ATE was observed. The definition of the composite endpoint ATE included stroke, 

transient ischaemic attack, myocardial infarction, unstable angina, and cardiovascular death (including 

death from unknown cause). In the final analysis of the observational study, the rate of ATE per 1,000 

patient years was 7.52 (115/15,286 patient years) for Xolair-treated patients and 5.12 (51/9,963 patient 

years) for control patients. In a multivariate analysis controlling for available baseline cardiovascular 

risk factors, the hazard ratio was 1.32 (95% confidence interval 0.91-1.91). In a separate analysis of 

pooled clinical trials, which included all randomised double-blind, placebo-controlled clinical trials 

lasting 8 or more weeks, the rate of ATE per 1,000 patient years was 2.69 (5/1,856 patient years) for 

Xolair-treated patients and 2.38 (4/1,680 patient years) for placebo patients (rate ratio 1.13, 95% 

confidence interval 0.24-5.71). 

 

Platelets 

In clinical trials few patients had platelet counts below the lower limit of the normal laboratory range. 

None of these changes were associated with bleeding episodes or a decrease in haemoglobin. No 

pattern of persistent decrease in platelet counts, as observed in non-human primates (see section 5.3), 

has been reported in humans (patients above 6 years of age), even though isolated cases of idiopathic 

thrombocytopenia, including severe cases, have been reported in the post-marketing setting. 

 

Parasitic infections 

In allergic patients at chronic high risk of helminth infection, a placebo-controlled trial showed a slight 

numerical increase in infection rate with omalizumab that was not statistically significant. The course, 

severity, and response to treatment of infections were unaltered (see section 4.4). 

 

Systemic lupus erythematosus 

Clinical trial and post-marketing cases of systemic lupus erythematosus (SLE) have been reported in 

patients with moderate to severe asthma and CSU. The pathogenesis of SLE is not well understood. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Maximum tolerated dose of Xolair has not been determined. Single intravenous doses up to 4,000 mg 

have been administered to patients without evidence of dose-limiting toxicities. The highest 

cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not 

result in any untoward acute effects. 

 

If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. 

Medical treatment should be sought and instituted appropriately. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


77 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for 

obstructive airway diseases, ATC code: R03DX05 

 

Omalizumab is a recombinant DNA-derived humanised monoclonal antibody that selectively binds to 

human immunoglobulin E (IgE). The antibody is an IgG1 kappa that contains human framework 

regions with the complementary-determining regions of a murine parent antibody that binds to IgE. 

 

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

 

Mechanism of action 

Omalizumab binds to IgE and prevents binding of IgE to FcRI (high-affinity IgE receptor) on 

basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the 

allergic cascade. Treatment of atopic subjects with omalizumab resulted in a marked down-regulation 

of FcRI receptors on basophils. Treatment with Xolair inhibits IgE-mediated inflammation, as 

evidenced by reduced blood and tissue eosinophils and reduced inflammatory mediators, including 

IL-4, IL-5, and IL-13 by innate, adaptive and non-immune cells. 

 

Pharmacodynamic effects 

Allergic asthma 

The in vitro histamine release from basophils isolated from Xolair-treated subjects was reduced by 

approximately 90% following stimulation with an allergen compared to pre-treatment values. 

 

In clinical studies in allergic asthma patients, serum free IgE levels were reduced in a dose-dependent 

manner within one hour following the first dose and maintained between doses. One year after 

discontinuation of Xolair dosing, the IgE levels had returned to pre-treatment levels with no observed 

rebound in IgE levels after washout of the medicinal product. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

In clinical studies in patients with CRSwNP, Xolair treatment led to a reduction in serum free IgE 

(approx. 95%) and an increase in serum total IgE levels, to a similar extent as observed in patients 

with allergic asthma. Total IgE levels in serum increased due to the formation of omalizumab-IgE 

complexes that have a slower elimination rate compared with free IgE. 

 

Chronic spontaneous urticaria (CSU) 

 

Mechanism of action 

Omalizumab binds to IgE and lowers free IgE levels. Subsequently, IgE receptors (FcεRI) on cells 

down-regulate. It is not entirely understood how this results in an improvement of CSU symptoms. 

 

Pharmacodynamic effects 

In clinical studies in CSU patients, maximum suppression of free IgE was observed 3 days after the 

first subcutaneous dose. After repeated dosing once every 4 weeks, pre-dose serum free IgE levels 

remained stable between 12 and 24 weeks of treatment. After discontinuation of Xolair, free IgE levels 

increased towards pre-treatment levels over a 16-week treatment-free follow-up period. 

 



78 

Clinical efficacy and safety 

 

Allergic asthma 

Adults and adolescents ≥12 years of age 

The efficacy and safety of Xolair were demonstrated in a 28-week double-blind placebo-controlled 

study (study 1) involving 419 severe allergic asthmatics, ages 12-79 years, who had reduced lung 

function (FEV1 40-80% predicted) and poor asthma symptom control despite receiving high dose 

inhaled corticosteroids and a long-acting beta2-agonist. Eligible patients had experienced multiple 

asthma exacerbations requiring systemic corticosteroid treatment or had been hospitalised or attended 

an emergency room due to a severe asthma exacerbation in the past year despite continuous treatment 

with high-dose inhaled corticosteroids and a long-acting beta2-agonist. Subcutaneous Xolair or 

placebo were administered as add-on therapy to >1,000 micrograms beclomethasone dipropionate (or 

equivalent) plus a long-acting beta2-agonist. Oral corticosteroid, theophylline and leukotriene-

modifier maintenance therapies were allowed (22%, 27%, and 35% of patients, respectively). 

 

The rate of asthma exacerbations requiring treatment with bursts of systemic corticosteroids was the 

primary endpoint. Omalizumab reduced the rate of asthma exacerbations by 19% (p = 0.153). Further 

evaluations which did show statistical significance (p<0.05) in favour of Xolair included reductions in 

severe exacerbations (where patient’s lung function was reduced to below 60% of personal best and 

requiring systemic corticosteroids) and asthma-related emergency visits (comprised of 

hospitalisations, emergency room, and unscheduled doctor visits), and improvements in Physician’s 

overall assessment of treatment effectiveness, Asthma-related Quality of Life (AQL), asthma 

symptoms and lung function. 

 

In a subgroup analysis, patients with pre-treatment total IgE ≥76 IU/ml were more likely to experience 

clinically meaningful benefit to Xolair. In these patients in study 1 Xolair reduced the rate of asthma 

exacerbations by 40% (p = 0.002). In addition more patients had clinically meaningful responses in the 

total IgE ≥76 IU/ml population across the Xolair severe asthma programme. Table 6 includes results in 

the study 1 population. 

 

Table 6 Results of study 1 

 

 Whole study 1 population 

 Xolair 

N=209 

Placebo 

N=210 

Asthma exacerbations   

Rate per 28-week period 0.74 0.92 

% reduction, p-value for rate ratio 19.4%, p = 0.153 

Severe asthma exacerbations   

Rate per 28-week period 0.24 0.48 

% reduction, p-value for rate ratio 50.1%, p = 0.002 

Emergency visits   

Rate per 28-week period 0.24 0.43 

% reduction, p-value for rate ratio 43.9%, p = 0.038 

Physician’s overall assessment   

% responders* 60.5% 42.8% 

p-value** <0.001 

AQL improvement   

% of patients ≥0.5 improvement 60.8% 47.8% 

p-value 0.008 

* marked improvement or complete control 

** p-value for overall distribution of assessment 

 

Study 2 assessed the efficacy and safety of Xolair in a population of 312 severe allergic asthmatics 

which matched the population in study 1. Treatment with Xolair in this open label study led to a 61% 

reduction in clinically significant asthma exacerbation rate compared to current asthma therapy alone. 

 



79 

Four additional large placebo-controlled supportive studies of 28 to 52 weeks duration in 1,722 adults 

and adolescents (studies 3, 4, 5, 6) assessed the efficacy and safety of Xolair in patients with severe 

persistent asthma. Most patients were inadequately controlled but were receiving less concomitant 

asthma therapy than patients in studies 1 or 2. Studies 3-5 used exacerbation as primary endpoint, 

whereas study 6 primarily evaluated inhaled corticosteroid sparing. 

 

In studies 3, 4 and 5 patients treated with Xolair had respective reductions in asthma exacerbation 

rates of 37.5% (p = 0.027), 40.3% (p<0.001) and 57.6% (p<0.001) compared to placebo. 

 

In study 6, significantly more severe allergic asthma patients on Xolair were able to reduce their 

fluticasone dose to 500 micrograms/day without deterioration of asthma control (60.3%) compared to 

the placebo group (45.8%, p<0.05). 

 

Quality of life scores were measured using the Juniper Asthma-related Quality of Life Questionnaire. 

For all six studies there was a statistically significant improvement from baseline in quality of life 

scores for Xolair patients versus the placebo or control group. 

 

Physician’s overall assessment of treatment effectiveness: 

Physician’s overall assessment was performed in five of the above studies as a broad measure of 

asthma control performed by the treating physician. The physician was able to take into account PEF 

(peak expiratory flow), day and night time symptoms, rescue medication use, spirometry and 

exacerbations. In all five studies a significantly greater proportion of Xolair treated patients were 

judged to have achieved either a marked improvement or complete control of their asthma compared 

to placebo patients. 

 

Children 6 to <12 years of age 

The primary support for safety and efficacy of Xolair in the group aged 6 to <12 years comes from one 

randomised, double-blind, placebo-controlled, multi-centre trial (study 7). 

 

Study 7 was a placebo-controlled trial which included a specific subgroup (n=235) of patients as 

defined in the present indication, who were treated with high-dose inhaled corticosteroids 

(≥500 µg/day fluticasone equivalent) plus long-acting beta agonist. 

 

A clinically significant exacerbation was defined as a worsening of asthma symptoms as judged 

clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least 

3 days and/or treatment with rescue systemic (oral or intravenous) corticosteroids for at least 3 days. 

 

In the specific subgroup of patients on high dose inhaled corticosteroids, the omalizumab group had a 

statistically significantly lower rate of clinically significant asthma exacerbations than the placebo 

group. At 24 weeks, the difference in rates between treatment groups represented a 34% (rate ratio 

0.662, p = 0.047) decrease relative to placebo for omalizumab patients. In the second double-blind 28-

week treatment period the difference in rates between treatment groups represented a 63% (rate ratio 

0.37, p<0.001) decrease relative to placebo for omalizumab patients. 

 

During the 52-week double-blind treatment period (including the 24-week fixed-dose steroid phase 

and the 28-week steroid adjustment phase) the difference in rates between treatment groups 

represented a 50% (rate ratio 0.504, p<0.001) relative decrease in exacerbations for omalizumab 

patients. 

 



80 

The omalizumab group showed greater decreases in beta-agonist rescue medication use than the 

placebo group at the end of the 52-week treatment period, although the difference between treatment 

groups was not statistically significant. For the global evaluation of treatment effectiveness at the end 

of the 52-week double-blind treatment period in the subgroup of severe patients on high-dose inhaled 

corticosteroids plus long-acting beta agonists, the proportion of patients rated as having ‘excellent’ 

treatment effectiveness was higher, and the proportions having ‘moderate’ or ‘poor’ treatment 

effectiveness lower in the omalizumab group compared to the placebo group; the difference between 

groups was statistically significant (p<0.001), while there were no differences between the 

omalizumab and placebo groups for patients’ subjective Quality of Life ratings. 

 

Chronic rhinosinusitis with nasal polyps (CRSwNP) 

The safety and efficacy of Xolair were evaluated in two randomised, double-blind, placebo-controlled 

trials in patients with CRSwNP (Table 8). Patients received Xolair or placebo subcutaneously every 2 

or 4 weeks (see section 4.2). All patients received background intranasal mometasone therapy 

throughout the study. Prior sino-nasal surgery or prior systemic corticosteroid usage were not required 

for inclusion in the studies. Patients received Xolair or placebo for 24 weeks followed by a 4-week 

follow-up period. Demographics and baseline characteristics, including allergic comorbidities, are 

described in Table 7. 

