Xolair Side Effects, and Drug Interactions - Omalizumab

Xolair Side Effects, and Drug Interactions - Omalizumab

SIDE EFFECTS

The most serious adverse reactions occurring in clinical studies with Xolair are malignancies and anaphylaxis (see WARNINGS). The observed incidence of malignancy among Xolair-treated patients (0.5%) was numerically higher than among patients in control groups (0.2%). Anaphylactic reactions were rare but temporally associated with Xolair administration.

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

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

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

Table 4 shows adverse events that occurred ³ 1% more frequently in patients receiving Xolair than in those receiving placebo in the placebo-controlled asthma studies. Adverse events were classified using preferred terms from the International Medical Nomenclature (IMN) dictionary. Injection site reactions were recorded separately from the reporting of other adverse events and are described following Table 4.

Age (among patients under age 65), race, and gender did not appear to affect the between group differences in the rates of adverse events.

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

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

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

Low titers of antibodies to Xolair were detected in approximately 1 / 1723 ( < 0.1%) of patients treated with Xolair. The data reflect the percentage of patients whose test results were considered positive for antibodies to Xolair in an ELISA assay and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Xolair with the incidence of antibodies to other products may be misleading.

Allergic symptoms, including urticaria, dermatitis, and pruritus were observed in patients treated with Xolair. There were also 3 cases of anaphylaxis observed within 2 hours of Xolair administration in which there were no other identifiable allergic triggers (see WARNINGS: Anaphylaxis).

DRUG INTERACTIONS

No formal drug interaction studies have been performed with Xolair. The concomitant use of Xolair and allergen immunotherapy has not been evaluated.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies have been performed in animals to evaluate the carcinogenic potential of Xolair.

No evidence of mutagenic activity was observed in Ames tests using six different strains of bacteria with and without metabolic activation at Omalizumab concentrations up to 5000 m g/mL.

The effects of Omalizumab on male and female fertility have been assessed in cynomolgus monkey studies. Administration of Omalizumab at doses up to and including 75 mg/kg/week did not elicit reproductive toxicity in male cynomolgus monkeys and did not inhibit reproductive capability, including implantation, in female cynomolgus monkeys. These doses provide a 2- to 16-fold safety factor based on total dose and 2- to 5-fold safety factor based on AUC over the range of adult clinical doses.

Pregnancy (Category B)

Reproduction studies in cynomolgus monkeys have been conducted with Omalizumab. Subcutaneous doses up to 75 mg/kg (12-fold the maximum clinical dose) of Omalizumab did not elicit maternal toxicity, embryotoxicity, or teratogenicity when administered throughout organogenesis and did not elicit adverse effects on fetal or neonatal growth when administered throughout late gestation, delivery, and nursing. IgG molecules are known to cross the placental barrier. There are no adequate and well-controlled studies of Xolair in pregnant women. Because animal reproduction studies are not always predictive of human response, Xolair should be used during pregnancy only if clearly needed.

Nursing Mothers

The excretion of Omalizumab in milk was evaluated in female cynomolgus monkeys receiving SC doses of 75 mg/kg/week. Neonatal plasma levels of Omalizumab after in utero exposure and 28 days of nursing were between 11% and 94% of the maternal plasma level. Milk levels of Omalizumab were 1.5% of maternal blood concentration. While Xolair presence in human milk has not been studied, IgG is excreted in human milk and therefore it is expected that Xolair will be present in human milk. The potential for Xolair absorption or harm to the infant are unknown; caution should be exercised when administering Xolair to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Geriatric Use

In clinical trials 134 patients 65 years of age or older were treated with Xolair. Although there were no apparent age-related differences observed in these studies, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients.