Hizentra: Uses, Side Effects and Dosage

Serious warnings and precautions box

What Hizentra is used for:

Hizentra (Hi - zen - tra) is a medicine used to treat conditions in which a person’s natural defense system (or immune system) does not function properly:

• Primary immunodeficiency (PID), secondary immunodeficiency (SID) and chronic inflammatory demyelinating polyneuropathy (CIDP).
• Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin. Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the injection. In case of shock, standard medical treatment should be administered.
• There is clinical evidence of an association between the administration of immunoglobulins and thromboembolic events such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis. Therefore, caution should be exercised when prescribing and administering immunoglobulins.
• Risk factors for thromboembolic events include: advanced age, use of estrogens, in-dwelling central vascular catheters, history of vascular disease or thrombotic episodes, acquired or inherited hypercoagulable states, prolonged periods of immobilization, severe hypovolemia, diseases which increase blood viscosity and cardiovascular risk factors (including obesity, hypertension, diabetes mellitus, history of atherosclerosis and/or impaired cardiac output).
• Thrombosis may occur even in the absence of known risk factors.

How Hizentra works:

Hizentra is a highly purified product, called an immunoglobulin, made from human plasma. Hizentra contains the antibody immunoglobulin G (IgG), which helps combat germs, such as bacteria and viruses. Antibodies are major components of Immunity and IgG is the main type of antibody found in blood allowing it to control infection of body tissues.

Hizentra is supplied as a sterile liquid in single-use vials or pre-filled syringes and is given by subcutaneous (under the skin) infusion.

Hizentra treats primary immunodeficiency, secondary immunodeficiency and chronic inflammatory demyelinating polyneuropathy, conditions in which a person’s natural defense system (or immune system), does not function properly.

Normally, our immune system helps protect us against infections by recognizing potentially harmful bacteria and viruses that enter our body every day. In response, the immune system produces special proteins called antibodies (Immunoglobulins) that fight these foreign invaders (germs). However, when our immune system is not working properly, it is unable to produce these valuable antibodies, leaving us more vulnerable to illness.

Hizentra is known as antibody replacement therapy because it replaces the missing and much-needed IgG antibodies in people who have low levels of these infection-fighting proteins. By replacing these important antibodies, Hizentra helps make people with immune deficiencies better able to avoid infections and fight them when they do occur.

For people with CIDP Hizentra is believed to help protect the nerve from being attacked.

The ingredients in Hizentra are:

Medicinal ingredient: Human Immunoglobulins (IgG)

Non-medicinal ingredient: L-proline

For a full listing of nonmedicinal ingredients see Part 1: Healthcare Professional Information.

Hizentra comes in the following dosage forms:

Hizentra is a solution for subcutaneous injection.

Hizentra is supplied in a single-use, tamper-evident vial or pre-filled syringe containing 0.2 grams of protein per mL of preservative-free liquid.

Do not use Hizentra if:

• You have had an anaphylactic or severe systemic reaction to the administration of human normal immunoglobulin or to components of Hizentra.
• You have hyperprolinemia type I and II (high levels of proline in the blood) because it contains the stabilizer L-proline.

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

• Are pregnant or think that you may be pregnant;

• Are nursing;
• Have a history of allergic or other adverse reactions to immunoglobulins;
• Recently have been vaccinated;
• Have been previously advised that you have IgA deficiency;
• Have a kidney disease;
• Have hyperprolinemia (high levels of proline in the blood);
• Have history of thromboembolic events (e.g. deep vein thrombosis, blockage of blood vessel, blood clots, stroke).

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 Hizentra:

• Hizentra may interfere with the response to certain viral vaccines such as measles, mumps, rubella, and varicella. Inform the immunizing physician of recent therapy with Hizentra so appropriate measures may be taken.
• Other products must not be mixed with the Hizentra solution.

