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Immune Globulin

Pronunciation

(i MYUN GLOB yoo lin)

Index Terms

  • Gamma Globulin
  • Human Normal Immunoglobulin
  • IG
  • IGIM
  • IGIV
  • IGSC
  • IMIG
  • Immune Globulin IV
  • Immune Globulin Subcutaneous (Human)
  • Immune Serum Globulin
  • ISG
  • IV Immune Globulin
  • IVIG
  • Normal Immunoglobulin
  • Panglobulin
  • Polygam
  • Sandoglobulin
  • SCIG

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Injectable, Intramuscular [preservative free]:

GamaSTAN S/D: 15% to 18% [150 to 180 mg/mL] (2 mL, 10 mL)

Kit, Subcutaneous:

Hyqvia: 2.5 g/25 mL, 5 g/50 mL, 10 g/100 mL, 20 g/200 mL, 30 g/300 mL [contains albumin human, edetate disodium dihydrate, mouse (murine) and/or hamster protein]

Solution, Injection [preservative free]:

Gammagard: 1 g/10 mL (10 mL); 2.5 g/25 mL (25 mL); 5 g/50 mL (50 mL); 10 g/100 mL (100 mL); 20 g/200 mL (200 mL); 30 g/300 mL (300 mL) [latex free]

Gammaked: 1 g/10 mL (10 mL); 2.5 g/25 mL (25 mL); 5 g/50 mL (50 mL); 10 g/100 mL (100 mL); 20 g/200 mL (200 mL) [latex free]

Gamunex-C: 1 g/10 mL (10 mL); 2.5 g/25 mL (25 mL); 5 g/50 mL (50 mL); 10 g/100 mL (100 mL); 20 g/200 mL (200 mL); 40 g/400 mL (400 mL) [latex free]

Solution, Intravenous [preservative free]:

Bivigam: 5 g/50 mL (50 mL); 10 g/100 mL (100 mL) [sugar free; contains polysorbate 80]

Flebogamma: 0.5 g/10 mL (10 mL [DSC])

Flebogamma DIF: 0.5 g/10 mL (10 mL); 5 g/50 mL (50 mL); 5 g/100 mL (100 mL); 10 g/100 mL (100 mL); 20 g/200 mL (200 mL); 20 g/400 mL (400 mL); 10 g/200 mL (200 mL); 2.5 g/50 mL (50 mL) [contains polyethylene glycol]

Gammaplex: 5 g/100 mL (100 mL); 20 g/400 mL (400 mL); 10 g/200 mL (200 mL); 2.5 g/50 mL (50 mL [DSC]) [contains polysorbate 80]

Octagam: 1 g/20 mL (20 mL); 2 g/20 mL (20 mL); 5 g/50 mL (50 mL); 5 g/100 mL (100 mL); 10 g/100 mL (100 mL); 20 g/200 mL (200 mL); 25 g/500 mL (500 mL); 10 g/200 mL (200 mL); 2.5 g/50 mL (50 mL) [sucrose free]

Privigen: 5 g/50 mL (50 mL); 10 g/100 mL (100 mL); 20 g/200 mL (200 mL); 40 g/400 mL (400 mL)

Solution, Subcutaneous [preservative free]:

Cuvitru: 1 g/5 mL (5 mL); 2 g/10 mL (10 mL); 4 g/20 mL (20 mL); 8 g/40 mL (40 mL)

Hizentra: 1 g/5 mL (5 mL); 2 g/10 mL (10 mL); 4 g/20 mL (20 mL); 10 g/50 mL (50 mL) [contains polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Carimune NF: 3 g (1 ea [DSC]); 6 g (1 ea); 12 g (1 ea)

Gammagard S/D: 2.5 g (1 ea [DSC]); 5 g (1 ea [DSC]); 10 g (1 ea [DSC])

Gammagard S/D Less IgA: 5 g (1 ea); 10 g (1 ea)

Brand Names: U.S.

  • Bivigam
  • Carimune NF
  • Cuvitru
  • Flebogamma DIF
  • Flebogamma [DSC]
  • GamaSTAN S/D
  • Gammagard
  • Gammagard S/D Less IgA
  • Gammagard S/D [DSC]
  • Gammaked
  • Gammaplex
  • Gamunex - C
  • Hizentra
  • Hyqvia
  • Octagam
  • Privigen

Pharmacologic Category

  • Blood Product Derivative
  • Immune Globulin

Pharmacology

Replacement therapy for primary and secondary immunodeficiencies, and IgG antibodies against bacteria, viral, parasitic and mycoplasma antigens; interference with Fc receptors on the cells of the reticuloendothelial system for autoimmune cytopenias and ITP; provides passive immunity by increasing the antibody titer and antigen-antibody reaction potential

Distribution

Vd: 0.05 to 0.13 L/kg

Intravascular portion (primarily): Healthy subjects: 41% to 57%; Patients with congenital humoral immunodeficiencies: ~70%

Onset of Action

IV: Provides immediate antibody levels

Immune thrombocytopenia: Initial response: 1 to 3 days; Peak response: 2 to 7 days (Neunert 2011)

Time to Peak

Plasma: SubQ: Cuvitru: ~4.4 days; Gammagard Liquid: 2.9 days; Hizentra: 2.9 days; HyQvia: ~5 days

Serum: IM: ~48 hours

Duration of Action

IM, IV: Immune effects: 3 to 4 weeks (variable)

Half-Life Elimination

IM: ~23 days; SubQ: ~59 days (HyQvia): IV: IgG (variable among patients): Healthy subjects: 14 to 24 days; Patients with congenital humoral immunodeficiencies: 26 to 40 days; hypermetabolism associated with fever and infection have coincided with a shortened half-life

Use: Labeled Indications

Chronic inflammatory demyelinating polyneuropathy: Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) (Gammaked, Gamunex-C)

Chronic lymphocytic leukemia: Prevention of bacterial infection in patients with hypogammaglobulinemia and/or recurrent bacterial infections with B-cell chronic lymphocytic leukemia (CLL) (Gammagard S/D)

Immune thrombocytopenia:

Treatment of acute immune thrombocytopenia (ITP) (Carimune NF, Gammagard S/D, Gammaked, Gamunex-C).