 

Table 7 Demographics and baseline characteristics of nasal polyp studies 

 
Parameter Nasal polyp study 1 

N=138 

Nasal polyp study 2 

N=127 

Mean age (years) (SD) 51.0 (13.2) 50.1 (11.9) 

% Male 63.8 65.4 

Patients with systemic 

corticosteroid use in the 

previous year (%) 

18.8 26.0 

Bilateral endoscopic nasal 

polyp score (NPS): mean (SD), 

range 0-8 

6.2 (1.0) 6.3 (0.9) 

Nasal congestion score (NCS): 

mean (SD), range 0-3 

2.4 (0.6) 2.3 (0.7) 

Sense of smell score: mean 

(SD), range 0-3 

2.7 (0.7) 2.7 (0.7) 

SNOT-22 total score: mean 

(SD) range 0-110 

60.1 (17.7) 59.5 (19.3) 

Blood eosinophils (cells/µl): 

mean (SD) 

346.1 (284.1) 334.6 (187.6) 

Total IgE IU/ml: mean (SD) 160.9 (139.6) 190.2 (200.5) 

Asthma (%) 53.6 60.6 

 Mild (%) 37.8 32.5 

 Moderate (%) 58.1 58.4 

 Severe (%) 4.1 9.1 

Aspirin exacerbated respiratory 

disease (%) 

19.6 35.4 

Allergic rhinitis 43.5 42.5 

SD = standard deviation; SNOT-22 = Sino-Nasal Outcome Test 22 Questionnaire; IgE = 

Immunoglobulin E; IU = international units. For NPS, NCS, and SNOT-22 higher scores indicate 

greater disease severity. 

 

The co-primary endpoints were bilateral nasal polyps score (NPS) and average daily nasal congestion 

score (NCS) at Week 24. In both nasal polyp studies 1 and 2, patients who received Xolair had 

statistically significant greater improvements from baseline at Week 24 in NPS and weekly average 

NCS than patients who received placebo. Results from nasal polyp studies 1 and 2 are shown in 

Table 8. 



81 

 
Table 8 Change from baseline at Week 24 in clinical scores from nasal polyp study 1, nasal 

polyp study 2, and pooled data 

 

 Nasal polyp 

study 1 

Nasal polyp 

study 2 

Nasal polyp 

pooled results 

 Placebo Xolair Placebo Xolair Placebo Xolair 

N 66 72 65 62 131 134 

Nasal polyp score    

Baseline mean 6.32 6.19 6.09 6.44 6.21 6.31 

LS mean change at 

Week 24 

0.06 -1.08 -0.31 -0.90 -0.13 -0.99 

Difference (95%) 

CI  

-1.14 (-1.59, -069) 

 

-0.59 (-1.05, -012) 

 

-0.86 (-1.18, -0.54) 

p-value <0.0001 0.0140 <0.0001 

7-day average of 

daily nasal 

congestion score 

   

Baseline mean 2.46 2.40 2.29 2.26 2.38 2.34 

LS mean change at 

Week 24 

-0.35 -0.89 -0.20 -0.70 -0.28 -0.80 

Difference (95%) 

CI 

-0.55 (-0.84, -0.25) 

 

-0.50 (-0.80, -0.19) 

 

-0.52 (-0.73, -0.31) 

p-value 0.0004 0.0017 <0.0001 

TNSS    

Baseline mean 9.33 8.56 8.73 8.37 9.03 8.47 

LS mean change at 

Week 24 

-1.06 -2.97 -0.44 -2.53 -0.77 -2.75 

Difference (95%) -1.91 (-2.85, -0.96) -2.09 (-3.00, -1.18)  -1.98 (-2.63, -1.33) 

p-value 0.0001 <0.0001 <0.0001 

SNOT-22    

Baseline mean 60.26 59.82 59.80 59.21 60.03 59.54 

LS mean change at 

Week 24 

-8.58 -24.70 -6.55 -21.59 -7.73 -23.10 

Difference (95%) -16.12 (-21.86, -10.38) -15.04 (-21.26, -8.82) -15.36 (-19.57, -11.16) 

p-value <0.0001 <0.0001 <0.0001 

(MID = 8.9)    

UPSIT    

Baseline mean 13.56 12.78 13.27 12.87 13.41 12.82 

LS mean change at 

Week 24 

0.63 4.44 0.44 4.31 0.54 4.38 

Difference (95%) 3.81 (1.38, 6.24) 3.86 (1.57, 6.15) 3.84 (2.17, 5.51) 

p-value 0.0024 0.0011 <0.0001 

LS=least-square; CI = confidence interval; TNSS = Total nasal symptom score; SNOT-22 = Sino-

Nasal Outcome Test 22 Questionnaire; UPSIT = University of Pennsylvania Smell Identification 

Test; MID = minimal important difference. 

 



82 

Figure 2 Mean change from baseline in nasal congestion score and mean change from 

baseline in nasal polyp score by treatment group in nasal polyp study 1 and study 2 

 

 
 

In a pre-specified pooled analysis of rescue treatment (systemic corticosteroids for 3 consecutive 

days or nasal polypectomy) during the 24-week treatment period, the proportion of patients requiring 

rescue treatment was lower in Xolair compared to placebo (2.3% versus 6.2%, respectively). The 

odds-ratio of having taken rescue treatment in Xolair compared to placebo was 0.38 (95% CI: 0.10, 

1.49). There were no sino-nasal surgeries reported in either study. 

 

Chronic spontaneous urticaria (CSU) 

 

The efficacy and safety of Xolair were demonstrated in two randomised, placebo-controlled phase III 

studies (study 1 and 2) in patients with CSU who remained symptomatic despite H1 antihistamine 

therapy at the approved dose. A third study (study 3) primarily evaluated the safety of Xolair in 

patients with CSU who remained symptomatic despite treatment with H1 antihistamines at up to four 

times the approved dose and H2 antihistamine and/or LTRA treatment. The three studies enrolled 

975 patients aged between 12 and 75 years (mean age 42.3 years; 39 patients 12-17 years, 54 patients 

≥65 years; 259 males and 716 females). All patients were required to have inadequate symptom 

control, as assessed by a weekly urticaria activity score (UAS7, range 0-42) of ≥16, and a weekly itch 

severity score (which is a component of the UAS7; range 0-21) of ≥8 for the 7 days prior to 

randomisation, despite having used an antihistamine for at least 2 weeks beforehand. 

 

In studies 1 and 2, patients had a mean weekly itch severity score of between 13.7 and 14.5 at baseline 

and a mean UAS7 score of 29.5 and 31.7 respectively. Patients in safety study 3 had a mean weekly 

itch severity score of 13.8 and a mean UAS7 score of 31.2 at baseline. Across all three studies, 

patients reported receiving on average 4 to 6 medications (including H1 antihistamines) for CSU 

symptoms prior to study enrollment. Patients received Xolair at 75 mg, 150 mg or 300 mg or placebo 

by subcutaneous injection every 4 weeks for 24 and 12 weeks in studies 1 and 2, respectively, and 

300 mg or placebo by subcutaneous injection every 4 weeks for 24 weeks in study 3. All studies had a 

16-week treatment-free follow-up period. 

 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

Study 1 / Placebo (N=66) 

Study 1 / Omalizumab (N=72) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Study 2 / Placebo (N=65) 

Study 2 / Omalizumab (N=62) 

 

Secondary 

efficacy analysis 

Secondary 

efficacy analysis 

Primary efficacy 

analysis 

Primary efficacy 

analysis 

Baseline 24 20 16 12 8 4 4 8 12 16 20 24 

Week Week 

Baseline 

M
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0.25 0.25 

0.00 0.00 

-0.25 -0.25 

-0.50 -0.50 

-0.75 -0.75 

-1.00 -1.00 

-1.25 -1.25 



83 

The primary endpoint was the change from baseline to week 12 in weekly itch severity score. 

Omalizumab at 300 mg reduced the weekly itch severity score by 8.55 to 9.77 (p <0.0001) compared 

to a reduction of 3.63 to 5.14 for placebo (see Table 9). Statistically significant results were further 

observed in the responder rates for UAS7≤6 (at week 12) which were higher for the 300 mg treatment 

groups, ranging from 52-66% (p<0.0001) compared to 11-19% for the placebo groups, and complete 

response (UAS7=0) was achieved by 34-44% (p<0.0001) of patients treated with 300 mg compared to 

5-9% of patients in the placebo groups. Patients in the 300 mg treatment groups achieved the highest 

mean proportion of angioedema-free days from week 4 to week 12, (91.0-96.1%; p<0.001) compared 

to the placebo groups (88.1-89.2%). Mean change from baseline to week 12 in the overall DLQI for 

the 300 mg treatment groups was greater (p<0.001) than for placebo showing an improvement ranging 

from 9.7-10.3 points compared to 5.1-6.1 points for the corresponding placebo groups. 

 

Table 9 Change from baseline to week 12 in weekly itch severity score, studies 1, 2 and 3 

(mITT population*) 

 

 

Placebo 

Omalizumab 

300 mg 

Study 1   

 N 80 81 

 Mean (SD) −3.63 (5.22) −9.40 (5.73) 

 Difference in LS means vs. placebo1 - −5.80 

 95% CI for difference - −7.49,−4.10 

 P-value vs. placebo2 - <0.0001 

Study 2   

 N 79 79 

 Mean (SD) −5.14 (5.58) −9.77 (5.95) 

 Difference in LS means vs. placebo1 - −4.81 

 95% CI for difference - −6.49,−3.13 

 P-value vs. placebo2 - <0.0001 

Study 3   

 N 83 252 

 Mean (SD) −4.01 (5.87) −8.55 (6.01) 

 Difference in LS means vs. placebo1 - -4.52 

 95% CI for difference - −5.97, −3.08 

 P-value vs. placebo2 - <0.0001 

*Modified intent-to-treat (mITT) population: included all patients who were randomised and received 

at least one dose of study medication. 

BOCF (Baseline Observation Carried Forward) was used to impute missing data. 
1 The LS mean was estimated using an ANCOVA model. The strata were baseline weekly itch severity 

score (<13 vs. ≥13) and baseline weight (<80 kg vs. ≥80 kg). 
2 p-value is derived from ANCOVA t-test. 

 

Figure 2 shows the mean weekly itch severity score over time in study 1. The mean weekly itch 

severity scores significantly decreased with a maximum effect around week 12 that was sustained over 

the 24-week treatment period. The results were similar in study 3. 

 

In all three studies the mean weekly itch severity score increased gradually during the 16-week 

treatment-free follow-up period, consistent with symptom re-occurrence. Mean values at the end of the 

follow-up period were similar to the placebo group, but lower than respective mean baseline values. 

 



84 

Figure 2 Mean weekly itch severity score over time, study 1 (mITT population) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BOCF=baseline observation carried forward; mITT=modified intention-to-treat population 

 

Efficacy after 24 weeks of treatment 

The magnitude of the efficacy outcomes observed at week 24 of treatment was comparable to that 

observed at week 12: 

For 300 mg, in studies 1 and 3, the mean decrease from baseline in weekly itch severity score was 9.8 

and 8.6, the proportion of patients with UAS7≤6 was 61.7% and 55.6%, and the proportion of patients 

with complete response (UAS7=0) was 48.1% and 42.5%, respectively, (all p<0.0001, when compared 

to placebo). 

 

There is limited clinical experience in re-treatment of patients with omalizumab. 

 

Clinical trial data on adolescents (12 to 17 years) included a total of 39 patients, of whom 11 received 

the 300 mg dose. Results for the 300 mg are available for 9 patients at week 12 and 6 patients at 

week 24, and show a similar magnitude of response to omalizumab treatment compared to the adult 

population. Mean change from baseline in weekly itch severity score showed a reduction of 8.25 at 

week 12 and of 8.95 at week 24. The responder rates were: 33% at week 12 and 67% at week 24 for 

UAS7=0, and 56% at week 12 and 67% at week 24 for UAS7≤6. 

 

5.2 Pharmacokinetic properties 
 

The pharmacokinetics of omalizumab have been studied in adult and adolescent patients with allergic 

asthma as well as in adult patients with CRSwNP, and adult and adolescent patients with CSU. The 

general pharmacokinetic characteristics of omalizumab are similar in these patient populations. 

 

Absorption 

 

After subcutaneous administration, omalizumab is absorbed with an average absolute bioavailability 

of 62%. Following a single subcutaneous dose in adult and adolescent patients with asthma or CSU, 

omalizumab was absorbed slowly, reaching peak serum concentrations after an average of 6-8 days. In 

patients with asthma, following multiple doses of omalizumab, areas under the serum concentration-

time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after the first dose. 

