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Patients & Caregivers

TRIAL INFORMATION

XOLAIR STUDIES:
DESIGN AND
PATIENT BASELINE
CHARACTERISTICS

Studies 1 and 2 design
Study 3 design
Study 4 design

Studies 1 and 2 design4,10,11

Identical 28-week, randomized, double-blind, placebo-controlled studies evaluating the number of exacerbations in a total of 1071 patients aged 12 to 76 years with moderate to severe persistent allergic asthma who were symptomatic despite ICS treatment.4,10,11

Patients received XOLAIR or placebo every 2 or 4 weeks for 16 weeks with an unchanged BDP dose unless an acute exacerbation necessitated an increase. Patients then entered a 12-week ICS-reduction phase during which ICS dose reduction was attempted in a stepwise manner.4,10

Primary endpoint: number of exacerbations.4,10

 

Study 3 design4

A 32-week, randomized, double-blind, placebo-controlled study designed to evaluate ICS reduction in 341 patients aged 12 to 76 years with severe allergic asthma. Exacerbation reduction was also evaluated as a secondary endpoint; however, this study was not powered to show statistical differences in exacerbation reduction.4

  • Unlike in Studies 1 and 2, there was no restriction on screening FEV1, and LABAs were allowed4
  • Patients were receiving ≥1000 µg/d ICS (fluticasone), and a subset was also receiving OCS4
    • No reductions in exacerbations were seen in patients who required OCS as maintenance therapy4

Exacerbation was defined as a worsening of asthma that required treatment with systemic corticosteroids or a doubling of the patient’s baseline ICS dose.4

Patients were stratified by use of ICS only or ICS with concomitant OCS. Patients received XOLAIR for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase. Patients then entered a 16-week ICS-reduction phase during which ICS dose reduction was attempted in a stepwise manner.4,8

PATIENT BASELINE CHARACTERISTICS

BROAD RANGE OF PATIENTS INCLUDED4,8,10,11

Select baseline characteristics in allergic asthma patients aged ≥12*

XOLAIR study design of demographic information and medical history, comorbidities, and Severity of asthma.
XOLAIR study design 1 of demographic information and medical history, comorbidities, and Severity of asthma.
XOLAIR study design 2 of demographic information and medical history, comorbidities, and Severity of asthma.
XOLAIR study design 3 of demographic information and medical history, comorbidities, and Severity of asthma.

Studies 1 and 2 evaluated patients with moderate to severe persistent asthma (1997 National Heart, Lung, and Blood Institute [NHLBI] Guidelines). Patients with FEV1 ≤65% of predicted and with a mean total symptom score of >4 at baseline were defined as severe; otherwise, they were defined as moderate. Study 3 evaluated patients with severe persistent asthma.4,8

*Dosing for XOLAIR in patients aged ≥12 years is based on pretreatment serum total IgE level (≥30 to 700 IU/mL) and body weight (66 to 330 pounds).4

Clinical Study in Pediatric Patients Aged 6 to <12 Years

Study 4 design4,31,32

A 52-week multicenter, randomized, double-blind, placebo-controlled study of 628 patients aged 6 to <12 years with moderate to severe allergic asthma evaluated XOLAIR as add-on therapy to ICS with or without additional controller medications. Patients received XOLAIR or placebo every 2 or 4 weeks for 24 weeks during the fixed-steroid treatment phase. Steroid doses remained constant from baseline unless an acute exacerbation necessitated an increase. Patients then entered a 28-week period during which steroid adjustment was allowed.4,31,32

Throughout the study, both groups were allowed to use additional controller medications, including inhaled and nebulized beta2-agonists and LTRA.31

Primary measure: rate of asthma exacerbations during the 24-week period.4
Exacerbation defined as: worsening of asthma symptoms requiring doubling of baseline ICS dose for at least 3 days and/or treatment with rescue systemic corticosteroids for at least 3 days.4

ICS=inhaled corticosteroid; LTRA=leukotriene receptor antagonist.

STUDIED IN A BROAD RANGE OF RACIALLY DIVERSE PATIENTS31

Select baseline characteristics in allergic asthma patients ages 6 to <12 years4

XOLAIR study design of pediatric allergic asthma patients age 6 to <12. Demographic information and medical history, comorbidities, and Severity of asthma.

