Gammaked

Gammaked Manufacturers

• Kedrion Biopharma, Inc
  

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  Gammaked | Kedrion Biopharma, Inc

  

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  GAMMAKED consists of 9%–11% protein in 0.16–0.24 M glycine. The buffering capacity of GAMMAKED is 35.0 mEq/L (0.35 mEq/g protein). A dose of 1 g/kg body weight therefore represents an acid load of 0.35 mEq/kg body weight. The total buffering capacity of whole blood in a normal individual is 45–50 mEq/L of blood, or 3.6 mEq/kg body weight. Thus, the acid load delivered with a dose of 1 g/kg of GAMMAKED would be neutralized by the buffering capacity of whole blood alone, even if the dose was infused instantaneously.

  2.1 Preparation and Handling Visually inspect GAMMAKED for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if turbid. Do not freeze. Do not use solutions that have been frozen. The GAMMAKED vial is for single use only. GAMMAKED contains no preservative. Use any vial that has been entered promptly.  Discard partially used vials. Infuse GAMMAKED using a separate line by itself, without mixing with other intravenous fluids or medications the subject might be receiving.  The GAMMAKED infusion line can be flushed with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection. If dilution is required, GAMMAKED may be diluted with 5% dextrose in water (D5/W). Do not dilute with saline. No other drug interactions or compatibilities have been evaluated. Content of vials may be pooled under aseptic conditions into sterile infusion bags and infused within 8 hours after pooling. Avoid simultaneous administration of GAMMAKED and Heparin through a single lumen delivery device due to GAMMAKED, Heparin incompatibilities. Flush Heparin Lock (Hep-Lock) through which GAMMAKED was administered with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection, and do not flush with Heparin. See table below. Additional Solutions Dilution Line Flush Delivery Device Flush 5% Dextrose in water Yes Yes Yes 0.9% Sodium Chloride No Yes Yes Heparin No No No Do not mix with immune globulin intravenous (IGIV) products from other manufacturers. Do not use after expiration date. 2.2 PI

  As there are significant differences in the half-life of IgG among patients with primary humoral immunodeficiencies, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response.

  Intravenous (IV)
  
  The dose of GAMMAKED for patients with PI is 300 to 600 mg/kg body weight (3-6 mL/kg) administered every 3 to 4 weeks. The dosage may be adjusted over time to achieve the desired trough levels and clinical responses.

  The recommended initial infusion rate is 1 mg/kg/min (0.01 mL/kg/min). If the infusion is well-tolerated, the rate may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min). For patients judged to be at risk for renal dysfunction or thrombosis, administer GAMMAKED at the minimum infusion rate practicable. (see Warnings and Precautions [5.2, 5.4])

  If a patient routinely receives a dose of less than 400 mg/kg of GAMMAKED every 3 to 4 weeks (less than 4 mL/kg), and is at risk of measles exposure (i.e., traveling to a measles endemic area), administer a dose of at least 400 mg/kg (4 mL/kg) just prior to the expected measles exposure. If a patient has been exposed to measles, a dose of 400 mg/kg (4 mL/kg) should be administered as soon as possible after exposure.

  Subcutaneous (SC)
  
  The dose should be individualized based on the patient’s clinical response to GAMMAKED therapy and serum IgG trough levels. Begin treatment with GAMMAKED one week after the patient’s last IGIV infusion. See below under "Initial Weekly Dose". Prior to switching treatment from IGIV to GAMMAKED, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments. See below under "Dose Adjustment".

  Establish the initial weekly dose of GAMMAKED 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. If the patient has not been previously treated with IV GAMMAKED, convert the monthly IGIV dose by multiplying by 1.37, then dividing this dose into weekly doses based on the patient’s previous IGIV treatment interval. Monitor the patient’s clinical response, and adjust dose accordingly.

  Initial Weekly Dose
  To calculate the initial weekly dose of subcutaneous administration of GAMMAKED, multiply the previous IGIV dose in grams by the dose adjustment factor of 1.37; then divide this by the number of weeks between doses during the patient’s IGIV treatment (i.e., 3 or 4).
  