 

0

5

10

15

0 4 8 12 16 20 24 28 32 36 40

      

Week 12 

Primary 

Endpoint Omalizumab 300 mg 

M
ea

n
 w

ee
k

ly
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tc
h

 s
ev

er
it

y
 s

co
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Week 

Omalizumab or placebo administered 

Placebo 



85 

The pharmacokinetics of omalizumab are linear at doses greater than 0.5 mg/kg. Following doses of 

75 mg, 150 mg or 300 mg every 4 weeks in patients with CSU, trough serum concentrations of 

omalizumab increased proportionally with the dose level. 

 

Administration of Xolair manufactured as a lyophilised or liquid formulation resulted in similar serum 

concentration-time profiles of omalizumab. 

 

Distribution 

 
In vitro, omalizumab forms complexes of limited size with IgE. Precipitating complexes and 

complexes larger than one million Daltons in molecular weight are not observed in vitro or in vivo. 

Based on population pharmacokinetics, distribution of omalizumab was similar in patients with 

allergic asthma and patients with CSU. The apparent volume of distribution in patients with asthma 

following subcutaneous administration was 78 ± 32 ml/kg. 

 

Elimination 

 
Clearance of omalizumab involves IgG clearance processes as well as clearance via specific binding 

and complex formation with its target ligand, IgE. Liver elimination of IgG includes degradation in the 

reticuloendothelial system and endothelial cells. Intact IgG is also excreted in bile. In asthma patients 

the omalizumab serum elimination half-life averaged 26 days, with apparent clearance averaging 

2.4  1.1 ml/kg/day. Doubling of body weight approximately doubled apparent clearance. In CSU 

patients, based on population pharmacokinetic simulations, omalizumab serum elimination half-life at 

steady state averaged 24 days and apparent clearance at steady state for a patient of 80 kg weight was 

3.0 ml/kg/day. 

 

Characteristics in patient populations 

 

Age, Race/ethnicity, Gender, Body Mass Index 

Patients with allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) 

The population pharmacokinetics of omalizumab were analysed to evaluate the effects of demographic 

characteristics. Analyses of these limited data suggest that no dose adjustments are necessary for age 

(6-76 years for patients with allergic asthma; 18 to 75 for patients with CRSwNP), race/ethnicity, 

gender or body mass index (see section 4.2). 

 

Patients with CSU 

The effects of demographic characteristics and other factors on omalizumab exposure were evaluated 

based on population pharmacokinetics. In addition, covariate effects were evaluated by analysing the 

relationship between omalizumab concentrations and clinical responses. These analyses suggest that 

no dose adjustments are necessary in patients with CSU for age (12-75 years), race/ethnicity, gender, 

body weight, body mass index, baseline IgE, anti-FcRI autoantibodies or concomitant use of H2 

antihistamines or LTRAs. 

 

Renal and hepatic impairment 

There are no pharmacokinetic or pharmacodynamic data in allergic asthma or CSU patients with renal 

or hepatic impairment (see sections 4.2 and 4.4). 

 

5.3 Preclinical safety data 
 

The safety of omalizumab has been studied in the cynomolgus monkey, since omalizumab binds to 

cynomolgus and human IgE with similar affinity. Antibodies to omalizumab were detected in some 

monkeys following repeated subcutaneous or intravenous administration. However, no apparent 

toxicity, such as immune complex-mediated disease or complement-dependent cytotoxicity, was seen. 

There was no evidence of an anaphylactic response due to mast-cell degranulation in cynomolgus 

monkeys. 

 



86 

Chronic administration of omalizumab at dose levels of up to 250 mg/kg (at least 14 times the highest 

recommended clinical dose in mg/kg according to the recommended dosing table) was well tolerated 

in non-human primates (both adult and juvenile animals), with the exception of a dose-related and age-

dependent decrease in blood platelets, with a greater sensitivity in juvenile animals. The serum 

concentration required to attain a 50% drop in platelets from baseline in adult cynomolgus monkeys 

was roughly 4- to 20-fold higher than anticipated maximum clinical serum concentrations. In addition, 

acute haemorrhage and inflammation were observed at injection sites in cynomolgus monkeys. 

 

Formal carcinogenicity studies have not been conducted with omalizumab. 

 

In reproduction studies in cynomolgus monkeys, subcutaneous doses up to 75 mg/kg per week (at least 

8 times the highest recommended clinical dose in mg/kg over a 4-week period) did not elicit maternal 

toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and did not 

elicit adverse effects on foetal or neonatal growth when administered throughout late gestation, 

delivery and nursing. 

 

Omalizumab is excreted in breast milk in cynomolgus monkeys. Milk levels of omalizumab were 

0.15% of the maternal serum concentration. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

L-arginine hydrochloride 

L-histidine hydrochloride 

L-histidine 

Polysorbate 20 

Water for injections 

 

6.2 Incompatibilities 
 

This medicinal product must not be mixed with other medicinal products. 

 

6.3 Shelf life 
 

15 months. 

 

The shelf life includes potential temperature excursions. The product may be kept for a total of 4 hours 

at 25C. If necessary, the product may be returned to the refrigerator for later use, but this must not be 

done more than once. 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Store in the original package in order to protect from light. 

 

6.5 Nature and contents of container 
 

1 ml solution in a pre-filled syringe barrel (type I glass) with staked needle (stainless steel), (type I) 

plunger stopper and needle cap. 

 

Pack containing 1 pre-filled syringe, and multipacks containing 4 (4 x 1); 6 (6 x 1) or 10 (10 x 1) pre-

filled syringes. 

 

Not all pack sizes may be marketed. 



87 

 

6.6 Special precautions for disposal and other handling 
 

Xolair 150 mg solution for injection is supplied in a single-use pre-filled syringe for individual use. 

The syringe should be taken out of the refrigerator 20 minutes before injecting to allow it to reach 

room temperature. 

 

Disposal instructions 

 

Dispose of the used syringe immediately in a sharps container. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/008 

EU/1/05/319/009 

EU/1/05/319/010 

EU/1/05/319/011 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 25 October 2005 

Date of latest renewal: 22 June 2015 

 

 

10. DATE OF REVISION OF THE TEXT 
 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

  

http://www.ema.europa.eu/


88 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 

BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 



89 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer of the biological active substance 

 

Novartis Pharma S.A.S. 

Centre de Biotechnologie 

8, rue de l’Industrie 

F-68330 Huningue 

France 

 

Novartis Singapore Pharmaceutical Manufacturing Pte. Ltd. 

BioProduction Operations Singapore 

8 Tuas Bay Lane 

Singapore 636986 

Singapore 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 

and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 

and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

  



90 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



91 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



92 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 75 mg powder and solvent for solution for injection 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 75 mg omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Powder: sucrose, L-histidine, L-histidine hydrochloride monohydrate and polysorbate 20. 

Solvent: water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 x 75 mg vial 

1 x 2 ml solvent ampoule 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



93 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Use immediately after reconstitution (may be stored at 2°C - 8°C for up to 8 hours or at 25°C for 

2 hours). 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 75 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 



94 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Xolair 75 mg powder for solution for injection 

omalizumab 

Subcutaneous use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

75 mg 

 

 

6. OTHER 

 

Store in a refrigerator. 

 

  



95 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

AMPOULE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Solvent for Xolair 

Water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

Use 0.9 ml and discard the rest. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2 ml 

 

 

6. OTHER 

 

 

  



96 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

CARTON CONTAINING 1 VIAL AND 1 AMPOULE AS UNIT PACK (INCLUDING BLUE 

BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg powder and solvent for solution for injection 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Powder: sucrose, L-histidine, L-histidine hydrochloride monohydrate and polysorbate 20. 

Solvent: water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 x 150 mg vial 

1 x 2 ml solvent ampoule 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



97 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Use immediately after reconstitution (may be stored at 2°C - 8°C for up to 8 hours or at 25°C for 

2 hours). 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 



98 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR INTERMEDIATE PACK (WITHOUT BLUE BOX) OF MULTIPACKS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg powder and solvent for solution for injection 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Powder: sucrose, L-histidine, L-histidine hydrochloride monohydrate and polysorbate 20. 

Solvent: water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 x 150 mg vial 

1 x 2 ml solvent ampoule 

1 vial and 1 ampoule. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



99 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Use immediately after reconstitution (may be stored at 2°C - 8°C for up to 8 hours or at 25°C for 

2 hours). 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/003 Multipack comprising 4 packs 

EU/1/05/319/004 Multipack comprising 10 packs 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



100 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

WRAPPER LABEL ON MULTIPACKS WRAPPED IN FOIL (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg powder and solvent for solution for injection 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Powder: sucrose, L-histidine, L-histidine hydrochloride monohydrate and polysorbate 20. 

Solvent: water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Multipack: 4 (4 x 1) vials and 4 (4 x 1) ampoules 

Multipack: 10 (10 x 1) vials and 10 (10 x 1) ampoules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



101 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Use immediately after reconstitution (may be stored at 2°C - 8°C for up to 8 hours or at 25°C for 

2 hours). 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/003 Multipack comprising 4 packs 

EU/1/05/319/004 Multipack comprising 10 packs 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



102 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Xolair 150 mg powder for solution for injection 

omalizumab 

Subcutaneous use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

150 mg 

 

 

6. OTHER 

 

Store in a refrigerator. 

 

  



103 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

AMPOULE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Solvent for Xolair 

Water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

Use 1.4 ml and discard the rest. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2 ml 

 

 

6. OTHER 

 

 

  



104 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 75 mg solution for injection in pre-filled syringe 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 0.5 ml solution contains 75 mg of omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, polysorbate 20, water 

for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in pre-filled syringe 

 

1 pre-filled syringe 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



105 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Dispose of the used syringe immediately in a sharps container. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/005 75 mg solution for injection in pre-filled syringe 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 75 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 



106 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



107 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 75 mg solution for injection in pre-filled syringe 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 0.5 ml solution contains 75 mg of omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, polysorbate 20, water 

for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in pre-filled syringe 

 

Multipack: 4 (4 x 1) pre-filled syringes 

Multipack: 10 (10 x 1) pre-filled syringes 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



108 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Dispose of the used syringe immediately in a sharps container. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/006 75 mg solution for injection in pre-filled syringe (4 x 1) 

EU/1/05/319/007 75 mg solution for injection in pre-filled syringe (10 x 1) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 75 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 



109 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



110 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 75 mg solution for injection in pre-filled syringe 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 0.5 ml solution contains 75 mg of omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, polysorbate 20, water 

for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in pre-filled syringe 

 

1 pre-filled syringe. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



111 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Dispose of the used syringe immediately in a sharps container. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/006 75 mg solution for injection in pre-filled syringe (4 x 1) 

EU/1/05/319/007 75 mg solution for injection in pre-filled syringe (10 x 1) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 75 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



112 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER OF PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 75 mg injection 

omalizumab 

SC 

Single use 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

  



113 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Xolair 75 mg injection 

omalizumab 

SC 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

0.5 ml 

 

 

6. OTHER 

 

 

  



114 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg solution for injection in pre-filled syringe 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 1 ml solution contains 150 mg of omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, polysorbate 20, water 

for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in pre-filled syringe 

 

1 pre-filled syringe 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



115 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Dispose of the used syringe immediately in a sharps container. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/008 150 mg solution for injection in pre-filled syringe 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 



116 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



117 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg solution for injection in pre-filled syringe 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 1 ml solution contains 150 mg of omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, polysorbate 20, water 

for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in pre-filled syringe 

 

Multipack: 4 (4 x 1) pre-filled syringes 

Multipack: 6 (6 x 1) pre-filled syringes 

Multipack: 10 (10 x 1) pre-filled syringes 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



118 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Dispose of the used syringe immediately in a sharps container. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/009 150 mg solution for injection in pre-filled syringe (4 x 1) 

EU/1/05/319/010 150 mg solution for injection in pre-filled syringe (10 x 1) 

EU/1/05/319/011 150 mg solution for injection in pre-filled syringe (6 x 1) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 



119 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



120 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg solution for injection in pre-filled syringe 

omalizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 1 ml solution contains 150 mg of omalizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, polysorbate 20, water 

for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in pre-filled syringe 

 

1 pre-filled syringe. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Use only as directed by a doctor. 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



121 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Dispose of the used syringe immediately in a sharps container. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/05/319/009 150 mg solution for injection in pre-filled syringe (4 x 1) 

EU/1/05/319/010 150 mg solution for injection in pre-filled syringe (10 x 1) 

EU/1/05/319/011 150 mg solution for injection in pre-filled syringe (6 x 1) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Xolair 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



122 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER OF PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Xolair 150 mg injection 

omalizumab 

SC 

Single use 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

  



123 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Xolair 150 mg injection 

omalizumab 

SC 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1 ml 

 

 

6. OTHER 

 

 

  



124 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



125 

Package leaflet: Information for the user 

 

Xolair 75 mg powder and solvent for solution for injection 

omalizumab 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Xolair is and what it is used for 

2. What you need to know before you are given Xolair 

3. How Xolair is given 

4. Possible side effects 

5. How to store Xolair 

6. Contents of the pack and other information 

 

 

1. What Xolair is and what it is used for 
 

Xolair contains the active substance omalizumab. Omalizumab is a man-made protein that is similar to 

natural proteins produced by the body. It belongs to a class of medicines called monoclonal antibodies. 