SABA=short-acting beta2 agonist.
*Study 4 evaluated patients with moderate to severe persistent asthma (1997 NHLBI Guidelines, National Asthma Education Prevention Program 2002 update).8

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      Santos AF, Riggioni C, Agache I, et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy. 2023;78(12):3057​-3076.

    • Oettgen HC. Mast cells in food allergy: inducing immediate reactions and shaping long-term immunity. J Allergy Clin Immunol. 2023;151(1):21-25.

      Oettgen HC. Mast cells in food allergy: inducing immediate reactions and shaping long-term immunity. J Allergy Clin Immunol. 2023;151(1):21-25.

    • Anvari S, Miller J, Yeh CY, Davis CM. IgE-mediated food allergy. Clinic Rev Allergy Immunol. 2019;57(2):244​-260.

      Anvari S, Miller J, Yeh CY, Davis CM. IgE-mediated food allergy. Clinic Rev Allergy Immunol. 2019;57(2):244​-260.

    • Zablotsky B, Black LI, Akinbami LJ. Diagnosed allergic conditions in children aged 0–17 years: United States, 2021. NCHS Data Brief. 2023;(459):1-8.

      Zablotsky B, Black LI, Akinbami LJ. Diagnosed allergic conditions in children aged 0–17 years: United States, 2021. NCHS Data Brief. 2023;(459):1-8.

    • Mahdavinia M, Fox SR, Smith BM, et al. Racial differences in food allergy phenotype and health care utilization among US children. J Allergy Clin Immunol Pract. 2017;5(2):352​-357.e1.

      Mahdavinia M, Fox SR, Smith BM, et al. Racial differences in food allergy phenotype and health care utilization among US children. J Allergy Clin Immunol Pract. 2017;5(2):352​-357.e1.

    • Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol. 2018;141(1):41-58.

      Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol. 2018;141(1):41-58.

    • Lieberman JA, Chehade M. Use of omalizumab in the treatment of food allergy and anaphylaxis. Curr Allergy Asthma Rep. 2013;13(1):78-84.

      Lieberman JA, Chehade M. Use of omalizumab in the treatment of food allergy and anaphylaxis. Curr Allergy Asthma Rep. 2013;13(1):78-84.

    • El Ansari YS, Kanagaratham C, Oettgen HC. Mast cells as regulators of adaptive immune responses in food allergy. Yale J Biol Med. 2020;93(5):711​-718.

      El Ansari YS, Kanagaratham C, Oettgen HC. Mast cells as regulators of adaptive immune responses in food allergy. Yale J Biol Med. 2020;93(5):711​-718.

    • Ruiter B, Shreffler WG. The role of dendritic cells in food allergy. J Allergy Clin Immunol. 2012;129(4):921​-928.

      Ruiter B, Shreffler WG. The role of dendritic cells in food allergy. J Allergy Clin Immunol. 2012;129(4):921​-928.

    • Gupta S, Warren C, Seetasith A, Schuldt R, Gupta R, Casale TB. Mental health concerns of patients and their caregivers in the food allergy research & education (FARE) patient registry add to the burden of food allergy. Poster presented at: American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Scientific Meeting; February 24-27, 2023; San Antonio, TX.

      Gupta S, Warren C, Seetasith A, Schuldt R, Gupta R, Casale TB. Mental health concerns of patients and their caregivers in the food allergy research & education (FARE) patient registry add to the burden of food allergy. Poster presented at: American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Scientific Meeting; February 24-27, 2023; San Antonio, TX.

    • Vandenplas Y. Prevention and management of cow’s milk allergy in non-exclusively breastfed infants. Nutrients. 2017;9(7):731.

      Vandenplas Y. Prevention and management of cow’s milk allergy in non-exclusively breastfed infants. Nutrients. 2017;9(7):731.

    • Don’t let hidden holiday allergies ruin your good cheer. American College of Allergy, Asthma & Immunology. Published April 11, 2019. Accessed February 12, 2024. https://acaai.org/news/dont-let-hidden-holiday-allergies-ruin-your-good-cheer/

      Don’t let hidden holiday allergies ruin your good cheer. American College of Allergy, Asthma & Immunology. Published April 11, 2019. Accessed February 12, 2024. https://acaai.org/news/dont-let-hidden-holiday-allergies-ruin-your-good-cheer/

    • Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol. 2004;15(5):435​-441.

      Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol. 2004;15(5):435​-441.

    • Fierstein JL, Brown D, Gupta R, Bilaver L. Understanding food-related allergic reactions through a US national patient registry. J Allergy Clin Immunol Pract. 2021;9(1):206​-215.e1.

      Fierstein JL, Brown D, Gupta R, Bilaver L. Understanding food-related allergic reactions through a US national patient registry. J Allergy Clin Immunol Pract. 2021;9(1):206​-215.e1.

    • Permaul P, Stutius LM, Sheehan WJ, et al. Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results. Allergy Asthma Proc. 2009;30(6):643​-648.

      Permaul P, Stutius LM, Sheehan WJ, et al. Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results. Allergy Asthma Proc. 2009;30(6):643​-648.

    • Soy. American College of Allergy, Asthma & Immunology. Updated April 9, 2019. Accessed July 22, 2024. https://acaai.org/allergies/allergic-conditions/food/soy/

      Soy. American College of Allergy, Asthma & Immunology. Updated April 9, 2019. Accessed July 22, 2024. https://acaai.org/allergies/allergic-conditions/food/soy/

    • Sokol K, Rasooly M, Dempsey C, et al. Prevalence and diagnosis of sesame allergy in children with IgE-mediated food allergy. Pediatr Allergy Immunol. 2020;31(2):214​-218.

      Sokol K, Rasooly M, Dempsey C, et al. Prevalence and diagnosis of sesame allergy in children with IgE-mediated food allergy. Pediatr Allergy Immunol. 2020;31(2):214​-218.

    • Verstege A, Mehl A, Rolinck-Werninghaus C, et al. The predictive value of the skin prick test weal size for the outcome of oral food challenges. Clin Exp Allergy. 2005;35(9):1220​-1226.

      Verstege A, Mehl A, Rolinck-Werninghaus C, et al. The predictive value of the skin prick test weal size for the outcome of oral food challenges. Clin Exp Allergy. 2005;35(9):1220​-1226.

    • Giannetti A, Ruggi A, Ricci G, Giannì G, Caffarelli C. Natural history of hazelnut allergy and current approach to its diagnosis and treatment. Children (Basel). 2023;10(3):585.

      Giannetti A, Ruggi A, Ricci G, Giannì G, Caffarelli C. Natural history of hazelnut allergy and current approach to its diagnosis and treatment. Children (Basel). 2023;10(3):585.

    • Cortot CF, Sheehan WJ, Permaul P, et al. Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg. Allergy Asthma Proc. 2012;33(3):275​-281.

      Cortot CF, Sheehan WJ, Permaul P, et al. Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg. Allergy Asthma Proc. 2012;33(3):275​-281.

    • Koplin JJ, Perrett KP, Sampson HA. Diagnosing peanut allergy with fewer oral food challenges. J Allergy Clin Immunol Pract. 2019;7(2):375​-380.

      Koplin JJ, Perrett KP, Sampson HA. Diagnosing peanut allergy with fewer oral food challenges. J Allergy Clin Immunol Pract. 2019;7(2):375​-380.

    • Feng C, Kim JH. Beyond avoidance: the psychosocial impact of food allergies. Clin Rev Allergy Immunol. 2019;57(1):74-82.

      Feng C, Kim JH. Beyond avoidance: the psychosocial impact of food allergies. Clin Rev Allergy Immunol. 2019;57(1):74-82.

    • Chokshi NY, Maskatia Z, Miller S, Guffey D, Minard CG, Davis CM. Risk factors in pediatric shrimp allergy. Allergy Asthma Proc. 2015;36(4):65-71.

      Chokshi NY, Maskatia Z, Miller S, Guffey D, Minard CG, Davis CM. Risk factors in pediatric shrimp allergy. Allergy Asthma Proc. 2015;36(4):65-71.

    • Saleh-Langenberg J, Flokstra-de Blok BM, Goossens NJ, Kemna JC, van der Velde JL, Dubois AE. The compliance and burden of treatment with the epinephrine auto-injector in food-allergic adolescents. Pediatr Allergy Immunol. 2016;27(1):28-34.

