Prior Auth Protocol

FDA Approved Indications:

For immune globulin intravenous (IVIG) (including Gamunex-C, Gammaked and Gammagard when used intravenously)

Replacement therapy for primary immunodeficiency (PI) This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
Treatment of patients with idiopathic thrombocytopenic purpura (ITP) to raise platelet counts to prevent bleeding or to allow a patient with ITP to undergo surgery.
Maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN).
Prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia (CLL).
Prevention of coronary artery aneurysms associated with Kawasaki syndrome.
Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.

For immune globulin subcutaneous (including Gamunex-C, Gammaked, Gammagard Liquid, Hizentra, and Hyqvia when used subcutaneously)

Treatment of/replacement therapy for patients with primary immunodeficiency (PI). This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of Primary Immunodeficiencies (PI), including subclass deficiencies or functional antibody deficiencies including any of the following:
- Selective IgA Immunodeficiency
- Selective IgM Immunodeficiency
- Selective IgG subclass deficiency
- Congenital hypogammaglobulinemia
- Immunodeficiency with near/normal IgM (absent IgG, IgA) - a.k.a. Hyper IgM syndrome
- Severe combined immunodeficiency disorders (e.g., X-SCID, jak3, ZAP70, ADA, PNP, RAG defects, Ataxia Telangiectasia, Wiskott-Aldrich syndrome, DiGeorge syndrome)
- Subclass Deficiency or Functional Antibody Deficiency (see General Information)

AND

Hypogammaglobulinemia (below normal for age)

AND

Patient has one documented, very serious, laboratory-proven bacterial infection within the preceding 6 months

OR

Patient has had two or more bacterial infections in the preceding year requiring IV antibiotic infusion therapy in the home or in the hospital

OR

Diagnosis of Severe Combined Immunodeficiency (SCID)

OR

Diagnosis of Common variable immunodeficiency (CVID)

AND

Laboratory reports demonstrating a IgG levels below normal for age or normal total IgG with low subclass IgG (see general info)

OR

Laboratory reports demonstrating a lack of ability to produce or sustain an antibody response to protein or carbohydrate antigens (e.g., tetanus, pneumococcal capsular polysaccharides such as pneumovax)

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature
A list of specific indications for which coverage is not authorized may be found in the PA guideline: Immune Globulin Conditions Not Medically Necessary - NATL.
Initiation or continuation of IVIG therapy for patients with mild sinopulmonary disease. Some examples of severe sinopulmonary diseases include bronchitis, pneumonia, or bronchiectasis.
Patients with normal humoral immunity but recurrent infections, particularly upper respiratory infections.
Secondary immunodeficiency states - correction of the underlying condition is the preferred approach.

General Information:

Common variable immunodeficiency (CVID), the most frequently diagnosed primary immunodeficiency, is characterized by a low serum IgG level antibody deficiency at least 2 SDs below the mean for age, with most patients having concurrent deficiencies of IgA and IgM. Many Patients with CVID have IgG levels below 639 that require IVIG. However, there are rare instances when a patient will have normal IgG levels. The serum immunoglobulin measurement alone does not establish a diagnosis of CVID. A definitive diagnosis of CVID is established when a patient does not demonstrate a prolonged antibody response to immunization with protein antigens (e.g., tetanus) or carbohydrate antigens (e.g., pneumococcal capsular polysaccharides such as pneumovax).
The gamma globulin band consists of 5 immunoglobulins: about 80% immunoglobulin G (IgG), 15% immunoglobulin A (IgA), 5% immunoglobulin M (IgM), 0.2% immunoglobulin D (IgD), and a trace of immunoglobulin E (IgE).
The use of intravenous immune globulin should be reserved for patients with serious defects of antibody function. All immune deficiency conditions require ongoing monitoring of the patients clinical condition with measurement of pre-infusion (trough) serum IgG levels.
For lifelong treatment serum trough IgG levels should be measured before the infusion, then monitored every 3 months to maintain low normal level (usually 400 600 mg/dl).
Black Box Warning: Thrombosis, renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur.
The Mayo Clinic suggests the following reference ranges of immune gluobulins:

