Haegarda: Uses, Side Effects and Dosage

What is HAEGARDA used for?

HAEGARDA is an injectable medicine used to prevent swelling and/or painful attacks in adults and adolescents with Hereditary Angioedema (HAE). HAEGARDA should not be used to treat an acute HAE attack. In the event of an acute attack, seek medical attention.

How does HAEGARDA work?

HAE is caused by the deficiency, absence or defective production of C1 esterase inhibitor (C1-INH), an important protein in regulating multiple chemical reactions in the body. C1-INH is involved in keeping the immune and blood clotting systems healthy. C1-INH is also important in controlling inflammation in the body. When C1-INH levels are low or when the protein doesn’t work properly, blood vessels and capillaries in the body can become leaky and allow fluid to build up in the surrounding areas. This leakage and fluid build-up leads to the swelling and pain experienced during an HAE attack. HAEGARDA contains human C1-INH that replaces the missing or defective C1-INH made by the body.

What are the ingredients in HAEGARDA?

Medicinal ingredients:

• C1 Esterase Inhibitor (Human)

Non-medicinal ingredients:

• Glycine
• Sodium chloride
• Sodium citrate

HAEGARDA comes in the following dosage forms:

HAEGARDA is supplied as a white lyophilized powder in the following two formats:

• 2000 IU: which contains 2000 IU of C1-INH per injection vial accompanied with 4 mL diluent (Sterile Water for Injection) for reconstitution. After reconstitution, the concentration is 500 IU/mL.
• 3000 IU: which contains 3000 IU of C1-INH per injection vial accompanied with 5.6 mL diluent (Sterile Water for Injection) for reconstitution. After reconstitution, the concentration is 500 IU/mL.

The product package includes:

• 1 vial with HAEGARDA powder
• 1 vial of diluent (Sterile Water for Injection)
• 1 Mix2Vial® transfer device for reconstitution
• 1 inner carton

The inner carton contains:

• 1 syringe (10 mL) for withdrawal
• 1 SC infusion set
• 1 hypodermic needle

The components used in the packaging for HAEGARDA are latex-free.

Do not use HAEGARDA if:

• You have experienced life threatening immediate hypersensitivity reactions, including anaphylaxis, to the product.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take HAEGARDA. Talk about any health conditions or problems you may have, including if you:

• Are pregnant or planning to become pregnant. The effect of HAEGARDA on your unborn baby is not known.

• Are breastfeeding or plan to breastfeed. It is not known if HAEGARDA passes into your breast milk or if it can affect your baby.
• Have a history of blood clotting problems. Blood clots have occurred in patients receiving HAEGARDA. Very high doses of C1-INH could increase the risk of blood clots. Tell your healthcare professional if you have a history of heart or blood vessel disease, stroke, blood clots, or have thick blood, an indwelling catheter/access device in one of your veins, or have been immobile for some time. These factors may increase your risk of having a blood clot after using HAEGARDA. Also, tell your healthcare professional what drugs you are using, as some drugs, such as birth control pills or certain androgens, may increase your risk of developing a blood clot.

Other warnings you should know about:

Products made from human plasma may contain infectious agents such as viruses and, theoretically, the agent responsible for the Creutzfeldt-Jakob disease (CJD).

Appropriate vaccination (hepatitis A and B) should be generally considered for subjects in regular/repeated receipt of human plasma-derived products.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with HAEGARDA:

No formal drug interaction studies have been conducted with HAEGARDA. To date, no relevant interactions are known.

How to take HAEGARDA:

Home Treatment/Self-administration

You should prepare the prescribed dose of HAEGARDA for self administration as directed by your healthcare professional.

• Do not attempt to self administer unless you have been taught how by your healthcare professional.
• See the following step by step instructions for reconstitution and administering HAEGARDA. The steps listed below are general guidelines for using HAEGARDA. If you are unsure of the steps, please contact your healthcare professional before using.
• Your healthcare professional will prescribe the dose that you should administer, which is based on your body weight.
• Talk to your healthcare professional before traveling to make sure you have an adequate supply of HAEGARDA.
• Use a new needle for each HAEGARDA injection.

Reconstitution and Administration

HAEGARDA is intended for self-administration by subcutaneous injection only. The patient or caregiver should be trained on how to administer HAEGARDA as needed.

General Instructions

• The reconstituted solution for HAEGARDA should be colourless and clear to slightly opalescent.
• Reconstitution is generally achieved within 5 minutes but may take as long as 10 minutes.
• After filtering/withdrawal (see below) reconstituted product should be inspected visually for particulate matter and discoloration prior to administration. Do not use solutions that have particles or deposits in them.
• Reconstitution and withdrawal must be carried out using aseptic techniques.
• In the absence of compatibility studies HAEGARDA must not be mixed with other medicinal products and diluents.
• Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
• The suggested infusion site for the injection of HAEGARDA is the abdominal area, however other subcutaneous injection areas can be used. In the clinical trials, HAEGARDA was injected into a single site each administration and subsequent injection sites were rotated.
• The reconstituted preparation should be administered by subcutaneous injection at a rate tolerated by the patient.
• If the reconstituted product is not administered immediately, storage shall not exceed 8 hours at room temperature. The reconstituted product should only be stored in the vial.

Follow the steps below and use aseptic technique to reconstitute and administer HAEGARDA:

Use the Mix2Vial^® filter transfer set, syringe and either the SC infusion set or the hypodermic needle provided with HAEGARDA (see section DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).

HAEGARDA 2000 IU should be reconstituted with the provided 4 mL of Sterile Water for Injection (Diluent).

HAEGARDA 3000 IU should be reconstituted with the provided 5.6 mL of Sterile Water for Injection (Diluent).

	Step 12: While keeping the syringe plunger pressed, turn the system upside down and draw the solution into the syringe by pulling the plunger back slowly.
	Step 13: Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial® adapter from the syringe by unscrewing counter- clockwise. The reconstituted solution should be colorless, clear and free from visible particles. Do not use if particulate matter or discoloration is observed.
Administration:
Step 14: Prepare injection site Select an area on the abdomen (stomach; Figure 1) or another subcutaneous area for the injection as discussed with a healthcare professional. Use a different place from your last injection; you should rotate the places where you are injecting. New injection sites should be at least 5 centimeters (2 inches) away from the place where you gave yourself an injection before. Never give yourself an injection in areas where the skin is itchy, swollen, painful, bruised, or red. Avoid giving yourself injections in places where you have scars or stretch marks. Clean the skin at the injection site with an alcohol swab and let the skin dry (Figure 2).		Figure 1 Figure 2

Step 15: Injection in the abdominal area or other subcutaneous injection area As instructed by your healthcare provider: Attach a hypodermic needle or SC infusion set. Prime the needle or tubing as required and instructed.		Figure 3
Injection with Hypodermic Needle: Insert the needle into the fold of skin (Figure 3).
Injection by SC Infusion Set: Insert the needle into the fold of skin (Figure 4).	Figure 4
Step 16: Clean up After injecting the entire amount of HAEGARDA, remove the needle. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Step 17: Record treatment Record the lot number from the HAEGARDA vial label in your treatment diary or log book with the date and time of infusion every time you use HAEGARDA.

Usual dose:

The recommended usual dose is 60 IU per kg of body weight twice weekly (every 3 or 4 days) administered after reconstitution by subcutaneous injection at a rate tolerated by the patient. HAEGARDA is administered subcutaneously in the abdominal area or other subcutaneous injection sites.

The maximum tolerated dose used in patients in clinical studies was 10,000 IU, corresponding to a volume of 20 mL, twice weekly by subcutaneous injection.

Overdose:

No cases of overdose have been reported.

Missed Dose:

Proceed with your next dose immediately and continue at regular intervals as advised by your healthcare professional. Do not take a double dose to make up for a forgotten dose.

What are possible side effects from using HAEGARDA?

These are not all the possible side effects you may have when taking HAEGARDA. If you experience any side effects not listed here, tell your healthcare professional.

Allergic reactions may occur with HAEGARDA. Talk to your healthcare professional right away if you have any of the following symptoms after using HAEGARDA:

• Wheezing
• Difficulty breathing
• Chest tightness
• Turning blue (look at lips and gums)
• Fast heartbeat
• Swelling of the face
• Rash or hives

Signs of a blood clot include:

• Pain and/or swelling of an arm or leg with warmth over the affected area
• Discoloration of an arm or leg
• Unexplained shortness of breath
• Chest pain or discomfort that worsens on deep breathing
• Unexplained rapid pulse
• Numbness or weakness on one side of the body

The most common side effects with HAEGARDA are injection site reactions (pain, redness, swelling), hypersensitivity (itching and rash), nasopharyngitis (runny or stuffy nose, sneezing, watery eyes) and dizziness.

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

We recommend that CSL Behring Canada, Inc. be copied when reporting suspected side effects, at the following address:

AdverseReporting@CSLBehring.com

Storage:

Keep the non-reconstituted HAEGARDA in its original carton to protect from light until ready to use. The shelf life of HAEGARDA is 36 months. When stored in the refrigerator or at room temperature (at +2°C to +30°C), HAEGARDA is stable for the period indicated by the expiration date on its label. Do not freeze.

Storage after reconstitution: If the reconstituted product is not administered immediately, storage shall not exceed 8 hours at room temperature. The reconstituted product should only be stored in the vial. Do not freeze the reconstituted solution.

Keep out of reach and sight of children.

If you want more information about HAEGARDA:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website (www.cslbehring.ca), or by calling 1-866-773-7721.

Last Revised APR 13, 2022