Get your patient on Firazyr (Icatibant Acetate)

FIRAZYR^® (icatibant) is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

• 30 mg injected subcutaneously in the abdominal area. (
  2.1 Recommended Dosing

  The recommended dose of FIRAZYR is 30 mg administered by subcutaneous (SC) injection in the abdominal area. Additional doses may be administered at intervals of at least 6 hours if response is inadequate or if symptoms recur. No more than 3 doses may be administered in any 24 hour period.
  )
• If response is inadequate or symptoms recur, additional injections of 30 mg may be administered at intervals of at least 6 hours. (
  2.1 Recommended Dosing

  The recommended dose of FIRAZYR is 30 mg administered by subcutaneous (SC) injection in the abdominal area. Additional doses may be administered at intervals of at least 6 hours if response is inadequate or if symptoms recur. No more than 3 doses may be administered in any 24 hour period.
  )
• Do not administer more than 3 injections in 24 hours. (
  2.1 Recommended Dosing

  The recommended dose of FIRAZYR is 30 mg administered by subcutaneous (SC) injection in the abdominal area. Additional doses may be administered at intervals of at least 6 hours if response is inadequate or if symptoms recur. No more than 3 doses may be administered in any 24 hour period.
  )
• Patients may self-administer upon recognition of an HAE attack. (
  2.2 Administration Instructions

  FIRAZYR should be inspected visually for particulate matter and discoloration prior to administration. The drug solution should be clear and colorless. Do not administer if the product contains particulates or is discolored.

  Attach the provided 25 gauge needle to the syringe hub and screw on securely. Do not use a different needle. Disinfect the injection site and administer FIRAZYR by subcutaneous injection over at least 30 seconds.

  Patients may self-administer FIRAZYR upon recognition of symptoms of an HAE attack after training under the guidance of a healthcare professional

  [seePatient Counseling Information (17)]

  .
  )

FIRAZYR injection is supplied in a prefilled syringe delivering 30 mg icatibant. Each syringe delivers 3 mL solution with a concentration of 10 mg per mL.

Elderly patients demonstrate increased systemic exposure to icatibant. Differences in efficacy and safety between elderly and younger patients have not been identified. (

None.

Laryngeal attacks: Following treatment of laryngeal attacks with FIRAZYR, advise patients to seek immediate medical attention. (

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. (

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

FIRAZYR (icatibant) is a synthetic decapeptide with five non-proteinogenic amino acids. The chemical structure of icatibant acetate is presented in Figure 1.

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.

Two-year studies were conducted in CD1 mice and Wistar rats to assess the carcinogenic potential of FIRAZYR. No evidence of tumorigenicity was observed in mice and rats at icatibant subcutaneous doses up to 15 mg/kg/day (twice per week) and 6 mg/kg/day (daily), respectively (approximately 10-fold and 6-fold greater than the MRHD on an AUC basis, respectively).

Icatibant tested negative for genotoxicity in the

Daily subcutaneous administration of icatibant to rats and dogs caused ovarian, uterine, and testicular atrophy/degeneration and adverse effects on the mammary and prostate glands. In rats, testicular atrophy, reduced prostate gland secretion, decreased testosterone levels and degenerate corpora lutea occurred at doses greater than or equal to 3 mg/kg (approximately 5-fold greater than the MRHD in males and 2-fold greater than the MRHD in females on an AUC basis) and a decrease in developing ovarian follicles, mammary gland masculinization, and uterine atrophy occurred at doses greater than or equal to 10 mg/kg (approximately 6-fold greater than MRHD in females on an AUC basis). In dogs, reduced sperm counts and uterine atrophy occurred at doses greater than or equal to 1 mg/kg (approximately 2-fold greater than the MRHD on an AUC basis). Atrophy of the testes and prostate with decreased testosterone levels, decreased ovary size and decreased number of developing follicles occurred at a dose of 10 mg/kg (approximately 30-fold greater than the MRHD in males and 15-fold greater than at the MRHD in females on an AUC basis).

In contrast to the effects of daily icatibant administration, toxicity to the ovary, uterus, testis, mammary gland, and prostate did not occur in dogs treated twice a week for 9 months. AUC exposures from a dose of 3 mg/kg in these dogs were 5- and 3-fold the MRHD exposures in men and women, respectively. Sperm counts and testosterone remained unaffected over the course of the study in male dogs dosed twice a week.

Reproduction studies in male mice and rats with daily administration of icatibant found no effects on fertility or reproductive performance with intravenous doses up to 81 mg/kg (approximately 5-fold greater than the MRHD on a mg/m² basis) or subcutaneous doses up to 10 mg/kg (approximately 11-fold greater than the MRHD on an AUC basis), respectively.

The efficacy and safety of FIRAZYR for the treatment of acute attacks of HAE in adults were studied in three controlled clinical trials. Among the 223 patients in these studies, the mean age was 38 years, 64% were female, and 95% were white. Approximately 57% of patients reported use of attenuated androgens, antifibrinolytic agents, or C1 inhibitors. 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 with a median age of 36 years. Patients who had developed moderate to severe cutaneous or abdominal or mild to moderate laryngeal attacks of HAE were randomized to receive either FIRAZYR 30 mg or placebo by subcutaneous injection. Patients with severe laryngeal attacks of HAE received open-label FIRAZYR 30 mg. 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-item VAS score (Figure 2). 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 2.0 hours [95% CI 1.5, 3.0] versus 19.8 hours [95% CI 6.1, 26.3], respectively (p<0.001).

Other evaluated 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 8.0 versus 36.0 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 30 mg 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 2.0 to 2.3 hours.

FIRAZYR is supplied as a single-dose, prefilled syringe for subcutaneous administration. Each syringe delivers 3 mL of a sterile solution of icatibant 30 mg (as icatibant acetate). Each glass syringe has a bromobutyl plunger stopper, which is not made of latex natural rubber.

FIRAZYR is available in cartons containing one single-dose, prefilled syringe and one 25 G Luer lock needle. NDC 54092-702-02.

FIRAZYR is also available in a pack containing 3 cartons; each carton contains one single-dose, prefilled syringe and one 25 G Luer lock needle. NDC 54092-702-03.

• Wash your hands with soap and water.
• You will need the following supplies:
  • Your FIRAZYR carton that includes 1 single-dose FIRAZYR prefilled syringe and 1 needle.
  • 1 alcohol wipe
  • The medicine inside your FIRAZYR prefilled syringe should be clear and colorless. Do not use your FIRAZYR prefilled syringe if the solution contains particles, is cloudy, or has an unusual color.

    

  Figure A

Step 2. Remove the prefilled syringe and needle from the carton. See

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See

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See

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Step 5. Firmly screw the needle on the prefilled syringe. Be careful not to remove the needle from the needle cap. See

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See

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The area you choose for injection should be at least 2 inches (5 cm) away from any scars. Do not choose an area that is bruised, swollen, or painful.

Step 7. Clean your FIRAZYR injection site with an alcohol wipe and allow it to dry. See

Do not pull up on the plunger. See

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Step 9. Hold the FIRAZYR prefilled syringe in 1 hand, between your fingers and thumb. See

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Step 10. Use your other hand to gently pinch the fold of skin you cleaned with the alcohol wipe between your thumb and fingers for your injection. See

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Step 11. Hold the syringe between a 45-to-90 degree angle to your skin with the needle facing the fold of skin you are holding. See

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Step 12. Hold the fold of skin. Bring the syringe to the skin and quickly insert the needle into the skin fold. See

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Step 13. Push the plunger, at the top of the syringe, for at least 30 seconds until no FIRAZYR is in the syringe. See

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Step 14. Release the skin fold and gently pull the needle out. See

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• made of a heavy-duty plastic,
• can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
• upright and stable during use,
• leak-resistant, and
• properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at:

Distributed by:

Takeda Pharmaceuticals America, Inc.

Cambridge, MA 02142

FIRAZYR and the FIRAZYR Logo are registered trademarks of Shire Orphan Therapies GmbH. Takeda and are registered trademarks of Takeda Pharmaceutical Company Limited.

©2025 Takeda Pharmaceutical Company Limited. All rights reserved.

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.

Revised: June 2025

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.