Treatment of chronic ITP (Carimune NF, Flebogamma DIF 10%, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam 10%, Privigen)

Immunodeficiency syndromes: Treatment of primary humoral immunodeficiency syndromes (congenital agammaglobulinemia, severe combined immunodeficiency syndromes [SCIDS], common variable immunodeficiency, X-linked immunodeficiency, Wiskott-Aldrich syndrome) (Bivigam, Carimune NF, Cuvitru, Flebogamma DIF, HyQvia, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Hizentra, Octagam 5%, Privigen)

Kawasaki syndrome: Prevention of coronary artery aneurysms associated with Kawasaki syndrome (in combination with aspirin) (Gammagard S/D)

Multifocal motor neuropathy: Treatment of multifocal motor neuropathy (MMN) (Gammagard Liquid)

Passive immunity: Provision of passive immunity in the following susceptible individuals (GamaSTAN S/D):

Hepatitis A: Pre-exposure prophylaxis; postexposure: within 14 days and/or prior to manifestation of disease

Measles: For use within 6 days of exposure in an unvaccinated person, who has not previously had measles

Rubella: Postexposure prophylaxis to reduce the risk of infection and fetal damage in exposed pregnant women who will not consider therapeutic abortion

Varicella: For immunosuppressed patients when varicella zoster immune globulin is not available

Use: Unlabeled

Acquired hypogammaglobulinemia secondary to malignancy; Guillain-Barré syndrome; hematopoietic stem cell transplantation (HSCT), to prevent bacterial infections among allogeneic recipients with severe hypogammaglobulinemia (IgG <400 mg/dL) at <100 days posttransplant (CDC guidelines); HIV-associated thrombocytopenia; multiple sclerosis (relapsing, remitting when other therapies cannot be used); Lambert-Eaton myasthenic syndrome (LEMS); myasthenia gravis; refractory dermatomyositis/polymyositis

Contraindications

Hypersensitivity to immune globulin or any component of the formulation; IgA deficiency (with anti-IgA antibodies and history of hypersensitivity); hyperprolinemia (Hizentra, Privigen); isolated IgA deficiency (GamaSTAN S/D); severe thrombocytopenia or coagulation disorders where IM injections are contraindicated (GamaSTAN S/D); hypersensitivity to corn (Octagam); hereditary intolerance to fructose (excluding Flebogamma); infants/neonates for whom sucrose or fructose tolerance has not been established (Gammaplex); hypersensitivity to hyaluronidase or recombinant human hyaluronidase (HyQvia)

Dosing: Adult

Note: Some clinicians may administer IGIV formulations FDA approved only for intravenous administration as a subcutaneous infusion based on clinical judgment and patient tolerability.

B-cell chronic lymphocytic leukemia (CLL) with hypogammaglobulinemia, prevention of bacterial infections (Gammagard S/D): IV: 400 mg/kg every 3 to 4 weeks

Chronic inflammatory demyelinating polyneuropathy (CIDP) (Gammaked, Gamunex-C): IV: Loading dose: 2,000 mg/kg (given in divided doses over 2 to 4 consecutive days); Maintenance: 1,000 mg/kg every 3 weeks. Alternatively, administer 500 mg/kg/day for 2 consecutive days every 3 weeks.

Hepatitis A (GamaSTAN S/D): IM:

Preexposure prophylaxis upon travel into endemic areas (hepatitis A vaccine preferred):

0.02 mL/kg for anticipated risk of exposure <3 months

0.06 mL/kg for anticipated risk of exposure ≥3 months; repeat every 4 to 6 months.

Postexposure prophylaxis: 0.02 mL/kg given within 14 days of exposure and/or prior to manifestation of disease; not needed if at least 1 dose of hepatitis A vaccine was given at ≥1 month before exposure (CDC 2006)

Immune thrombocytopenia (ITP):

Carimune NF: IV: Initial: 400 mg/kg/day for 2 to 5 consecutive days (6% solution recommended); Maintenance: 400 mg/kg (no more frequent than daily) as needed to maintain platelet count ≥30,000/mm3 and/or to control significant bleeding; may increase dose if needed (range: 800 to 1,000 mg/kg).

Flebogamma DIF 10%: IV: 1,000 mg/kg once daily for 2 consecutive days

Gammagard S/D: IV: 1,000 mg/kg; up to 3 total doses may be given on alternate days based on patient response and/or platelet count.

Gammaked, Gamunex-C: IV: 1,000 mg/kg/day for 2 consecutive days (second dose may be withheld if adequate platelet response in 24 hours) or 400 mg/kg once daily for 5 consecutive days

Gammaplex, Octagam 10%, Privigen: IV: 1,000 mg/kg/day for 2 consecutive days

American Society of Hematology Guidelines: Newly diagnosed ITP with platelets <30,000/mm3: First line treatment: IV: 1,000 mg/kg as a single dose, may repeat if necessary (Neunert 2011)

Measles:

GamaSTAN S/D: IM:

Immunocompetent: 0.25 mL/kg given within 6 days of exposure

Immunocompromised children: 0.5 mL/kg (maximum dose: 15 mL) immediately following exposure

Postexposure prophylaxis, any nonimmune person (off-label population): Patients ≤30 kg: 0.5 mL/kg (maximum dose: 15 mL) within 6 days of exposure. If patient >30 kg, patient will have lower titers than what is recommended due to the maximum volume that can be administered (CDC 2013)

Gammaked, Gamunex-C, Octagam 5%: IV:

Preexposure prophylaxis in patients with primary humoral immunodeficiency (ONLY if routine dose is <400 mg/kg): ≥400 mg/kg immediately before expected exposure followed by resumption of prior dosing in 3 to 4 weeks.

Postexposure prophylaxis in patients with primary humoral immunodeficiency: 400 mg/kg administered as soon as possible after exposure followed by resumption of prior dosing in 3 to 4 weeks.

Postexposure prophylaxis, any nonimmune person (off-label population): 400 mg/kg within 6 days of exposure (CDC 2013)

Hizentra: SubQ infusion:

Preexposure prophylaxis in patients with primary humoral immunodeficiency at risk of measles exposure (eg, during an outbreak; travel to endemic area):

Patients receiving weekly or more frequent dosing: Ensure total weekly dose of ≥200 mg/kg for 2 consecutive weeks followed by resumption of prior dosing schedule

Patients receiving biweekly dosing: Administer ≥400 mg/kg once followed by resumption of prior dosing schedule.

Postexposure prophylaxis in patients with primary humoral immunodeficiency regardless of prior dosing schedule (daily, weekly, or biweekly): 400 mg/kg administered as soon as possible after exposure followed by resumption of prior dosing schedule.

ACIP recommendations: The Advisory Committee on Immunization Practices (ACIP) recommends postexposure prophylaxis with immune globulin (IG) to any nonimmune person exposed to measles. The following patient groups are at risk for severe measles complications and should receive IG therapy: Infants <12 months of age, pregnant women without evidence of immunity; severely compromised persons (eg, persons with severe primary immunodeficiency; some bone marrow transplant patients; some ALL patients; and some patients with AIDS or HIV infection [refer to guidelines for additional details]). IGIM is recommended for infants <12 months of age. IGIV is recommended for pregnant women and immunocompromised persons. Although prophylaxis may be given to any nonimmune person, priority should be given to those at greatest risk for measles complications and also to persons exposed in settings with intense, prolonged, close contact (eg, households, daycare centers, classrooms). Following IG administration, any nonimmune person should then receive the measles mumps and rubella (MMR) vaccine if the person is ≥12 months of age at the time of vaccine administration and the vaccine is not otherwise contraindicated. MMR should not be given until 6 months following IGIM or 8 months following IGIV administration. If a person is already receiving IGIV therapy, a dose of 400 mg/kg IV within 3 weeks prior to exposure (or 200 mg/kg SubQ for 2 consecutive weeks prior to exposure if previously on SubQ therapy) should be sufficient to prevent measles infection. IG therapy is not indicated for any person who already received one dose of a measles-containing vaccine at ≥12 months of age unless they are severely immunocompromised (CDC 2013).

Multifocal motor neuropathy (MMN) (Gammagard Liquid): IV: 500 to 2400 mg/kg/month based upon response

Primary humoral immunodeficiency disorders:

IV infusion dosing:

Bivigam, Gammaplex: IV: 300 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response

Carimune NF: IV: 400 to 800 mg/kg every 3 to 4 weeks. Note: In previously untreated agammaglobulinemic or hypogammaglobulinemic patients use a 3% solution; may administer subsequent infusions with a higher concentration if patient tolerates lower concentration.

Flebogamma DIF 5%, Flebogamma DIF 10%, Gammagard Liquid, Gammagard S/D, Gammaked, Gamunex-C, Octagam 5%: IV: 300 to 600 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response

Privigen: IV: 200 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response

Switching to weekly subcutaneous infusion dosing:

Gammagard Liquid, Gammaked, Gamunex-C: SubQ infusion: Begin 1 week after last IV dose. Use the following equation to calculate initial dose:

Initial weekly dose (grams) = [1.37 x IGIV dose (grams)] divided by [IV dose interval (weeks)]

Note: For subsequent dose adjustments, refer to product labeling.

Hizentra: SubQ infusion: For weekly or frequent (up to daily) dosing, begin 1 week after last IV infusion or SubQ infusion. For biweekly (every 2 week) dosing, begin 1 or 2 weeks after last IV infusion or 1 week after the last SubQ weekly infusion. Note: Patient should have received an IV immune globulin routinely for at least 3 months before switching to SubQ. Use the following equation to calculate initial weekly dose:

Initial weekly dose (grams) = [Previous IGIV dose (grams)] divided by [IV dose interval (eg, 3 or 4 weeks)] then multiply by 1.37. For patients switching to Hizentra from a different SubQ formulation, the previous weekly SubQ dose should be used initially. To convert the dose (in grams) to mL, multiply the calculated dose (in g) by 5.

Note: Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly (every 2 weeks) may be used. For patients switching to Hizentra from a different SubQ formulation, the previous weekly SubQ dose should be used initially. Use the following calculations to calculate frequent or biweekly dosing:

Biweekly dosing (grams) = multiply the calculated or previous weekly dose by 2.

Frequent (2 to 7 times per week) dosing (grams) = divide the calculated or previous weekly dose by the desired number of times per week (eg, for 3 times per week dosing, divide weekly dose by 3)

Note: For subsequent dose adjustments, refer to product labeling.

SubQ infusion dosing:

Cuvitru: SubQ:

Patients switching from another IG SubQ product: SubQ infusion:

Weekly dosing (grams): Weekly dose is the same as the prior immune globulin subcutaneous weekly dose

Biweekly dosing (grams): Multiply the calculated weekly dose by 2

Frequent (2 to 7 times per week) dosing (grams): Divide the calculated weekly dose by the desired number of administration times per week

Note: For subsequent dose adjustments, refer to product labeling.

Patients switching from IGIV therapy or Hyqvia: SubQ infusion: Begin treatment one week after patient’s last immune globulin IV or Hyqvia infusion

Initial weekly dosing (grams): Divide the previous immune globulin IV or Hyqvia dose (grams) by the number of weeks between IV doses, then multiply this dose by 1.3 (dose adjustment factor)

Biweekly dosing (grams): Multiply the calculated weekly dose by 2

Frequent (2 to 7 times per week) dosing (grams): Divide the calculated weekly dose by the desired number of times per week

Note: For subsequent dose adjustments, refer to product labeling.

