FIRAZYR

What it is

FIRAZYR is icatibant acetate supplied as a solution for injection. Each pre-filled syringe delivers 3 mL containing icatibant acetate equivalent to 30 mg icatibant. Icatibant is a selective competitive antagonist at the bradykinin type 2 (B2) receptor. It is a synthetic decapeptide with a structure similar to bradykinin, but with 5 non-proteinogenic amino acids.

Approved indications

— Symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults, adolescents and children aged 2 years and older with C1-esterase-inhibitor deficiency.

Dosing overview

The recommended dose of FIRAZYR for adults is one subcutaneous injection of 30 mg. In the majority of cases a single injection of FIRAZYR is sufficient to treat an attack. In case of insufficient relief or recurrence of symptoms, a second injection of FIRAZYR can be administered after 6 hours. If the second injection produces insufficient relief or a recurrence of symptoms is observed, a third injection of FIRAZYR can be administered after a further 6 hours. No more than 3 injections of FIRAZYR should be administered in a 24-hour period. For children and adolescents aged 2 to 17 years, the recommended dose based on body weight is: 12–25 kg: 10 mg (1.0 mL); 26–40 kg: 15 mg (1.5 mL); 41–50 kg: 20 mg (2.0 mL); 51–65 kg: 25 mg (2.5 mL); over 65 kg: 30 mg (3.0 mL). FIRAZYR is intended for subcutaneous injection preferably in the abdominal area.

Key safety warnings

Icatibant has been shown to aggravate induced cardiac ischaemia in several non-clinical models, including a study in dogs involving coronary ligation, probably as a result of left ventricular failure. Bradykinin and the B2 receptors have been shown to have cardioprotective properties in animals, which were attenuated by icatibant. Under ischaemic conditions, a deterioration of cardiac function and a decrease in coronary blood flow could theoretically arise from antagonism of the B2 receptor. Caution should therefore be observed in the administration of FIRAZYR to patients with acute ischaemic heart disease or unstable angina pectoris. There is a theoretical possibility that icatibant may attenuate the positive late phase neuroprotective effects of bradykinin. Accordingly, caution should be observed in the administration of icatibant to patients in the weeks following a stroke. Almost all subjects who were treated with subcutaneous icatibant in clinical trials developed reactions at the site of injection including erythema, swelling, warm sensation, burning, itching and/or cutaneous pain. These reactions were generally mild in severity, transient, and resolved without further intervention. Patients who self inject should be advised to seek urgent medical attention if there is no evidence of resolution of the HAE attack within 2 hours of self-injection, or immediately should the HAE attack progress to involve the face, lips or pharyngolaryngeal area. Patients whose initial HAE attack involves the face, lips or pharyngolaryngeal area should seek urgent medical attention, regardless of their response to FIRAZYR following self-injection.

Contraindications

FIRAZYR is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

PBS listing

PBS listing information is not provided in the available source documents.

Regulatory history

FIRAZYR icatibant acetate 30 mg/3 mL injection pre-filled syringe was first listed on the ARTG on 3 September 2010. The TGA approved FIRAZYR on 7 June 2010 for the symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults with C1-esterase-inhibitor deficiency. FIRAZYR is subject to additional monitoring in Australia, which will allow quick identification of new safety information. In July 2017, the PBAC recommended a change to allow up to 12 injections per authority prescription to encourage further clinical review of patients experiencing high frequency of attacks.