      Saleh-Langenberg J, Flokstra-de Blok BM, Goossens NJ, Kemna JC, van der Velde JL, Dubois AE. The compliance and burden of treatment with the epinephrine auto-injector in food-allergic adolescents. Pediatr Allergy Immunol. 2016;27(1):28-34.

    • Portnoy JM. Appropriate allergy testing and interpretation. Mo Med. 2011;108(5):339​-343.

      Portnoy JM. Appropriate allergy testing and interpretation. Mo Med. 2011;108(5):339​-343.

    • Sicherer SH, Warren CM, Dant C, Gupta RS, Nadeau KC. Food allergy from infancy through adulthood. J Allergy Clin Immunol Pract. 2020;8(6):1854​-1864.

      Sicherer SH, Warren CM, Dant C, Gupta RS, Nadeau KC. Food allergy from infancy through adulthood. J Allergy Clin Immunol Pract. 2020;8(6):1854​-1864.

    • Li PH, Rutkowski K, Kennard L, et al. Challenge-confirmed peanut allergy in older patients: performance of skin tests, specific immunoglobulin E, and ara h 2. Ann Allergy Asthma Immunol. 2018;120(3):334​-335.

      Li PH, Rutkowski K, Kennard L, et al. Challenge-confirmed peanut allergy in older patients: performance of skin tests, specific immunoglobulin E, and ara h 2. Ann Allergy Asthma Immunol. 2018;120(3):334​-335.

    • Groetch M, Mudd K, Woch M, et al. Retail food equivalents for post-oral immunotherapy dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) clinical trial. J Allergy Immunol Pract. 2023;11(2):572​-580.e2.

      Groetch M, Mudd K, Woch M, et al. Retail food equivalents for post-oral immunotherapy dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) clinical trial. J Allergy Immunol Pract. 2023;11(2):572​-580.e2.

    IMPORTANT SAFETY INFORMATION

    INDICATION

    XOLAIR® (omalizumab) is indicated for:

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


      Limitations of Use: XOLAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.

    WARNING: Anaphylaxis

    Anaphylaxis presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of XOLAIR. Anaphylaxis has occurred as early as after the first dose of XOLAIR, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, initiate XOLAIR therapy in a healthcare setting and closely observe patients for an appropriate period of time after XOLAIR administration. Health care providers administering XOLAIR should be prepared to manage anaphylaxis which can be life-threatening. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should symptoms occur. Selection of patients for self-administration of XOLAIR should be based on criteria to mitigate risk from anaphylaxis.


    CONTRAINDICATIONS

    XOLAIR is contraindicated in patients with a severe hypersensitivity reaction to XOLAIR or to any ingredient of XOLAIR.

    WARNINGS AND PRECAUTIONS

    Anaphylaxis: Anaphylaxis has been reported to occur after administration of XOLAIR in premarketing clinical trials and in postmarketing spontaneous reports. In premarketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3507 (0.1%) patients. Anaphylaxis occurred with the first dose of XOLAIR in two patients and with the fourth dose in one patient. The time to onset of anaphylaxis was 90 minutes after administration in two patients and 2 hours after administration in one patient.

    A case-control study in asthma patients showed that, among XOLAIR users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with XOLAIR, compared to those with no prior history of anaphylaxis.

    In postmarketing spontaneous reports, the frequency of anaphylaxis attributed to XOLAIR use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. Approximately 60% to 70% of anaphylaxis cases have been reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.

    Initiate XOLAIR only in a healthcare setting equipped to manage anaphylaxis which can be life-threatening. Observe patients closely for an appropriate period of time after administration of XOLAIR, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing spontaneous reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.

    Once XOLAIR therapy has been established, administration of XOLAIR prefilled syringe or autoinjector outside of a healthcare setting by a patient or a caregiver may be appropriate for selected patients. Patient selection, determined by the healthcare provider in consultation with the patient, should take into account the pattern of anaphylaxis events seen in premarketing clinical trials and postmarketing spontaneous reports, as well as individual patient risk factors (e.g. prior history of anaphylaxis), ability to recognize signs and symptoms of anaphylaxis, and ability to perform subcutaneous injections with XOLAIR prefilled syringe or autoinjector with proper technique according to the prescribed dosing regimen and Instructions for Use.

    Discontinue XOLAIR in patients who experience a severe hypersensitivity reaction.

