Billing and Coding: Off-Label Use of Intravenous Immune Globulin (IVIG)

Language quoted from Centers for Medicare and Medicaid Services (CMS), National Coverage Determinations (NCDs) and coverage provisions in interpretive manuals is italicized throughout the policy. NCDs and coverage provisions in interpretive manuals are not subject to the LCD Review Process (42 CFR 405.860[b] and 42 CFR 426 [Subpart D]). In addition, an administrative law judge may not review an NCD. See Section 1869(f)(1)(A)(i) of the Social Security Act.

Unless otherwise specified, italicized text represents quotation from one or more of the following CMS sources:

Title XVIII of the Social Security Act (SSA):

Section 1862(a)(1)(A) excludes expenses incurred for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Section 1833(e) prohibits Medicare payment for any claim which lacks the necessary information to process the claim.

CMS Publications

CMS Publication Pub 100-02, Medicare Benefit Policy Manual, Chapter 15:

50 - Drugs and Biologicals

50.4.5 - Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen

CMS Publication 100-04, Medicare Claims Processing Manual, Chapter 17:

10 - Payment Rules for Drugs and Biologicals

This article contains coding or other guidelines that complement the local coverage determination (LCD) for Off-Label Use of Intravenous Immune Globulin (IVIG). The use of IVIG for labeled indications is not addressed in this article.

The LCD and this article address off-label uses for IVIG. We define off-label as not in Medicare approved compendia or in the FDA label. However, for the convenience of providers, we have added a list of labeled and compendia approved diagnoses in the Group 2 section for ICD-10-CM Codes that Support Medical Necessity below.

Coding Information:

Procedure codes may be subject to National Correct Coding Initiative (NCCI) edits or OPPS packaging edits. Refer to NCCI and OPPS requirements prior to billing Medicare.

For services requiring a referring/ordering physician, the name and NPI of the referring/ordering physician must be reported on the claim.

A claim submitted without a valid ICD-10-CM diagnosis code will be returned to the provider as an incomplete claim under Section 1833(e) of the Social Security Act.

The diagnosis code(s) must best describe the patient's condition for which the service was performed.

Specific coding guidelines for this policy:

When administering IVIG to patients over continuous days, providers should report each day’s dosage on a separate line of coding, using the appropriate date of service with the units reported in the NOS field of the claim form.

When separately identifiable evaluation and management services are provided and documented on the same day as intravenous administration, they may be billed using modifier 25.

For claims submitted to the Part B MAC:

All services/procedures performed on the same day for the same beneficiary by the physician/provider should be billed on the same claim. 

Utilization:

The dose and frequency of administration should be consistent with the FDA approved package insert. When dose and/or frequency are different from the FDA approved package insert, literature support for the specific schedule chosen should be available.

Claims submitted for procedures performed at unusually frequent intervals or high dosages may be reviewed for medical necessity. If coverage of IVIG is denied, the administration and pre-administration services associated with IVIG will also be denied.

Documentation Requirements:

Medical record documentation maintained by the treating physician must clearly document the medical necessity to initiate intravenous immune globulin therapy and the continued need thereof. Required documentation of medical necessity should include:

• history and physical;
• office/progress notes(s);
• test results with written interpretation;
• accurate weight in kilograms should be documented prior to the infusion, since the dosage is based on a mg/kg dosage;
• documentation of prior treatment therapies (where appropriate or referenced by this policy);
• evidence of blood level results demonstrating a significant deficiency in gammaglobulin levels prior to initial treatment (where appropriate or referenced by this policy);
• history of recurrent and severe infections;
• current effectiveness of IVIG therapy; and
• goals and/or treatment plan

Diagnostic testing appropriate for the condition under treatment should be documented, and this may include nerve conduction study (NCS), electromyography (EMG), cerebral spinal fluid (CSF), serum immunoprotein, or biopsy (muscle-nerve). The reason for choosing IVIG as a treatment must be well supported on review of records. Previous treatment failures with alternative agents should be documented.

