BlueCross BlueShield of Tennessee Medical Policy Manual

Intravenous Immune Globulin (IVIG) Therapy

NDC CODE(S)

69800-0250-xx Asceniv 5 GM/50ML SOLN (ADMA BIOLOGICS)

59730-6502-xx Bivigam 5 GM/50ML SOLN (BIOTEST PHARMACEUTICALS)

44206-0417-xx Carimune NF 6 GM SOLR (CSL BEHRING)

44206-0418-xx Carimune NF 12 GM SOLR (CSL BEHRING)

61953-0004-xx Flebogamma DIF 0.5 GM/10ML SOLN (GRIFOLS USA) (0.5 GM, 2.5 GM, 5 GM, 10 GM and 20 GM vials)

61953-0005-xx Flebogamma DIF 5 GM/50ML SOLN (GRIFOLS USA) (5 GM, 10 GM and 20 GM vials)

00944-2700-02 Gammagard 1 GM/10ML SOLN (BAXALTA) (1 GM, 2.5 GM, 5 GM, 10 GM, 20 GM and 30 GM vials)

00944-2656-xx Gammagard S/D Less IgA 5 GM SOLR (BAXALTA)

00944-2658-xx Gammagard S/D Less IgA 10 GM SOLR (BAXALTA)

76125-0900-01 Gammaked 1 GM/10ML SOLN (KEDRION BIOPHARMA)(1 GM, 2.5 GM, 5 GM, 10 GM and 20 GM vials)

64208-8234-xx Gammaplex 5 GM/100ML SOLN (5 GM, 10 GM and 20 GM vials)

64208-8235-xx Gammaplex 5 GM/50ML SOLN (5 GM, 10 GM and 20 GM vials)

13533-0800-xx Gamunex-C 1 GM/10ML SOLN (GRIFOLS USA)

DESCRIPTION

Immune globulins or immunoglobulins (Ig) are specialized glycoproteins which function in the body as antibodies in the immune system.  Produced by plasma cells, there are five human isotypes of immunoglobulins, IgA, IgD, IgE, IgG and IgM.  Of these, IgG, IgA and IgM are referred to as natural antibodies as they are produced without deliberate immunization or antigen exposure.  IgD and IgE are generally produced in response to the introduction of foreign antigens to which they bind and deactivate.  Together, all immunoglobulin isotypes are vital components of the body’s immune response.

IgG is the most common of the immunoglobulins.  It has multiple functions including placental antibody transfer, phagocytic cell surface binding and the activation of complement.  Commercial preparations of intravenous immune globulins (IVIGs) are sterile, highly purified IgG products manufactured from large pools of human plasma, typically from 1000 or more healthy blood donors.  They contain more than 95% unmodified IgG but only trace amounts of IgA and/or IgM.  IVIG products are used in the treatment of multiple conditions.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

RENEWAL CRITERIA

 

Dosing Recommendations:

 

 

  • Patient’s dose should be reduced to the lowest necessary to maintain benefit for their condition.  Patients who are stable, or who have reached the maximum therapeutic response, should have a trial of dose reduction (e.g., 25-50% reduction in dose every 3 months)

  • Patients who have tolerated dose reduction and continue to show sustained improvement should have had a trial of treatment discontinuation; with the following exceptions:

    • PID would be excluded from a trial of discontinuation

    • HIV-infected children should show satisfactory control of the underlying disease [e.g., undetectable viral load, CD4 counts elevated above 200 or >15% (ages 9 months – 5 years) on antiretroviral therapy, etc.]

    • Solid organ transplant, CLL, and MM patients should not be at an increased risk of infection

 

Dosing should be calculated using adjusted body weight if one or more of the following criteria are met:

This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide. Patient-specific variables should be taken into account. 

