FIRAZYR
Manufacturer:
Shire US, Inc.
Pharmacological Class:
Bradykinin B2 receptor antagonist.
Active Ingredient(s):
Icatibant 10mg/mL; soln for SC inj; preservative-free.
Indication(s):
Treatment of acute attacks of hereditary angioedema (HAE).
Pharmacology:
Icatibant is a competitive antagonist selective for the bradykinin B2 receptor, with an affinity similar to bradykinin. Hereditary angioedema is caused by an absence or dysfunction of C1-esterase-inhibitor, a key regulator of the Factor XII/kallikrein proteolytic cascade that leads to bradykinin production. Bradykinin is a vasodilator which is thought to be responsible for the characteristic HAE symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.
Clinical Trials:
The efficacy and safety of Firazyr for the treatment of acute attacks of HAE in adults were studied in three controlled clinical trials. Response to therapy was primarily assessed using visual analog scores on a 100 mm scale and patient- and physician-reported symptom scores for abdominal and cutaneous pain and swelling.
Trial 1 was a randomized, placebo-controlled, double-blind, parallel-group study of 98 adult patients. Patients who had developed moderate-to-severe cutaneous or abdominal or mild-to-moderate laryngeal attacks of HAE were randomized to receive either Firazyr 30mg or placebo by SC injection. Patients with severe laryngeal attacks of HAE received open-label Firazyr 30mg. The primary endpoint was assessed using a 3-item composite visual analog score (VAS), comprised of averaged assessments of skin swelling, skin pain, and abdominal pain. Response was defined as at least a 50% reduction from the pretreatment composite 3-itemVAS score. The median time to 50% reduction in symptoms for patients with cutaneous or abdominal attacks treated with Firazyr (n=43) compared to placebo (n=45) was 2 hours versus 19.8 hours, respectively. Other eva luated endpoints included time to almost complete symptom relief (VAS<10 mm) and rescue medication use. In Trial 1, the median times to almost complete symptom relief were 8 versus 36 hours for Firazyr and placebo, respectively. In terms of rescue medication use, 3/43 (7%) patients treated with Firazyr used additional rescue medication in comparison to 18/45 (40%) patients treated with placebo.
In a second placebo-controlled trial and an active-controlled trial, a total of 26 and 35 patients, respectively, received Firazyr 30mg for the treatment of an acute HAE attack. Across the three trials, Firazyr had a median time to 50% reduction from baseline symptoms ranging from 2 to 2.3 hours.
In all three controlled trials, patients were eligible for treatment of subsequent attacks in an open-label extension. Patients were treated with Firazyr 30mg and could receive up to 3 doses of Firazyr 30mg administered at least 6 hours apart for each attack. A total of 225 patients were treated with 1,076 doses of 30mg Firazyr for 987 attacks of acute HAE in these trials. In an assessment of the first 5 Firazyr-treated attacks (621 doses for 582 attacks), the median times to a 50% reduction from the pretreatment composite 3-item VAS score were similar across attacks (2, 2, 2.4, 2, 1.5 hours). The majority (93%) of these attacks of HAE were treated with a single dose of Firazyr.
Legal Classification:
Rx
Adults:
≥18yrs: 30mg SC in abdominal area; may give additional doses at intervals of at least 6 hours if response inadequate or symptoms recur. Max 3 doses/24hrs.
Children:
<18yrs: not recommended.
Warnings/Precautions:
Advise patients to seek medical attention after treating laryngeal attack given the potential for airway obstruction. Elderly. Labor & delivery. Pregnancy (Cat.C). Nursing mothers.
Interaction(s):
May attenuate the antihypertensive effect of ACE inhibitors.
Adverse Reaction(s):
Inj site reactions, pyrexia, transaminase increase, dizziness, rash.
How Supplied:
Single-use prefilled syringe (3mL)—1, 3 |