 

Xolair is used for the treatment of: 

- allergic asthma 
- chronic rhinosinusitis (inflammation of the nose and sinuses) with nasal polyps 
 

Allergic asthma 

This medicine is used to prevent asthma from getting worse by controlling symptoms of severe 

allergic asthma in adults, adolescents and children (6 years of age and older) who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high-dose 

steroid inhalers and beta-agonist inhalers. 

 

Chronic rhinosinusitis with nasal polyps 

This medicine is used to treat chronic rhinosinusitis with nasal polyps in adults (18 years of age and 

older) who are already receiving intranasal corticosteroids (corticosteroid nasal spray), but whose 

symptoms are not well controlled by these medicines. Nasal polyps are small growths on the lining of 

the nose. Xolair helps to reduce the size of the polyps and improves symptoms including nasal 

congestion, loss of sense of smell, mucus in the back of the throat and runny nose. 

 

Xolair works by blocking a substance called immunoglobulin E (IgE), which is produced by the body. 

IgE contributes to a type of inflammation that plays a key role in causing allergic asthma and chronic 

rhinosinusitis with nasal polyps. 

 

 

2. What you need to know before you are given Xolair 
 

You should not be given Xolair: 

- if you are allergic to omalizumab or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic to any of the ingredients, tell your doctor as you should not be given 

Xolair. 

 



126 

Warnings and precautions 
Talk to your doctor before you are given Xolair: 

- if you have kidney or liver problems. 
- if you have a disorder where your own immune system attacks parts of your own body 

(autoimmune disease). 

- if you are travelling to a region where infections caused by parasites are common - Xolair may 
weaken your resistance to such infections. 

- if you have had a previous severe allergic reaction (anaphylaxis) for example resulting from a 
medicine, an insect bite or food. 

 

Xolair does not treat acute asthma symptoms, such as a sudden asthma attack. Therefore Xolair should 

not be used to treat such symptoms. 

 

Xolair is not meant to prevent or treat other allergy-type conditions, such as sudden allergic reactions, 

hyperimmunoglobulin E syndrome (an inherited immune disorder), aspergillosis (a fungus-related 

lung disease), food allergy, eczema or hay fever because Xolair has not been studied in these 

conditions. 

 

Look out for signs of allergic reactions and other serious side effects 

Xolair can potentially cause serious side effects. You must look out for signs of these conditions while 

you use Xolair. Seek medical help immediately if you notice any signs indicating a possible serious 

side effect. Such signs are listed under “Serious side effects” in section 4. The majority of severe 

allergic reactions occur within the first 3 doses of Xolair. 

 

Children and adolescents 

Allergic asthma 

Xolair is not recommended for children under 6 years of age. Its use in children under 6 years of age 

has not been studied. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair is not recommended for children and adolescents under 18 years of age. Its use in patients 

under 18 years of age has not been studied. 

 

Other medicines and Xolair 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 

This is especially important if you are taking: 

- medicines to treat an infection caused by a parasite, as Xolair may reduce the effect of your 
medicines, 

- inhaled corticosteroids and other medicines for allergic asthma. 
 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 

advice before using this medicine. Your doctor will discuss with you the benefits and potential risks of 

being given this medicine during pregnancy. 

 

If you become pregnant while being treated with Xolair, tell your doctor immediately. 

 

Xolair may pass into breast milk. If you are breast-feeding or plan to breast-feed, ask your doctor for 

advice before using this medicine. 

 

Driving and using machines 

It is unlikely that Xolair will affect your ability to drive and use machines. 

 

 



127 

3. How Xolair is given 
 

Instructions on how to use Xolair are given in the section “Information for the healthcare 

professional”. 

 

Xolair is given to you by a doctor or nurse as an injection just under the skin (subcutaneously). 

 

Follow carefully all instructions given by your doctor or nurse. 

 

How much you will be given 

Your doctor will decide how much Xolair you need and how often you will be given it. This depends 

on your body weight and the results of a blood test carried out before the start of the treatment to 

measure the amount of IgE in your blood. 

 

You will be given 1 to 4 injections at a time, either every two weeks, or every four weeks. 

 

Keep taking your current asthma and/or nasal polyps medicine during Xolair treatment. Do not stop 

taking any asthma and/or nasal polyps medicine without talking to your doctor. 

 

You may not see an immediate improvement after beginning Xolair therapy. In patients with nasal 

polyps effects have been seen 4 weeks after the start of the treatment. In asthma patients it usually 

takes between 12 and 16 weeks to have the full effect. 

 

Use in children and adolescents 

Allergic asthma 

Xolair can be given to children and adolescents aged 6 years and older, who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high dose 

steroid inhalers and beta-agonist inhalers. Your doctor will work out how much Xolair your child 

needs and how often it needs to be given. This will depend on your child’s weight and the results of a 

blood test carried out before the start of the treatment to measure the amount of IgE in his/her blood. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair should not be given to children and adolescents under 18 years of age. 

 

If a dose of Xolair is missed 
Contact your doctor or hospital as soon as possible to re-schedule your appointment. 

 

If you stop treatment with Xolair 

Do not stop treatment with Xolair unless your doctor tells you to. Interrupting or stopping the 

treatment with Xolair may cause your symptoms to come back. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

  



128 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 

effects caused by Xolair are usually mild to moderate but can occasionally be serious. 

 

Serious side effects: 

 

Seek medical attention immediately if you notice any signs of the following side effects: 

Rare (may affect up to 1 in 1,000 people) 

- Severe allergic reactions (including anaphylaxis). Symptoms may include rash, itching or hives 
on the skin, swelling of the face, lips, tongue, larynx (voice box), windpipe or other parts of the 

body, fast heartbeat, dizziness and light-headedness, confusion, shortness of breath, wheezing or 

trouble breathing, blue skin or lips, collapsing and losing consciousness. If you have a history of 

severe allergic reactions (anaphylaxis) unrelated to Xolair you may be more at risk of 

developing a severe allergic reaction following use of Xolair. 

- Systemic lupus erythematosus (SLE). Symptoms may include muscle pain, joint pain and 
swelling, rash, fever, weight loss, and fatigue. 

 

Not known (frequency cannot be estimated from the available data) 

- Churg-Strauss syndrome or hypereosinophilic syndrome. Symptoms may include one or more 
of the following: swelling, pain or rash around blood or lymph vessels, high level of a specific 

type of white blood cells (marked eosinophilia), worsening problems with breathing, nasal 

congestion, heart problems, pain, numbness, tingling in the arms and legs. 

- Low blood platelet count with symptoms such as bleeding or bruising more easily than normal. 
- Serum sickness. Symptoms may include one or more of the following: joint pain with or 

without swelling or stiffness, rash, fever, swollen lymph nodes, muscle pain. 

 

Other side effects include: 

Very common (may affect more than 1 in 10 people) 

- fever (in children) 
 

Common (may affect up to 1 in 10 people) 

- reactions at the injection site including pain, swelling, itching and redness 
- pain in the upper part of the tummy 
- headache (very common in children) 
- feeling dizzy 
- pain in joints (arthralgia) 
 

Uncommon (may affect up to 1 in 100 people) 

- feeling sleepy or tired 
- tingling or numbness of the hands or feet 
- fainting, low blood pressure while sitting or standing (postural hypotension), flushing 
- sore throat, coughing, acute breathing problems 
- feeling sick (nausea), diarrhoea, indigestion 
- itching, hives, rash, increased sensitivity of the skin to sun 
- weight increase 
- flu-like symptoms 
- swelling arms 
 

Rare (may affect up to 1 in 1,000 people) 

- parasitic infection 
 

Not known (frequency cannot be estimated from the available data) 

- muscle pain and joint swelling 
- hair loss 
 



129 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Xolair 

 

- Keep this medicine out of the sight and reach of children. 
- Do not use this medicine after the expiry date which is stated on the label. The expiry date refers 

to the last day of that month. 

- Store in a refrigerator (2°C - 8°C). Do not freeze. 
 

 

6. Contents of the pack and other information 

 

What Xolair contains 

- The active substance is omalizumab. One vial contains 75 mg of omalizumab. After 
reconstitution one vial contains 125 mg/ml of omalizumab (75 mg in 0.6 ml). 

- The other ingredients are sucrose, L-histidine, L-histidine hydrochloride monohydrate and 
polysorbate 20. 

 

What Xolair looks like and contents of the pack 

Xolair 75 mg powder and solvent for solution for injection is supplied as a white to off-white powder 

in a small glass vial together with an ampoule containing 2 ml of water for injections. The powder is 

reconstituted in the water before it is injected by a doctor or nurse. 

 

Xolair is available in packs containing one vial of powder for solution for injection and one ampoule 

of 2 ml water for injections. 

 

Xolair is also available in vials with 150 mg omalizumab. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


130 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



131 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


132 

INFORMATION FOR THE HEALTHCARE PROFESSIONAL 
 

The following information is intended for healthcare professionals only: 

 

The lyophilised medicinal product takes 15-20 minutes to dissolve, although in some cases it may take 

longer. The fully reconstituted medicinal product will appear clear to slightly opalescent, colourless to 

pale brownish-yellow and may have a few small bubbles or foam around the edge of the vial. Because 

of the viscosity of the reconstituted medicinal product care must be taken to withdraw all of the 

medicinal product from the vial before expelling any air or excess solution from the syringe in order to 

obtain the 0.6 ml. 

 

To prepare Xolair 75 mg vials for subcutaneous administration, please adhere to the following 

instructions: 

 

1. Draw 0.9 ml of water for injections from the ampoule into a syringe equipped with a large-bore 

18-gauge needle. 

 

2. With the vial placed upright on a flat surface, insert the needle and transfer the water for 

injections into the vial containing the lyophilised powder using standard aseptic techniques, 

directing the water for injections directly onto the powder. 

 

3. Keeping the vial in an upright position, vigorously swirl it (do not shake) for approximately 

1 minute to evenly wet the powder. 

 

4. To aid in dissolution after completing step 3, gently swirl the vial for 5-10 seconds 

approximately every 5 minutes in order to dissolve any remaining solids. 

 

Note that in some cases it may take longer than 20 minutes for the powder to dissolve 

completely. If this is the case, repeat step 4 until there are no visible gel-like particles in the 

solution. 

 

When the medicinal product is fully dissolved, there should be no visible gel-like particles in 

the solution. Small bubbles or foam around the edge of the vial are common. The reconstituted 

medicinal product will appear clear to slightly opalescent, colourless to pale brownish-yellow. 

Do not use if solid particles are present. 

 

5. Invert the vial for at least 15 seconds in order to allow the solution to drain towards the stopper. 

Using a new 3-ml syringe equipped with a large-bore, 18-gauge needle, insert the needle into 

the inverted vial. Keeping the vial inverted position the needle tip at the very bottom of the 

solution in the vial when drawing the solution into the syringe. Before removing the needle 

from the vial, pull the plunger all the way back to the end of the syringe barrel in order to 

remove all of the solution from the inverted vial. 

 

6. Replace the 18-gauge needle with a 25-gauge needle for subcutaneous injection. 

 

7. Expel air, large bubbles, and any excess solution in order to obtain the required 0.6 ml dose. A 

thin layer of small bubbles may remain at the top of the solution in the syringe. Because the 

solution is slightly viscous, it may take 5-10 seconds to administer the solution by subcutaneous 

injection. 