HyQvia: SubQ: See manufacturer’s labeling for initial ramp-up schedule (initiating treatment with a full monthly dose has not been evaluated); dose adjusted based on monitored trough serum IgG concentrations and clinical response after initial ramp-up. Note: For patients previously on another IgG treatment, administer the first dose ~1 week after the last infusion of previous treatment.

Patients naive to IgG therapy or switching from IG SubQ therapy: SubQ infusion: 300 to 600 mg/kg every 3 to 4 weeks, after the initial dose ramp-up

Patients switching from IGIV therapy: SubQ infusion: Administer the same dose and frequency as the previous IGIV therapy after the initial dose ramp-up. For subsequent dose adjustments, refer to product labeling.

Rubella (GamaSTAN S/D): IM: Postexposure prophylaxis during pregnancy: 0.55 mL/kg

Varicella (GamaSTAN S/D): IM: Prophylaxis: 0.6 to 1.2 mL/kg (varicella zoster immune globulin preferred) within 72 hours of exposure (Gershon 1978). Note: For patients at risk of thrombosis, administer at the lower end of the recommended dosage range.

Off-label uses: IV:

Acquired hypogammaglobulinemia secondary to malignancy (off-label use): 400 mg/kg/dose every 3 weeks; reevaluate every 4 to 6 months (Anderson 2007)

Antibody-mediated rejection in cardiac transplantation, treatment (off-label use): Dose/frequency/duration of treatment varies greatly: 100 to 2,000 mg/kg (dose may be divided into 2 or 4 doses) 1 to 3 times per week, often given after each plasmapheresis; may be re-dosed monthly, if re-dose necessary and based on response (AHA [Colvin 2015]; ISHLT [Costanzo 2010]).

Dermatomyositis/polymyositis (refractory) (use in combination with other agents in patients with dermatomyositis) (off-label use): 2,000 mg/kg per treatment course administered in divided doses over 2 to 5 consecutive days (eg, 400 mg/kg/day for 5 days); maximum (per treatment course): 2,000 mg/kg (Feasby 2007).

Guillain-Barré syndrome (off-label use): A total dose of 2 g/kg per treatment course, given in divided doses over 2 to 5 consecutive days (eg, 400 mg/kg/day for 5 days) (Feasby 2007; Hughes 2014). European Federation of Neurological Societies (EFNS) guidelines recommend the 5-day treatment regimen (Elovaara, 2008).

Hematopoietic cell transplantation (HCT) with hypogammaglobulinemia (IgG <400 mg/dL), prevention of bacterial infection (off-label use): Note: Increase dose or frequency to maintain IgG concentration >400 mg/dL.

≤100 days post-HCT: 500 mg/kg/dose once weekly (Tomblyn 2009)

>100 days post-HCT: 500 mg/kg/dose every 3 to 4 weeks (Tomblyn 2009)

HIV-associated thrombocytopenia (off-label use): 1,000 mg/kg/day for 2 days (Anderson 2007)

Lambert-Eaton myasthenic syndrome (LEMS) (off-label use): 1,000 mg/kg/day for 2 days (Bain 1996; Patwa 2012)

Myasthenia gravis (acute exacerbation) (off-label use): Adjunctive therapy: 2 g/kg per treatment course, administered in divided doses over 2 to 5 consecutive days (eg, 400 mg/kg/day for 5 days) (Barth 2011; Feasby 2007; Zinman 2007). Note: A single dose of 1 g/kg may have similar efficacy to 1 g/kg given on 2 consecutive days (Gajdos 2005)

Relapsing-remitting multiple sclerosis (off-label use): 1,000 mg/kg per month, with or without an induction of 400 mg/kg/day for 5 days (Feasby 2007). Optimal dosing has not been established.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: HyQvia and Octagam 10% are not FDA-approved for use in children.

Children and Adolescents:

Hepatitis A: Refer to adult dosing.

Immune thrombocytopenia (ITP):

Carimune NF: IV: Initial: 400 mg/kg/day for 2 to 5 consecutive days (6% solution recommended); Maintenance: 400 mg/kg (no more frequent than daily) as needed to maintain platelet count ≥30,000/mm3 and/or to control significant bleeding; may increase dose if needed (range: 800 to 1,000 mg/kg). For acute ITP, may discontinue after day 2 if platelet response is adequate (30,000 to 50,000/mm3) after the first 2 doses.

Flebogamma DIF 10%: Children ≥2 years and Adolescents: IV: 1,000 mg/kg once daily for 2 consecutive days

Gammaked, Gamunex-C: IV: 1,000 mg/kg/day for 2 consecutive days (second dose may be withheld if adequate platelet response in 24 hours) or 400 mg/kg once daily for 5 consecutive days.

Privigen: IV: 1,000 mg/kg/day for 2 consecutive days (not approved for use in pediatric patients <15 years of age).

American Society of Hematology Guidelines: Newly diagnosed ITP: Initial pharmacologic management: Children and Adolescents: IV: 800 to 1,000 mg/kg as a single dose (Neunert 2011).

Kawasaki syndrome: IV:

Gammagard S/D: 1,000 mg/kg as a single dose or 400 mg/kg/day for 4 consecutive days. Begin within 7 days of onset of fever.

AHA guidelines (2004): 2,000 mg/kg as a single dose within 10 days of disease onset

Note: Must be used in combination with aspirin: 80 to 100 mg/kg/day orally, divided every 6 hours for up to 14 days (until fever resolves for at least 48 hours); then decrease dose to 3 to 5 mg/kg/day once daily. In patients without coronary artery abnormalities, give lower dose for 6 to 8 weeks. In patients with coronary artery abnormalities, low-dose aspirin should be continued indefinitely.

Measles: Refer to adult dosing.

Primary humoral immunodeficiency disorders:

IV infusion dosing:

Bivigam: IV: Children ≥6 years and Adolescents: 300 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response

Carimune NF: IV: Children and Adolescents: 400 to 800 mg/kg every 3 to 4 weeks. Note: In previously untreated agammaglobulinemic or hypogammaglobulinemic patients use a 3% solution; may administer subsequent infusions with a higher concentration if patient tolerates lower concentration.