INDICATION(S)

DOSAGE & ADMINISTRATION

PID

200 to 800 mg/kg every 21 to 28 days

CIDP

2 g/kg divided over 2-5 days initially, then 1 g/kg administered in 1-2 infusions every 21 days

ITP

2 g/kg divided over 5 days or 1 g/kg once daily for 2 consecutive days in a 28-day cycle

FAIT

1 g/kg/week until delivery

Kawasaki’s Disease (Pediatric Patients)

1 g/kg to 2 g/kg x 1 course

Multifocal Motor Neuropathy

Up to 2 g/kg divided over 5 days in a 28-day cycle

Acquired immune deficiency: CLL, MM and ALL

400 mg/kg every 3 to 4 weeks

Pediatric HIV

400 mg/kg every 2 to 4 weeks

Guillain-Barre

2 g/kg divided over 5 days x 1 course

Myasthenia Gravis

1-2 g/kg divided as either 0.5 g/kg daily x 2 days or 0.4 g/kg daily x 5 days x 1 course

Auto-immune blistering diseases

Up to 2 g/kg divided over 5 days in a 28-day cycle

Dermatomyositis/Polymyositis

2 g/kg divided over 2 to 5 days in a 28-day cycle

Bone Marrow or Stem Cell Transplant

500 mg/kg once weekly x 90 days, then 500 mg/kg every 3 to 4 weeks

Complications of transplanted solid organ: (kidney, liver, lung, heart, pancreas) transplant

2 g/kg divided over 5 days in a 28-day cycle

Stiff Person

2 g/kg divided over 5 days in a 28-day cycle

Toxic shock syndrome

2 g/kg divided over 5 days x 1 course

Neonatal Alloimmune Thrombocytopenia

1 g/kg x 1 dose, may be repeated once if needed

Management of Immune Checkpoint Inhibitor Related Toxicity

2 g/kg divided over 5 days x 1 course

*Dosing for IVIG is highly variable depending on numerous patient specific factors, indication(s), and the specific product selected. For specific dosing regimens refer to current prescribing literature.

LENGTH OF AUTHORIZATION

Initial and renewal authorization periods vary by specific covered indication.

Unless otherwise specified, the initial authorization will be provided for 6 months and may be renewed.

Refer to DOSAGE LIMITS below

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

*For Reference Use Only

Brand Name/ Formulation

FDA Indication

Contraindications

Product Specs

Comments

Asceniv

PID (≥12yo)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: ≤200 mcg/mL

Osmolality: N/A

Stabilizer: Glycine

Other stabilizer used is Polysorbate 80

Bivigam (liquid)

PID (peds ≥6)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: ≤200 mcg/mL

Osmolarity: 510 mOsm/kg

Stabilizer: glycine

 

Carimune NF (lyophilized)

PID

(peds/adults) a/cITP

(peds/adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: 1000-2000 mcg/mL (6% soln)

Osmolarity: 192 to 1074 mOsm/kg (depends on diluent and final conc)

Stabilizer: sucrose

1.67 gm of sugar per gm of protein

 

Flebogamma 5% (liquid)

PID (peds ≥2)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: <50 mcg/mL

Osmolarity: 240 to 370 mOsm/kg

Stabilizer: sorbitol

 

Flebogamma 10% (liquid)

PID (peds ≥2) ITP (peds ≥2)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: <32 mcg/mL

Osmolarity: 240 to 370 mOsm/L

Stabilizer: sorbitol

 

Gammagard (liquid)

PID (peds ≥2) MMN (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: 37 mcg/mL

Osmolality: 240 to 300 mOsm/kg

Stabilizer: glycine

May be used SC (see policy for criteria

Gammagard S/D (lyophilized)

PID ITP CLL

Kawasaki (adults/peds for all indx)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: <1 mcg/mL (5% solution)

Osmolality: 636 mOsm/L (5% soln)

Stabilizer: glycine

Contains some sugar (20mg/mL when prepared)

Gammaked (liquid)

PID (peds ≥2) ITP

(peds/adults) CIDP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: 46 mcg/mL

