Comparison of Immune Globulin Products

 

Full update September 2019

 

Intravenous immune globulin (IVIG) products are made from human plasma. Over the years, products have come and gone as manufacturing processes have become safer.14 All but one available IVIG product are indicated for primary immunodeficiencies, while not all are indicated for immune thrombocytopenic purpura, etc. More than half of IVIG use is off-label. There’s an increased risk of anaphylaxis with use of IVIG in patients with IgA deficiency, especially with products that have higher concentrations of IgA. IVIG is generally contraindicated in patients with IgA antibodies and a history of hypersensitivity.14 However, Gammagard S/D can be used for patients who have not had an anaphylactic or serious hypersensitivity reaction to a 5% IVIG product with <1 mcg/mL of IgA.4,14 Tolerability of the different IVIG products isn’t always predictable.14 Starting therapy with a low concentration and infusion rate, usually 0.5 mg/kg/min, may help prevent infusion-related reaction (chills, nausea, etc). This may be especially true when patients start therapy or switch products. In addition, a lower concentration and infusion rate may help reduce the risk of kidney damage and thrombosis in patients at risk. Other ways to lower risk of adverse effects include avoiding products with sugar-based stabilizers and using products near physiologic osmolality/osmolarity (around 300 mOsm/kg or 300 mOsm/L).13,14 Premedication with acetaminophen and an antihistamine 30 to 60 minutes before infusion of IVIG is a common practice for reducing the risk of infusion-related reactions in some patients. When dosing IVIG products, consider data that support using ideal body weight rather than actual body weight. For obese patients, data are limited with regard to whether an adjusted body weight or ideal body weight should be used.10,11,15,27 The following chart compares the IVIG products available in the U.S. Subcutaneous infusion and IM immune globulin products are also included (see more info below the chart).

Brand Name
Formulation
Route

FDA-Approved
Indications

Product Specifics

Storage

Comments

Asceniv23

 

10% liquid

 

5 gm bottles

 

IV infusion


  • Primary immunodeficiencies

IgA: ≤200 mcg/mL
Osmolality: Not available from manufacturer.
Stabilizer: glycine and polysorbate 80

  • Refrigerate unopened bottles.

 

  • Dilution is not recommended.
  • Filter not required.

 

 

Bivigam16

 

10% liquid

 

5, 10 gm bottles

 

IV infusion

  • Primary immunodeficiencies

IgA: ≤200 mcg/mL
Osmolality: ≤510 mOsm/kg21
Stabilizer: glycine

  • Refrigerate unopened bottles.

 

  • Dilution is not recommended.
  • Filter not required.

 

 

Cutaquig**24

 

16.5% liquid

 

1, 1.65, 2, 3.3, 4,
8 gm bottles

 

Subcutaneous infusion only

  • Primary immunodeficiencies

IgA: ≤600 mcg/mL
Osmolality: 310 to 380 mOsm/kg
Stabilizer: maltose

  • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
  • Dilution is not recommended.
  • Filter not required.
  • Maltose may falsely elevate blood glucose with some glucometers and strips.

 

 

Cuvitru**17

 

20% liquid

 

1, 2, 4, 8, 10 gm bottles

 

Subcutaneous infusion only

 

 

  • Primary immunodeficiencies

IgA: 80 mcg/mL
Osmolality: 280 to 292 mOsm/kg
Stabilizer: glycine

  • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
  • Dilution is not recommended.

Flebogamma 5% DIF2

 

5% liquid

 

0.5, 2.5, 5, 10,

20 gm bottles

 

IV infusion

 

 

 

  • Primary immunodeficiencies

IgA: <50 mcg/mL
Osmolarity: 240 to 370 mOsm/kg
Stabilizer: sorbitol

 

  • Store unopened bottles at room temp.
  • Dilution is not recommended.
  • Filter not required.

 

 

 

Flebogamma 10% DIF12

 

10% liquid

 

5, 10, 20 gm bottles

 

IV infusion

 

 

  • Primary immunodeficiencies
  • Immune thrombocytopenia

IgA: <100 mcg/mL
Osmolarity: 240 to 370 mOsm/L
Stabilizer: sorbitol

 

  • Store unopened bottles at room temp.
  • Dilution is not recommended.
  • Filter not required.

 

Gamastan***25

 

16.5% liquid

 

2 and 10 mL bottles

 

IM injection only


  • Hepatitis A prophylaxis
  • To prevent or modify measles, and to modify rubella or varicella in specific patient populations.

IgA: Not applicable
Osmolarity: Not applicable
Stabilizer: none


  • Refrigerate unopened bottles.
  • Dilution is not recommended.
  • Filter not required.

 

Gammagard Liquid3

 

10% liquid

 

1, 2.5, 5, 10, 20,

30 gm bottles

 

IV or subcutaneous** (for primary immunodeficiencies only) infusion

 

  • Primary immunodeficiencies
  • Multifocal motor neuropathy
  •  

     

    IgA: 37 mcg/mL
    Osmolality: 240 to 300 mOsm/kg
    Stabilizer: glycine

     

     

    • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.

     

    • If diluent is used, choose D5W.
    • Use of an in-line filter is optional.

     

    Gammagard S/D4

     

    Powder for dilution to 5% or 10%

     

    5, 10 gm bottles

     

    IV infusion

     

     

    • Primary immunodeficiencies
    • Immune thrombocytopenia
    • Chronic lymphocytic leukemia
    • Kawasaki syndrome

     

    IgA: <1 mcg/mL
    (5% solution)
    Osmolality: 636 mOsm/L21
    (5% solution)
    Stabilizer: glycine

     

     

     

    • Store powder at room temp or refrigerated.
    • Store in refrigerator for a max of 24 hours after reconstitution.*
    • Comes with sterile water as a diluent.
    • Comes with administration set which contains a 15 micron filter.

    Gammaked18


    10% liquid

     

    1, 2.5, 5, 10, 20 gm bottles

     

    IV or subcutaneous** (for primary immunodeficiencies only) infusion

     

     

    • Primary immunodeficiencies
    • Immune thrombocytopenia
    • Inflammatory demyelinating polyneuropathy

    IgA: 46 mcg/mL
    Osmolality: 258 mOsm/kg
    Stabilizer: glycine

    • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
    • If bottles are pooled to make a dose, start the infusion within eight hours after pooling.*
    • If diluent is used, choose D5W.
    • Filter not required.

     

    Gammaplex22

     

    5% liquid

     

    5, 10, 20 gm bottles

     

    IV infusion



    • Primary immunodeficiencies
    • Immune thrombocytopenia

     

    IgA: <10 mcg/mL
    Osmolality: 420 to 500 mOsm/kg
    Stabilizer: glycine, polysorbate 80, and sorbitol

     


    • Store unopened bottles at room temp or refrigerated.
    • If bottles are pooled to make a dose, start the infusion within two hours after pooling.*
    • Dilution is not recommended.
    • Filter not required.

     

     

    Gammaplex5

     

    10% liquid

     

    5, 10, 20 gm bottles

     

    IV infusion

     

     

    • Primary immunodeficiencies
    • Immune thrombocytopenia

     

    IgA: <20 mcg/mL
    Osmolality: 280 to 288 mOsm/kg
    Stabilizer: glycine and polysorbate 80

     

     

    • Store unopened bottles at room temp or refrigerated.

     

    • Dilution is not recommended.
    • Filter not required.

     

     

    Gamunex-C6

     

    10% liquid

     

    1, 2.5, 5,

    10, 20, 40 gm bottles

     

    IV or subcutaneous** (primary immunodeficiencies only) infusion

     

    • Primary immunodeficiencies
    • Immune thrombocytopenia
    • Inflammatory

    demyelinating polyneuropathy

    IgA: 46 mcg/mL
    Osmolality: 258 mOsm/kg
    Stabilizer: glycine

     

     

     

    • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
    • If bottles are pooled to make a dose, start the infusion within eight hours after pooling.*
    • If diluent is used, choose D5W.
    • Filter not required.

    Hizentra**7

     

    20% liquid

     

    1, 2, 4, 10 gm bottles

     

    Subcutaneous infusion only

     

    • Primary immunodeficiencies
    • Inflammatory demyelinating polyneuropathy

     

    IgA: ≤50 mcg/mL
    Osmolality: 380 mOsm/kg21
    Stabilizer: L-proline

     

    • Store unopened bottles at room temp.
    • Dilution is not recommended.
    • High concentration may be advantageous in patients who are volume restricted.

     

     

     

     

    HyQvia**20


    10% liquid

     

    2.5, 5, 10, 20,
    30 gm bottles

     

    Subcutaneous infusion only

     

    • Primary immunodeficiencies

    IgA: 37 mcg/mL
    Osmolality: 240 to 300 mOsm/kg
    Stabilizer: glycine


    • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
    • Dilution is not recommended.
    • Formulated with recombinant human hyaluronidase to temporarily break down tissue and facilitate delivery of a higher volume of immune globulin by subcutaneous injection.

     

     

     

     

     

    Octagam 5%8

     

    5% liquid

     

    1, 2.5, 5, 10,

    25 gm bottles

     

    IV infusion

    • Primary immunodeficiencies

    IgA: ≤200 mcg/mL
    Osmolality: 310 to 380 mOsm/kg
    Stabilizer: maltose

     

    • Store unopened bottles at room temp or refrigerated.
    • If bottles are pooled to make a dose, start the infusion within eight hours after pooling.*
    • Dilution is not recommended.
    • Use of an in-line filter between 0.2 and
      200 microns is optional.
    • Contraindicated in patients with corn allergy. Maltose comes from corn.
    • Maltose may falsely elevate blood glucose with some glucometers and strips.

     

     

     

     

     

    Octagam 10%19


    10% liquid

     

    2, 5, 10, 20, 30 gm bottles

     

    IV infusion

     

    • Immune thrombocytopenia

    IgA: 106 mcg/mL
    Osmolality: 310 to 380 mOsm/kg
    Stabilizer: maltose

    • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
    • If bottles are pooled to make a dose, infuse within eight hours after pooling.*
    • Dilution is not recommended.
    • Use of an in-line filter between 0.2 and
      200 microns is optional.
    • Use with caution in patients with corn allergy. Maltose comes from corn.
    • Maltose may falsely elevate blood glucose with some glucometers and strips.

     

    Panzyga26

     

    10% liquid

     

    1, 2.5, 5, 10, 20,
    30 gm bottles

     

    IV infusion

     


    • Primary immunodeficiencies

       

    • Immune thrombocytopenia

    IgA: 100 mcg/mL
    Osmolarity: 240 to 310 mOsm/L
    Stabilizer: glycine


    • Store unopened bottles at room temp or refrigerated. Storage duration at room temp is shorter. See product labeling for details.
    • If bottles are pooled to make a dose, infuse within eight hours after pooling.*

     

    • Dilution is not recommended.
    • Use of an in-line filter between 0.2 and
      200 microns is optional.

     

    Privigen9

     

    10% liquid

     

    5, 10, 20, 40 gm bottles

     

    IV infusion

     

    • Primary immunodeficiencies
    • Immune thrombocytopenia
    • Inflammatory demyelinating polyneuropathy

     

    IgA: ≤25 mcg/mL
    Osmolality: 240 to 440 mOsm/kg
    Stabilizer: L-proline

    • Store unopened bottles at room temp.
    • If bottles are pooled to make a dose, start the infusion within eight hours after pooling.*
    • If diluent is used, choose D5W.
    • No filter required.

     

    Xembify**1

     

    20% liquid

     

    1, 2, 4, 10 gm bottles

     

    Subcutaneous infusion only



    • Primary immunodeficiencies

     

     

    IgA: not available from manufacturer
    Osmolality: 280 to 404 mOsm/kg
    Stabilizer: glycine and others

    • Store unopened bottles at room temp or refrigerated.
    • Dilution is not recommended.
    • No filter required.

