Hyqvia

For subcutaneous use only.

2.1 Dosage

Initiation of Treatment with HYQVIA

• For patients previously on another IgG treatment, administer the first dose approximately one week after the last infusion of their previous treatment.  • Increase the dose and frequency from a 1-week dose to a 3- or 4-week dose (see ramp-up schedule in Table 1).  • Initiating treatment at a full monthly dose was not evaluated in the clinical trial.  Table 1 Initial Treatment Interval/Dosage Ramp-Up Schedule

Week

Infusion Number

Dose Interval

Example for 30 grams per 4 weeks

1

1st infusion

1-week-dose

7.5 grams

2

2nd infusion

2-week-dose

15 grams

3

No infusion

4

3rd infusion

3-week-dose

22.5 grams

5

No infusion

6

No infusion

7

4th infusion (if required)

4-week-dose

30 grams

For patients switching from Immune Globulin Intravenous (Human) [IGIV] treatment:

Administer HYQVIA at the same dose and frequency as the previous intravenous treatment, after the initial dose ramp-up.

For patients naïve to IgG treatment or switching from Immune Globulin Subcutaneous (Human) [IGSC]:

Administer HYQVIA at 300 to 600 mg/kg at 3 to 4 week intervals, after initial ramp-up.

Individualization of Dose

If HYQVIA is administered at the same dose and frequency, the serum IgG levels from HYQVIA should be comparable to serum IgG levels from intravenous treatment.

For dose adjustment:

• Calculate the difference between the patient's serum IgG trough level during HYQVIA treatment and the IgG trough level during the previous intravenous treatment. • Find this difference (in mg/dL) in the columns of Table 2 and the corresponding amount (in mL) by which to increase or decrease the dose based on the patient's body weight and desired change in IgG trough level. Table 2 Individualization in Volume Administered per Dosing Interval for Intended Change in IgG Trough Levela Difference in IgG Trough Levels Body Weight 100 mg/dL 200 mg/dL 300 mg/dL 400 mg/dL

10 kg

3 mL

6 mL

9 mL

12 mL

20 kg

6 mL

12 mL

18 mL

24 mL

30 kg

9 mL

18 mL

27 mL

36 mL

40 kg

12 mL

24 mL

36 mL

48 mL

50 kg

15 mL

30 mL

45 mL

61 mL

60 kg

18 mL

36 mL

55 mL

73 mL

70 kg

21 mL

42 mL

64 mL

85 mL

80 kg

24 mL

48 mL

73 mL

97 mL

90 kg

27 mL

55 mL

82 mL

109 mL

100 kg

30 mL

61 mL

91 mL

121 mL

110 kg

33 mL

67 mL

100 mL

133 mL

120 kg

36 mL

73 mL

109 mL

145 mL

130 kg

39 mL

79 mL

118 mL

158 mL

140 kg

42 mL

85 mL

127 mL

170 mL

  aDerived using a slope of 3.3 kg/dL

Example 1: A patient with a body weight of 80 kg has a measured IgG trough level of 800 mg/dL and the reference trough level is 1000 mg/dL. The trough level difference is 200 mg/dL (1000 mg/dL minus 800 mg/dL). The dose of HYQVIA would be increased by 48 mL (4.8 grams) per dosing interval.

Example 2: A patient with a body weight of 60 kg has a measured IgG trough level of 1000 mg/dL and the reference trough level is 900 mg/dL. The trough level difference is -100 mg/dL (900 mg/dL minus 1000 mg/dL). The dose of HYQVIA would be decreased by 18 mL (1.8 grams) per dosing interval.

HYQVIA can be used to administer a full therapeutic dose in one site up to every four weeks. Adjust the frequency and number of infusion sites taking into consideration volume, total infusion time, and tolerability. Adjust the frequency as needed so that the patient receives the same weekly equivalent dose.