    Malignancy: Malignant neoplasms were observed in 20 of 4127 (0.5%) XOLAIR-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies of adults and adolescents (≥12 years of age) with asthma and other allergic disorders. The observed malignancies in XOLAIR-treated patients were a variety of types, with breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each. The majority of patients were observed for less than 1 year. The impact of longer exposure to XOLAIR or use in patients at higher risk for malignancy (e.g., elderly, current smokers) is not known.

    A subsequent 5-year observational study of 5007 XOLAIR-treated and 2829 non-XOLAIR-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen found that the incidence rates of primary malignancies (per 1000 patient years) were similar in both groups (12.3 vs 13.0, respectively). Study limitations which include the observational study design, the bias introduced by allowing enrollment of patients previously exposed to XOLAIR (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%) preclude definitively ruling out a malignancy risk with XOLAIR.

    Acute Asthma Symptoms and Deteriorating Disease: XOLAIR has not been shown to alleviate asthma exacerbations acutely. Do not use XOLAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with XOLAIR.

    Corticosteroid Reduction: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of XOLAIR therapy for asthma. Decrease corticosteroids gradually under the direct supervision of a physician.

    Eosinophilic Conditions: In rare cases, patients with asthma on therapy with XOLAIR may present with serious systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between XOLAIR and these underlying conditions has not been established.

    Fever, Arthralgia, and Rash: In post-approval use, some patients have experienced a constellation of signs and symptoms, including arthritis/arthralgia, rash, fever, and lymphadenopathy with an onset 1 to 5 days after the first or subsequent injections of XOLAIR. These signs and symptoms have recurred after additional doses in some patients. Physicians should stop XOLAIR if a patient develops this constellation of signs and symptoms.

    Parasitic (Helminth) Infection: Monitor patients at high risk of geohelminth infection while on XOLAIR therapy. Insufficient data are available to determine the length of monitoring required for geohelminth infections after stopping XOLAIR treatment.

    Laboratory Tests: Due to formation of XOLAIR:IgE complexes, serum total IgE levels increase following administration of XOLAIR and may remain elevated for up to 1 year following discontinuation of XOLAIR. Do not use serum total IgE levels obtained less than 1 year following discontinuation to reassess the dosing regimen for asthma patients, because these levels may not reflect steady state free IgE levels.

    Potential Medication Error Related to Emergency Treatment of Anaphylaxis
    XOLAIR should not be used for the emergency treatment of allergic reactions, including anaphylaxis. In studies to simulate use, some patients and caregivers did not understand that XOLAIR is not intended for the emergency treatment of allergic reactions, including anaphylaxis. The safety and effectiveness of XOLAIR for emergency treatment of allergic reactions, including anaphylaxis, have not been established. Instruct patients that XOLAIR is for maintenance use to reduce allergic reactions, including anaphylaxis, while avoiding food allergens.

    ADVERSE REACTIONS

    Asthma: In patients ≥12 years of age, the most common adverse reactions (≥1% more frequent in XOLAIR-treated patients) were: arthralgia (8%), pain (general) (7%), leg pain (4%), fatigue (3%), dizziness (3%), fracture (2%), arm pain (2%), pruritus (2%), dermatitis (2%), and earache (2%). In pediatric patients 6 to <12 years of age, the most commonly observed adverse reactions (≥3% more frequent in XOLAIR-treated pediatric patients) were: nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.

    Injection Site Reactions: In adults and adolescents with asthma, injection site reactions of any severity occurred at a rate of 45% in XOLAIR-treated patients compared with 43% in placebo-treated patients. Severe injection site reactions occurred more frequently in XOLAIR-treated patients compared with patients in the placebo group (12% vs 9%, respectively). The types of injection site reactions in asthma studies included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.

    Injection Site Reactions in Healthy Adults: In an open label trial in healthy adults, in which the 300 mg/2 mL autoinjector was compared to the 300 mg/2 mL prefilled syringe, injection site reactions (e.g., induration, pain, erythema, hemorrhage, swelling, discomfort, bruising, hypoesthesia, edema, pruritus) were observed in 24% (16/66) of subjects treated with the autoinjector compared with 14% (9/64) of subjects treated with the prefilled syringe.

    Cardiovascular and Cerebrovascular Events from Clinical Studies in Patients with Asthma: A 5-year observational study was conducted in 5007 XOLAIR-treated and 2829 non-XOLAIR-treated patients ≥12 years of age for a different indication to evaluate the long term safety of XOLAIR, including the risk of malignancy. The results suggest a potential increased risk of serious cardiovascular and cerebrovascular events in patients treated with XOLAIR, however the observational study design, the inclusion of patients previously exposed to XOLAIR (88% for a mean of 8 months), baseline imbalances in cardiovascular risk factors between the treatment groups, an inability to adjust for unmeasured risk factors, and the high study discontinuation rate (44%) limit the ability to quantify the magnitude of the risk.

    Pregnancy: Data with XOLAIR use in pregnant women are insufficient to inform on drug associated risk.

    You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555 or Novartis Pharmaceuticals Corporation at (888) 669-6682.

    Please see full Prescribing Information, including Boxed WARNING and Medication Guide, for additional Important Safety Information.

    WARNING: Anaphylaxis

    Anaphylaxis presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of XOLAIR. Anaphylaxis has occurred as early as after the first dose of XOLAIR, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, initiate XOLAIR therapy in a healthcare setting and closely observe patients for an appropriate period of time after XOLAIR administration. Health care providers administering XOLAIR should be prepared to manage anaphylaxis which can be life-threatening. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should symptoms occur. Selection of patients for self-administration of XOLAIR should be based on criteria to mitigate risk from anaphylaxis.

    INDICATION

    XOLAIR® (omalizumab) is indicated for:

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


      Limitations of Use: XOLAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.


    CONTRAINDICATIONS

    XOLAIR is contraindicated in patients with a severe hypersensitivity reaction to XOLAIR or to any ingredient of XOLAIR.

    WARNINGS AND PRECAUTIONS

    Anaphylaxis: Anaphylaxis has been reported to occur after administration of XOLAIR in premarketing clinical trials and in postmarketing spontaneous reports. In premarketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3507 (0.1%) patients. Anaphylaxis occurred with the first dose of XOLAIR in two patients and with the fourth dose in one patient. The time to onset of anaphylaxis was 90 minutes after administration in two patients and 2 hours after administration in one patient.

    A case-control study in asthma patients showed that, among XOLAIR users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with XOLAIR, compared to those with no prior history of anaphylaxis.

    In postmarketing spontaneous reports, the frequency of anaphylaxis attributed to XOLAIR use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. Approximately 60% to 70% of anaphylaxis cases have been reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.

    Initiate XOLAIR only in a healthcare setting equipped to manage anaphylaxis which can be life-threatening. Observe patients closely for an appropriate period of time after administration of XOLAIR, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing spontaneous reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.

    Once XOLAIR therapy has been established, administration of XOLAIR prefilled syringe or autoinjector outside of a healthcare setting by a patient or a caregiver may be appropriate for selected patients. Patient selection, determined by the healthcare provider in consultation with the patient, should take into account the pattern of anaphylaxis events seen in premarketing clinical trials and postmarketing spontaneous reports, as well as individual patient risk factors (e.g. prior history of anaphylaxis), ability to recognize signs and symptoms of anaphylaxis, and ability to perform subcutaneous injections with XOLAIR prefilled syringe or autoinjector with proper technique according to the prescribed dosing regimen and Instructions for Use.

    Discontinue XOLAIR in patients who experience a severe hypersensitivity reaction.

    Malignancy: Malignant neoplasms were observed in 20 of 4127 (0.5%) XOLAIR-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies of adults and adolescents (≥12 years of age) with asthma and other allergic disorders. The observed malignancies in XOLAIR-treated patients were a variety of types, with breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each. The majority of patients were observed for less than 1 year. The impact of longer exposure to XOLAIR or use in patients at higher risk for malignancy (e.g., elderly, current smokers) is not known.

    A subsequent 5-year observational study of 5007 XOLAIR-treated and 2829 non-XOLAIR-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen found that the incidence rates of primary malignancies (per 1000 patient years) were similar in both groups (12.3 vs 13.0, respectively). Study limitations which include the observational study design, the bias introduced by allowing enrollment of patients previously exposed to XOLAIR (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%) preclude definitively ruling out a malignancy risk with XOLAIR.

    Acute Asthma Symptoms and Deteriorating Disease: XOLAIR has not been shown to alleviate asthma exacerbations acutely. Do not use XOLAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with XOLAIR.

    Corticosteroid Reduction: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of XOLAIR therapy for asthma. Decrease corticosteroids gradually under the direct supervision of a physician.

    Eosinophilic Conditions: In rare cases, patients with asthma on therapy with XOLAIR may present with serious systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between XOLAIR and these underlying conditions has not been established.

    Fever, Arthralgia, and Rash: In post-approval use, some patients have experienced a constellation of signs and symptoms, including arthritis/arthralgia, rash, fever, and lymphadenopathy with an onset 1 to 5 days after the first or subsequent injections of XOLAIR. These signs and symptoms have recurred after additional doses in some patients. Physicians should stop XOLAIR if a patient develops this constellation of signs and symptoms.

    Parasitic (Helminth) Infection: Monitor patients at high risk of geohelminth infection while on XOLAIR therapy. Insufficient data are available to determine the length of monitoring required for geohelminth infections after stopping XOLAIR treatment.

    Laboratory Tests: Due to formation of XOLAIR:IgE complexes, serum total IgE levels increase following administration of XOLAIR and may remain elevated for up to 1 year following discontinuation of XOLAIR. Do not use serum total IgE levels obtained less than 1 year following discontinuation to reassess the dosing regimen for asthma patients, because these levels may not reflect steady state free IgE levels.

    Potential Medication Error Related to Emergency Treatment of Anaphylaxis
    XOLAIR should not be used for the emergency treatment of allergic reactions, including anaphylaxis. In studies to simulate use, some patients and caregivers did not understand that XOLAIR is not intended for the emergency treatment of allergic reactions, including anaphylaxis. The safety and effectiveness of XOLAIR for emergency treatment of allergic reactions, including anaphylaxis, have not been established. Instruct patients that XOLAIR is for maintenance use to reduce allergic reactions, including anaphylaxis, while avoiding food allergens.

    ADVERSE REACTIONS

    Asthma: In patients ≥12 years of age, the most common adverse reactions (≥1% more frequent in XOLAIR-treated patients) were: arthralgia (8%), pain (general) (7%), leg pain (4%), fatigue (3%), dizziness (3%), fracture (2%), arm pain (2%), pruritus (2%), dermatitis (2%), and earache (2%). In pediatric patients 6 to <12 years of age, the most commonly observed adverse reactions (≥3% more frequent in XOLAIR-treated pediatric patients) were: nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.

    Injection Site Reactions: In adults and adolescents with asthma, injection site reactions of any severity occurred at a rate of 45% in XOLAIR-treated patients compared with 43% in placebo-treated patients. Severe injection site reactions occurred more frequently in XOLAIR-treated patients compared with patients in the placebo group (12% vs 9%, respectively). The types of injection site reactions in asthma studies included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.

    Injection Site Reactions in Healthy Adults: In an open label trial in healthy adults, in which the 300 mg/2 mL autoinjector was compared to the 300 mg/2 mL prefilled syringe, injection site reactions (e.g., induration, pain, erythema, hemorrhage, swelling, discomfort, bruising, hypoesthesia, edema, pruritus) were observed in 24% (16/66) of subjects treated with the autoinjector compared with 14% (9/64) of subjects treated with the prefilled syringe.

    Cardiovascular and Cerebrovascular Events from Clinical Studies in Patients with Asthma: A 5-year observational study was conducted in 5007 XOLAIR-treated and 2829 non-XOLAIR-treated patients ≥12 years of age for a different indication to evaluate the long term safety of XOLAIR, including the risk of malignancy. The results suggest a potential increased risk of serious cardiovascular and cerebrovascular events in patients treated with XOLAIR, however the observational study design, the inclusion of patients previously exposed to XOLAIR (88% for a mean of 8 months), baseline imbalances in cardiovascular risk factors between the treatment groups, an inability to adjust for unmeasured risk factors, and the high study discontinuation rate (44%) limit the ability to quantify the magnitude of the risk.

    Pregnancy: Data with XOLAIR use in pregnant women are insufficient to inform on drug associated risk.

    You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555 or Novartis Pharmaceuticals Corporation at (888) 669-6682.

    Please see full Prescribing Information, including Boxed WARNING and Medication Guide, for additional Important Safety Information.