Comparison of IVIG Products

Intravenous immune globulin (IVIG) products are made from human plasma. Over the years, several products have come and gone as manufacturing processes have improved their safety.¹⁴ All of the available IVIG products 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 is 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 contraindicated in patients with IgA antibodies and a history of hypersensitivity.^1-9,12 Tolerability of the different IVIG products isn’t necessarily predictable.¹⁴ Starting therapy with a low concentration and infusion rate, usually 0.5 mg/kg/min, may help prevent infusion-related reaction such as chills, nausea, etc. This may be especially true when patients are starting therapy or switching products. Other factors that may be associated with a lower risk for adverse effects include the presence of proline stabilizers and 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. The following chart details similarities and differences between IVIG products available in the U.S.

Brand Name Formulation Route	Indications	Product Specifics	Storage	Comments
*Carimune* NF^1,10 Powder for dilution to 3%, 6%, 9%, or 12% 3, 6, 12 gm bottles IV infusion	Idiopathic thrombocytopenic purpura Primary immunodeficiencies	IgA: 1000 to 2000 mcg/mL (6% solution) Osmolality: 192 to 1074 mOsm/kg (depends on diluent and final concentration) Stabilizer: sucrose	Store unreconstituted powder at room temp Refrigerate after reconstitution Start administration within 24 hours after reconstitution*	Latex-free Dilute with D5W, NS, or sterile water Filter not required Use of sucrose as a stabilizer may increase the risk for acute renal failure
*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/L Stabilizer: sorbitol	Store unopened bottles at room temp	Latex-free Dilution is not recommended Use an in-line filter of 15 to 20 microns. A 0.2 micron filter can be used, but might slow the infusion.
*Flebogamma* 10% DIF¹² 10% liquid 5, 10, 20 gm bottles IV infusion	Primary immunodeficiencies	IgA: <100 mcg/mL Osmolarity: 240 to 370 mOsm/L Stabilizer: sorbitol	Store unopened bottles at room temp	Latex-free Dilution is not recommended Filter not required
*Gammagard Liquid*³ 10% liquid 1, 2.5, 5, 10, 20, 30 gm bottles IV or subcutaneous infusion	Primary immunodeficiencies	IgA: 37 mcg/mL Osmolality: 240 to 300 mOsm/kg Stabilizer: glycine	Store unopened bottles at room temp or refrigerated. Storage at room temp is shorter. See product labeling for details.	Latex-free If diluent is used, choose D5W Use of an in-line filter is optional
*Gammagard S/D*^4,11 Powder for dilution to 5% or 10% 2.5, 5, 10 gm bottles IV infusion	Chronic lymphocytic leukemia Idiopathic thrombocytopenic purpura Kawasaki syndrome Primary immunodeficiencies	IgA: 2.2 mcg/mL (5% solution) Osmolality: 636 mOsm/kg (5% solution) Stabilizer: glycine	Store unreconstituted powder at room temp or refrigerated Store in refrigerator for a max of 24 hours after reconstitution*	Bottles have latex Comes with sterile water as a diluent Comes with administration set which contains a 15 micron filter
*Gammaplex*⁵ 5% liquid 2.5, 5, 10 gm bottles IV infusion	Primary immunodeficiencies	IgA: <10 mcg/mL Osmolality: 420 to 500 mOsm/kg Stabilizer: glycine and others	Store unopened bottles at room temp or refrigerated If bottles are pooled to make a dose, start the infusion within two hours after pooling*	Bottles have latex Dilution is not recommended Infuse through a 15 to 20 micron filter
*Gamunex*-C⁶ 10% liquid 1, 2.5, 5, 10, 20 gm bottles IV or subcutaneous infusion	Chronic inflammatory demyelinating polyneuropathy Idiopathic thrombocytopenic purpura Primary immunodeficiencies	IgA: 46 mcg/mL Osmolality: 258 mOsm/kg Stabilizer: glycine	Store unopened bottles in refrigerator. May be stored for six months at room temp anytime during the shelf-life, but must be discarded at the end of the six months. If bottles are pooled to make a dose, start the infusion within eight hours after pooling*	Latex-free If diluent is used, choose D5W Filter not required
*Hizentra***^,^7,15 20% liquid 1, 2, 4 gm bottles Subcutaneous infusion only	Primary immunodeficiencies	IgA: 50 mcg/mL Osmolality: 380 mOsm/kg Stabilizer: proline	Store unopened bottles at room temp	Latex-free Start one week after patient’s last IVIG dose, after the patient has been getting IVIG at regular intervals for at least three months High concentration may be advantageous in patients who are volume restricted
*Octagam*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*	Latex-free 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
*Privigen*⁹ 10% liquid 5, 10, 20 gm bottles IV infusion	Idiopathic thrombocytopenic purpura Primary immunodeficiencies	IgA: 25 mcg/mL Osmolality: 320 mOsm/kg Stabilizer: proline	Store unopened bottles at room temp If bottles are pooled to make a dose, start the infusion within eight hours after pooling*	Latex-free If diluent is used, choose D5W 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, it is included because some patients may be switched to Hizentra after at least three months of IVIG therapy.

Project Leader in preparation of this PL Detail-Document: Stacy A. Hester, R.Ph., BCPS, Assistant Editor

References

Product information for Carimune NF. CSL Behring. Kankakee, IL 60901 October 2010.
Product information for Flebogamma 5% DIF. Grifols Biologicals. Los Angeles, CA 90032. January 2010.
Product information for Gammagard Liquid. Baxter. Westlake Village, CA 91362. July 2011.
Product information for Gammagard S/D. Baxter. Deerfield, IL 60015. December 2010.
Product information for Gammaplex. FFF Enterprises. Temecula, CA 92591. September 2009.
Product information for Gamunex-C. Talecris. Research Triangle Park, NC 27709. October 2010.
Product information for Hizentra. CSL Behring. Kankakee, IL 60901. February 2011.
Product information for Octagam. Octapharma. Hoboken, NJ 07030. September 2009.
Product information for Privigen. CSL Behring. Kankakee, IL 60901. February 2011.
Personal communication (written). M. Rebbie. Medical Information. CSL Behring. King of Prussia, PA 19406. October 13, 2011.
Personal communication (written). K. Tomblin. Medical Information. Baxter. Westlake Village, CA 91362.
Product information for Flebogamma 10% DIF. Grifols Biologicals. Los Angeles, CA 90032. July 2010.
Mark SM. Comparison of intravenous immunoglobulin formulations: product, formulary, and cost considerations. Hosp Pharm 2011;46:668-76.
Cherin P, Cabane J. Relevant criteria for selecting an intravenous immunoglobulin preparation for clinical use. BioDrugs 2010;24:211-23.
Personal communication (written). M. Rebbie. Medical Information. CSL Behring. King of Prussia, PA 19406. October 13, 2011.

Cite this document as follows: PL Detail-Document, Comparison of IVIG Products. Pharmacist’s Letter/Pharmacy Technician’s Letter. November 2011.