Example: When adjusting a dose of 30 grams administered every 3 weeks; administer 40 grams of HYQVIA every 4 weeks. If a higher trough level is required, relative to intravenous treatment at 3 or 4 week intervals, increase the dose or decrease the dosing interval. Evaluate the use ofa second site or infusing at shorter intervals when the volume of HYQVIA is greater than 600 mL.

If a patient misses a dose, administer the missed dose as soon as possible and then resume scheduled treatments as applicable.

If HYQVIA is administered at a different interval than the previous treatment, either intravenously or subcutaneously, then Table 2 should not be used and the dose of HYQVIA should be adjusted, if necessary, based on clinical response.

2.2 Administration

HYQVIA should be administered by a healthcare professional, caregiver or self-administered by the patient after appropriate training.

• Infusion requires an infusion pump capable of infusing a patient’s therapeutic dose at infusion rates up to 300 mL/hr/site. The pump must have the ability to titrate the flow rate up or down if required to improve tolerability. To ensure maximum flow rates, use a subcutaneous needle set that is 24 gauge and labeled for high flow rates. • Infuse the two components of HYQVIA sequentially, beginning with the Recombinant Human Hyaluronidase. • Initiate the infusion of the full dose of the Immune Globulin Infusion 10% (Human) through the same subcutaneous needle set within approximately 10 minutes of the Recombinant Human Hyaluronidase infusion. • For each full or partial vial of Immune Globulin Infusion 10% (Human) used, administer the entire contents of the Recombinant Human Hyaluronidase vial.

Selection of Infusion Site(s)

The suggested site(s) for the infusion of HYQVIA are the abdomen and thighs. If two sites are used, the two infusion sites should be on opposite sides of the body. Avoid bony prominences, or areas that are scarred, inflamed or infected.

Volume per Site

Administer up to 600 mL per site for patients greater than or equal to 40 kg and up to 300 mL per site for patients less than 40 kg.

A second site can be used at the discretion of the physician and patient based on tolerability and total volume. If a second site is used, administer half of total volume of the Recombinant Human Hyaluronidase of HYQVIA in each site.

Rate of Infusion

Administer the Recombinant Human Hyaluronidase of HYQVIA at an initial rate per site of approximately 1 to 2 mL per minute, or as tolerated.

Administer Immune Globulin Infusion 10% (Human) of HYQVIA at rates as shown in Table 3 for the initial infusions. If the patient tolerates these infusions at the full dose and maximum rate, adjust both the time intervals and number of rate changes of the ramp-up used for successive infusions at the discretion of the physician and patient.

Table 3 Immune Globulin Infusion 10% (Human) Infusion Rates

First 2 Infusions

Subsequent 2 or 3 Infusions

Subjects < 40 kg (< 88lbs)

Subjects ≥ 40 kg (≥ 88lbs)

Subjects < 40 kg (< 88lbs)

Subjects ≥ 40 kg (≥ 88lbs)

Intervals

Rate per site

Rate per site

Rate per site

Rate per site

Minutes

mL per hour

mL per hour

mL per hour

mL per hour

  5 - 15

5

10

10

10

  5 - 15

10

30

20

30

  5 - 15

20

60

40

120

  5 - 15

40

120

80

240

Remainder of infusion

80

240

160

300

2.3 Preparation and Handling • Visually inspect both vials of HYQVIA for discoloration and particulate matter prior to administration. • The appearance of the Immune Globulin Infusion 10% (Human) of HYQVIA can vary from clear or slightly opalescent and colorless or pale yellow. • The appearance of the Recombinant Human Hyaluronidase of HYQVIA should be clear and colorless. • Do not use either component of HYQVIA if either solution is cloudy or has particulates. • Allow refrigerated product to come to room temperature before use. Do not apply heat or place in microwave. • Do not shake HYQVIA. • Do not mix the Recombinant Human Hyaluronidase and the Immune Globulin Infusion 10% (Human) of HYQVIA into the same container prior to administration. • Do not mix or administer components of HYQVIA with other products. Administer components of HYQVIA sequentially. Do not use either component alone. • Flush the infusion line with normal saline or Dextrose 5% in water (D5W) if required. • HYQVIA contains no preservative. Discard any unused product according to local standards for biohazard products 2.4 Instructions for Administration

Use aseptic technique when preparing and administering HYQVIA for infusion.