       

     

    *Storage requirements and beyond-use information after preparation is given based on the assumption that the product was prepared in a laminar flow hood.

    **Although not an IVIG formulation, product is included because some patients may be switched to subcutaneous infusions from IVIG. Check product labeling for how long a patient should be maintained on IVIG before switching, and for the recommended interval between the last IVIG dose and the first subcutaneous dose (usually one week).1,3,6,7,17,18,20,24

    ***Not an IVIG formulation, but product is included to contrast indications and for completeness.25

    Project Leader in preparation of this clinical resource (350922): Stacy A. Hester, R.Ph., BCPS, Associate Editor

    References

    1. Product information for Xembify. Grifols. Research Triangle Park, NC 27709. July 2019.
    2. Product information for Flebogamma 5% DIF. Grifols Biologicals. Los Angeles, CA 90032. July 2017.
    3. Product information for Gammagard Liquid. Baxalta. Lexington, MA 02421. July 2017.
    4. Product information for Gammagard S/D. Baxalta. Lexington, MA 02421. August 2017.
    5. Product information for Gammaplex 10%. BPL. Durham, NC 27701. December 2018.
    6. Product information for Gamunex-C. Grifols Therapeutics. Research Triangle Park, NC 27709. June 2018.
    7. Product information for Hizentra. CSL Behring. Kankakee, IL 60901. March 2018.
    8. Product information for Octagam. Octapharma. Hoboken, NJ 07030. January 2019.
    9. Product information for Privigen. CSL Behring. Kankakee, IL 60901. September 2017.
    10. Hodkinson JP. Considerations for dosing immunoglobulin in obese patients. Clin Exp Immunol 2017;188:353-62.
    11. Anderson CR, Olson JA. Correlation of weight-based i.v. immune globulin doses with changes in serum immunoglobulin G levels. Am J Health Syst Pharm 2015; 72:285-9.
    12. Product information for Flebogamma 10% DIF. Grifols Biologicals. Los Angeles, CA 90032. July 2017.
    13. Mark SM. Comparison of intravenous immunoglobulin formulations: product formulary, and cost considerations. Hosp Pharm 2011;46:668-76.
    14. Cherin P, Cabane J. Relevant criteria for selecting an intravenous immunoglobulin preparation for clinical use. BioDrugs 2010;24:211-23.
    15. ASHP. Immune globulin, intravenous or subcutaneous (human). July 15, 2019. https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=527. (Accessed August 16, 2019).
    16. Product information for Bivigam. ADMA Biologics. Boca Raton, FL 33487. July 2019.
    17. Product information for Cuvitru. Baxalta. West Lake Village, CA 91362. May 2019.
    18. Product information for Gammaked. Kedrion Biopharma. Fort Lee, NJ 07024. June 2018.
    19. Product information for Octagam 10%. Octapharma. Hoboken, NJ 07030. August 2018.
    20. Product information for HyQvia. Baxalta. Lexington, MA 02421. January 2019.
    21. Immune Deficiency Foundation. Characteristics of immunoglobulin products used to treat immunodeficiency diseases licensed for use in the United States. https://primaryimmune.org/wp-content/uploads/2017/02/IVIG-Chart-2.2017.pdf. (Accessed August 13, 2019).
    22. Product information for Gammaplex 5%. BPL. Durham, NC 27701. December 2018.
    23. Product information for Asceniv. ADMA Biologics. Boca Raton, FL 33487. April 2019.
    24. Product information for Cutaquig. Octapharma. Hoboken, NJ 07030. December 2018.
    25. Product information for Gamastan. Grifols. Research Triangle Park, NC 27709. February 2018.
    26. Product information for Panzyga. Pfizer. New York, NY 10017. April 2019.
    27. Lagasse C, Hatton RC, Pyles E. A survey of intravenous immune globulin (IVIG) dosing strategies. Ann Pharmacother 2015;49:254-7.

    Cite this document as follows: Clinical Resource, Comparison of Immune Globulin Products. Hospital Pharmacist’s Letter/Prescriber’s Letter. September 2019.

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