Xolair Adverse Reactions

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 9 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). (See Table 9.)

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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 10) 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 10 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). (See Table 10.)

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In a 48-week study, 81 CSU patients received omalizumab 300 mg every 4 weeks (see Pharmacology: Pharmacodynamics under Actions). The safety profile of long-term use was similar to the safety profile observed in 24-week studies in CSU.
Description of selected adverse reactions: Immune system disorders: For further information, see Precautions.
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 Pharmacology: Toxicology: Preclinical safety data under Actions), 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 Precautions).
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.