Age	IgG	IgA	IgM
0-<5 months:	100-334 mg/dL	7-37 mg/dL	26-122 mg/dL
5-<9 months:	164-588 mg/dL	16-50 mg/dL	32-132 mg/dL
9-<15 months:	246-904 mg/dL	27-66 mg/dL	40-143 mg/dL
15-<24 months:	313-1,170 mg/dL	36-79 mg/dL	46-152 mg/dL
2-<4 years:	295-1,156 mg/dL	27-246 mg/dL	37-184 mg/dL
4-<7 years:	386-1,470 mg/dL	29-256 mg/dL	37-224 mg/dL
7-<10 years:	462-1,682 mg/dL	34-274 mg/dL	38-251 mg/dL
10-<13 years:	503-1,719 mg/dL	42-295 mg/dL	41-255 mg/dL
13-<16 years:	509-1,580 mg/dL	52-319 mg/dL	45-244 mg/dL
16-<18 years:	487-1,327 mg/dL	60-337 mg/dL	49-201 mg/dL
> or =18 years:	767-1,590 mg/dL	61-356 mg/dL	37-286 mg/d

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
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* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
(IVIG) Bivigam, Gammaplex	Adult: 300 to 800 mg/kg body weight given every 3 to 4 weeks	6 months or to member's renewal period, whichever is sooner
(IGSC) Gammaked, Gamunex-C, Gammagard	Initial weekly subcutaneous dose can be calculated by multiplying the previous IVIG dose by 1.37, and then dividing this dose into weekly doses based on the patient's previous IVIG treatment interval. Gammagard is approved for ages 2 and over but does not give specific dosing recommendations.	6 months or to member's renewal period, whichever is sooner
(IGSC) Hizentra	Administer SC at regular intervals from daily up to every two weeks (biweekly). To calculate the initial weekly dose of Hizentra, multiply the previous IVIG dose in grams by the dose adjustment factor of 1.37; then divide this by the number of weeks between doses during the patient`s IVIG treatment (i.e., 3 or 4). Weekly Dosing: Administer calculated weekly dose starting 1 week after the last IVIG infusion Biweekly Dosing: Administer twice the calculated weekly dose starting 1 or 2 weeks after the last IVIG infusion or 1 week after the last IGSC infusion. Frequent Dosing (2 to 7 times per week): Divide the calculated weekly dose by the desired number of times per week. Start Hizentra 1 week after the last IVIG or IGSC infusion. To convert the Hizentra dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 5.	6 months or to member's renewal period, whichever is sooner
(IGSC) HyQvia	Infuse the two components of HyQvia sequentially, beginning with the recombinant human hyaluronidase. Initiate the IGSC within 10 minutes of the recombinant human hyaluronidase infusion. Initiation of treatment: Increase dose and frequency from a 1-week dose to a 3- or 4-week dose (see ramp-up schedule below) For patients previously on another IG treatment, administer the first dose of HyQvia approximately one week after the last infusion of their previous treatment Initial dosage ramp-up schedule (e.g., every 4-week dosing): Week 1: [1-week dose interval] 1/4 of target dose Week 2: [2-week dose interval] 1/2 of target dose Week 3: no infusion Week 4: [3-week dose interval] 3/4 of target dose Week 5: no infusion Week 6: no infusion Week 7: [4-week dose interval] target dose, repeat every 4 weeks Switching from IGIV: Administer at the same dose and frequency as the previous intravenous treatment, after the initial dose ramp-up Naive to IG treatment or switching from IGSC: 300 to 600 mg/kg at 3 to 4 week intervals, after initial ramp-up Dose adjustments: See details in prescribing information	6 months or to member's renewal period, whichever is sooner
(IVIG) Flebogamma,Gammagard, Gammagard S/D, Gammaked, Gamunex-C, Octagam	Adult: 300 to 600 mg/kg of body weight given every 3 to 4 weeks Gammagard and Gammagard S/D are approved for ages 2 and over but does not give specific dosing recommendations	6 months or to member's renewal period, whichever is sooner
(IVIG) Cariumune NF	Adult: 400 to 800 mg/kg of body weight given every 3 to 4 weeks	6 months or to member's renewal period, whichever is sooner
(IVIG) Privigen	Adult: 200 to 800 mg/kg of body weight given every 3 to 4 weeks	6 months or to member's renewal period, whichever is sooner

Product Availability:

Intravenous Immunoglobulin

Bivigam: 10% (1 g/10 mL) in 50 mL, 100 mL vials

Carimune NF powder for injection: 3 g, 6 g, 12 g bottles

Flebogamma DIF: 5% (50 mg/mL) in 10 mL, 50 mL, 100 mL, 200 mL, 400 mL vials; 10% (5 g/50 mL) in 50 mL, 100 mL, 200 mL vials

Gammagard: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials

Gammagard S/D powder for injection: 2.5 g, 5 g, 10 g bottles

Gammaked: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials

Gammaplex: 5% (50 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials

Gamunex-C: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 400 mL vials

Octagam: 5% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL, 500 mL

Octagam: 10% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL

Privigen: 10% (100 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials

Subcutaneous Immunoglobulin

Gammagard: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials

Gammaked: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials

Gamunex-C: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 400 mL vials

Hizentra protein solution for subcutaneous injection: 20% (0.2 g/mL) in 5 mL, 10 mL, 20 mL, 50 mL vials

HyQvia: 10% (1 g/10 mL) in 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials and 160 U/mL recombinant human hyaluronidase in 1.25 mL, 2.5 mL, 5 mL, 10 mL, 15 mL vials

References:

Micromedex^R Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 02, 2015.
Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 9, 2013.
Gammagard S/D [Prescribing Information], Westlake Village, CA; Baxter: December 2009.
Gammaplex [Prescribing Information]. Elstree, Herts, UK. ; Bio Products Laboratory Limited: June 2014.
Gamunex-C [Prescribing Information]. Research Triangle Park, NC. Grifolis Therapeutics Inc.: July 2014.
Hizentra [Prescribing Information], Bern, Switzerland; CSL Behring AG, January 2015.
Carimune NF [Prescribing Information], CSL Behring AG, September 2013.
Privigen [Prescribing Information], CSL Behring AG, November 2013.
Gammagard Liquid [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
Elovaara I, Apostolski S, van Doorn P, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol. 2008 Sep;15(9):893-908. Available at: http://www.cpgn.net/web/uploadfile/2011/0125/20110125015723259.pdf
Ahn S, Mayer L, Cunningham-Rundles C. Treatment and prognosis of common variable immunodeficiency. UpToDate. August 23, 2010.
Ahn S, Mayer L, Cunningham-Rundles C. Pathogenesis of common variable immunodeficiency. UpToDate. October 20, 2011.
Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001 Aug 7;135(3):165-74.
Stiehm ER. Human intravenous immunoglobulin in primary and secondary antibody deficiencies. Pediatr Infect Dis J. 1997 Jul;16(7):696-707.
Argawal S, Cunningham-Rundles C. Assessment and clinical interpretation of reduced IgG values. Annals of Allergy, Asthma and Immunology Sept 2007 99;3:281-283
Bivigam [Prescribing Information], Boca Raton, FL : Biotest Pharmaceuticals Corp.; April 2014.
Flebogamma [Prescribing Information],Barcelona, Spain; Institutio Grifols, S.A.; September 2013.
Gammaked [Prescribing Information], Research Triangle Park, NC; Grifolis Therapeutics Inc.; September 2013.
Octagam 5% [Prescribing Information], Hoboken, NJ: Octapharma USA; October 2013.
Octagam 10% [Prescribing Information], Hoboken, NJ: Octapharma USA; July 2014.
HyQvia [Prescribing Information]. Westlake Village, CA; Baxter: September 2014.
Mayo Clinic immune globulin lab values accessed at: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8156