Osmolality: 258 mOsm/kg

Stabilizer: glycine

May be used SC (see policy for criteria

Gammaplex

5% (liquid)

PID (peds ≥2)

cITP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

Fructose intolerance

IgA: <10 mcg/mL

Osmolality: 420 to 500 mOsm/kg

Stabilizer: glycine

Other stabilizer used is

Polysorbate 80

Gammaplex 10% (liquid)

PID (adults) cITP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: <20 mcg/mL

Osmolality: 280 mOsm/kg

Stabilizer: glycine

Other stabilizer used is Polysorbate 80

Gamunex-C (liquid)

PID (peds ≥2) ITP

(peds/adults) CIDP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: 46 mcg/mL

Osmolality: 258 mOsm/kg

Stabilizer: glycine

May be used SC (see policy for criteria

Octagam 5% (liquid)

PID (peds≥6)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

Corn allergy

IgA: ≤200 mcg/mL

Osmolality: 310 to 380 mOsm/kg

Stabilizer: maltose

 

Octagam 10% (liquid)

ITP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: 106 mcg/mL

Osmolality: 310 to 390 mOsm/kg

Stabilizer: maltose

 

Privigen

(liquid)

PID

cITP (ped ≥15) CIDP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

Hyperprolinemia

IgA: ≤25 mcg/mL

Osmolality: 320 mOsm/kg

Stabilizer: L-proline

 

Panzyga

PID (peds ≥2) cITP (adults)

History of anaphylaxis to IgG

IgA-deficient with IgA antibodies

IgA: ≤100 mcg/mL

Osmolality: 240-310 mOsm/kg

Stabilizer: Glycine

 

  • All intravenous immunoglobulins are derived from human plasma.

  • Products with higher IgA content pose a greater risk for anaphylactic reactions, especially in patients with IgA deficiencies.

  • All products may predispose patients to nephrotoxicity especially those with sugar-based or proline-based stabilizers. To lower risks, lower concentration products and infusions rates should be used as well as

  • using products with osmolality/osmolarity that is near physiologic range (around 300 mOsm/kg or mOsm/L).

  • Premedications (e.g., acetaminophen, antihistamine, etc) are recommended to reduce the risk of infusion related reactions.

Adapted from: Professional Resource, Comparison of IVIG Products. Pharmacist’s Letter/Prescriber’s Letter. December 2016.

SOURCES

Attarian, S., Boucraut, J., Uzenot, D., Delmont, E., Verschueren, A., Franques, J., et al. (2010). Chronic ataxic neuropathies associated with antii-GD1b IgM antibodies: response to IVIG therapy. The Journal of Neurology, Neurosurgery and Psychiatry, 81: 61-64.

Bhatti, A., Gazali, Z. (2015, December). Recent advances and review on treatment of stiff person syndrome in adults and pediatric patients. Cureus, 7(12): e427. DOI 10.7759.

BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2017). Immune globulin therapy (8.01.05). Retrieved September 26, 2018 from BlueWeb.

Lexicomp Online. (2018, February). AHFS DI. Immune Globulin. Retrieved May 7, 2019 from Lexicomp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2018, September). Immune globulin. Retrieved May 7, 2019 from MICROMEDEX Healthcare Series.

National Organization for Rare Disorders (NORD). (2010). Stiff person syndrome. Retrieved June 3, 2016 from http://rarediseases.org/rare-diseases/stiff-person-syndrome/.

U. S. Food and Drug Administration. (2019, April). Center for Biologics Evaluation and Research. Immune globulin intravenous (human-sira), 10% liquid, AscenivTM. Retrieved May 7, 2019 from https://www.fda.gov/media/122525/download 

U. S. Food and Drug Administration.  (2012, June). Center for Biologics Evaluation and Research. Gammagard® liquid, immune globulin infusion (human), 10% Solution, for intravenous and subcutaneous administration. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM070010.pdf.