 

The vial delivers 0.6 ml (75 mg) of Xolair. 

 

8. The injections are administered subcutaneously in the deltoid region of the arm, the lower 

abdomen (but not the area 5 centimetres around the navel) or the thigh. 



133 

Package leaflet: Information for the user 

 

Xolair 150 mg powder and solvent for solution for injection 

omalizumab 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Xolair is and what it is used for 

2. What you need to know before you are given Xolair 

3. How Xolair is given 

4. Possible side effects 

5. How to store Xolair 

6. Contents of the pack and other information 

 

 

1. What Xolair is and what it is used for 
 

Xolair contains the active substance omalizumab. Omalizumab is a man-made protein that is similar to 

natural proteins produced by the body. It belongs to a class of medicines called monoclonal antibodies. 

 

Xolair is used for the treatment of: 

- allergic asthma 
- chronic rhinosinusitis (inflammation of the nose and sinuses) with nasal polyps 
- chronic spontaneous urticaria (CSU) 
 

Allergic asthma 

This medicine is used to prevent asthma from getting worse by controlling symptoms of severe 

allergic asthma in adults, adolescents and children (6 years of age and older) who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high-dose 

steroid inhalers and beta-agonist inhalers. 

 

Chronic rhinosinusitis with nasal polyps 

This medicine is used to treat chronic rhinosinusitis with nasal polyps in adults (18 years of age and 

older) who are already receiving intranasal corticosteroids (corticosteroid nasal spray), but whose 

symptoms are not well controlled by these medicines. Nasal polyps are small growths on the lining of 

the nose. Xolair helps to reduce the size of the polyps and improves symptoms including nasal 

congestion, loss of sense of smell, mucus in the back of the throat and runny nose. 

 

Chronic spontaneous urticaria (CSU) 

This medicine is used to treat chronic spontaneous urticaria in adults and adolescents (12 years of age 

and older) who are already receiving antihistamines but whose CSU symptoms are not well controlled 

by these medicines. 

 

Xolair works by blocking a substance called immunoglobulin E (IgE), which is produced by the body. 

IgE contributes to a type of inflammation that plays a key role in causing allergic asthma, chronic 

rhinosinusitis with nasal polyps and CSU. 

 

 



134 

2. What you need to know before you are given Xolair 
 

You should not be given Xolair: 

- if you are allergic to omalizumab or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic to any of the ingredients, tell your doctor as you should not be given 

Xolair. 

 

Warnings and precautions 
Talk to your doctor before you are given Xolair: 

- if you have kidney or liver problems. 
- if you have a disorder where your own immune system attacks parts of your own body 

(autoimmune disease). 

- if you are travelling to a region where infections caused by parasites are common - Xolair may 
weaken your resistance to such infections. 

- if you have had a previous severe allergic reaction (anaphylaxis) for example resulting from a 
medicine, an insect bite or food. 

 

Xolair does not treat acute asthma symptoms, such as a sudden asthma attack. Therefore Xolair should 

not be used to treat such symptoms. 

 

Xolair is not meant to prevent or treat other allergy-type conditions, such as sudden allergic reactions, 

hyperimmunoglobulin E syndrome (an inherited immune disorder), aspergillosis (a fungus-related 

lung disease), food allergy, eczema or hay fever because Xolair has not been studied in these 

conditions. 

 

Look out for signs of allergic reactions and other serious side effects 

Xolair can potentially cause serious side effects. You must look out for signs of these conditions while 

you use Xolair. Seek medical help immediately if you notice any signs indicating a possible serious 

side effect. Such signs are listed under “Serious side effects” in section 4. The majority of severe 

allergic reactions occur within the first 3 doses of Xolair. 

 

Children and adolescents 

Allergic asthma 

Xolair is not recommended for children under 6 years of age. Its use in children under 6 years of age 

has not been studied. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair is not recommended for children and adolescents under 18 years of age. Its use in patients 

under 18 years of age has not been studied. 

 

Chronic spontaneous urticaria (CSU) 

Xolair is not recommended for children under 12 years of age. Its use in children under 12 years of age 

has not been studied. 

 

Other medicines and Xolair 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 

This is especially important if you are taking: 

- medicines to treat an infection caused by a parasite, as Xolair may reduce the effect of your 
medicines, 

- inhaled corticosteroids and other medicines for allergic asthma. 
 



135 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 

advice before using this medicine. Your doctor will discuss with you the benefits and potential risks of 

being given this medicine during pregnancy. 

 

If you become pregnant while being treated with Xolair, tell your doctor immediately. 

 

Xolair may pass into breast milk. If you are breast-feeding or plan to breast-feed, ask your doctor for 

advice before using this medicine. 

 

Driving and using machines 

It is unlikely that Xolair will affect your ability to drive and use machines. 

 

 

3. How Xolair is given 
 

Instructions on how to use Xolair are given in the section “Information for the healthcare 

professional”. 

 

Xolair is given to you by a doctor or nurse as an injection just under the skin (subcutaneously). 

 

Follow carefully all instructions given by your doctor or nurse. 

 

How much you will be given 

Allergic asthma and chronic rhinosinusitis with nasal polyps 

Your doctor will decide how much Xolair you need and how often you will be given it. This depends 

on your body weight and the results of a blood test carried out before the start of the treatment to 

measure the amount of IgE in your blood. 

 

You will be given 1 to 4 injections at a time, either every two weeks, or every four weeks. 

 

Keep taking your current asthma and/or nasal polyps medicine during Xolair treatment. Do not stop 

taking any asthma and/or nasal polyps medicine without talking to your doctor. 

 

You may not see an immediate improvement after beginning Xolair therapy. In patients with nasal 

polyps effects have been seen 4 weeks after the start of the treatment. In asthma patients it usually 

takes between 12 and 16 weeks to have the full effect. 

 

Chronic spontaneous urticaria (CSU) 

You will be given two 150 mg injections at a time every four weeks. 

 

Keep taking your current medicine for CSU during Xolair treatment. Do not stop taking any medicine 

without talking to your doctor. 

 

Use in children and adolescents 

Allergic asthma 

Xolair can be given to children and adolescents aged 6 years and older, who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high dose 

steroid inhalers and beta-agonist inhalers. Your doctor will work out how much Xolair your child 

needs and how often it needs to be given. This will depend on your child’s weight and the results of a 

blood test carried out before the start of the treatment to measure the amount of IgE in his/her blood. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair should not be given to children and adolescents under 18 years of age. 

 



136 

Chronic spontaneous urticaria (CSU) 

Xolair can be given to adolescents aged 12 years and older, who are already receiving antihistamines 

but whose CSU symptoms are not well controlled by these medicines. The dose for adolescents aged 

12 years and above is the same as for adults. 

 

If a dose of Xolair is missed 
Contact your doctor or hospital as soon as possible to re-schedule your appointment. 

 

If you stop treatment with Xolair 

Do not stop treatment with Xolair unless your doctor tells you to. Interrupting or stopping the 

treatment with Xolair may cause your symptoms to come back. 

 

However, if you are being treated for CSU, your doctor may stop Xolair treatment from time to time 

so that your symptoms can be assessed. Follow your doctor’s instructions. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 

effects caused by Xolair are usually mild to moderate but can occasionally be serious. 

 

Serious side effects: 

 

Seek medical attention immediately if you notice any signs of the following side effects: 

Rare (may affect up to 1 in 1,000 people) 

- Severe allergic reactions (including anaphylaxis). Symptoms may include rash, itching or hives 
on the skin, swelling of the face, lips, tongue, larynx (voice box), windpipe or other parts of the 

body, fast heartbeat, dizziness and light-headedness, confusion, shortness of breath, wheezing or 

trouble breathing, blue skin or lips, collapsing and losing consciousness. If you have a history of 

severe allergic reactions (anaphylaxis) unrelated to Xolair you may be more at risk of 

developing a severe allergic reaction following use of Xolair. 

- Systemic lupus erythematosus (SLE). Symptoms may include muscle pain, joint pain and 
swelling, rash, fever, weight loss, and fatigue. 

 

Not known (frequency cannot be estimated from the available data) 

- Churg-Strauss syndrome or hypereosinophilic syndrome. Symptoms may include one or more 
of the following: swelling, pain or rash around blood or lymph vessels, high level of a specific 

type of white blood cells (marked eosinophilia), worsening problems with breathing, nasal 

congestion, heart problems, pain, numbness, tingling in the arms and legs. 

- Low blood platelet count with symptoms such as bleeding or bruising more easily than normal. 
- Serum sickness. Symptoms may include one or more of the following: joint pain with or 

without swelling or stiffness, rash, fever, swollen lymph nodes, muscle pain. 

 

Other side effects include: 

Very common (may affect more than 1 in 10 people) 

- fever (in children) 
 

Common (may affect up to 1 in 10 people) 

- reactions at the injection site including pain, swelling, itching and redness 
- pain in the upper part of the tummy 
- headache (very common in children) 
- upper respiratory tract infection, such as inflammation of the pharynx and common cold 
- feeling of pressure or pain in the cheeks and forehead (sinusitis, sinus headache) 
- pain in joints (arthralgia) 
- feeling dizzy 



137 

 

Uncommon (may affect up to 1 in 100 people) 

- feeling, sleepy or tired 
- tingling or numbness of the hands or feet 
- fainting, low blood pressure while sitting or standing (postural hypotension), flushing 
- sore throat, coughing, acute breathing problems 
- feeling sick (nausea), diarrhoea, indigestion 
- itching, hives, rash, increased sensitivity of the skin to sun 
- weight increase 
- flu-like symptoms 
- swelling arms 
 

Rare (may affect up to 1 in 1,000 people) 

- parasitic infection 
 

Not known: frequency cannot be estimated from the available data 

- muscle pain and joint swelling 
- hair loss 
 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Xolair 

 

- Keep this medicine out of the sight and reach of children. 
- Do not use this medicine after the expiry date which is stated on the label. The expiry date refers 

to the last day of that month. 

- Store in a refrigerator (2°C - 8°C). Do not freeze. 
 

 

6. Contents of the pack and other information 

 

What Xolair contains 

- The active substance is omalizumab. One vial contains 150 mg of omalizumab. After 
reconstitution one vial contains 125 mg/ml of omalizumab (150 mg in 1.2 ml). 

- The other ingredients are sucrose, L-histidine, L-histidine hydrochloride monohydrate and 
polysorbate 20. 

 

What Xolair looks like and contents of the pack 

Xolair 150 mg powder and solvent for solution for injection is supplied as a white to off-white powder 

in a small glass vial together with an ampoule containing 2 ml of water for injections. The powder is 

reconstituted in the water before it is injected by a doctor or nurse. 

 

Xolair 150 mg powder and solvent for solution for injection is available in packs containing 1 vial of 

powder and 1 ampoule of water for injections, and in multipacks containing 4 (4 x 1) vials of powder 

and 4 (4 x 1) ampoules of water for injections or 10 (10 x 1) vials of powder and 10 (10 x 1) ampoules 

of water for injections. Not all pack sizes may be marketed. 

 

Xolair is also available in vials with 75 mg omalizumab. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


138 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 



139 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


140 

INFORMATION FOR THE HEALTHCARE PROFESSIONAL 
 

The following information is intended for healthcare professionals only: 

 

The lyophilised medicinal product takes 15-20 minutes to dissolve, although in some cases it may take 

longer. The fully reconstituted medicinal product will appear clear to slightly opalescent, colourless to 

pale brownish-yellow and may have a few small bubbles or foam around the edge of the vial. Because 

of the viscosity of the reconstituted medicinal product care must be taken to withdraw all of the 

medicinal product from the vial before expelling any air or excess solution from the syringe in order to 

obtain the 1.2 ml. 

 

To prepare Xolair 150 mg vials for subcutaneous administration, please adhere to the following 

instructions: 

 

1. Draw 1.4 ml of water for injections from the ampoule into a syringe equipped with a large-bore 

18-gauge needle. 

 

2. With the vial placed upright on a flat surface, insert the needle and transfer the water for 

injections into the vial containing the lyophilised powder using standard aseptic techniques, 

directing the water for injections directly onto the powder. 

 

3. Keeping the vial in an upright position, vigorously swirl it (do not shake) for approximately 

1 minute to evenly wet the powder. 

 

4. To aid in dissolution after completing step 3, gently swirl the vial for 5-10 seconds 

approximately every 5 minutes in order to dissolve any remaining solids. 