Flebogamma DIF 5%: IV: Children ≥2 years, and Adolescents: 300 to 600 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response

Gammagard Liquid, Gammagard S/D: IV: Children ≥2 years and Adolescents: 300 to 600 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response.

Gammaked, Gamunex-C, Octagam 5%: IV: Children and Adolescents: 300 to 600 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response.

Gammaplex: IV: Children ≥2 years, and Adolescents: 300 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response.

Privigen: IV: Children ≥3 years and Adolescents: 200 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response

Switching to weekly subcutaneous infusion dosing:

Gammagard Liquid: Children ≥2 years and Adolescents:

SubQ infusion: Begin 1 week after last IV dose. Use the following equation to calculate initial dose:

Initial weekly dose (grams) = [1.37 x IGIV dose (grams)] divided by [IV dose interval (weeks)]

Note: For subsequent dose adjustments, refer to product labeling.

Hizentra: SubQ infusion: Children ≥2 years and Adolescents: For weekly or frequent (up to daily) dosing, begin 1 week after last IV infusion or SubQ infusion. For biweekly (every 2 week) dosing, begin 1 or 2 weeks after last IV infusion or 1 week after the last SubQ weekly infusion. Note: Patient should have received an IV immune globulin routinely for at least 3 months before switching to SubQ. Use the following equation to calculate initial weekly dose:

Initial weekly dose (grams) = [Previous IGIV dose (grams)] divided by [IV dose interval (eg, 3 or 4 weeks)] then multiply by 1.37. If switching from a different SubQ formulation to Hizentra, maintain previous weekly SubQ dose initially. To convert the dose (in grams) to mL, multiply the calculated dose (in grams) by 5.

Note: Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly (every 2 weeks) may be used. Use the following calculations to calculate frequent or biweekly dosing:

Biweekly dosing (grams) = multiply the calculated or previous weekly dose by 2.

Frequent (2 to 7 times per week) dosing (grams) = divide the calculated or previous weekly dose by the desired number of times per week (eg, for 3 times per week dosing, divide weekly dose by 3).

Note: For subsequent dose adjustments, refer to product labeling.

SubQ infusion dosing:

Cuvitru: SubQ infusion: Children ≥2 years and Adolescents: Refer to adult dosing.

Varicella: Refer to adult dosing.

Dermatomyositis/polymyositis (refractory) (use in combination with other agents in patients with dermatomyositis) (off-label use): IV: 2,000 mg/kg per treatment course administered in divided doses over 2 consecutive days (eg, 1,000 mg/kg/day for 2 days); maximum (per treatment course): 2,000 mg/kg (Feasby 2007)

Guillain-Barré syndrome (off-label use): Children and Adolescents: IV: 1,000 mg/kg/day for 2 days (Feasby 2007; Korinthenberg 2005) or 400 mg/kg/day for 5 days (El-Bayoumi 2011; Korinthenberg 2005).Two-day regimens have been associated with a higher incidence of early relapse (Korinthenberg 2005). American Academy of Neurology guidelines state optimal dosing has not been established (Patwa 2012).

Hematopoietic cell transplantation (HCT) with hypogammaglobulinemia (IgG <400 mg/dL), prevention of bacterial infection (off-label use) (Tomblyn 2009): IV: Note: Increase dose or frequency to maintain IgG concentration >400 mg/dL.

≤100 days post-HCT:

Infants and Children (Allogeneic HCT recipients): IV: 400 mg/kg/dose once monthly

Adolescents: IV: 500 mg/kg/dose once weekly

>100 days post-HCT: Infants, Children, and Adolescents: IV: 500 mg/kg/dose every 3 to 4 weeks

Myasthenia gravis (acute exacerbation) (off-label use): Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

IV: Use with caution due to risk of immune globulin-induced renal dysfunction; the rate of infusion and concentration of solution should be minimized. Discontinue if renal function deteriorates during treatment.

IM: There are no dosage adjustments provided in the manufacturer’s labeling.

SubQ infusion: There are no dosage adjustments provided in the manufacturer's labeling; consider lower, more frequent dosing.

Dosing: Hepatic Impairment

IM, IV, SubQ infusion: There are no dosage adjustments provided in manufacturer’s labeling.

Dosing: Obesity

Some clinicians dose IGIV on ideal body weight or an adjusted ideal body weight in morbidly obese patients (Siegel 2010).

Reconstitution

Dilution is dependent upon the manufacturer and brand. Gently swirl; do not shake; avoid foaming. Do not heat. Do not mix products from different manufacturers together. Discard unused portion of vials.

Bivigam: Dilution is not recommended.

Carimune NF: In a sterile laminar air flow environment, reconstitute with NS, D5W, or SWFI. Complete dissolution may take up to 20 minutes. Begin infusion within 24 hours.

Cuvitru: Do not dilute.

Flebogamma DIF: Dilution is not recommended.

Gammagard Liquid: May dilute in D5W only.

Gammagard S/D: Reconstitute with SWFI.

Gammaked: May dilute in D5W only.

Gamunex-C: May dilute in D5W only.

HyQvia: Bring refrigerated product to room temperature before use. Do not mix hyaluronidase and immune globulin prior to administration.

Octagam 10%: Do not dilute. Bottles may be pooled into sterile infusion bags and infused within 8 hours after pooling.

Privigen: If necessary to further dilute, D5W may be used.

Administration

Note: If plasmapheresis employed for treatment of condition, administer immune globulin after completion of plasmapheresis session.

IM: Administer IM in the anterolateral aspects of the upper thigh or deltoid muscle of the upper arm. Avoid gluteal region due to risk of injury to sciatic nerve. Divide doses >10 mL and inject in multiple sites.

GamaSTAN S/D is for IM administration only.

