Firazyr

Firazyr (icatibant) is a prescription injection used to treat acute attacks of hereditary angioedema (HAE) in adults 18 years and older. It comes as a single-dose prefilled syringe that is injected under the skin (subcutaneously) of the stomach area. After training from a healthcare professional, you can inject Firazyr yourself as soon as you recognize the symptoms of an HAE attack.

Firazyr is used to treat attacks once they start. It is not used to prevent HAE attacks.

Firazyr belongs to a class of medicines called bradykinin B2 receptor antagonists. It gained FDA approval on August 25, 2011. Generic icatibant injection is also available.

HAE is caused by a lack of, or poorly working, C1 esterase inhibitor. This leads to the production of too much bradykinin, a substance that widens blood vessels and is thought to cause the swelling, inflammation, and pain of an HAE attack. Firazyr is a synthetic peptide that blocks bradykinin from attaching to its B2 receptor, which treats the symptoms of an acute attack.

Firazyr is absorbed quickly after injection, reaching peak levels in about 45 minutes, and has a short half-life of about 1.4 hours.

Firazyr was studied in three controlled trials (FAST-1 [NCT00097695], FAST-2 [NCT00500656], and FAST-3 [NCT00912093]) in 223 adults with acute HAE attacks. In the placebo-controlled trial of adults with skin (cutaneous) or abdominal attacks:

Across all three trials, the median time to a 50% reduction in symptoms ranged from 2.0 to 2.3 hours. Results were similar in 60 patients treated for laryngeal (throat) attacks. When patients were treated for repeat attacks, 93% of attacks needed only a single injection. In a study of 56 patients who injected Firazyr themselves, the median time to 50% symptom reduction was 2.6 hours.

Read the Instructions for Use that come with Firazyr. Use Firazyr exactly as your healthcare provider tells you. You or your caregiver should be trained to give Firazyr before an attack happens, so you can respond right away.

• Inject one 30 mg dose (1 prefilled syringe) under the skin of the stomach area as soon as you recognize an HAE attack.
• If symptoms continue or come back, you may give another 30 mg injection at least 6 hours after the previous one.
• Do not give more than 3 injections in 24 hours.
• If you have a laryngeal attack, inject Firazyr and then go to the nearest hospital emergency room right away.

How to inject Firazyr

• Wash your hands with soap and water. Check that the solution is clear and colorless. Do not use it if it is cloudy, discolored, or has particles in it.
• Twist the needle cap lid to break the seal, keeping the needle inside its cap. Unscrew the protective cap from the syringe and firmly screw on the 25 gauge needle provided. Do not use a different needle.
• Choose a fold of skin on your stomach about 2 to 4 inches (5 to 10 cm) below your belly button on either side, at least 2 inches (5 cm) from any scars. Do not inject into skin that is bruised, swollen, or painful.
• Clean the site with an alcohol wipe and let it dry.
• Remove the needle from the needle cap without pulling up on the plunger. Pinch a fold of skin, hold the syringe at a 45 to 90 degree angle, and quickly insert the needle.
• Push the plunger slowly over at least 30 seconds until the syringe is empty, then release the skin and gently remove the needle.
• Put the used syringe, with the needle attached, in an FDA-cleared sharps disposal container right away.

Each prefilled syringe is for one use only. The syringe plunger stopper is not made with natural rubber latex.

See How do you administer/inject Firazyr for more information.

There are no conditions in which Firazyr must never be used (no contraindications). Before using Firazyr, tell your healthcare provider about all your medical conditions, including if you:

• Have reduced blood flow to the heart (coronary ischemia), unstable angina, or have had a recent stroke
• Take an ACE inhibitor for blood pressure or heart problems
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Firazyr is not approved for children and teenagers younger than 18 years.

Older adults (over 65 years) and women may have higher levels of Firazyr in the blood, but no differences in safety or effectiveness have been found and no dose adjustment is needed. No dose adjustment is needed for people with liver or kidney problems.