  

  To convert the GAMMAKED dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 10.

  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 may be considered, measure the patient’s serum IgG trough level on IGIV and as early as 5 weeks after switching from IGIV to subcutaneous. The target serum IgG trough level on weekly SC treatment is projected to be the last IGIV trough level plus 340 mg/dL. To determine if further dose adjustments are necessary, monitor the patient’s IgG trough level every 2 to 3 months.

  To adjust the dose based on trough levels, calculate the difference (in mg/dL) of the patient’s serum IgG trough level from the target IgG trough level (the last IGIV trough level + 340 mg/dL). Then find this difference in Table 1 and the corresponding amount (in mL) by which to increase or decrease the weekly dose based on the patient’s body weight. However, the patient’s clinical response should be the primary consideration in dose adjustment.

  Table 1: Adjustment (±mL) of the Weekly Subcutaneous Dose Based on the Difference (±mg/dL) From the Target Serum IgG Trough Level * Dose adjustment in mL is based on the slope of the serum IgG trough level response to subcutaneous administration of GAMMAKED dose increments (about 6.0 mg/dL per increment of 1 mg/kg per week). 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)*  50 1 1 2 3 3 4 5 6 7 8 8 9 10 100 2 3 3 5 7 8 10 12 13 15 17 18 20 150 3 4 5 8 10 13 15 18 20 23 25 28 30 200 3 5 7 10 13 17 20 23 27 30 33 37 40 250 4 6 8 13 17 21 25 29 33 38 42 46 50 300 5 8 10 15 20 25 30 35 40 45 50 55 60 350 6 9 12 18 23 29 35 41 47 53 58 64 70 400 7 10 13 20 27 33 40 47 53 60 67 73 80 450 8 11 15 23 30 38 45 53 60 68 75 83 90 500 8 13 17 25 33 42 50 58 67 75 83 92 100

  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 1000 mg/dL, this results in a difference of 100 mg/dL. Therefore, increase the weekly dose of subcutaneous dose by 12 mL.

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

  Dosage requirements for patients switching to GAMMAKED from another Immune Globulin Subcutaneous (IGSC) product have not been studied. If a patient on GAMMAKED 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 to achieve a desired IGSC trough level.

  2.3 ITP

         DO NOT ADMINISTER SUBCUTANEOUSLY (see Warnings and Precautions [5.10])

  GAMMAKED may be administered at a total dose of 2 g/kg, divided in two doses of 1 g/kg (10 mL/kg) given on two consecutive days or into five doses of 0.4 g/kg (4 mL/kg) given on five consecutive days. If after administration of the first of two daily 1 g/kg (10 mL/kg) doses, an adequate increase in the platelet count is observed at 24 hours, the second dose of 1 g/kg (10 mL/kg) body weight may be withheld.

  Forty-eight ITP subjects were treated with 2 g/kg GAMMAKED, divided in two 1 g/kg doses (10 mL/kg) given on two successive days. With this dose regimen 35/39 subjects (90%) responded with a platelet count from less than or equal to 20 x109/L to more than or equal to 50 x109/L within 7 days after treatment. The high dose regimen (1 g/kg × 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern.

  The recommended initial infusion rate is 1 mg/kg/min (0.01 mL/kg/min). If the infusion is well-tolerated, the rate may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min). For patients judged to be at risk for renal dysfunction or thrombosis, administer GAMMAKED at the minimum infusion rate practicable. (see Warnings and Precautions [5.2, 5.4])

  2.4 CIDP

  GAMMAKED may be initially administered as a total loading dose of 2 g/kg (20 mL/kg) given in divided doses over two to four consecutive days. GAMMAKED may be administered as a maintenance infusion of 1 g/kg (10 mL/kg) administered over 1 day or divided into two doses of 0.5 g/kg (5 mL/kg) given on two consecutive days, every 3 weeks.

