SAJAZIR

6 ADVERSE REACTIONS The most commonly reported adverse reactions were injection site reactions, which occurred in almost all patients (97%) in clinical trials. Other common adverse reactions occurring in greater than 1% of patients included pyrexia, transaminase increase, dizziness, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Cycle Pharmaceuticals Ltd at 1-800-836-4380 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience The safety of icatibant was evaluated in three controlled trials that included 223 patients who received icatibant injection 30 mg (n=113), placebo (n=75), or comparator (n=38). The mean age at study entry was 38 years (range 18 to 83 years), 64% were female, and 95% were white. The data described below represent adverse reactions observed from the two placebo-controlled trials, consisting of 77 patients who received icatibant injection at a dose of 30 mg SC, and 75 who received placebo. The most frequently reported adverse reactions (occurring in greater than 1% of patients and at a higher rate with icatibant injection versus placebo) are shown in Table 1. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 1 Adverse reactions observed in >1% of patients with acute attacks of HAE and at a higher rate with Icatibant injection versus placebo in the placebo-controlled trials a a Events occurring within 14 days of study drug administration b Injection site bruising, Injection site hematoma, Injection site burning, Injection site erythema, Injection site hypoesthesia, Injection site irritation, Injection site numbness, Injection site edema, Injection site pain, Injection site pressure sensation, Injection site pruritus, Injection site swelling, Injection site urticaria, and Injection site warmth I catibant injection (N =77) Placebo (N = 75) System Organ Class Preferred Term Subjects (%) Subjects (%) General disorders and administration site conditions Injection site reaction b 75 (97) 25 (33) Pyrexia 3 (4) 0 Investigations Transaminase increased 3 (4) 0 Nervous system disorders Dizziness 2 (3) 1 (1) The third trial was active-controlled and was comprised of 35 patients who received icatibant injection 30 mg and 38 patients who received the comparator. Adverse reactions for icatibant injection were similar in nature and frequency to those reported in Table 1. In all three controlled trials, patients were eligible for treatment of subsequent attacks in an open-label extension. Patients were treated with icatibant injection 30 mg and could receive up to 3 doses of icatibant injection 30 mg administered at least 6 hours apart for each attack. A total of 225 patients were treated with 1,076 doses of 30 mg icatibant injection for 987 attacks of acute HAE. Adverse reactions similar in nature and frequency were observed to those seen in the controlled phase of the trials. Other adverse reactions reported included rash, nausea, and headache in patients exposed to icatibant injection. The safety of self-administration was evaluated in a separate, open-label trial in 56 patients with HAE. In this trial, the safety profile of icatibant injection in patients who self-administered icatibant injection was similar in nature and frequency to that of patients whose therapy was administered by healthcare professionals. 6.2 Immunogenicity Across repeated treatment in the controlled trials, 4 patients tested positive for anti-icatibant antibodies. Three of these patients had subsequent tests which were negative. No hypersensitivity or anaphylactic reactions were reported with icatibant injection. No association between anti-icatibant antibodies and efficacy was observed. 6.3 Postmarketing Experience The following adverse reactions have been identified during post approval use of icatibant: urticaria. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.