When used for neuromuscular disorders, when there is improvement and continued treatment is necessary, then quantitative assessment to monitor progress is required. Quantitative monitoring may use any accepted measure, such as medical research council (MRC) scale and activities of daily living (ADL) measurements. Changes in these measures must be clearly documented. Subjective or experiential improvement alone is insufficient to support continued use of IVIG.

When used for chronic neuromuscular or immunologic conditions, there should be an attempt made to wean the dosage when improvement has occurred and an attempt to discontinue IVIG infusion when improvement is sustained with dosage reduction. In addition, when improvement does not occur with IVIG, then continued infusion would not be considered reasonable or necessary.

When used for recurrent severe infection and documented severe deficiency or absence of IgG subclass deficiency, a serum IgG subclass trough level should be monitored at least every three months prior to the dose of intravenous immune globulin, along with clinical progress of signs and symptoms for which intravenous immune globulin therapy is required.

When used for clinically significant functional deficiency of humoral immunity as evidenced by documented failure to produce antibodies to specific antigens and a history of recurrent infections, the deficient antibody(ies) should be monitored at least every 3 months, prior to the dose of intravenous immune globulin, along with clinical progress of signs and symptoms for which intravenous immune globulin therapy is required.

When used for the treatment of autoimmune mucocutaneous blistering disease please refer to CMS Publication 100-03, Medicare National Coverage Decisions Manual, Chapter 1, Section 250.3.

When used for bone marrow/stem cell transplantation, a) the recipient was seropositive for cytomegalovirus (CMV) before transplantation or b) after allogeneic transplantation for hematologic neoplasm when the donor(s) and recipient were seronegative.

When used for solid organ transplantation, the donor was seropositive and the recipient was seronegative for cytomegalovirus (CMV) before transplantation.

Documentation must be available to Medicare upon request.

FDA and Compendia Review:

American Society of Health-System Pharmacists, Inc. AHFS Drug Information®. Bethesda, MD:2007

Clinical Pharmacology Web site. http://www.clinicalpharmacology.com/. Accessed 04/22/2022.

FDA label information:

1. Bivigam™ [Product Information]. Boca Raton, FL. Biotest Pharmaceuticals Corporation. September 23, 2013. Available at: Bivigam-FDA. Accessed on May 17, 2019.
2. Flebogamma 5% DIF® [Product Information]. Los Angeles, CA. Grifols Biologicals, Inc. September 23, 2013. Available at: Flebogamma-FDA . Accessed on May 17, 2019.
3. Gammagard Liquid® [Product Information]. Westlake Village, CA. Baxter Healthcare Corporation. September 23, 2013. Available at: Gammagard Liquid-FDA . Accessed on May 17, 2019.
4. Gammaked™ [Product Information]. Research Triangle Park, NC. Talecris Biotherapeutics, Inc. September 2013. Available at: http://www.gammaked.com/filebin/pdf/2013-09-gammaked.pdf. Accessed on May 17, 2019.
5. Gammaplex® [Product Information]. Temecula, CA. FFF Enterprises, Inc. September 23, 2013. Available at: Gammaplex-FDA . Accessed on May 17, 2019.
6. Gamunex-C® [Product Information]. Research Triangle Park, NC. Talecris Biotherapeutics, Inc. September 23, 2013. Available at: Gamunex-C-FDA . Accessed on May 17, 2019.
7. Octagam® [Product Information]. Centreville, VA. Octapharma USA, Inc. July 11, 2014. Available at: Octagam-FDA . Accessed on May 17, 2019.
8. Privigen® [Product Information]. Kankakee, IL. CSL Behring, LLC. September 23, 2013. Available at: Privigen-FDA . Accessed on May 17, 2019
9. Asceniv™ Available at: Asceniv-FDA . Accessed on December 12/09/2020.

Lexi-Drugs Web site. http://online.lexi.com/lco/action/home. Accessed 04/22/2022.

Micromedex DrugDex® Thomson Web site. http://www.thomsonhc.com/home/dispatch. Accessed 04/22/2022.

National Comprehensive Cancer Network Web site. http://www.nccn.org/index.asp. Accessed 04/22/2022.

U.S. Food and Drug Administration label accessed on line at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ on 07/11/2007.