For subcutaneous infusion only. Do not inject into a blood vessel.
2.1 Preparation and Handling
Hizentra is a clear and pale yellow to light brown solution. Do not use if the solution is cloudy or contains particulates.
Prior to administration, visually inspect each vial of Hizentra for particulate matter or discoloration, whenever the solution and container permit.
Do not freeze. Do not use any solution that has been frozen.
Check the product expiration date on the vial label. Do not use beyond the expiration date.
Do not mix Hizentra with other products.
Do not shake the Hizentra vial.
Use aseptic technique when preparing and administering Hizentra.
The Hizentra vial is for single-use only. Discard all used administration supplies and any unused product immediately after each infusion in accordance with local requirements.
2.2 Dosage
Hizentra can be administered at regular intervals from daily up to every two weeks (biweekly).
Individualize the dose based on the patient's clinical response to Hizentra therapy and serum immunoglobulin G (IgG) trough levels.
Before receiving treatment with Hizentra:
Ensure that patients have received Immune Globulin Intravenous (Human) (IGIV) treatment at regular intervals for at least 3 months.
Obtain the patient's serum IgG trough level to guide subsequent dose adjustments (see below under Dose Adjustment).
Dosage for patients switching to Hizentra from Immune Globulin Intravenous (Human) (IGIV)
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.
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 1.37. [see Pharmacokinetics (12.3, Table 8)]
Initial Hizentra dose =
Previous IGIV dose (in grams)
× 1.37
Number of weeks between IGIV doses
To convert the Hizentra dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 5.
Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used and will result in systemic serum IgG exposure that is comparable to the previous IGIV or weekly Hizentra treatment [see Pharmacokinetics (12.3)].
For biweekly dosing, multiply the calculated Hizentra weekly dose by 2.
For frequent dosing (2 to 7 times per week), divide the calculated weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide weekly dose by 3).
Dosage for patients switching to Hizentra from IGSC
The previous weekly IGSC dose should be maintained.
For biweekly dosing, multiply the previous weekly dose by 2.
For frequent dosing (2 to 7 times per week), divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide weekly dose by 3).
Start Hizentra treatment:
For weekly or frequent dosing, start treatment with Hizentra 1 week after the patient's last IGIV infusion or Hizentra/IGSC infusion.
For biweekly dosing, start treatment 1 or 2 weeks after the last IGIV infusion or 1 week after the last weekly Hizentra/IGSC infusion.
Dose Adjustment
Over time, the dose may need to be adjusted to achieve the desired clinical response and serum IgG trough level, irrespective of the frequency of administration. To determine if a dose adjustment should be considered, measure the patient's serum IgG trough level 2 to 3 months after switching to Hizentra.
Weekly dosing: When switching from IGIV to weekly Hizentra dosing, the target serum IgG trough level is projected to be approximately 16% higher than the last trough level during prior IGIV therapy [see Pharmacokinetics (12.3)].
Biweekly dosing: When switching from IGIV to biweekly Hizentra dosing, the target serum IgG trough level is projected to be approximately 10% higher than the last IGIV trough level. When switching from weekly to biweekly Hizentra dosing, the target trough is projected to be approximately 5% lower than the last trough level on weekly therapy [see Pharmacokinetics (12.3)].
Frequent dosing: When switching from weekly dosing to more frequent Hizentra dosing, the target serum IgG trough level is projected to be approximately 3 to 4% higher than the last trough level on weekly therapy [see Pharmacokinetics (12.3)].
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 for weekly or biweekly dosing. Then find this difference in Table 1 (Column 1) and, based on the Hizentra dosing frequency (for weekly or biweekly) and the patient's body weight, locate the corresponding adjustment amount (in mL) by which to increase (or decrease) the dose. For frequent dosing, add the weekly increment from Table 1 to the weekly-equivalent dose and then divide by the number of days of dosing.
Use the patient's clinical response as 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: Incremental Adjustment (mL)* of the Hizentra Dose† Based on the Difference (±mg/dL) from the Target Serum IgG Trough Level
Difference From Target Serum IgG Trough Level (mg/dL)
Dosing Frequency
Weight Adjusted Dose Increment (mL)*
Weight Group
>10 to 30 kg
>30 to 50 kg
>50 to 70 kg
>70 to 90 kg
>90 kg
n/a, not applicable.
*
Incremental adjustments based on slopes of the pharmacometric model-predicted relationship between serum IgG trough level and Hizentra dose increments of 1 mg/kg per week.
†
Includes biweekly, weekly or frequent dosing.
‡
To determine the dose increment for frequent dosing, add the weekly increment to the weekly-equivalent dose and then divide by the number of days of dosing.
50
Weekly‡
n/a
2.5
5
5
10
Biweekly
5
5
10
10
20
100
Weekly
2.5
5
10
10
15
Biweekly
5
10
20
20
30
200
Weekly
5
10
15
20
30
Biweekly
10
20
30
40
60
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 10 mL. For biweekly dosing, increase the biweekly dose by 20 mL. For 2 times per week dosing, increase the dose by 5 mL.
Monitor the patient's clinical response, and repeat the dose adjustment as needed.
Dosage requirements for patients switching to Hizentra from another IGSC product: 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
Administer a minimum total weekly Hizentra dose of 200 mg/kg body weight for two consecutive weeks 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. For biweekly dosing, one infusion of a minimum of 400 mg/kg is recommended. If a patient has been exposed to measles, ensure this minimum dose is administered as soon as possible after exposure.
2.3 Administration
Hizentra is for subcutaneous infusion only. Do not inject into a blood vessel.
Hizentra is intended for 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. Use up to 4 sites simultaneously or up to 12 sites consecutively per infusion. Injection sites should be at least 2 inches apart. Change the actual site of injection with each 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 for the fifth infusion and then to 25 mL per site as tolerated.
Rate – For the first infusion of Hizentra, the recommended flow rate is 15 mL per hour per site. For subsequent infusions, the flow rate may be increased to 25 mL per hour per site as tolerated.
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.
Clean surface – Thoroughly clean a flat surface using an alcohol wipe.
3.
Wash hands – Thoroughly wash and dry hands. The use of gloves when preparing and administering Hizentra is optional.
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.
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. 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; or up to 12 consecutively per infusion. Injection sites 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 or scan the vial if recording the infusion electronically.
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.