 

Note that in some cases it may take longer than 20 minutes for the powder to dissolve 

completely. If this is the case, repeat step 4 until there are no visible gel-like particles in the 

solution. 

 

When the medicinal product is fully dissolved, there should be no visible gel-like particles in 

the solution. Small bubbles or foam around the edge of the vial are common. The reconstituted 

medicinal product will appear clear to slightly opalescent, colourless to pale brownish-yellow. 

Do not use if solid particles are present. 

 

5. Invert the vial for at least 15 seconds in order to allow the solution to drain towards the stopper. 

Using a new 3-ml syringe equipped with a large-bore, 18-gauge needle, insert the needle into 

the inverted vial. Keeping the vial inverted position the needle tip at the very bottom of the 

solution in the vial when drawing the solution into the syringe. Before removing the needle 

from the vial, pull the plunger all the way back to the end of the syringe barrel in order to 

remove all of the solution from the inverted vial. 

 

6. Replace the 18-gauge needle with a 25-gauge needle for subcutaneous injection. 

 

7. Expel air, large bubbles, and any excess solution in order to obtain the required 1.2 ml dose. A 

thin layer of small bubbles may remain at the top of the solution in the syringe. Because the 

solution is slightly viscous, it may take 5-10 seconds to administer the solution by subcutaneous 

injection. 

 

The vial delivers 1.2 ml (150 mg) of Xolair. For a 75 mg dose, draw up 0.6 ml into the syringe 

and discard the remaining solution. 

 

8. The injections are administered subcutaneously in the deltoid region of the arm, the lower 

abdomen (but not the area 5 centimetres around the navel) or the thigh. 



141 

Package leaflet: Information for the user 

 

Xolair 75 mg solution for injection in pre-filled syringe 

omalizumab 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Xolair is and what it is used for 

2. What you need to know before you use Xolair 

3. How to use Xolair 

4. Possible side effects 

5. How to store Xolair 

6. Contents of the pack and other information 

 

 

1. What Xolair is and what it is used for 
 

Xolair contains the active substance omalizumab. Omalizumab is a man-made protein that is similar to 

natural proteins produced by the body. It belongs to a class of medicines called monoclonal antibodies. 

 

Xolair is used for the treatment of: 

- allergic asthma 
- chronic rhinosinusitis (inflammation of the nose and sinuses) with nasal polyps 
 

Allergic asthma 

This medicine is used to prevent asthma from getting worse by controlling symptoms of severe 

allergic asthma in adults, adolescents and children (6 years of age and older) who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high-dose 

steroid inhalers and beta-agonist inhalers. 

 

Chronic rhinosinusitis with nasal polyps 

This medicine is used to treat chronic rhinosinusitis with nasal polyps in adults (18 years of age and 

older) who are already receiving intranasal corticosteroids (corticosteroid nasal spray), but whose 

symptoms are not well controlled by these medicines. Nasal polyps are small growths on the lining of 

the nose. Xolair helps to reduce the size of the polyps and improves symptoms including nasal 

congestion, loss of sense of smell, mucus in the back of the throat and runny nose. 

 

Xolair works by blocking a substance called immunoglobulin E (IgE), which is produced by the body. 

IgE contributes to a type of inflammation that plays a key role in causing allergic asthma and chronic 

rhinosinusitis with nasal polyps. 

 

 

  



142 

2. What you need to know before you use Xolair 
 

Do not use Xolair: 

- if you are allergic to omalizumab or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic to any of the ingredients, tell your doctor as you should not use 

Xolair. 

 

Warnings and precautions 

Talk to your doctor before using Xolair: 

- if you have kidney or liver problems. 
- if you have a disorder where your own immune system attacks parts of your own body 

(autoimmune disease). 

- if you are travelling to region where infections caused by parasites are common - Xolair may 
weaken your resistance to such infections. 

- if you have had a previous severe allergic reaction (anaphylaxis), for example resulting from a 
medicine, an insect bite or food. 

- if you have ever had an allergic reaction to latex. The needle cap of the syringe may contain dry 
rubber (latex). 

 

Xolair does not treat acute asthma symptoms, such as a sudden asthma attack. Therefore Xolair should 

not be used to treat such symptoms. 

 

Xolair is not meant to prevent or treat other allergy-type conditions, such as sudden allergic reactions, 

hyperimmunoglobulin E syndrome (an inherited immune disorder), aspergillosis (a fungus-related 

lung disease), food allergy, eczema or hay fever because Xolair has not been studied in these 

conditions. 

 

Look out for signs of allergic reactions and other serious side effects 

Xolair can potentially cause serious side effects. You must look out for signs of these conditions while 

you use Xolair. Seek medical help immediately if you notice any signs indicating a severe allergic 

reaction or other serious side effects. Such signs are listed under “Serious side effects” in section 4. 

 

It is important that you receive training from your doctor in how to recognise early symptoms of 

severe allergic reactions, and how to manage these reactions if they occur, before you inject Xolair 

yourself or before a non-healthcare professional gives you a Xolair injection (see section 3, “How to 

use Xolair”). The majority of severe allergic reactions occur within the first 3 doses of Xolair. 

 

Children and adolescents 

Allergic asthma 

Xolair is not recommended for children under 6 years of age. Its use in children under 6 years of age 

has not been studied. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair is not recommended for children and adolescents under 18 years of age. Its use in patients 

under 18 years of age has not been studied. 

 

Other medicines and Xolair 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 

This is especially important if you are taking: 

- medicines to treat an infection caused by a parasite, as Xolair may reduce the effect of your 

medicines, 

- inhaled corticosteroids and other medicines for allergic asthma. 

 



143 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 

advice before using this medicine. Your doctor will discuss with you the benefits and potential risks of 

using this medicine during pregnancy. 

 

If you become pregnant while being treated with Xolair, tell your doctor immediately. 

 

Xolair may pass into breast milk. If you are breast-feeding or plan to breast-feed, ask your doctor for 

advice before using this medicine. 

 

Driving and using machines 

It is unlikely that Xolair will affect your ability to drive and use machines. 

 

 

3. How to use Xolair 
 

Always use this medicine exactly as your doctor has told you. Check with your doctor, nurse or 

pharmacist if you are not sure. 

 

How Xolair is used 

Xolair is used as an injection under your skin (known as a subcutaneous injection). 

 

Injecting Xolair 

- You and your doctor will decide if you should inject Xolair yourself. The first 3 doses are 
always given by or under the supervision of a healthcare professional (see section 2). 

- It is important to be properly trained on how to inject the medicine before injecting yourself. 
- A caregiver (for example a parent) may also give you your Xolair injection after he or she has 

received proper training. 

 

For detailed instructions on how to inject Xolair, see “Instructions for use of Xolair pre-filled syringe” 

at the end of this leaflet. 

 

Training to recognise serious allergic reactions 

It is also important that you do not inject Xolair yourself until you have been trained by your doctor or 

nurse on: 

- how to recognise the early signs and symptoms of serious allergic reactions. 
- what to do if the symptoms occur. 
For more information about the early signs and symptoms of serious allergic reactions, see section 4. 

 

How much to use 

Your doctor will decide how much Xolair you need and how often you will need it. This depends on 

your body weight and the results of a blood test carried out before the start of the treatment to measure 

the amount of IgE in your blood. 

 

You will need 1 to 4 injections at a time. You will need the injections either every two weeks, or every 

four weeks. 

 

Keep taking your current asthma and/or nasal polyps medicine during Xolair treatment. Do not stop 

taking any asthma and/or nasal polyps medicine without talking to your doctor. 

 

You may not see an immediate improvement after beginning Xolair treatment. In patients with nasal 

polyps effects have been seen 4 weeks after the start of the treatment. In asthma patients it usually 

takes between 12 and 16 weeks to have the full effect. 

 



144 

Use in children and adolescents 

Allergic asthma 

Xolair can be used in children and adolescents aged 6 years and older, who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high dose 

steroid inhalers and beta-agonist inhalers. Your doctor will work out how much Xolair your child 

needs and how often it needs to be given. This will depend on your child’s weight and the results of a 

blood test carried out before the start of the treatment to measure the amount of IgE in his/her blood. 

 

Children (6 to 11 years of age) are not expected to self-administer Xolair. However, if considered 

appropriate by their doctor, a caregiver may give them their Xolair injection after proper training. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair should not be used in children and adolescents under 18 years of age. 

 

If a dose of Xolair is missed 

If you have missed an appointment, contact your doctor or hospital as soon as possible to re-schedule 

it. 

 

If you have forgotten to give yourself a dose of Xolair, inject the dose as soon as you remember. Then 

talk to your doctor to discuss when you should inject the next dose. 

 

If you stop treatment with Xolair 

Do not stop treatment with Xolair unless your doctor tells you to. Interrupting or stopping the 

treatment with Xolair may cause your symptoms to come back. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 

effects caused by Xolair are usually mild to moderate but can occasionally be serious. 

 

Serious side effects: 

 

Seek medical attention immediately if you notice any signs of the following side effects: 

Rare (may affect up to 1 in 1,000 people) 

- Severe allergic reactions (including anaphylaxis). Symptoms may include rash, itching or hives 
on the skin, swelling of the face, lips, tongue, larynx (voice box), windpipe or other parts of the 

body, fast heartbeat, dizziness and light-headedness, confusion, shortness of breath, wheezing or 

trouble breathing, blue skin or lips, collapsing and losing consciousness. If you have a history of 

severe allergic reactions (anaphylaxis) unrelated to Xolair you may be more at risk of 

developing a severe allergic reaction following use of Xolair. 

- Systemic lupus erythematosus (SLE). Symptoms may include muscle pain, joint pain and 
swelling, rash, fever, weight loss, and fatigue. 

 

Not known (frequency cannot be estimated from the available data) 

- Churg-Strauss syndrome or hypereosinophilic syndrome. Symptoms may include one or more 
of the following: swelling, pain or rash around blood or lymph vessels, high level of a specific 

type of white blood cells (marked eosinophilia), worsening problems with breathing, nasal 

congestion, heart problems, pain, numbness, tingling in the arms and legs. 

- Low blood platelet count with symptoms such as bleeding or bruising more easily than normal. 
- Serum sickness. Symptoms may include one or more of the following: joint pain with or 

without swelling or stiffness, rash, fever, swollen lymph nodes, muscle pain. 

 



145 

Other side effects include: 

Very common (may affect more than 1 in 10 people) 

- fever (in children) 
 

Common (may affect up to 1 in 10 people) 

- reactions at the injection site including pain, swelling, itching and redness 
- pain in the upper part of the tummy 
- headache (very common in children) 
- feeling dizzy 
- pain in joints (arthralgia) 
 

Uncommon (may affect up to 1 in 100 people) 

- feeling sleepy or tired 
- tingling or numbness of the hands or feet 
- fainting, low blood pressure while sitting or standing (postural hypotension), flushing 
- sore throat, coughing, acute breathing problems 
- feeling sick (nausea), diarrhoea, indigestion 
- itching, hives, rash, increased sensitivity of the skin to sun 
- weight increase 
- flu-like symptoms 
- swelling arms 
 

Rare (may affect up to 1 in 1,000 people) 

- parasitic infection 
 

Not known (frequency cannot be estimated from the available data) 

- muscle pain and joint swelling 
- hair loss 
 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Xolair 

 

- Keep this medicine out of the sight and reach of children. 
- Do not use this medicine after the expiry date which is stated on the label. The expiry date refers 

to the last day of that month. 

- Store in the original package in order to protect from light. 
- Store in a refrigerator (2°C – 8°C). Do not freeze. 
- Do not use any pack that is damaged or shows signs of tampering. 
 

 

6. Contents of the pack and other information 

 

What Xolair contains 

- The active substance is omalizumab. One syringe of 0.5 ml solution contains 75 mg 
omalizumab. 

- The other ingredients are L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, 

Polysorbate 20 and water for injections. 

- The needle cap of the syringe may contain dry rubber (latex). 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


146 

What Xolair looks like and contents of the pack 

Xolair solution for injection is supplied as a clear to slightly opalescent, colourless to pale 

brownish-yellow solution in a pre-filled syringe. 

 

Xolair 75 mg solution for injection is available in packs containing 1 pre-filled syringe and in 

multipacks containing 4 (4 x 1) or 10 (10 x 1) pre-filled syringes. 

