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

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._

**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. BivigamTM [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. GammakedTM [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. AscenivTM 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.