IV infusion: Infuse over 2 to 24 hours; administer in separate infusion line from other medications; if using primary line, flush with NS or D5W (product specific; consult product prescribing information) prior to administration. Decrease dose, rate and/or concentration of infusion in patients who may be at risk of renal failure. Decreasing the rate or stopping the infusion may help relieve some adverse effects (flushing, changes in pulse rate, changes in blood pressure). Epinephrine should be available during administration. For initial treatment or in the elderly, a lower concentration and/or a slower rate of infusion should be used. Initial rate of administration and titration is specific to each IGIV product. Refrigerated product should be warmed to room temperature prior to infusion. Some products require filtration; refer to individual product labeling. Antecubital veins should be used, especially with concentrations ≥10% to prevent injection site discomfort.

Bivigam 10%: Primary humoral immunodeficiency: Initial (first 10 minutes): 0.5 mg/kg/minute (0.3 mL/kg/hour); Maintenance: Increase every 20 minutes (if tolerated) by 0.8 mg/kg/minute (0.48 mL/kg/hour) up to 6 mg/kg/minute (3.6 mL/kg/hour)

Carimune NF: Refer to product labeling.

Flebogamma DIF 5%: Primary humoral immunodeficiency: Initial: 0.5 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Increase slowly (if tolerated) up to 5 mg/kg/minute (6 mL/kg/hour)

Flebogamma DIF 10%: Primary humoral immunodeficiency or immune thrombocytopenia: Initial: 1 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Increase slowly (if tolerated) up to 8 mg/kg/minute (4.8 mL/kg/hour)

Gammagard Liquid 10%:

Multifocal motor neuropathy (MMN): Initial: 0.8 mg/kg/minute (0.5 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 9 mg/kg/minute (5.4 mL/kg/hour)

Primary humoral immunodeficiency: Initial (first 30 minutes): 0.8 mg/kg/minute (0.5 mL/kg/hour); Maintenance: Increase every 30 minutes (if tolerated) up to: 8 mg/kg/minute (5 mL/kg/hour)

Gammagard S/D: 5% solution: Initial: 0.5 mL/kg/hour; may increase (if tolerated) to a maximum rate of 4 mL/kg/hour. If 5% solution is tolerated at maximum rate, may administer 10% solution with an initial rate of 0.5 mL/kg/hour; may increase (if tolerated) to a maximum rate of 8 mL/kg/hour

Gammaked 10%:

CIDP: Initial (first 30 minutes): 2 mg/kg/minute (1.2 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 8 mg/kg/minute (4.8 mL/kg/hour)

Primary humoral immunodeficiency or ITP: Initial (first 30 minutes): 1 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 8 mg/kg/minute (4.8 mL/kg/hour)

Gammaplex 5%: Primary humoral immunodeficiency or ITP: Initial (first 15 minutes): 0.5 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Increase every 15 minutes (if tolerated) up to 4 mg/kg/minute (4.8 mL/kg/hour)

Gamunex-C 10%:

CIDP: Initial (first 30 minutes): 2 mg/kg/minute (1.2 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 8 mg/kg/minute (4.8 mL/kg/hour)

Primary humoral immunodeficiency or ITP: Initial (first 30 minutes): 1 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 8 mg/kg/minute (4.8 mL/kg/hour)

Octagam 5%: Primary humoral immunodeficiency: Initial (first 30 minutes): 0.5 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Double infusion rate (if tolerated) every 30 minutes up to a maximum rate of <3.33 mg/kg/minute (4.2 mL/kg/hour)

Octagam 10%: ITP: Initial (first 30 minutes):1 mg/kg/minute (0.6 mL/kg/hour); Maintenance: Double infusion rate (if tolerated) every 30 minutes up to a maximum rate of 12 mg/kg/minute (7.2 mL/kg/hour)

Privigen 10%:

ITP: Initial: 0.5 mg/kg/minute (0.3 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 4 mg/kg/minute (2.4 mL/kg/hour)

Primary humoral immunodeficiency: Initial: 0.5 mg/kg/minute (0.3 mL/kg/hour); Maintenance: Increase gradually (if tolerated) up to 8 mg/kg/minute (4.8 mL/kg/hour)

SubQ infusion: Initial dose should be administered in a healthcare setting capable of providing monitoring and treatment in the event of hypersensitivity. Using aseptic technique, follow the infusion device manufacturer’s instructions for filling the reservoir and preparing the pump. Remove air from administration set and needle by priming. For products excluding HyQvia, appropriate injection sites include the abdomen, thigh, upper arm, lower back, and/or lateral hip; dose may be infused into multiple sites (spaced ≥2 inches apart) simultaneously. HyQvia may be injected into the middle to upper abdomen or thigh (avoid bony prominences, or areas that are scarred, inflamed, or infected). If two sites are used simultaneously for HyQvia, the two infusion sites should be on opposite sides of the body. After the sites are clean and dry, insert subcutaneous needle and prime administration set. Attach sterile needle to administration set, gently pull back on the syringe to assure a blood vessel has not been inadvertently accessed (do not use needle and tubing if blood present). Repeat for each injection site; deliver the dose following instructions for the infusion device. Rotate the site(s) between successive infusions. Treatment may be transitioned to the home/home care setting in the absence of adverse reactions.

Cuvitru:

Injection sites: ≤4 simultaneous injection sites (spaced 4 inches apart or more).

Maximum infusion rate: 10 to 20 mL/hour per injection site (first 2 infusions); may be increased to 60 mL/hour per injection site (as tolerated) for subsequent infusions.