For more detail on steps, see accompanying Information for Patients.

1. Inspect the vials:Inspect for clarity, color, and expiration date(s) 2. Prepare for infusion: • Gather supplies: HYQVIA dual vial unit(s), ancillary supplies, sharps container and infusion pump (program pump per physician recommendation following manufacturer’s instructions). • Prepare a clean work area. • Wash hands. • If the Immune Globulin Infusion 10% (Human) and Recombinant Human Hyaluronidase are pooled into separate containers, skip to Step 5. 3. Prepare the Recombinant Human Hyaluronidase of HYQVIA (Labeled as HY): • Remove the protective cap. • Wipe each stopper with a sterile alcohol wipe and allow to dry. • Attach a syringe to a needle/needle-less transfer device (to prevent stopper push through or coring), inject air and then draw the full contents of each vial labeled “HY” into a single syringe, if possible. • Attach the syringe containing the Recombinant Human Hyaluronidase to the subcutaneous needle set and prime up to the needle hub. 4. Prepare Immune Globulin Infusion 10% (Human) of HYQVIA (Labeled as “IG”): • Wipe each stopper with a sterile alcohol wipe and allow to dry. • Transfer the vial(s) labeled “IG” using one of the following methods: • Pool into an infusion bag, using a transfer device per manufacturer’s directions. Attach and prime the pump administrating tubing; or- • Directly spike the vial using a vented pump administration tubing and prime as directed.

If using a syringe driver, transfer into syringe(s), preferably using a vented spike.

5. Prepare the infusion site(s): • Potential sites for infusion include the middle to upper abdomen and thigh. • Avoid: bony prominences, blood vessels, scars, or areas that are inflamed or infected. • If two sites are desired, a bifurcated needle set may be used on opposite sides of the body. • Rotate sites by choosing opposite sides of the body between successive infusions. • Cleanse the infusion site(s) with a sterile alcohol wipe beginning at the center of each infusion site and moving outward in a circular motion. Allow the infusion site(s) to dry. 6. Insert and secure the 24 gauge subcutaneous needle: • Pinch at least one inch of skin between two fingers. Insert the needle at a 90-degree angle into the subcutaneous tissue and secure the needle with sterile tape. • Check placement: gently pull back on the plunger of attached syringe and monitor for any blood return in the tubing. • If blood is seen in the tubing, remove and discard the needle and repeat steps 3, 5 and 6 with a new subcutaneous needle and infusion site. • Secure the needle in place with a sterile protective dressing. 7. Administer the Recombinant Human Hyaluronidase of HYQVIA:

Administer the entire Recombinant Human Hyaluronidase dose first. Start at a rate of 1 to 2 mL per minute per site and increase as tolerated. If more than one site is used, divide the contents equally between sites. At the end of infusion, disconnect the empty syringe and attach pump tubing/syringe containing the Immune Globulin Infusion 10% (Human) of HYQVIA to the same subcutaneous needle set.

8. Administer the Immune Globulin Infusion 10% (Human) of HYQVIA:

Within approximately 10 minutes of completing the infusion of the Recombinant Human Hyaluronidase of HYQVIA, start the variable rate program of the infusion pump to initiate the infusion of the full therapeutic dose of Immune Globulin Infusion 10% (Human) of HYQVIA. At the end of infusion, flush infusion tubing up to the needle with normal saline or Dextrose 5% in water (D5W), if required.

9. Remove subcutaneous needle(s) from the infusion site(s):

After the infusion is complete, remove the needle set and cover with a protective dressing. Discard any partially used vial(s) and disposable supplies in accordance with local requirements.

10. Document the infusion:

Remove the peel-off label from each Immune Globulin Infusion 10% (Human) vial of HYQVIA used and affix to the patient’s treatment record or infusion log. In addition, record the time, date, dose, infusion site location and any reactions after each infusion.

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