  The recommended initial infusion rate is 2 mg/kg/min (0.02 mL/kg/min). If the infusion is well tolerated, the rate may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min). For patients judged to be at risk for renal dysfunction or thrombosis, administer GAMMAKED at the minimum infusion rate practicable. (see Warnings and Precautions [5.2, 5.4])

  2.5 Administration

  Administer intravenously for PI, ITP and CIDP.

  GAMMAKED may also be administered subcutaneously for the treatment of PI.

  Administer GAMMAKED at room temperature. Inspect GAMMAKED visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. Do not use if turbid and/or if discoloration is observed.

  Intravenous

  Use only 18 gauge needles to penetrate the stopper for dispensing product from the 10 mL vial. Use 16 gauge needles or dispensing pins only with 25 mL vial sizes and larger. Insert needles or dispensing pins only once and be within the stopper area delineated by the raised ring. Penetrate the stopper perpendicular to the plane of the stopper within the ring. GAMMAKED™ vial size Gauge of needle to penetrate stopper 10 mL 18 gauge 25, 50, 100, 200 mL 16 gauge Use promptly any vial that has been opened. Discard partially used vials. If dilution is required, GAMMAKED may be diluted with 5% dextrose in water (D5/W). Do not dilute with saline. Infuse GAMMAKED using a separate line by itself, without mixing with other intravenous fluids or medications the subject might be receiving.  The GAMMAKED infusion line can be flushed with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection.

  Subcutaneous for PI Only

  Instructions for Administration

  Prior to use, allow the solution to reach ambient room temperature. DO NOT SHAKE. Do not use if the solution is cloudy or has particulates. Check the product expiration date on the vial. Do not use beyond the expiration date. Use aseptic technique when preparing and administering GAMMAKED for injection. Remove the protective cap from the vial to expose the central portion of the rubber stopper. Wipe the rubber stopper with alcohol and allow to dry. Using a sterile syringe and needle, prepare to withdraw GAMMAKED by first injecting air into the vial that is equivalent to the amount of GAMMAKED to be withdrawn. Then withdraw the desired volume of GAMMAKED. If multiple vials are required to achieve the desired dose, repeat this step. (Figure 1)  Follow the manufacturer’s instructions for filling the pump reservoir and preparing the pump, administration tubing and Y-site connection tubing, if needed. 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 GAMMAKED. Select the number and location of injection sites. (Figure 2) 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 two inches apart. (Figure 3)  Grasp the skin between two fingers and insert the needle into the subcutaneous tissue. (Figure 4)  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. (Figure 5) If using multiple, simultaneous injection sites, use Y-site connection tubing and secure to the administration tubing. Infuse GAMMAKED following the manufacturer’s instructions for the pump. (Figure 6)

  Rate of Administration

  Intravenous

  Following initial infusion (see table below), the infusion rate may be gradually increased to a maximum of 0.08 mL/kg per minute (8 mg/kg per minute) as tolerated.

  Indication Initial Infusion Rate
  (first 30 minutes) Maximum Infusion Rate
  (if tolerated) PI 1 mg/kg/min 8 mg/kg/min ITP 1 mg/kg/min 8 mg/kg/min CIDP 2 mg/kg/min 8 mg/kg/min

  Monitor patient vital signs throughout the infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient.

  Certain severe adverse drug reactions may be related to the rate of infusion. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

  Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients at risk of renal dysfunction or thrombosis, administer GAMMAKED at the minimum infusion rate practicable and discontinue GAMMAKED if renal function deteriorates.

  Subcutaneous for PI Only

  For PI, it is recommended that GAMMAKED is infused at a rate of 20 mL/hr per infusion site.

  In the SC clinical study, the mean volume administered per infusion site was 34 mL (17–69 mL) and the majority of infusions were administered at a rate of 20 mL/hr per site. Multiple simultaneous infusion sites were enabled by administration tubing and Y-site connection tubing. Most subjects utilized 4 infusion sites per infusion with abdomen and thighs being the most commonly used sites. The maximum number of infusion sites is 8. Injection sites should be at least 2 inches apart.

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