Maximum infusion volume:

Patients <40 kg: 20 mL per injection site (first 2 infusions); may increase to 60 mL per site for subsequent infusions

Patients ≥40 kg: 60 mL per injection site

Gammagard Liquid:

Injection sites: ≤8 simultaneous injection sites

Initial infusion rate:

<40 kg: 15 mL/hour per injection site (maximum volume: 20 mL per injection site)

≥40 kg: 20 mL/hour per injection site (maximum volume: 30 mL per injection site)

Maintenance infusion rate:

<40 kg: 15 to 20 mL/hour per injection site (maximum volume: 20 mL per injection site)

≥40 kg: 20 to 30 mL/hour per injection site (maximum volume: 30 mL per injection site)

Gammaked, Gamunex-C:

Injection sites: ≤8 simultaneous injection sites

Recommended infusion rate: 20 mL/hour per injection site

Hizentra:

Injection sites: ≤4 simultaneous injection sites or ≤12 sites consecutively per infusion

Maximum infusion rate: First infusion: 15 mL/hour per injection site; subsequent infusions: 25 mL/hour per injection site

Maximum infusion volume: First 4 infusions: 15 mL per injection site; subsequent infusions: 20 mL per injection site (maximum: 25 mL per site as tolerated)

HyQvia: Administer components of HyQvia (immune globulin and hyaluronidase) sequentially; do not use either component alone. Infusion pump capable of infusing rates up to 300 mL/hour/site required; must also have the ability to titrate the flow rate. Use a 24 gauge subcutaneous needle set labeled for high flow rates. Infuse the two components of HyQvia sequentially, beginning with the hyaluronidase. Initiate the infusion of the full dose of the immune globulin through the same subcutaneous needle set within ~10 minutes of hyaluronidase infusion. For each full or partial vial of immune globulin used, administer the entire contents of the hyaluronidase vial. A second site can be used based on tolerability and total volume; if a second site is used, administer half of total volume of the hyaluronidase in each site. Flush the infusion line with NS or D5W if required.

Injection sites:

Volume per site:

<40 kg: ≤300 mL per injection site

≥40 kg: ≤600 mL per injection site

Infusion rate:

Hyaluronidase: ~1 to 2 mL/minute, or as tolerated.

Immune globulin:

First 2 infusions:

<40 kg: 5 mL/hour for 5 to 15 minutes; 10 mL/hour for 5 to 15 minutes; 20 mL/hour for 5 to 15 minutes; 40 mL/hour for 5 to 15 minutes; then 80 mL/hour for remainder of infusion

≥40 kg: 10 mL/hour for 5 to 15 minutes; 30 mL/hour for 5 to 15 minutes; 60 mL/hour for 5 to 15 minutes; 120 mL/hour for 5 to 15 minutes; then 240 mL/hour for remainder of infusion

Next 2 or 3 infusions:

<40 kg: 10 mL/hour for 5 to 15 minutes; 20 mL/hour for 5 to 15 minutes; 40 mL/hour for 5 to 15 minutes; 80 mL/hour for 5 to 15 minutes; then 160 mL/hour for remainder of infusion

≥40 kg: 10 mL/hour for 5 to 15 minutes; 30 mL/hour for 5 to 15 minutes; 120 mL/hour for 5 to 15 minutes; 240 mL/hour for 5 to 15 minutes; then 300 mL/hour for remainder of infusion

Dietary Considerations

Some products may contain sodium.

Compatibility

Variable: consult detailed reference.

Storage

Stability is dependent upon the manufacturer and brand. Do not freeze (do not use if previously frozen). Do not shake. Do not heat (do not use if previously heated).

Bivigam: Store under refrigeration at 2°C to 8°C (36°F to 46°F). Dilution is not recommended.

Carimune NF: Prior to reconstitution, store at or below 30°C (86°F). Do not freeze. Following reconstitution in a sterile laminar air flow environment, store under refrigeration.

Cuvitru: Store at 2°C to 8°C (36°F to 46°F) for up to 36 months or at room temperature (≤25°C [≤77°F]) for up to 12 months; do not return vial to refrigerator after it has been stored at room temperature. Do not freeze. Keep in original carton to protect from light.

Flebogamma DIF: Store at 2°C to 25°C (36°F to 77°F). Keep in original carton to protect from light. Do not freeze or use if solution has been frozen.

GamaSTAN S/D: Store under refrigeration at 2°C to 8°C (36°F to 46°F). The following stability information has also been reported for GamaSTAN S/D: May be exposed to room temperature for a cumulative 7 days (Cohen, 2007).

Gammagard Liquid: Prior to use, store at 2°C to 8°C (36°F to 46°F). May store at room temperature of 25°C (77°F) within the first 24 months of manufacturing. Storage time at room temperature varies with length of time previously refrigerated; refer to product labeling for details.

Gammagard S/D: Store at ≤25°C (≤77°F). May store diluted solution under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 24 hours if originally prepared in a sterile laminar air flow environment.

Gammaked: Store at 2°C to 8°C (36°F to 46°F); may be stored at ≤25°C (≤77°F) for up to 6 months.

Gammaplex: Store at 2°C to 25°C (36°F to 77°F). Keep in original carton to protect from light. Do not freeze or use if solution has been frozen.

Gamunex-C: Store at 2°C to 8°C (36°F to 46°F); may be stored at ≤25°C (≤77°F) for up to 6 months.

Hizentra: Store at ≤25°C (≤77°F). Keep in original carton to protect from light. Do not freeze or use if solution has been frozen.

HyQvia: Store at 2°C to 8°C (36°F to 46°F) for up to 36 months; may store at ≤25°C (≤77°F) for up to 3 months during the first 24 months from the date of manufacture (after 3 months at room temperature, discard); do not return vial to refrigerator after it has been stored at room temperature.

Octagam 5%: Store at 2°C to 25°C (36°F to 77°F).

Octagam 10%: Store at 2°C to 8°C (36°F to 46°F) for 24 months from the date of manufacture; within these first 12 months, may store up to 9 months at ≤25°C (77°F); after storage at ≤25°C (77°F), the product must be used or discarded.

Privigen: Store at ≤25°C (≤77°F). Do not freeze. Protect from light.

Drug Interactions

Estrogen Derivatives: May enhance the thrombogenic effect of Immune Globulin. Monitor therapy

Vaccines (Live): Immune Globulins may diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Exceptions: Influenza Virus Vaccine (Live/Attenuated); Rotavirus Vaccine; Yellow Fever Vaccine; Zoster Vaccine. Consider therapy modification

Test Interactions

Octagam 5% and Octagam 10% contain maltose. Falsely elevated blood glucose levels may occur when glucose monitoring devices and test strips utilizing the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) based methods are used. Glucose monitoring devices and test strips which utilize the glucose-specific method are recommended. Passively transferred antibodies may yield false-positive serologic testing results; may yield false-positive direct and indirect Coombs’ test. Skin testing should not be performed with GamaSTAN S/D because local chemical irritation can occur and be misinterpreted as a positive reaction.