 

Not all pack sizes may be marketed in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 



147 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


148 

INSTRUCTIONS FOR USE OF XOLAIR PRE-FILLED SYRINGE 

 

Read ALL the way through these instructions before injecting. If your doctor decides that you or a 

caregiver may be able to give your injections of Xolair at home, you need to be trained by your doctor, 

nurse or pharmacist before you inject yourself or others. Children (6 to less than 12 years of age) are not 

expected to inject Xolair themselves, however, if deemed appropriate by their doctor, a caregiver may give 

them their Xolair injection after proper training. The box contains Xolair pre-filled syringe(s) individually 

sealed in a plastic tray. 

 

Your Xolair 75 mg pre-filled syringe 

 

 
 

After the medicine has been injected, the syringe guard will be activated to cover the needle. This is 

intended to protect against accidental needlestick injuries. 

 

Other items you need for your injection: 

 

 Alcohol swab. 

 Cotton ball or gauze. 

 Sharps disposal container. 

 
 

Important safety information 

Caution: Keep the syringe out of the sight and reach of children. 

 The needle cap of the syringe may contain dry rubber (latex), which should not be handled by 
anyone who is sensitive to this substance. 

 Do not open the sealed outer box until you are ready to use this medicine. 

 Do not use this medicine if either the seal on the outer box or the seal of the plastic tray is 
broken, as it may not be safe for you to use. 

 Never leave the syringe where others might tamper with it. 

 Do not shake the syringe. 

 Be careful not to touch the syringe guard wings before use. If the wings are touched, the syringe 
guard may be activated too early. 

 Do not remove the needle cap until just before you give the injection. 

 The syringe cannot be re-used. Dispose of the used syringe immediately after use in a sharps 
container. 

 

  

Needle 
cap 

Syringe guard 

Viewing window 
Label & expiry date 

Finger grips Syringe 
guard wings 

 
Plunger 

Plunger head 



149 

Storage of the Xolair pre-filled syringe 

 Store this medicine sealed in its outer box to protect it from light. Store in the refrigerator 
between 2°C and 8°C. DO NOT FREEZE. 

 Remember to take the syringe out of the refrigerator and allow it to reach room temperature 
(25°C) before preparing it for injection (it will take about 20 minutes). Leave the syringe in the 

box to protect it from light. The time that the syringe is kept at room temperature (25°C) before 

use must not exceed 4 hours. 

 Do not use the syringe after the expiry date which is stated on the outer box and syringe label. If 
it has expired, return the entire pack to the pharmacy. 

 

The injection site 

 

 

 
 

The injection site is the place on the body where you are going to use 

the syringe. 

 The recommended site is the front of the thighs. You may also 
use the lower abdomen, but not the area 5 centimetres around 

the navel (belly button). 

 If you need to give more than one injection for the full dose, 
choose a different injection site each time you inject. 

 Do not inject into areas where the skin is tender, bruised, red, 
or hard. Avoid areas with scars or stretch marks. 

If a caregiver is giving the injection, the outer upper arms may also 

be used. 

 



150 

Preparing the Xolair pre-filled syringe for use 

 

Note: Depending on the dose prescribed to you by your doctor, you may need to prepare one or more 

pre-filled syringes, and inject the contents of them all. The following table gives examples of how 

many injections of each dose strength you need for a given dose: 

 
 

1. Take the box containing the syringe out of the refrigerator and leave it unopened for about 

20 minutes so that it reaches room temperature (leave the syringe in the box to protect it from 

light). 

2. When you are ready to use the syringe, wash your hands thoroughly with soap and water. 

3. Clean the injection site with an alcohol swab. 

4. Remove the plastic tray from the box, peel back the paper cover. Gripping the middle of the 

blue syringe guard, lift the syringe out of the tray. 

5. Inspect the syringe. The liquid should be clear to slightly cloudy. Its colour may vary from 

colourless to pale brownish-yellow. You may see an air bubble, which is normal. DO NOT USE 

if the syringe is broken or if the liquid looks distinctly cloudy or distinctly brown, or contains 

particles. In all these cases, return the entire pack to the pharmacy. 

6. Holding the syringe horizontally look into the viewing window to check the expiry date printed 

on the label. Note: It is possible to rotate the inner part of the syringe assembly so that the label 

can be read in the viewing window. DO NOT USE if the product has expired. If expired, return 

the entire pack to the pharmacy. 

 

Dose Syringes needed for the dose 

75 mg 1 blue (75 mg) 

150 mg 1 purple (150 mg) 

225 mg 1 blue (75 mg) 1 purple (150 mg) 

300 mg 2 purple (150 mg) 

375 mg 1 blue (75 mg) 2 purple (150 mg) 

450 mg 3 purple (150 mg) 

525 mg 1 blue (75 mg) 3 purple (150 mg) 

600 mg 4 purple (150 mg) 



151 

How to use the Xolair pre-filled syringe 

 

 

 
 

Carefully remove the needle cap from the syringe. 

Discard the needle cap. You may see a drop of 

liquid at the end of the needle. This is normal. 

 

 
 

Gently pinch the skin at the injection site and 

insert the needle as shown. Push the needle all the 

way in to ensure that the medicine can be fully 

administered. 

 

 
 

Hold the syringe as shown. Slowly depress the 

plunger as far as it will go so that the plunger 

head is completely between the syringe guard 

wings. 

1 

2 

3 



152 

 

 
 

Keep the plunger fully depressed while you 

carefully lift the needle straight out from the 

injection site. 

 

 
 

Slowly release the plunger and allow the syringe 

guard to automatically cover the exposed needle. 

 

There may be a small amount of blood at the 

injection site. You can press a cotton ball or 

gauze over the injection site and hold it for 

30 seconds. Do not rub the injection site. You 

may cover the injection site with a small adhesive 

bandage, if needed. 

 

Disposal instructions 

 

 

 

 

 

 

Dispose of the used syringe immediately in a 

sharps container (closable, puncture resistant 

container). For the safety and health of you and 

others, needles and used syringes must never be 

re-used. Any unused medicinal product or waste 

material should be disposed of in accordance with 

local requirements. Do not throw away any 

medicines via wastewater or household waste. 

Ask your pharmacist how to throw away 

medicines you no longer use. These measures will 

help protect the environment. 

 

4 

5 



153 

Package leaflet: Information for the user 

 

Xolair 150 mg solution for injection in pre-filled syringe 

omalizumab 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Xolair is and what it is used for 

2. What you need to know before you use Xolair 

3. How to use Xolair 

4. Possible side effects 

5. How to store Xolair 

6. Contents of the pack and other information 

 

 

1. What Xolair is and what it is used for 
 

Xolair contains the active substance omalizumab. Omalizumab is a man-made protein that is similar to 

natural proteins produced by the body. It belongs to a class of medicines called monoclonal antibodies. 

 

Xolair is used for the treatment of: 

- allergic asthma 
- chronic rhinosinusitis (inflammation of the nose and sinuses) with nasal polyps 
- chronic spontaneous urticaria (CSU) 
 

Allergic asthma 

This medicine is used to prevent asthma from getting worse by controlling symptoms of severe 

allergic asthma in adults, adolescents and children (6 years of age and older) who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high-dose 

steroid inhalers and beta-agonist inhalers. 

 

Chronic rhinosinusitis with nasal polyps 

This medicine is used to treat chronic rhinosinusitis with nasal polyps in adults (18 years of age and 

older) who are already receiving intranasal corticosteroids (corticosteroid nasal spray), but whose 

symptoms are not well controlled by these medicines. Nasal polyps are small growths on the lining of 

the nose. Xolair helps to reduce the size of the polyps and improves symptoms including nasal 

congestion, loss of sense of smell, mucus in the back of the throat and runny nose. 

 

Chronic spontaneous urticaria (CSU) 

This medicine is used to treat chronic spontaneous urticaria in adults and adolescents (12 years of age 

and older) who are already receiving antihistamines but whose CSU symptoms are not well controlled 

by these medicines. 

 

Xolair works by blocking a substance called immunoglobulin E (IgE), which is produced by the body. 

IgE contributes to a type of inflammation that plays a key role in causing allergic asthma, chronic 

rhinosinusitis with nasal polyps and CSU. 

 

 



154 

2. What you need to know before you use Xolair 
 

Do not use Xolair: 

- if you are allergic to omalizumab or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic to any of the ingredients, tell your doctor as you should not use 

Xolair. 

 

Warnings and precautions 

Talk to your doctor before using Xolair: 

- if you have kidney or liver problems. 
- if you have a disorder where your own immune system attacks parts of your own body 

(autoimmune disease). 

- if you are travelling to region where infections caused by parasites are common - Xolair may 
weaken your resistance to such infections. 

- if you have had a previous severe allergic reaction (anaphylaxis), for example resulting from a 
medicine, an insect bite or food. 

- if you have ever had an allergic reaction to latex. The needle cap of the syringe may contain dry 
rubber (latex). 

 

Xolair does not treat acute asthma symptoms, such as a sudden asthma attack. Therefore Xolair should 

not be used to treat such symptoms. 

 

Xolair is not meant to prevent or treat other allergy-type conditions, such as sudden allergic reactions, 

hyperimmunoglobulin E syndrome (an inherited immune disorder), aspergillosis (a fungus-related 

lung disease), food allergy, eczema or hay fever because Xolair has not been studied in these 

conditions. 

 

Look out for signs of allergic reactions and other serious side effects 

Xolair can potentially cause serious side effects. You must look out for signs of these conditions while 

you use Xolair. Seek medical help immediately if you notice any signs indicating a severe allergic 

reaction or other serious side effects. Such signs are listed under “Serious side effects” in section 4. 

 

It is important that you receive training from your doctor in how to recognise early symptoms of 

severe allergic reactions, and how to manage these reactions if they occur, before you inject Xolair 

yourself or before a non-healthcare professional gives you a Xolair injection (see section 3, “How to 

use Xolair”). The majority of severe allergic reactions occur within the first 3 doses of Xolair. 

 

Children and adolescents 

Allergic asthma 

Xolair is not recommended for children under 6 years of age. Its use in children under 6 years of age 

has not been studied. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair is not recommended for children and adolescents under 18 years of age. Its use in patients 

under 18 years of age has not been studied. 

 

Chronic spontaneous urticaria (CSU) 

Xolair is not recommended for children under 12 years of age. Its use in children under 12 years of age 

has not been studied. 

 

  



155 

Other medicines and Xolair 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 

This is especially important if you are taking: 

- medicines to treat an infection caused by a parasite, as Xolair may reduce the effect of your 

medicines, 

- inhaled corticosteroids and other medicines for allergic asthma. 

 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 

advice before using this medicine. Your doctor will discuss with you the benefits and potential risks of 

using this medicine during pregnancy. 

 

If you become pregnant while being treated with Xolair, tell your doctor immediately. 

 

Xolair may pass into breast milk. If you are breast-feeding or plan to breast-feed, ask your doctor for 

advice before using this medicine. 

 

Driving and using machines 

It is unlikely that Xolair will affect your ability to drive and use machines. 

 

 

3. How to use Xolair 
 

Always use this medicine exactly as your doctor has told you. Check with your doctor, nurse or 

pharmacist if you are not sure 

 

How Xolair is used 

Xolair is used as an injection under your skin (known as a subcutaneous injection). 

 

Injecting Xolair 

- You and your doctor will decide if you should inject Xolair yourself. The first 3 doses are 
always given by or under the supervision of a healthcare professional (see section 2). 

- It is important to be properly trained on how to inject the medicine before injecting yourself. 
- A caregiver (for example a parent) may also give you your Xolair injection after he or she has 

received proper training. 

 

For detailed instructions on how to inject Xolair, see “Instructions for use of Xolair pre-filled syringe” 

at the end of this leaflet. 

 

Training to recognise serious allergic reactions 

It is also important that you do not inject Xolair yourself until you have been trained by your doctor or 

nurse on: 

- how to recognise the early signs and symptoms of serious allergic reactions 
- what to do if the symptoms occur. 
For more information about the early signs and symptoms of serious allergic reactions, see section 4. 

 

How much to use 

Allergic asthma and chronic rhinosinusitis with nasal polyps 

Your doctor will decide how much Xolair you need and how often you will need it. This depends on 

your body weight and the results of a blood test carried out before the start of the treatment to measure 

the amount of IgE in your blood. 

 

You will need 1 to 4 injections at a time. You will need the injections either every two weeks, or every 

four weeks. 

