BlueCross BlueShield of Tennessee Medical Policy Manual

Subcutaneous Immune Globulins

NDC CODE(S)

44206-0451-XX  Hizentra 1 GM/5 ML SOLN (CSL BEHRING AG)

44206-0452-XX  Hizentra 2 GM/10 ML SOLN (CSL BEHRING)

44206-0454-XX  Hizentra 4 GM/20 ML SOLN (CSL BEHRING)

44206-0455-XX  Hizentra 10 GM/50 ML SOLN (CSL BEHRING)

76125-0900-XX  Gammaked 1 GM/10 ML SOLN (KEDRION BIOPHARMA)

76125-0900-XX  Gammaked 2.5 GM/25 ML SOLN (KEDRION BIOPHARMA)

76125-0900-XX  Gammaked 5 GM/50 ML SOLN (KEDRION BIOPHARMA)

76125-0900-XX  Gammaked 10 GM/100 ML SOLN (KEDRION BIOPHARMA)

76125-0900-XX  Gammaked 20 GM/200 ML SOLN (KEDRION BIOPHARMA)

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

13533-0800-XX  Gamunex-C 2.5 GM/25 ML SOLN (GRIFOLS USA)

13533-0800-XX  Gamunex-C 5 GM/50 ML SOLN (GRIFOLS USA)

13533-0800-XX  Gamunex-C 10 GM/100 ML SOLN (GRIFOLS USA)

13533-0800-XX  Gamunex-C 20 GM/200 ML SOLN (GRIFOLS USA)

13533-0800-XX  Gamunex-C 40 GM/400 ML SOLN (GRIFOLS USA)

00944-2700-XX  Gammagard 1 GM/10 ML (BAXALTA)

00944-2700-XX  Gammagard 2.5 GM/25 ML (BAXALTA)

00944-2700-XX  Gammagard 5 GM/50 ML (BAXALTA)

00944-2700-XX  Gammagard 10 GM/100ML SOLN (BAXALTA)

00944-2700-XX  Gammagard 20 GM/200 ML SOLN (BAXALTA)

00944-2700-XX  Gammagard 30 GM/300 ML (BAXALTA)

00944-2700-XX  Gammagard LIQUID 10% VIAL (BAXALTA USA INC)

00944-2510-XX  Hyqvia 2.5 GM/25 ML KIT (BAXALTA)

00944-2511-XX  Hyqvia 5 GM/50 ML KIT (BAXALTA)

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 generally considered to be 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 produced in response to the introduction of specific 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 immune globulins.  It has multiple functions including placental antibody transfer, phagocytic cell surface binding and the activation of complement.  Commercial preparations of immune globulins 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. Immune globulins are utilized in the treatment of various conditions.  Various immune globulins are commercially available preparations and labelled information must be specific for administration intravenously (IV), intramuscularly (IM) or subcutaneously (SQ).

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

** Initial IVIG criteria:  (Reference Use Only)

  • Patient’s disease course is progressive or relapsing and remitting for 2 months or longer;  AND

  • Patient has abnormal or absent deep tendon reflexes in upper or lower limbs; AND

  • Electrodiagnostic testing indicating demyelination:

    • Partial motor conduction block in at least two motor nerves or in 1 nerve plus one other  demyelination criterion listed here in at least 1 other nerve; OR

    • Distal CMAP duration increase in at least 1 nerve plus one other demyelination criterion listed here in at least 1 other nerve; OR

    • Abnormal temporal dispersion conduction must be present in at least 2 motor nerves; OR

    • Reduced conduction velocity in at least 2 motor nerves; OR

    • Prolonged distal motor latency in at least 2 motor nerves; OR

    • Absent F wave in at least two motor nerves plus one other demyelination criterion listed here in  at least 1 other nerve; OR

    • Prolonged F wave latency in at least 2 motor nerves; AND

  • Cerebrospinal fluid analysis indicates the following:

    • CSF white cell count of <10 cells/mm3; AND

    • CSF protein is elevated; AND

  • Patient is refractory or intolerant to corticosteroids (e.g., prednisolone, prednisone, etc.) given in therapeutic doses over at least three months; AND

  • Baseline in strength/weakness has been documented using an objective clinical measuring tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.)

RENEWAL CRITERIA

DOSAGE & ADMINISTRATION

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

Use the following dosing formulas to calculate the adjusted body weight (round dose to nearest 5 gram increment in adult patients):

Dosing formulas

BMI = 703 x (weight in pounds/height in inches2)

IBW (kg) for males = 50 + [2.3 (height in inches - 60)]

IBW (kg) for females = 45.5 + [2.3 x (height in inches - 60)]

Adjusted body weight = IBW + 0.5 (actual body weight - IBW)

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

Chronic Inflammatory Demyelinating Polyneuropathy

Hizentra ONLY:

  • Initiate therapy 1 week after the last IVIG dose

  • The recommended subcutaneous dose is 0.2 g/kg (1 mL/kg) body weight per week, administered in 1 or 2 sessions over 1 or 2 consecutive days.

  • If CIDP symptoms worsen, consider re-initiating treatment with an IVIG while discontinuing Hizentra.

    • If improvement and stabilization are observed during IVIG treatment, consider reinitiating Hizentra at the dose of 0.4 g/kg body weight per week, administered in 2 sessions per week over 1 or 2 consecutive days, while discontinuing IVIG.

    • If CIDP symptoms worsen on the 0.4 g/kg body weight per week dose, consider reinitiating therapy with an IVIG while discontinuing Hizentra.

Primary immune deficiency including Wiskott-Aldrich Syndrome

Hizentra:

  • Weekly dose: 1.37*(previous IVIG dose(g)/number of weeks between IVIG doses)

  • Biweekly dose: twice the weekly dose (using calculation above)

Gamunex-C/Gammaked/Gammagard Liquid:

  • Weekly dose: 1.37*(previous IVIG dose(g)/number of weeks between IVIG doses)

HyQvia:

  • Naïve to IgG or switching from SCIG: 300 to 600 mg/kg at 3 to 4 week intervals after initial ramp-up*

  • Switching from IGIV: use the same dose and frequency as the previous IV treatment after initial ramp-up*

Cuvitru:

  • Switching from IVIG or HyQvia:

    • Weekly dose: 1.30*(previous IVIG or HyQvia dose (g)/number of weeks between IVIG or HyQvia doses)

    • May be administered from daily up to every two weeks (biweekly)

    • Biweekly dose: twice the weekly dose (using calculation above)

    • Frequent dosing (2-7 times per week): divide the calculated weekly dose by the desired number of times per week

  • Switching from SCIG

    • Weekly dose (in grams) should be same as the weekly dose of prior SCIG treatment (in grams)

    • Biweekly dose: multiply the calculated weekly dose by 2

    • Frequent dosing (2-7 times per week): divide the calculated weekly dose by the desired number of times per week

Dosing for immunoglobulin products 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.

*HyQvia initial treatment interval/dosage ramp-up schedule:

Week

Infusion Number

3-week treatment interval

4-week treatment interval

1

1st infusion

Dose in Grams X 0.33

Dose in Grams X 0.25

2

2nd infusion

Dose in Grams X 0.67

Dose in Grams X 0.50

4

3rd infusion

Total Dose in grams

Dose in Grams X 0.75

7

4th infusion

N/A

Total Dose in grams

LENGTH OF AUTHORIZATION

Initial coverage will be provided for 6 months and may be renewed annually thereafter.

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).

SOURCES 

BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2017). Immune globulin therapy (8.01.05). Retrieved April 27, 2018 from BlueWeb.

Lexi-Comp Online. (2018, February). AHFS DI. Immune globulin. Retrieved April 27, 2018 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2018, March). Immune globulin. Retrieved April 27, 2018 from MICROMEDEX Healthcare Series.

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 April  27, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM070010.pdf.

U. S. Food and Drug Administration. (2014, September). Center for Biologics Evaluation and Research. HyQvia®[immune globulin infusion 10% (human) with recombinant human hyaluronidase] solution for subcutaneous administration. Retrieved April 27,2018 fromhttp://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM414440.pdf.

U. S. Food and Drug Administration. (2015, December) Center for Biologics Evaluation and Research.Gamunex®-C. [Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified]. Retrieved April 27, 2018 from http://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm069968.pdf.

U. S. Food and Drug Administration. (2016, September). Center for Biologics Evaluation and Research. Cuvitru®, immune globulin subcutaneous (human), 20% solution. Retrieved April 27, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM520587.pdf.

U. S. Food and Drug Administration. (2018, March). Center for Biologics Evaluation and Research.  Hizentra®, immune globulin subcutaneous (human), 20% liquid.  Retrieved April 27, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM203150.pdf.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:  8/14/2018

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.

 

 

DOSAGE LIMITS

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

Drug Name

Billable units/28 days

Hizentra

960 (PID)

1840 (CIDP)

Gamunex-C & Gammaked

192

Gammagard liquid

192

HyQvia

690

Cuvitru

920