Xembify

Dose

XEMBIFY can be administered at regular intervals from daily up to every two weeks (biweekly).

Doses divided over the course of a week, once weekly, or biweekly achieve similar exposure when administered regularly at steady-state.

Individualize the dose based on the patient’s pharmacokinetic and clinical response.

Monitor serum IgG trough levels regularly to guide subsequent dose adjustments and dosing intervals as needed (see Dose adjustments).

If a patient is switching to XEMBIFY, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments.

Switching to XEMBIFY from intravenous immune globulin (IVIG) Begin treatment with XEMBIFY one week after the patient’s last IVIG infusion.

Calculate the initial weekly dose of XEMBIFY. Divide the previous monthly (or every 3 weeks) IVIG dose in grams by the number of weeks between IVIG infusions, then multiply this dose by the dose adjustment factor of 1.37.

To convert the XEMBIFY dose (in grams) to milliliters (mL), multiply the calculated Initial SC dose (in grams) by 5.

To determine the dose for alternative regular dosing intervals:
-Frequent dosing (2-7 times per week): Divide the calculated weekly dose by the desired number of times per week.
-Biweekly dosing: Multiply the calculated weekly dose by 2.

To guide dose adjustments, see section Dose adjustments .

Switching to XEMBIFY from subcutaneous immune globulin (IGSC)

Administer the same weekly dose of XEMBIFY (in grams) as the weekly dose of prior IGSC treatment (in grams).

To convert the XEMBIFY dose (in grams) to milliliters (mL), multiply the calculated Initial SC dose (in grams) by 5.

To determine the dose for alternative regular dosing intervals:
-Frequent dosing (2-7 times per week): Divide the calculated weekly dose by the desired number of times per week.
-Biweekly dosing: Multiply the calculated weekly dose by 2.

To guide dose adjustments, see section Dose adjustments .

Treatment-naïve patients

The recommended dosage for treatment naïve patients with Primary Immunodeficiency is shown in Table 1.

To guide dose adjustments, see section Dose adjustments .

Dose adjustments

For dose adjustments, calculate the difference (in mg/dL) of the patient’s serum IgG trough level from the target IgG trough level, then find this difference in Table 2 (below). Locate the corresponding amount (in mL) by which to increase or decrease the weekly dose based on the patient’s body weight. 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 level is 1,000 mg/dL, this results in a difference of 100 mg/dL. Therefore, increase the weekly dose of subcutaneous dose by 5 mL.

The patient’s clinical response should be the primary consideration in dose adjustment. If a patient on XEMBIFY does not maintain an adequate clinical response or a serum IgG trough level equivalent to that of a previous treatment, adjust the dose accordingly.

Preparation and Handling

XEMBIFY is a clear to slightly opalescent, and colorless or pale yellow solution.

Visually inspect XEMBIFY for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use if the solution is cloudy or turbid.

Do not shake.

Do not dilute.

The XEMBIFY vial is for single use only.

Do not store any vial that has been entered by a needle during preparation for infusion, punctured, partially used, or opened.

Administer within 8 hours after beginning infusion preparation (i.e., once XEMBIFY is transferred from the vial into a syringe).

Administer XEMBIFY separately from other drugs or medications that the patient may be receiving.

Do not mix XEMBIFY with other medications including immune globulins from other manufacturers.

Do not use after expiration date.

Discard unused portion.

Administration

Prior to use, allow the solution to reach ambient room temperature.

Do not shake.

Follow the steps below and use aseptic technique to administer XEMBIFY.

     1.  Inspect the vials: inspect for clarity, color, and expiration date (s).

     2.  Prepare for infusion:

          Gather supplies: XEMBIFY vial(s), ancillary supplies, sharps container, patient’s
          treatment diary/logbook, and the infusion pump.

          Prepare a clean work area.

          Wash hands.

     3.  Remove the protective cap from the vial to expose the central portion of the stopper. 

          If the packaging shows any sign of tampering, do not use the product and notify
          Grifols Therapeutics LLC immediately [1-800-520-2807].

     4.  Wipe the stopper with alcohol and allow to dry.

5. Using a sterile syringe and needle, prepare to withdraw XEMBIFY by first injecting air into the vial that is equivalent to the amount of XEMBIFY to be withdrawn. Then withdraw the desired volume of XEMBIFY. If multiple vials are required to achieve the desired dose, repeat this step. (Figure 1) 6. Use XEMBIFY as soon as practicable, within 2 hours to avoid the potential formation of particles caused by siliconized syringes.
7. Follow the manufacturer’s instructions for preparing the pump and administration tubing. Be sure to prime the administration tubing to ensure that no air is left in the tubing or needle by filling the tubing/needle with XEMBIFY.
8. Select the number and location of injection sites. Rotate sites for each administration. (Figure 2) Infuse XEMBIFY in the abdomen, thigh, upper arm, sides, back and/or lateral hip. Avoid bony areas, scars, areas of inflammation, superficial infection or blood vessels.
9. Cleanse the injection site(s) with antiseptic solution using a circular motion working from the center of the site and moving to the outside. Sites should be clean, dry, and at least 2 inches (5 cm) apart. (Figure 3)
10. Grasp the skin between 2 fingers (pinch at least one inch (2.5 cm) of skin) and insert the needle at a 90-degree angle into the subcutaneous tissue. (Figure 4)
11. After inserting each needle, make sure that a blood vessel has not been accidentally entered. Attach a sterile syringe to the end of the primed administration tubing, pull back on the plunger, and if you see blood, remove and discard the needle and administration tubing. (Figure 5)

     12. Repeat priming and needle insertion steps using a new needle, administration tubing
           and a new infusion site. Secure the needle in place by applying sterile gauze or
           transparent dressing over the site.

     13. Infuse XEMBIFY at a maximum rate as per Table 3 using up to 6 infusion sites. Ensure
           that the infusion sites are at least 2 inches (5 cm) apart for patients of all ages. The
           number of infusion sites is at healthcare provider discretion. Children will require less
           total volume for a specific XEMBIFY dose (mg/kg body weight) than adults. The
           healthcare provider may choose a smaller volume/site for children and/or fewer infusion
           sites to achieve the target total dose, depending on the needs of the child. The total dose
           volume of XEMBIFY is divided by the desired volume (mL/site) to obtain number
           of infusion sites to be used.

            Record information about the infusion (e.g., lot number, expiration date, dose, date,
            time, infusion site location(s), side effects) in a patient treatment record or infusion 
            log.

     14.  Discard the needle(s) and infusion line(s) in an appropriate container. Follow the
            manufacturer’s instructions for storage of the infusion pump.

     15.  Discard partially used vial(s).

Pregnancy

Risk Summary

No human data are available to indicate the presence or absence of drug associated risk. Animal reproduction studies have not been conducted with XEMBIFY. It is not known whether XEMBIFY can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. XEMBIFY should be given to a pregnant woman only if clearly indicated. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

Risk Summary

No human data are available to indicate the presence or absence of drug associated risk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XEMBIFY and any potential adverse effects on the breastfed infant from XEMBIFY or from the underlying maternal condition.

Pediatric Use

XEMBIFY was evaluated in 14 pediatric patients (2-16 years of age) with PI in a multi-center clinical trial (Study 1) and in 29 pediatric patients in Study 2 [see Clinical Studies (14)]. The safety and efficacy profiles were similar to adult patients. No pediatric-specific dose requirements were necessary to achieve the desired serum IgG levels.

The safety and effectiveness of XEMBIFY in pediatric patients below 2 years of age have not been established.

Geriatric Use

Clinical studies of XEMBIFY did not include sufficient numbers of patients over age 65 years to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.