 



156 

Keep taking your current asthma and/or nasal polyps medicine during Xolair treatment. Do not stop 

taking any asthma and/or nasal polyps medicine without talking to your doctor. 

 

You may not see an immediate improvement after beginning Xolair treatment. In patients with nasal 

polyps effects have been seen 4 weeks after the start of the treatment. In asthma patients it usually 

takes between 12 and 16 weeks to have the full effect. 

 

Chronic spontaneous urticaria (CSU) 

You will need two 150 mg injections at a time every four weeks. 

 

Keep taking your current medicine for CSU during Xolair treatment. Do not stop taking any medicine 

without talking to your doctor. 

 

Use in children and adolescents 

Allergic asthma 

Xolair can be used in children and adolescents aged 6 years and older, who are already receiving 

asthma medicine, but whose asthma symptoms are not well controlled by medicines such as high dose 

steroid inhalers and beta-agonist inhalers. Your doctor will work out how much Xolair your child 

needs and how often it needs to be given. This will depend on your child’s weight and the results of a 

blood test carried out before the start of the treatment to measure the amount of IgE in his/her blood. 

 

Children (6 to 11 years of age) are not expected to self-administer Xolair. However, if considered 

appropriate by their doctor, a caregiver may give them their Xolair injection after proper training. 

 

Chronic rhinosinusitis with nasal polyps 

Xolair should not be used in children and adolescents under 18 years of age. 

 

Chronic spontaneous urticaria (CSU) 

Xolair can be used in adolescents aged 12 years of age and older, who are already receiving 

antihistamines but whose CSU symptoms are not well controlled by these medicines. The dose for 

adolescents aged 12 years and above is the same as for adults. 

 

If a dose of Xolair is missed 
If you have missed an appointment, contact your doctor or hospital as soon as possible to re-schedule 

it. 

 

If you have forgotten to give yourself a dose of Xolair, inject the dose as soon as you remember. Then 

talk to your doctor to discuss when you should inject the next dose. 

 

If you stop treatment with Xolair 

Do not stop treatment with Xolair unless your doctor tells you to. Interrupting or stopping the 

treatment with Xolair may cause your symptoms to come back. 

 

However, if you are being treated for CSU, your doctor may stop Xolair treatment from time to time 

so that your symptoms can be assessed. Follow your doctor’s instructions. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

  



157 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 

effects caused by Xolair are usually mild to moderate but can occasionally be serious. 

 

Serious side effects: 

 

Seek medical attention immediately if you notice any signs of the following side effects: 

Rare (may affect up to 1 in 1,000 people) 

- Severe allergic reactions (including anaphylaxis). Symptoms may include rash, itching or hives 
on the skin, swelling of the face, lips, tongue, larynx (voice box), windpipe or other parts of the 

body, fast heartbeat, dizziness and light-headedness, confusion, shortness of breath, wheezing or 

trouble breathing, blue skin or lips, collapsing and losing consciousness. If you have a history of 

severe allergic reactions (anaphylaxis) unrelated to Xolair you may be more at risk of 

developing a severe allergic reaction following use of Xolair. 

- Systemic lupus erythematosus (SLE). Symptoms may include muscle pain, joint pain and 
swelling, rash, fever, weight loss, and fatigue. 

 

Not known (frequency cannot be estimated from the available data) 

- Churg-Strauss syndrome or hypereosinophilic syndrome. Symptoms may include one or more 
of the following: swelling, pain or rash around blood or lymph vessels, high level of a specific 

type of white blood cells (marked eosinophilia), worsening problems with breathing, nasal 

congestion, heart problems, pain, numbness, tingling in the arms and legs. 

- Low blood platelet count with symptoms such as bleeding or bruising more easily than normal. 
- Serum sickness. Symptoms may include one or more of the following: joint pain with or 

without swelling or stiffness, rash, fever, swollen lymph nodes, muscle pain. 

 

Other side effects include: 

Very common (may affect more than 1 in 10 people) 

- fever (in children) 
 

Common (may affect up to 1 in 10 people) 

- reactions at the injection site including pain, swelling, itching and redness 
- pain in the upper part of the tummy 
- headache (very common in children) 
- upper respiratory tract infection, such as inflammation of the pharynx and common cold 
- feeling of pressure or pain in the cheeks and forehead (sinusitis, sinus headache) 
- pain in joints (arthralgia) 
- feeling dizzy 
 

Uncommon (may affect up to 1 in 100 people) 

- feeling sleepy or tired 
- tingling or numbness of the hands or feet 
- fainting, low blood pressure while sitting or standing (postural hypotension), flushing 
- sore throat, coughing, acute breathing problems 
- feeling sick (nausea), diarrhoea, indigestion 
- itching, hives, rash, increased sensitivity of the skin to sun 
- weight increase 
- flu-like symptoms 
- swelling arms 
 

Rare (may affect up to 1 in 1,000 people) 

- parasitic infection 
 

Not known (frequency cannot be estimated from the available data) 

- muscle pain and joint swelling 
- hair loss 



158 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Xolair 

 

- Keep this medicine out of the sight and reach of children. 
- Do not use this medicine after the expiry date which is stated on the label. The expiry date refers 

to the last day of that month. 

- Store in the original package in order to protect from light. 
- Store in a refrigerator (2°C – 8°C). Do not freeze. 
- Do not use any pack that is damaged or shows signs of tampering. 
 

 

6. Contents of the pack and other information 

 

What Xolair contains 

- The active substance is omalizumab. One syringe of 1 ml solution contains 150 mg 
omalizumab. 

- The other ingredients are L-arginine hydrochloride, L-histidine hydrochloride, L-histidine, 

Polysorbate 20 and water for injections. 

- The needle cap of the syringe may contain dry rubber (latex). 

 

What Xolair looks like and contents of the pack 

Xolair solution for injection is supplied as a clear to slightly opalescent, colourless to pale 

brownish-yellow solution in a pre-filled syringe. 

 

Xolair 150 mg solution for injection is available in packs containing 1 pre-filled syringe and in 

multipacks containing 4 (4 x 1), 6 (6 x 1) or 10 (10 x 1) pre-filled syringes. 

 

Not all pack sizes may be marketed in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


159 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



160 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

http://www.ema.europa.eu/


161 

INSTRUCTIONS FOR USE OF XOLAIR PRE-FILLED SYRINGE 

 

Read ALL the way through these instructions before injecting. If your doctor decides that you or a 

caregiver may be able to give your injections of Xolair at home, you need to be trained by your doctor, 

nurse or pharmacist before you inject yourself or others. Children (6 to less than 12 years of age) are not 

expected to inject Xolair themselves, however, if deemed appropriate by their doctor, a caregiver may give 

them their Xolair injection after proper training. The box contains Xolair pre-filled syringe(s) individually 

sealed in a plastic tray. 

 

Your Xolair 150 mg pre-filled syringe 

 

 
 

After the medicine has been injected, the syringe guard will be activated to cover the needle. This is 

intended to protect against accidental needlestick injuries. 

 

Other items you need for your injection: 

 

 Alcohol swab. 

 Cotton ball or gauze. 

 Sharps disposal container. 

 
 

Important safety information 

Caution: Keep the syringe out of the sight and reach of children. 

 The needle cap of the syringe may contain dry rubber (latex), which should not be handled by 
anyone who is sensitive to this substance. 

 Do not open the sealed outer box until you are ready to use this medicine. 

 Do not use this medicine if either the seal on the outer box or the seal of the plastic tray is 
broken, as it may not be safe for you to use. 

 Never leave the syringe where others might tamper with it. 

 Do not shake the syringe. 

 Be careful not to touch the syringe guard wings before use. If the wings are touched, the syringe 
guard may be activated too early. 

 Do not remove the needle cap until just before you give the injection. 

 The syringe cannot be re-used. Dispose of the used syringe immediately after use in a sharps 
container. 

 

  

Needle 
cap 

Syringe guard 

Viewing window 
Label & expiry date 

Syringe 
guard wings 

 

Finger Grips 

Plunger 

Plunger 
head 



162 

Storage of the Xolair pre-filled syringe 

 Store this medicine sealed in its outer box to protect it from light. Store in the refrigerator 
between 2°C and 8°C. DO NOT FREEZE. 

 Remember to take the syringe out of the refrigerator and allow it to reach room temperature 
(25°C) before preparing it for injection (it will take about 20 minutes). Leave the syringe in the 

box to protect it from light. The time that the syringe is kept at room temperature (25°C) before 

use must not exceed 4 hours. 

 Do not use the syringe after the expiry date which is stated on the outer box and syringe label. If 
it has expired, return the entire pack to the pharmacy. 

 

The injection site 

 

 

 
 

The injection site is the place on the body where you are going to 

use the syringe. 

 The recommended site is the front of the thighs. You may 
also use the lower abdomen, but not the area 5 centimetres 

around the navel (belly button). 

 If you need to give more than one injection for the full 
dose, choose a different injection site each time you inject. 

 Do not inject into areas where the skin is tender, bruised, 
red, or hard. Avoid areas with scars or stretch marks. 

If a caregiver is giving the injection, the outer upper arms may 

also be used. 

 



163 

Preparing the Xolair pre-filled syringe for use 

 

Note: Depending on the dose prescribed to you by your doctor, you may need to prepare one or more 

pre-filled syringes, and inject the contents of them all. The following table gives examples of how 

many injections of each dose strength you need for a given dose: 

 
 

1. Take the box containing the syringe out of the refrigerator and leave it unopened for about 
20 minutes so that it reaches room temperature (leave the syringe in the box to protect it from 

light). 

2. When you are ready to use the syringe, wash your hands thoroughly with soap and water. 

3. Clean the injection site with an alcohol swab. 

4. Remove the plastic tray from the box and peel back the paper cover. Gripping the middle of the 

purple syringe guard, lift the syringe out of the tray. 

5. Inspect the syringe. The liquid should be clear to slightly cloudy. Its colour may vary from 

colourless to pale brownish-yellow. You may see an air bubble, which is normal. DO NOT USE 

if the syringe is broken or if the liquid looks distinctly cloudy or distinctly brown, or contains 

particles. In all these cases, return the entire pack to the pharmacy. 

6. Holding the syringe horizontally, look into the viewing window to check the expiry date printed 

on the label. Note: It is possible to rotate the inner part of the syringe assembly so that the label 

can be read in the viewing window. DO NOT USE if the product has expired. If expired, return 

the entire pack to the pharmacy. 

 

Dose Syringes needed for the dose 

75 mg 1 blue (75 mg) 

150 mg 1 purple (150 mg) 

225 mg 1 blue (75 mg) 1 purple (150 mg) 

300 mg 2 purple (150 mg) 

375 mg 1 blue (75 mg) 2 purple (150 mg) 

450 mg 3 purple (150 mg) 

525 mg 1 blue (75 mg) 3 purple (150 mg) 

600 mg 4 purple (150 mg) 



164 

How to use the Xolair pre-filled syringe 
 

 

 
 

Carefully remove the needle cap from the syringe. 

Discard the needle cap. You may see a drop of 

liquid at the end of the needle. This is normal. 

 

 
 

Gently pinch the skin at the injection site and 

insert the needle as shown. Push the needle all the 

way in to ensure that the medicine can be fully 

administered. 

 

 
 

Hold the syringe as shown. Slowly depress the 

plunger as far as it will go so that the plunger 

head is completely between the syringe guard 

wings. 

1 

2 

3 



165 

 

 
 

Keep the plunger fully depressed while you 

carefully lift the needle straight out from the 

injection site. 

 

 
 

Slowly release the plunger and allow the syringe 

guard to automatically cover the exposed needle. 

 

There may be a small amount of blood at the 

injection site. You can press a cotton ball or 

gauze over the injection site and hold it for 

30 seconds. Do not rub the injection site. You 

may cover the injection site with a small adhesive 

bandage, if needed. 

 

Disposal instructions 

 

 

 

 
 

Dispose of the used syringe immediately in a 

sharps container (closable, puncture resistant 

container). For the safety and health of you and 

others, needles and used syringes must never be 

re-used. Any unused medicinal product or waste 

material should be disposed of in accordance with 

local requirements. Do not throw away any 

medicines via wastewater or household waste. 

Ask your pharmacist how to throw away 

medicines you no longer use. These measures will 

help protect the environment. 

 

4 

5 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET