1 INDICATIONS AND USAGE

Xolair (omalizumab) is indicated for adults and adolescents (12 years of age and above) 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.

Xolair has been shown to decrease the incidence of asthma exacerbations in these patients.

Important Limitations of Use

• Xolair is not indicated for treatment of other allergic conditions.
• Xolair is not indicated for the relief of acute bronchospasm or status asthmaticus.
• Xolair is not indicated for use in pediatric patients less than 12 years of age.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing

Administer Xolair (omalizumab) 150 to 375 mg by subcutaneous (SC) injection every 2 or 4 weeks. Determine doses (mg) and dosing frequency by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). See the dose determination charts below (Table 1 and Table 2) for appropriate dose assignment.

Periodically reassess the need for continued therapy based upon the patient’s disease severity and level of asthma control.

2.2 Dosing Adjustments

Adjust doses for significant changes in body weight (see Table 1 and Table 2).

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.

• Interruptions lasting less than one year: Dose based on serum IgE levels obtained at the initial dose determination.
• Interruptions lasting one year or more: Re-test total serum IgE levels for dose determination.

2.3 Preparation and Administration

Prepare Xolair for subcutaneous injection using Sterile Water for Injection (SWFI), USP, ONLY. Each vial of Xolair is for single use only and contains no preservatives.

Reconstitution

The lyophilized product takes 15-20 minutes to dissolve. The fully reconstituted product will appear clear or slightly opalescent and it is acceptable if there are a few small bubbles or foam around the edge of the vial. The reconstituted product is somewhat viscous; in order to obtain the full 1.2 mL dose, ALL OF THE PRODUCT MUST BE WITHDRAWN from the vial before expelling any air or excess solution from the syringe.

Use the solution within 8 hours following reconstitution when stored in the vial at 2-8ºC (36-46ºF), or within 4 hours of reconstitution when stored at room temperature. Reconstituted Xolair vials should be protected from sunlight.

Preparation

STEP 1: Draw 1.4 mL of SWFI, USP into a 3  mL syringe equipped with a 1 inch, 18-gauge needle.

STEP 2: Place the vial upright on a flat surface and using standard aseptic technique, insert the needle and inject the SWFI, USP directly onto the product.

STEP 3: Keeping the vial upright, gently swirl the upright vial for approximately 1 minute to evenly wet the powder. Do not shake.

STEP 4: After completing STEP 3, gently swirl the vial for 5-10 seconds approximately every 5 minutes in order to dissolve any remaining solids. There should be no visible gel like particles in the solution. Do not use if foreign particles are present.

Note: If it takes longer than 20 minutes to dissolve completely, repeat STEP 4 until there are no visible gel-like particles in the solution. Do not use if the contents of the vial do not dissolve completely by 40 minutes.

STEP 5: Invert the vial for 15 seconds in order to allow the solution to drain toward the stopper. Using a new 3 mL syringe equipped with a 1-inch, 18-gauge needle, insert the needle into the inverted vial. Position the needle tip at the very bottom of the solution in the vial stopper 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.

STEP 6: Replace the 18-gauge needle with a 25-gauge needle for subcutaneous injection.

STEP 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.

Administration

Administer Xolair by subcutaneous injection. The injection may take 5-10 seconds to administer because the solution is slightly viscous. Each vial delivers 1.2 mL (150 mg) of Xolair. Do not administer more than 150 mg per injection site. Divide doses of more than 150 mg among two or more injection sites. (Table 3).

3 DOSAGE FORMS AND STRENGTHS

150 mg of omalizumab as lyophilized, sterile powder in a single-use 5 mLvial.

4 CONTRAINDICATIONS

The use of Xolair is contraindicated in the following:

Severe hypersensitivity reaction to Xolair or any ingredient of Xolair [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Anaphylaxis

Anaphylaxis has been reported to occur after administration of Xolair in premarketing clinical trials and in postmarketing spontaneous reports. Signs and symptoms in these reported cases have included bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue. Some of these events have been life-threatening. In premarketing clinical trials the frequency of anaphylaxis attributed to Xolair use was estimated to be 0.1%. 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. Anaphylaxis has occurred as early as after the first dose of Xolair, but also has occurred beyond one year after beginning regularly scheduled treatment.

Administer Xolair only in a healthcare setting by healthcare providers prepared to manage anaphylaxis that 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 [see Adverse Reactions (6)]. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.

Discontinue Xolair in patients who experience a severe hypersensitivity reaction [see Contraindications (4)].

5.2 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 [see Adverse Reactions (6)].

5.3 Acute Asthma Symptoms

Xolair has not been shown to alleviate asthma exacerbations acutely. Do not use Xolair to treat acute bronchospasm or status asthmaticus.

5.4 Corticosteroid Reduction

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of Xolair therapy. Decrease corticosteroids gradually under the direct supervision of a physician.

5.5 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, a condition which is often treated with systemic corticosteroid therapy. 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.

5.6 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.

In a one-year clinical trial conducted in Brazil in patients at high risk for geohelminthic infections (roundworm, hookworm, whipworm, threadworm), 53% (36/68) of Xolair-treated patients experienced an infection, as diagnosed by standard stool examination, compared to 42% (29/69) of placebo controls. The point estimate of the odds ratio for infection was 1.96, with a 95% confidence interval (0.88, 4.36) indicating that in this study a patient who had an infection was anywhere from 0.88 to 4.36 times as likely to have received Xolair than a patient who did not have an infection. Response to appropriate anti-geohelminth treatment of infection as measured by stool egg counts was not different between treatment groups.

5.7 Laboratory Tests

Serum total IgE levels increase following administration of Xolair due to formation of Xolair:IgE complexes [see Clinical Pharmacology (12.2)]. Elevated serum total IgE levels may persist 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 because these levels may not reflect steady state free IgE levels.