Pregnancy

Available data from Firazyr use in pregnant women have not identified a drug-related risk of major birth defects, miscarriage, or other harm to the mother or baby. Talk with your healthcare provider about whether Firazyr is right for you.

Breastfeeding

It is not known if Firazyr passes into human breast milk, although it was found in the milk of rats. Firazyr is not expected to be absorbed by a baby who swallows it in breast milk. Talk to your healthcare provider about the best way to feed your baby.

The most common side effect of Firazyr is an injection site reaction, which occurred in almost all patients (97%) in clinical trials. These reactions include redness, bruising, swelling, warmth, burning, itching, irritation, hives, numbness, pressure, or pain at the injection site.

Nausea, headache, and rash were also reported in longer-term use, and hives (urticaria) has been reported since approval. Tiredness, drowsiness, and dizziness can also happen. Side effects were similar in people who injected Firazyr themselves and in those treated by a healthcare professional.

Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all of the possible side effects of Firazyr. Call your doctor for medical advice about side effects. You may report side effects to Takeda at 1-877-TAKEDA-7 (1-877-825-3327) or to the FDA at 1-800-FDA-1088.

Laryngeal (throat) attacks

Laryngeal attacks can block your airway and become life-threatening. If you have a laryngeal attack, inject Firazyr and then go to the nearest hospital emergency room right away.

Heart and stroke risk

Bradykinin may help protect the heart when blood flow is reduced. Animal studies suggest that blocking bradykinin could have harmful effects on the heart during reduced blood flow, and there is limited experience with Firazyr in people with this problem. Firazyr should be used during acute coronary ischemia (reduced blood flow to the heart), unstable angina, or in the weeks after a stroke only if the benefit is greater than the possible risk.

Do not use more than 3 injections within 24 hours. Call your healthcare provider if your symptoms do not improve or get worse after using Firazyr.

Usual adult dose for an acute HAE attack:

• 30 mg (1 prefilled syringe) subcutaneously in the abdominal area.
• If the response is not adequate or symptoms come back, additional 30 mg doses may be given at least 6 hours apart.
• Maximum: 3 doses (90 mg) in 24 hours.

Firazyr is used only when needed to treat an attack, so it does not have a regular dosing schedule. Call your healthcare provider if your symptoms do not improve after using it.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. In studies, a 90 mg dose given as three injections had side effects similar to a single 30 mg dose. A much higher dose given into a vein in healthy volunteers caused redness, itching, and low blood pressure.

Tiredness, drowsiness, and dizziness can happen after using Firazyr. If this happens, do not drive, use machinery, or do anything that needs you to be alert.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

• ACE inhibitors (such as lisinopril or enalapril). Firazyr may reduce the blood pressure-lowering effect of these medicines. People taking ACE inhibitors were not included in clinical trials.

Firazyr is broken down by enzymes that are not part of the cytochrome P450 system, so interactions with medicines processed by these liver enzymes are not expected.

• Store Firazyr between 36°F and 77°F (2°C and 25°C), in the refrigerator or at room temperature.
• Do not freeze.
• Keep the syringe in its original carton until you are ready to use it.

Keep Firazyr and all medicines out of the reach of children.

Active ingredient: icatibant acetate, equivalent to 30 mg icatibant in 3 mL (10 mg per mL).

Inactive ingredients: sodium chloride, glacial acetic acid, sodium hydroxide, and water. Firazyr contains no preservatives.

Firazyr is available in cartons containing one prefilled syringe and one 25 gauge needle, and in packs of 3 cartons.

Firazyr is distributed by Takeda Pharmaceuticals America, Inc., Cambridge, MA 02142. Firazyr is a registered trademark of Shire Orphan Therapies GmbH. For more information, visit www.firazyr.com or call 1-877-TAKEDA-7 (1-877-825-3327).