How to take Hizentra:

• Your doctor or healthcare professional will teach you the proper techniques for administering Hizentra. Only after such instruction should you follow the instructions below.
• Hizentra is to be infused subcutaneously (under your skin) only. DO NOT inject Hizentra into a blood vessel (vein or artery). You will use needles and tubing to infuse Hizentra. You may have more than one needle inserted subcutaneously into different places of your body at one time. You can have infusions as often as every day up to every 2 weeks. For weekly infusions, it takes about 1 to 2 hours to complete an infusion; however, this time may be shorter or longer depending on the dose and frequency your doctor has prescribed for you.
• Your HCP will instruct you how to dispose of unused product or waste material.
• If you have any further questions on the use of this product, please ask your HCP.

Instructions for administration:

The following instructions are intended only as a guide. Before administering Hizentra, you should be under the care of a doctor and should have received proper training on preparation and administration from an HCP.

Please ensure that you have received proper guidance from your doctor or healthcare professional in case you experience a severe adverse reaction.

Follow the steps below and use aseptic technique to administer Hizentra.
1	Clean surface Clean a table or other flat surface.
2	Assemble supplies Gather the Hizentra pre-filled syringe(s) and/or vial(s). The vials/pre-filled syringes must be at room temperature before administration. Gather the following supplies (not provided with Hizentra): Infusion administration set(s) (tubing & needle: butterflies or "multi-needle" sets). Antiseptic wipes and/or alcohol swabs. Syringe(s) (if required) Transfer device (vial to syringe), syringe-to-syringe transfer device and/or transfer needle (if required). Gauze and tape, or transparent dressing. Sharps disposal container. Treatment diary or logbook. Infusion pump (if required please ensure ready to use – according to manufacturer’s instructions). Rate regulator (if required) Gloves (if recommended by your HCP).
3	Wash hands Thoroughly wash and dry your hands (Figure 1).		Figure 1
4	Check Vials or Pre-Filled Syringes If using pre-filled syringes, carefully peel back the transparent covering from the tray and inspect the protective cap. Peel back the outer layer of the wrap-around label to allow for viewing of Hizentra through the fully transparent inner layer, but don’t remove the label completely (Figure 2).		Figure 2
	If using vials, inspect the protective cap of the vials (Figure 3). Hizentra is a pale yellow to light brown clear solution. Check for particles or color changes.		Figure 3
	Do not use the pre-filled syringe or vial if: The liquid looks cloudy, contains particles, or has changed color It is damaged, or the protective cap of the pre-filled syringe or the vial is missing or defective The expiration date on label has passed.
5	Prepare Hizentra for infusion If using Hizentra pre-filled syringes, go to Step 5.1 If using Hizentra vials, go to Step 5.2
	5.1: Hizentra pre-filled syringe(s) The 5 mL, 10 mL, 20 mL and 50 mL pre-filled syringes are supplied ready to use. The 5 mL and 10 mL pre-filled syringes are fully assembled (Figure 4). For the 20 mL and 50 mL pre-filled syringes (Figure 5), screw the plunger rod onto the pre-filled syringe stopper prior to use (Figure 6). If you are using a syringe pump, Hizentra pre-filled syringes can be placed directly in the syringe pump if the pre-filled syringe size matches the pump requirements. Please follow the manufacturer’s instructions, and then go to Step 6. NOTE: An additional adapter may be required for the Hizentra pre-filled syringes to fit properly in the infusion pump. Check with the provider of your supplies for the appropriate adapter and installation instructions. If the Hizentra pre-filled syringe size does not match the infusion pump requirements, transfer the contents of the pre-filled syringe to another empty sterile syringe of a size specific for the infusion pump by following the directions below: Use a syringe-to-syringe transfer device (Figure 7) to transfer the contents of the pre-filled syringe to the empty sterile syringe specific for the infusion pump. Remove the protective cap from the pre-filled syringe. Attach the transfer device by twisting it onto the pre-filled syringe. Attach the empty syringe by screwing it onto the other side of the transfer device (Figure 8). Make sure you transfer the amount needed to achieve the prescribed dose. Push the plunger of the pre-filled syringe to transfer Hizentra from the pre-filled syringe to the empty syringe (e.g., using your fingers, thumb or the palm of your hand). If multiple pre-filled syringes are necessary to achieve the prescribed dose, repeat this step. Remove the emptied pre-filled syringe and attach another pre-filled syringe to the transfer device. After the transfer is complete, remove the empty pre-filled			Figure 4 Figure 5 Figure 6 Figure 7 Figure 8
	syringe and the transfer device by unscrewing them from the syringe specific for your pump. Connect the filled syringe to the infusion tubing. Go to Step 6. 5.2: Transfer Hizentra from vial(s) to syringe Take the protective cap off the vial (Figure 9). Clean the vial stopper with an antiseptic wipe (Figure 10). Let the stopper dry. Attach a needle or transfer device to a syringe tip, using aseptic technique. If using a transfer device, follow the instructions provided by the device manufacturer. If using a needle and a syringe to transfer Hizentra, follow the instructions below: Attach a sterile transfer needle to a sterile syringe (Figure 11). Pull out the plunger of the syringe to fill the syringe with air. Make sure the amount of air is the same as the amount of Hizentra you will transfer from the vial. Put the Hizentra vial on a flat surface. Keeping the vial upright, insert the transfer needle into the center of the rubber stopper. Check that the tip of the needle is not in the liquid. Then, push the plunger of the syringe down. This will inject the air from the syringe into the airspace of the vial. Leaving the needle in the stopper, carefully turn the vial upside down (Figure 12). Slowly pull back on the plunger of the syringe to fill the syringe with Hizentra. Take the filled syringe and needle out of the stopper. Take off the needle and throw it away in the sharps disposal container. When using multiple vials to achieve the prescribed dose, repeat step 5.2.			Figure 9 Figure 10 Figure 11 Figure 12
	Go to Step 6.
6	Prepare the administration tubing Prior to priming the administration tubing, make sure you have the prescribed dose in the syringe(s) and the administration tubing is attached. If a rate regulator is required, prime with tubing. Prime (fill) the infusion tubing. To prime the tubing, connect the syringe filled with Hizentra to the infusion tubing and gently push on the syringe plunger (e.g., using your fingers or thumb or the palm of your hand) to fill the tubing with Hizentra (Figure 13). Stop priming before Hizentra fluid reaches the capped needle tip.		Figure 13
7	Prepare infusion pump Prior to preparing the pump(s), make sure you have the prescribed dose in the syringe(s) and the infusion tubing is attached. Prepare the infusion pump (following the manufacturer’s instructions, including attaching any necessary adapters). Do not remove the needle caps until you are ready to infuse. Insert the syringe filled with Hizentra into the pump.
8	Prepare injection site(s) Select an area on your abdomen, thigh, upper arm, or side of upper leg/hip for the infusion (Figure 14). Never infuse into areas where the skin is tender, bruised, red, or hard. Avoid infusing into scars or stretch marks. Use a different site with every Hizentra injection. New sites should be at least 1 inch (2.5 cm) from a previous injection site. If you are using more than one injection site at the same time, be sure the injection sites are at least 2 inches (5 cm) apart. Clean the skin at each infusion site with an antiseptic skin prep (Figure 15). Let the skin dry.		Figure 14 Figure 15
9	Insert needle Use one needle per site. If injecting in more than one site, the following steps should be completed for each needle, one at a Remove the needle cap. Using two fingers, pinch together the skin around the injection site. With a quick dart-like motion, insert the needle under the skin (Figure 16). Put sterile gauze and tape or a transparent dressing over the injection site (Figure 17). This will keep the needle from coming out.	Figure 16 Figure 17
10	Infuse Hizentra Start infusion. If using an infusion pump, follow the manufacturer’s instructions to turn it on and start the infusion. When you have finished the infusion, take off the dressing and take the needle out of the injection site.
11	Record treatment Peel off the removable part of the label of the Hizentra vial or pre-filled syringe. Put this label in your treatment diary or logbook with the date and time of the infusion and include the exact amount of Hizentra that you infused. Scan the vial or pre-filled syringe if recording the infusion electronically.
12	Clean up Remove the needle set from the skin and cover the injection site(s) with a protective dressing. Remove the syringe from the infusion pump. Throw away the used supplies (for example: needle, infusion tubing, transfer device…) in the sharps disposal container in accordance with local requirements. Clean and store the infusion pump, following the manufacturer’s instructions.

Be sure to tell your HCP about any problems you have doing your infusions. Your HCP may ask to see your treatment diary or logbook, so please follow instructions given by the healthcare team.

Usual dose:

Your healthcare professional should individualize your dose based on your clinical response to Hizentra therapy and serum immunoglobulin G (IgG) trough levels.

Doses may be adjusted over time to achieve the desired clinical response and serum IgG levels.

Your healthcare professional will discuss the transition from IVIG to SCIG with you.

In general, for weekly or frequent dosing, start treatment with Hizentra 1 week after your last IVIG infusion or Hizentra/SCIG infusion. For biweekly dosing, start treatment 1 or 2 weeks after the last IVIG infusion or 1 week after the last weekly Hizentra/SCIG infusion.

Overdose:

The consequences of an overdose are not known with Hizentra.

If you think you, or a person you are caring for, have taken too much Hizentra, contact a healthcare professional, hospital emergency department, regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669) immediately, even if there are no signs or symptoms.

Missed Dose:

Inform your HCP if you missed a dose. A missed dose should be administered as soon as possible to ensure adequate IgG serum levels.

Possible side effects from using Hizentra:

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

No related serious adverse drug reactions were observed in subjects treated with Hizentra during the clinical studies evaluating its safety. However, there have been reports of serious thrombotic events (blood clots) following the use of other Subcutaneous Immunoglobulin (Human).

Reactions at the injection site are a common occurrence with SCIG infusions and this side effect is expected. Overall, the adverse events were mild or moderate in intensity.

The following symptoms are common: local reactions at the injection sites (e.g., swelling, redness, heat, pain, and itching), headaches, diarrhea, back pain, nausea, pain in extremity, cough, rash, vomiting, abdominal pain (upper), migraine, pain, pruritus, urticaria, fatigue and nasopharyngitis.

In isolated cases: severe hypersensitivity (anaphylactic) reactions of the immune system, aseptic meningitis syndrome (AMS: a temporary and reversible non-infectious meningitis resulting in an inflammation of the protective membranes surrounding the brain and spinal cord), and thromboembolism (formation of blood clots, which may be carried off in the blood circulation and which may result in blockage of a blood vessel) have been observed in treatment with Hizentra.

If any of the above listed symptoms occur, are severe or if they worry you, talk to your HCP.

Tell your HCP right away or go to the emergency room if you have hives, trouble breathing, wheezing, dizziness, or fainting. These could be signs of a bad allergic reaction.

Tell your HCP right away if you have any of the following symptoms. They could be signs of a serious problem.

• Bad headache with nausea, vomiting, stiff neck, fever, and sensitivity to light. These could be signs of a brain swelling called meningitis.
• Pain, swelling, warmth, redness, or a lump in your legs or arms, 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, sudden confusion, or trouble speaking. These could be signs of a blood clot.
• Fever over 37.8°C (100ºF). This could be a sign of an infection.

This is not a complete list of side effects. Tell your HCP about any other side effects that concern you. You can ask your HCP to give you more information that is available to healthcare professionals.

1 RARE: may affect patients in less than 10 of 10,000 infusions

2 VERY RARE: may affect patients in less than 10 of 100,000 infusions

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.

Serious side effects and what to do about them:

Reporting Side Effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

• Visiting the Web page on Adverse Reaction Reporting (canada.ca/drug-device-reporting) for information on how to report online, by mail or by fax; or
• Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information about how to manage your side effects. The Canada Vigilance Program does not provide medical advice.

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

AdverseReporting@CSLBehring.com

Storage:

Hizentra can be stored either in the refrigerator or at room temperature (at +2°C to +25°C). Hizentra is stable for the period indicated by the expiration date printed on the outer carton and vial/pre-filled syringe label. Do not use after the expiration date. The Hizentra solution contains no preservatives and should be administered as soon as possible after opening the vial/pre-filled syringe. Do not freeze Hizentra. Do not use product that has been frozen. Do not shake. Keep Hizentra in its original carton to protect it from light.

Keep out of reach and sight of children.

If you want more information about Hizentra:

• 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 Drug Product Database website (Drug Product Database: Access the database); the manufacturer’s website (www.cslbehring.ca), or by calling 1-866-773-7721.

Date of Authorization: April 30, 2026