U. S. Food and Drug Administration.  (2014, XX). Center for Biologics Evaluation and Research.   Gammagard® S/D immune globulin intravenous (human). Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM197905.pdf.

U. S. Food and Drug Administration. (2017, September). Center for Biologics Evaluation and Research. Privigen®, immune globulin intravenous (human), 10% liquid. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM303092.pdf.

U. S. Food and Drug Administration. (2015, December). Center for Biologics Evaluation and Research. Gamunex®-C, [Immune Globulin Injection (Human). Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM069968.pdf.

U. S. Food and Drug Administration. (2015, July). Center for Biologics Evaluation and Research. Gammaplex® immune globulin intravenous (human), 5% liquid. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM182963.pdf.

U. S. Food and Drug Administration. (2017, February). Center for Biologics Evaluation and Research. Gammaplex® immune globulin intravenous (human), 10% liquid. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM182963.pdf.

U. S. Food and Drug Administration. (2014, August). Center for Biologics Evaluation and Research. Flebogamma® 5% DIF (immune globulin intravenous [human]), solution for intravenous administration. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM172599.pdf.

U. S. Food and Drug Administration. (2016, January). Center for Biologics Evaluation and Research. Flebogamma® 10% DIF [immune globulin intravenous (human)] for intravenous administration, 10% liquid preparation. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM296138.pdf.

U. S. Food and Drug Administration. (2013, September). Center for Biologics Evaluation and Research. Carimune® NF, nanofiltered: immune globulin intravenous (human). Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/UCM152763.pdf.

U. S. Food and Drug Administration. (2013, June). Center for Biologics Evaluation and Research. Immune globulin intravenous (human), 10% liquid, Bivigam®. Retrieved May 7, 2019 from http://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm334609.pdf.

U. S. Food and Drug Administration. (2014, July). Center for Biologics Evaluation and Research. Octagam® 10% [immune globulin intravenous (human)] liquid solution for intravenous administration. Retrieved May 7, 2019 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM064946.pdf.

U. S. Food and Drug Administration. (2018, August). Center for Biologics Evaluation and Research. Panzyga®, (immune globulin intravenous, human - ifas) 10% Liquid Preparation Retrieved May 7, 2019 from http://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/UCM615706.pdf.

Van Winkle P, Burchette R, Kim R, et al. Prevalence and Safety of Intravenous Immunoglobulin Administration During Maintenance Chemotherapy in Children with Acute Lymphoblastic Leukemia in First Complete Remission: A Health Maintenance Organization Perspective. Perm J. 2018; 22: 17-141.

ORIGINAL EFFECTIVE DATE: 12/4/97

MOST RECENT REVIEW DATE:  9/30/2019

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information.

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DOSAGE LIMITS

Maximum billable units per dose and over time by indication as a Medical Benefit

DIAGNOSIS

BILLABLE UNITS

MAXIMUM UNITS

Per # days

(unless otherwise specified)

PID

184

21

CIPD

Load:460

4

Maintenance:230

 21

Immune thrombocytopenia/ITP

460

28

FAIT

200

7

Kawasaki’s Disease (Pediatric Patients only)

232

1 dose only

Multifocal Motor Neuropathy

460

28

CLL/MM

92

21

ALL

92

21

HIV (Pediatric Patients only)

47

28

Guillain-Barre

460

5 (for one cycle only)

Myasthenia Gravis

460

28

Auto-immune blistering diseases

460

28

Bone Marrow or Stem Cell Transplant

115

7

Dermatomyositis/Polymyositis

460

28

Complications of transplanted solid organ

(kidney, liver, lung, heart and pancreas transplants)

460

28

Stiff Person

460

28

Toxic shock syndrome

460

5 (for one cycle only)

NAIT

16

2 doses only

Management of Immune Checkpoint Inhibitor Related Toxicity

460

5 (for one cycle only)