SAJAZIR (icatibant) safety profile

Warning and precautions1

Given the potential for airway obstruction during acute laryngeal hereditary angioedema (HAE) attacks, patients should be advised to inject SAJAZIR (icatibant) injection and then go to the nearest hospital emergency room right away.

Adverse reactions1​

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. ​

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.

Table 1. Adverse reactions observed in >1% of patients with acute attacks of HAEa and at a higher rate with icatibant versus placebo in the placebo-controlled trials1a

Adverse reactions observed in >1% of patients with acute attacks of HAE* and at a higher rate with icatibant versus placebo in the placebo-controlled trials1*

aEvents occurring within 14 days of study drug administration.​
bInjection site bruising, hematoma, burning, erythema, hypoesthesia, irritation, numbness, edema, pain, pressure sensation, pruritus, swelling, urticaria, and warmth.

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.​

You are encouraged to report side effects of prescription drugs. Visit www.fda.gov/medwatch, call 800 FDA-1088 or call Cycle Pharmaceuticals on 800 836-4380.

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.​

Drug interactions1​

SAJAZIR is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where icatibant may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors.​

Use in specific populations1​

Pregnancy

Available data from published literature and the pharmacovigilance database with icatibant injection use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.​

Lactation

There are no data on the presence of icatibant in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for icatibant injection and any potential adverse effects on the breastfed child from icatibant injection or from the underlying maternal condition.​

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.​

Geriatric Use

Clinical studies of icatibant injection did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are likely to have increased systemic exposure to SAJAZIR compared to younger (18–45 years) patients. Since other reported clinical experience has not identified differences in efficacy and safety between elderly and younger patients, no dose adjustment is recommended.




Reference

  1. SAJAZIR™ (icatibant) Injection. Prescribing Information. Cycle Pharmaceuticals Limited. ​
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Indication and Important Safety Information

SAJAZIR™ (Icatibant) injection is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

Warnings and precautions: Given the potential for airway obstruction during acute laryngeal HAE attacks, patients should be advised to seek medical attention in an appropriate healthcare facility immediately in addition to treatment with SAJAZIR.

Adverse reactions: The most commonly reported adverse reactions were injection-site reactions, which occurred in almost all patients (97%) in clinical trials. These injection-site reactions included bruising, hematoma, burning, erythema, hypoesthesia, irritation, numbness, edema, pain, pressure sensation, pruritus, swelling, urticaria, and warmth.

Other common adverse reactions included pyrexia (4%), transaminase increase (4%), and dizziness (3%), as well as rash, nausea, and headache.

Drug interactions: Icatibant is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where SAJAZIR may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors.

Use in specific populations: Clinical studies of Icatibant included a limited number of subjects aged 65 and over. Elderly patients are likely to have increased systemic exposure. Reported clinical experience has not identified differences in efficacy and safety between elderly and younger patients.

Safety and effectiveness in patients below 18 years of age have not been established.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

For more detailed information, please refer to the Full Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS contact Cycle Pharmaceuticals at 1-800-836-4380, or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch.