Hizentra

Indications and Usage for Hizentra

Hizentra Dosage and Administration

For subcutaneous infusion only. Do not inject into a blood vessel.

Dosage

​The dose should be individualized based on the patient's clinical response to Hizentra therapy and serum immunoglobulin G (IgG) trough levels.

​Start treatment with Hizentra 1 week after the patient's last Immune Globulin Intravenous (Human) (IGIV) infusion. Before receiving treatment with Hizentra, patients need to have received IGIV treatment at regular intervals for at least 3 months. Before switching to Hizentra, obtain the patient's serum IgG trough level to guide subsequent dose adjustments (see below under Dose Adjustment).

Establish the initial weekly dose of Hizentra by converting the monthly IGIV dose into a weekly equivalent and increasing it using a dose adjustment factor. The goal is to achieve a systemic serum IgG exposure (area under the concentration-time curve [AUC]) not inferior to that of the previous IGIV treatment (see Pharmacokinetics [12.3]).

​Initial Weekly Dose

​To calculate the initial weekly dose of Hizentra, divide the previous IGIV dose in grams by the number of weeks between doses during the patient's IGIV treatment (e.g., 3 or 4); then multiply this by the dose adjustment factor of 1.53.

​Initial Hizentra dose =

Previous IGIV dose (in grams) Number of weeks between IGIV doses

× 1.53

​To convert the Hizentra dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 5.

​Dose Adjustment

​Over time, the dose may need to be adjusted to achieve the desired clinical response and serum IgG trough level. To determine if a dose adjustment should be considered, measure the patient's serum IgG trough level 2 to 3 months after switching from IGIV to Hizentra. The target serum IgG trough level on weekly Hizentra treatment is projected to be approximately 290 mg/dL higher than the last trough level during prior IGIV therapy.

​To adjust the dose based on trough levels, calculate the difference (in mg/dL) between the patient's serum IgG trough level and the target IgG trough level. Then find this difference in Table 1 (Column 1) and, based on the patient's body weight, the corresponding amount (in mL) by which to increase (or decrease) the weekly dose. The patient's clinical response should be the primary consideration in dose adjustment. Additional dosage increments may be indicated based on the patient's clinical response (infection frequency and severity).

Table 1: Adjustment (±mL) of the Weekly Hizentra Dose Based on the Difference (±mg/dL) From the Target Serum IgG Trough Level

​Difference From Target IgG Trough Level (mg/dL)	Body Weight (kg)
	10	15	20	30	40	50	60	70	80	90	100	110	120
	Dose Adjustment (mL per Week)*
* Dose adjustment in mL is based on the slope of the serum IgG trough level response to Hizentra dose increments (5.3 mg/dL per increment of 1 mg/kg per week).
​100	1	1	2	3	4	5	6	7	8	8	9	10	11
​150	1	2	3	4	6	7	8	10	11	13	14	15	17
​200	2	3	4	6	8	9	11	13	15	17	19	21	23
​250	2	4	5	7	9	12	14	16	19	21	23	26	28
​300	3	4	6	8	11	14	17	20	23	25	28	31	34
​350	3	5	7	10	13	16	20	23	26	30	33	36	39
​400	4	6	8	11	15	19	23	26	30	34	38	41	45
​450	4	6	8	13	17	21	25	30	34	38	42	46	51
​500	5	7	9	14	19	23	28	33	38	42	47	52	56

For example, if a patient with a body weight of 70 kg has an actual IgG trough level of 900 mg/dL and the target trough level is 1000 mg/dL, this results in a difference of 100 mg/dL. Therefore, increase the weekly dose of Hizentra by 7 mL.

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Monitor the patient's clinical response, and repeat the dose adjustment as needed.

Dosage requirements for patients switching to Hizentra from another IGSC product have not been studied. If a patient on Hizentra does not maintain an adequate clinical response or a serum IgG trough level equivalent to that of the previous IGSC treatment, the physician may want to adjust the dose. For such patients, Table 1 also provides guidance for dose adjustment if their desired IGSC trough level is known.

Measles Exposure

If a patient is at risk of measles exposure (i.e., due to an outbreak in the US or travel to endemic areas outside of the US), the weekly Hizentra dose should be a minimum of 200 mg/kg body weight for two consecutive weeks. If a patient has been exposed to measles, ensure this minimum dose is administered as soon as possible after exposure.

Administration

Hizentra is for subcutaneous infusion only. Do not inject into a blood vessel.

Hizentra is intended for weekly subcutaneous administration using an infusion pump. Infuse Hizentra in the abdomen, thigh, upper arm, and/or lateral hip.

• ​Injection sites – A Hizentra dose may be infused into multiple injection sites. Do not use more than 4 sites simultaneously. However, if more injection sites are needed for the full weekly dose, they can be used consecutively. Injection sites should be at least 2 inches apart. Change the actual site of injection with each weekly administration.
• ​Volume – For the first infusion of Hizentra, do not exceed a volume of 15 mL per injection site. The volume may be increased to 20 mL per site after the fourth infusion and to a maximum of 25 mL per site as tolerated.
• ​Rate – For the first infusion of Hizentra, the maximum recommended flow rate is 15 mL per hour per site. For subsequent infusions, the flow rate may be increased to a maximum of 25 mL per hour per site as tolerated. However, the maximum flow rate is not to exceed a total of 50 mL per hour for all sites combined at any time.

​Follow the steps below and use aseptic technique to administer Hizentra.

1. ​Assemble supplies – Gather the Hizentra vial(s), disposable supplies (not provided with Hizentra), and other items (infusion pump, sharps or other container, patient's treatment diary/log book) needed for the infusion.
2. ​Wash hands – Thoroughly wash and dry hands. The use of gloves when preparing and administering Hizentra is optional.
3. ​Clean surface – Thoroughly clean a flat surface using an alcohol wipe.
4. ​Check vials – Carefully inspect each vial of Hizentra. Do not use the vial if the liquid looks cloudy, contains particles, or has changed color, if the protective cap is missing, or if the expiration date on the label has passed.
5. ​Transfer Hizentra from vial(s) to syringe ​Remove the protective cap from the vial to expose the central portion of the rubber stopper of the Hizentra vial. ​Clean the stopper with an alcohol wipe and allow it to dry. ​Attach a sterile transfer needle to a sterile syringe. Pull back on the plunger of the syringe to draw air into the syringe that is equal to the amount of Hizentra to be withdrawn. ​Insert the transfer needle into the center of the vial stopper and, to avoid foaming, inject the air into headspace of the vial (not into the liquid). ​Withdraw the desired volume of Hizentra.   ​When using multiple vials to achieve the desired dose, repeat this step.
6. ​Prepare infusion pump and tubing – Follow the manufacturer's instructions for preparing the pump, using subcutaneous administration sets and tubing, as needed. Be sure to prime the tubing with Hizentra to ensure that no air is left in the tubing.
7. ​Prepare injection site(s) ​The number and location of injection sites depends on the volume of the total dose. Infuse Hizentra into a maximum of 4 sites simultaneously; each injection site should be at least 2 inches apart.
​Using an antiseptic skin preparation, clean each site beginning at the center and working outward in a circular motion. Allow each site to dry before proceeding.
8. ​Insert needle(s) ​Grasp the skin between 2 fingers and insert the needle into the subcutaneous tissue. ​If necessary, use sterile gauze and tape or transparent dressing to hold the needle in place.
​Before starting the infusion, attach a sterile syringe to the end of the primed administration tubing and gently pull back on the plunger to make sure no blood is flowing back into the tubing. If blood is present, remove and discard the needle and tubing. Repeat the process beginning with step 6 (priming) using a new needle, new infusion tubing, and a different injection site.
9. ​Start infusion – Follow the manufacturer's instructions to turn on the infusion pump.
10. ​Record treatment – Remove the peel-off portion of the label from each vial used, and affix it to the patient's treatment diary/log book.
11. ​Clean up – After administration is complete, turn off the infusion pump. Take off the tape or dressing and remove the needle set from the infusion site(s). Disconnect the tubing from the pump. Immediately discard any unused product and all used disposable supplies in accordance with local requirements. Clean and store the pump according to the manufacturer's instructions.

For self-administration, provide the patient with instructions and training for subcutaneous infusion in the home or other appropriate setting.

Dosage Forms and Strengths

Hizentra is a 0.2 g/mL (20%) protein solution for subcutaneous injection.

Contraindications

Hizentra is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin or to components of Hizentra, such as polysorbate 80.

Hizentra is contraindicated in patients with hyperprolinemia because it contains the stabilizer L-proline (see Description [11]).

Hizentra is contraindicated in IgA-deficient patients with antibodies against IgA and a history of hypersensitivity (see Description [11]).

Warnings and Precautions

Adverse Reactions

The most common adverse reactions (ARs), observed in ≥5% of study subjects receiving Hizentra, were local reactions (i.e., swelling, redness, heat, pain, and itching at the injection site), headache, vomiting, pain, and fatigue.

Drug Interactions

USE IN SPECIFIC POPULATIONS

Hizentra Description

Hizentra, Immune Globulin Subcutaneous (Human), 20% Liquid, is a ready-to-use, sterile 20% (0.2 g/mL) protein liquid preparation of polyvalent human immunoglobulin G (IgG) for subcutaneous administration. Hizentra is manufactured from large pools of human plasma by a combination of cold alcohol fractionation, octanoic acid fractionation, and anion exchange chromatography. The IgG proteins are not subjected to heating or to chemical or enzymatic modification. The Fc and Fab functions of the IgG molecule are retained. Fab functions tested include antigen binding capacities, and Fc functions tested include complement activation and Fc-receptor-mediated leukocyte activation (determined with complexed IgG).

Hizentra has a purity of ≥98% IgG and a pH of 4.6 to 5.2. Hizentra contains approximately 250 (range: 210 to 290 mmol/L) L-proline (a nonessential amino acid) as a stabilizer, 10 to 30 mg/L polysorbate 80, and trace amounts of sodium. Hizentra contains ≤50 mcg/mL IgA. Hizentra contains no carbohydrate stabilizers (e.g., sucrose, maltose) and no preservative.

Plasma units used in the manufacture of Hizentra are tested using FDA-licensed serological assays for hepatitis B surface antigen and antibodies to human immunodeficiency virus (HIV)-1/2 and hepatitis C virus (HCV) as well as FDA-licensed Nucleic Acid Testing (NAT) for HIV-1 and HCV. All plasma units have been found to be nonreactive (negative) in these tests. For hepatitis B virus (HBV), an investigational NAT procedure is used and the plasma units found to be negative; however, the significance of a negative result has not been established. In addition, the plasma has been tested for B19 virus (B19V) DNA by NAT. Only plasma that passes virus screening is used for production, and the limit for B19V in the fractionation pool is set not to exceed 104 IU of B19V DNA per mL.

The manufacturing process for Hizentra includes three steps to reduce the risk of virus transmission. Two of these are dedicated virus clearance steps: pH 4 incubation to inactivate enveloped viruses; and virus filtration to remove, by size exclusion, both enveloped and non-enveloped viruses as small as approximately 20 nanometers. In addition, a depth filtration step contributes to the virus reduction capacity.12

These steps have been independently validated in a series of in vitro experiments for their capacity to inactivate and/or remove both enveloped and non-enveloped viruses. Table 5 shows the virus clearance during the manufacturing process for Hizentra, expressed as the mean log10 reduction factor (LRF).

The manufacturing process was also investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered a model for CJD and its variant (vCJD).12 Several of the production steps have been shown to decrease infectivity of an experimental TSE model agent. TSE reduction steps include octanoic acid fractionation (≥6.4 log10), depth filtration (2.6 log10), and virus filtration (≥5.8 log10). These studies provide reasonable assurance that low levels of vCJD/CJD agent infectivity, if present in the starting material, would be removed.

Hizentra - Clinical Pharmacology

Nonclinical Toxicology

Clinical Studies

A prospective, open-label, multicenter, single-arm, clinical study conducted in the US evaluated the efficacy, tolerability, and safety of Hizentra in adult and pediatric subjects with PI. Subjects previously receiving monthly treatment with IGIV were switched to weekly subcutaneous administration of Hizentra for 15 months (a 3-month wash-in/wash-out period followed by a 12-month efficacy period). The efficacy analyses included 38 subjects in the modified intention-to-treat (MITT) population. The MITT population consisted of subjects who completed the wash-in/wash-out period and received at least one infusion of Hizentra during the efficacy period.

Although 5% of the administered doses could not be verified, the weekly doses of Hizentra ranged from 72 to 379 mg per kg body weight, which was 149% (range: 114% to 180%) of the previous IGIV dose. Subjects received a total of 2264 infusions of Hizentra.

In the study, the number of injection sites per infusion ranged from 1 to 12. In 73% of infusions; the number of injection sites was 4 or fewer. Up to 4 simultaneous injection sites were permitted using 2 pumps; however, more than 4 sites could be used consecutively during one infusion. The infusion flow rate did not exceed 50 mL per hour for all injection sites combined. During the efficacy period, the median duration of a weekly infusion ranged from 1.6 to 2.0 hours.

The study evaluated the annual rate of serious bacterial infections (SBIs), defined as bacterial pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. The study also evaluated the annual rate of any infections, the use of antibiotics for infection (prophylaxis or treatment), the days out of work/school/kindergarten/day care or unable to perform normal activities due to infections, and hospitalizations due to infections.

Table 7 summarizes the efficacy results for subjects in the efficacy phase (MITT population) of the study. No subjects experienced an SBI in this study.

REFERENCES

1. Gabor EP, Meningitis and skin reaction after intravenous immune globulin therapy. Ann Intern Med 1997:127:1130.
2. Cayco AV, Perazella MA, Hayslett JP. Renal insufficiency after intravenous immune globulin therapy: a report of two cases and an analysis of the literature. J Am Soc Nephrol 1997;8:1788-1793.
3. Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology 1994;44:223-226.
4. Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet 1986;2:217-218.
5. Wolberg AS, Kon RH, Monroe DM, Hoffman M. Coagulation factor XI is a contaminant in intravenous immunoglobulin preparations. Am J Hematol 2000;65:30-34.
6. Copelan EA, Strohm PL, Kennedy MS, Tutschka PJ. Hemolysis following intravenous immune globulin therapy. Transfusion 1986;26:410-412.
7. Thomas MJ, Misbah SA, Chapel HM, Jones M, Elrington G, Newsom-Davis J. Hemolysis after high-dose intravenous Ig. Blood 1993;15:3789.
8. Wilson JR, Bhoopalam N, Fisher M. Hemolytic anemia associated with intravenous immunoglobulin. Muscle Nerve 1997;20:1142-1145.
9. Kessary-Shoham H, Levy Y, Shoenfeld Y, Lorber M, Gershon H. In vivo administration of intravenous immunoglobulin (IVIg) can lead to enhanced erythrocyte sequestration. J Autoimmun 1999;13:129-135.
10. Rizk A, Gorson KC, Kenney L, Weinstein R. Transfusion-related acute lung injury after the infusion of IVIG. Transfusion 2001;41:264-268.
11. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Trans Med Rev 2003;17:241-251.
12. Stucki M, Boschetti N, Schäfer W, et al. Investigations of prion and virus safety of a new liquid IVIG product. Biologicals 2008;36:239-247.
13. Smith GN, Griffiths B, Mollison D, Mollison PL. Uptake of IgG after intramuscular and subcutaneous injection. Lancet 1972;1:1208-1212.
14. Waniewski I, Gardulf A, Hammarström L. Bioavailability of γ-globulin after subcutaneous infusions in patients with common variable immunodeficiency. J Clin Immunol 1994;14:90-97.
15. Bavaresco CS, Streck EL, Netto CA, et al. Chronic hyperprolinemia provokes a memory deficit in the Morris Water Maze Task. Metabolic Brain Disease 2005;20:73-80.

How Supplied/Storage and Handling

Patient Counseling Information

• Self-administration – If self-administration is appropriate, ensure that the patient receives instructions and training on subcutaneous administration in the home or other appropriate setting and has demonstrated the ability to perform subcutaneous infusions.
  • Ensure patients understand the importance of adhering to the weekly administration schedule to maintain the steady levels of IgG in their blood.
  • Instruct patients to keep their treatment diary/log book current by recording, after each infusion, the time, date, dose, and any reactions, and by removing the peel-off portion of the label (containing the lot number) from the product vial and placing it in the treatment diary/log book.
  • Tell patients that mild to moderate local (injection-site) reactions (e.g., swelling and redness) are a common side effect of subcutaneous therapy, but to contact their healthcare professional if a local reaction persists for more than a few days.
  • Inform patients of the importance of having an infusion needle long enough to reach the subcutaneous tissue and of changing the actual site of injection with each infusion.
  • Inform patients to consider adjusting the injection-site location, volume per site, and rate of infusion based on how infusions are tolerated.
• Dose adjustments – Inform patients that they should be tested regularly to make sure they have the correct levels of Hizentra (IgG) in their blood. These tests may result in adjustments to the Hizentra dose.
• Hypersensitivity – Inform patients of the early signs of hypersensitivity reactions to Hizentra (including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis), and advise them to notify their physician if they experience any of these symptoms.
• AMS – Inform patients of the signs of AMS, including severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting, and advise them to notify their physician if they experience any of these symptoms.
• Interference with vaccines – Inform patients that administration of IgG may interfere with the response to live virus vaccines (e.g., measles, mumps, rubella, and varicella) and to notify their immunizing physician of recent therapy with Hizentra.
• Reactions reported to occur with IGIV treatment – Advise patients to be aware of and immediately report to their physician symptoms of the following potential reactions:
  • Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath, which may suggest kidney problems
  • Shortness of breath, changes in mental status, chest pain, and other manifestations of thrombotic and embolic events
  • Fatigue, increased heart rate, yellowing of the skin or eyes, and dark-colored urine, which may suggest hemolysis
  • Severe breathing problems, lightheadedness, drops in blood pressure, and fever, which may suggest TRALI (a condition typically occurring within 1 to 6 hours following transfusion)
• Transmissible infectious agents – Inform patients that Hizentra is made from human plasma (part of the blood) and may contain infectious agents that can cause disease (e.g., viruses and, theoretically, the CJD agent). Explain that the risk that Hizentra may transmit an infectious agent has been reduced by screening the plasma donors, by testing the donated plasma for certain virus infections, and by inactivating and/or removing certain viruses during manufacturing.

The attached Hizentra "Information for Patients" contains more detailed instructions for patients who will be self-administering Hizentra.

Hizentra
Immune Globulin Subcutaneous (Human), 20% Liquid

Information for Patients

This patient package insert summarizes important information about Hizentra. Please read it carefully before using this medicine. This information does not take the place of talking with your healthcare professional, and it does not include all of the important information about Hizentra. If you have any questions after reading this, ask your healthcare professional.

What is the most important information I should know about Hizentra?

Hizentra is supposed to be infused under your skin only. DO NOT inject Hizentra into a blood vessel (vein or artery).

What is Hizentra?

Hizentra (Hi – ZEN – tra) is a prescription medicine used to treat primary immune deficiency (PI). Hizentra is made from human plasma. It contains antibodies, called immunoglobulin G (IgG), that healthy people have to fight germs (bacteria and viruses).

People with PI get a lot of infections. Hizentra helps lower the number of infections you will get.

Who should NOT take Hizentra?

Do not take Hizentra if you have too much proline in your blood (called "hyperprolinemia") or if you have had reactions to polysorbate 80.

Tell your doctor if you have had a serious reaction to other immune globulin medicines or if you have been told that you also have a deficiency of the immunoglobulin called IgA.

How should I take Hizentra?

You will take Hizentra through an infusion under your skin. You will put up to 4 needles into different places of your body at one time. The needles are attached to a pump with an infusion tube. It usually takes about 60 minutes to do one infusion. You will need to have infusions once a week.

Instructions for using Hizentra are at the end of this patient package insert (see "How do I use Hizentra?"). Do not use Hizentra by yourself until you have been taught how by your doctor or healthcare professional.

What should I avoid while taking Hizentra?

Vaccines may not work well for you while you are taking Hizentra. Tell your doctor or healthcare professional that you are taking Hizentra before you get a vaccine.

Tell your doctor or healthcare professional if you are pregnant or plan to become pregnant, or if you are nursing.

What are possible side effects of Hizentra?

The most common side effects with Hizentra are:

• Redness, swelling, and itching at the injection site
• Headache/migraine
• Vomiting
• Pain (including pain in the back, joints, arms, legs)
• Fatigue
• Bruising
• Diarrhea
• Stomach ache
• Nausea
• Rash

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

• Reduced urination, sudden weight gain, or swelling in your legs. These could be signs of a kidney problem.
• Pain, swelling, warmth, redness, or a lump in your legs or arms. These could be signs of a blood clot.
• Bad headache with nausea, vomiting, stiff neck, fever, and sensitivity to light. These could be signs of a brain swelling called meningitis.
• Brown or red urine, fast heart rate, yellow skin or eyes. These could be signs of a blood problem.
• Chest pains or trouble breathing.
• Fever over 100ºF. This could be a sign of an infection.

Tell your doctor about any side effects that concern you. You can ask your doctor to give you more information that is available to healthcare professionals.

How do I use Hizentra?

Infuse Hizentra only after you have been trained by your doctor or healthcare professional. Below are step-by-step instructions to help you remember how to use Hizentra. Ask your doctor or healthcare professional about any instructions you do not understand.

Instructions for use

Hizentra comes in single-use vials.

Keep Hizentra in the storage box at room temperature.

Step 1: Assemble supplies Gather the Hizentra vial(s), the following disposable supplies (not provided with Hizentra), and other items (infusion pump, sharps or other container, treatment diary or log book):   Infusion administration tubing   Needle or catheter sets (for subcutaneous infusion)   Y-site connectors (if needed)   Alcohol wipes   Antiseptic skin preps   Syringes   Transfer needles   Gauze and tape, or transparent dressing   Gloves (if recommended by your doctor)
Step 2: Wash hands Thoroughly wash and dry your hands (Figure 1). If you have been told to wear gloves when preparing your infusion, put the gloves on.
Step 3: Clean surface Thoroughly clean a table or other flat surface using one of the alcohol wipes.
Step 4: Check vials Carefully look at the liquid in each vial of Hizentra (Figure 2). It should look clear and be pale yellow to light brown. Check for particles or color changes. Do not use the vial if: The liquid looks cloudy, contains particles, or has changed color. The protective cap is missing. The expiration date on the label has passed.
Step 5: Transfer Hizentra from vial(s) to syringe Take the protective cap off the vial (Figure 3).
Clean the vial stopper with an alcohol wipe (Figure 4). Let the stopper dry.
Attach a sterile transfer needle to a sterile syringe (Figure 5).
Pull out the plunger of the syringe to fill the syringe with air. The amount of air should be 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 6). 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 container.
When using multiple vials to achieve the desired dose, repeat this step.
Step 6: Prepare infusion pump and tubing Prepare the infusion pump (following the manufacturer's instructions) and 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 to fill the tubing with Hizentra (Figure 7).
Step 7: Prepare injection site(s) Select an area on your abdomen, thigh, upper arm, or side of upper leg/hip for the infusion (Figure 8). Use a different site from the last time you infused Hizentra. New sites should be at least 1 inch from a previous site. Never infuse into areas where the skin is tender, bruised, red, or hard. Avoid infusing into scars or stretch marks. If you are using more than one injection site, be sure each site is at least 2 inches apart. During an infusion, do not use more than 4 injection sites at the same time. Clean the skin at each site with an antiseptic skin prep (Figure 9). Let the skin dry.
Step 8: Insert needle(s) With two fingers, pinch together the skin around the injection site. Insert the needle under the skin (Figure 10).
Put sterile gauze and tape or a transparent dressing over the injection site (Figure 11). This will keep the needle from coming out.
Make sure you are not injecting Hizentra into a blood vessel. To test for this, attach a sterile syringe to the end of the infusion tubing. Pull the plunger back gently (Figure 12). If you see any blood flowing back into the tubing, take the needle out of the injection site. Throw away the tubing and needle. Start the infusion over at a different site with new infusion tubing and a new needle.
Step 9: Start infusion Follow the manufacturer's instructions to turn on the infusion pump (Figure 13).
Step 10: Record treatment (Figure 14) Peel off the removable part of the label of the Hizentra vial. Put this label in your treatment diary or log book with the date and time of the infusion. Also include the exact amount of Hizentra that you infused.
Step 11: Clean up When all the Hizentra has been infused, turn off the pump. Take off the dressing and take the needle out of the injection site. Disconnect the tubing from the pump. Throw away any Hizentra that is leftover in the single-use vial, along with the used disposable supplies, in the sharps container (Figure 15). Clean and store the infusion pump, following the manufacturer's instructions.

Be sure to tell your doctor about any problems you have doing your infusions. Your doctor may ask to see your treatment diary or log book, so be sure to take it with you each time you visit the doctor's office.

Call your doctor for medical advice about side effects. You can also report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Manufactured by:
CSL Behring AG
Bern, Switzerland
US License No. 1766

Distributed by:
CSL Behring LLC
Kankakee, IL 60901 USA

PRINCIPAL DISPLAY PANEL - 5 mL Vial Label

NDC 44206-451-01

A5614/876

Immune Globulin Subcutaneous
(Human), 20% Liquid
Hizentra™

Subcutaneous use only

Rx only

Each Hizentra single-use vial
contains 1 g IgG. Store Hizentra
up to 25°C (77°F). Do not freeze.

PRINCIPAL DISPLAY PANEL - 5 mL Vial Carton

NDC 44206-451-01

1 g
5 mL

Immune Globulin
Subcutaneous (Human),
20% Liquid
Hizentra™

Single-use vial

For Subcutaneous Administration
Only

Rx only

CSL Behring