Adverse Reactions

Adverse effects are reported as class effects rather than for specific products. Adverse effects occur with intravenous administration unless otherwise specified. Some clinical trials were extremely small and skewed the incidence upward ("≤" indicates this trend).

>10%

Cardiovascular: Hypotension (≤14%; children and adolescents: 25%), tachycardia (5%; children and adolescents: 25%), decreased diastolic blood pressure (5%; children and adolescents: 21%), decreased heart rate (16%)

Central nervous system: Headache (2% to 75%; children and adolescents: 42%; subcutaneous: 13% to 21%), fatigue (6% to 29%; subcutaneous: 11%), chills (5% to 19%), pain (5% to 15%), rigors (7% to 13%), dizziness (≤13%)

Dermatologic: Injection site pruritus (5% to 45%), ecchymosis (≤40%)

Gastrointestinal: Sore throat (11% to 35%), abdominal pain (6% to ≤33%; children and adolescents: 8%), diarrhea (5% to 28%; children and adolescents: 8%), vomiting (≤26%; children and adolescents: 8%; subcutaneous: 7%), nausea (5% to 22%; children and adolescents: 8%; subcutaneous: 7%), upper abdominal pain (6% to 20%; children and adolescents: ≤15%)

Hematologic & oncologic: Positive direct Coombs test (≤47%), purpura (≤40%), hemorrhage (29%), petechiae (21%), thrombocytopenia (15%), anemia (6% to 11%)

Hepatic: Increased serum ALT (all elevations were transient and generally mild: ≤18%, children and adolescents, >2.5 x ULN: ≤7%; subcutaneous: ≤3%), increased serum alkaline phosphatase (subcutaneous: ≤13%; mild and transient), hyperbilirubinemia (unconjugated: 11%; conjugated: 9%; total: 5%)

Immunologic: Antibody development (subcutaneous: 18%; non-neutralizing antibodies to recombinant human hyaluronidase)

Local: Pain at injection site (injection/infusion site: ≤21%), erythema at injection site (11% to 21%), infusion site reaction (6% to 13%; subcutaneous: 75%)

Neuromuscular and skeletal: Arthralgia (<5% to 20%; subcutaneous: 6%), limb pain (intravenous/subcutaneous: 6% to 15%), muscle cramps (≤14%), back pain (5% to 11%)

Otic: Otalgia (9% to 18%; subcutaneous: 6%)

Renal: Nephrolithiasis (≤16%)

Respiratory: Cough (6% to 54%), nasal congestion (≤52%), rhinitis (5% to 51%), sinusitis (≤50%), pharyngitis (5% to 41%), asthma (9% to 29%; including exacerbation), upper respiratory tract infection (8% to 25%), epistaxis (7% to 23%), bronchitis (5% to 22%), nasopharyngitis (17%), rhinorrhea (7% to 17%), sinus congestion (15%), nasal mucosa swelling (≤13%), wheezing (9% to 11%)

Miscellaneous: Fever (10% to 33%; subcutaneous: 6% to 7%), accidental injury (13%)

1% to 10%

Cardiovascular: Chest pain (≤9%), hypertension (≤9%), peripheral edema (8%), cardiac arrest (≤8%; Octagam: 5%), heart murmur (7%), chest discomfort (≤7%), flushing (6%), thrombosis (≤2%)

Central nervous system: Insomnia (9%), migraine (5% to 7%), lethargy (≤6%), fibromyalgia syndrome (exacerbation: 5%), malaise (≤5%), vertigo (≤5%)

Dermatologic: Skin rash (5% to 10%), urticaria (5% to 8%; may be transient), cellulitis (≤8%), hyperhidrosis (6%), eczema (≤5%; may be transient), xeroderma (≤5%)

Endocrine & metabolic: Ketonuria (≤8%; Octagam: 5%), dehydration (≤6%), increased lactate dehydrogenase (5%)

Gastrointestinal: Dyspepsia (6% to 9%), gastroenteritis (≤8%), pseudomembranous colitis (≤8%), gastritis (6%), stomach discomfort (6%)

Genitourinary: Vulvovaginal candidiasis (9%), urinary tract infection (≤9%), cystitis (≤5%), dysuria (≤5%)

Hematologic & oncologic: Decreased hematocrit (5%)

Hepatic: Increased serum AST (intravenous/subcutaneous: ≤9%), decreased serum alkaline phosphatase (subcutaneous: ≤3%)

Infection: Fungal infection (7% to 9%), influenza (5%), coxsackievirus (≤2%)

Local: Local swelling (at injection/infusion site: ≤8%), local inflammation (at infusion site: 7%)

Neuromuscular & skeletal: Weakness (≤10%), myalgia (≤8%), muscle spasm (7%), myasthenia (7%), neck pain (6%), joint effusion (≤6%), joint swelling (≤6%)

Ophthalmic: Conjunctivitis (9%), eye discharge (7%), eye irritation (7%)

Otic: Otitis media (7% to 8%)

Renal: Increased serum creatinine (9%)

Respiratory: Exacerbation of asthma (7% to 9%), tonsil disease (children: 8%), dyspnea (7% to 8%), pharyngolaryngeal pain (5% to 8%), pneumonia (≤8%), oropharyngeal pain (6% to 7%), post nasal drip (7%), throat irritation (7%), flu-like symptoms (6%)

Miscellaneous: Positive culture (≤8%)

Frequency not defined:

Cardiovascular: Facial flushing

Central nervous system: Drowsiness

Hematologic & oncologic: Hematoma

Local: Localized tenderness (intramuscular), local pain (intramuscular/subcutaneous)

Neuromuscular & skeletal: Leg cramps

Ophthalmic: Blurred vision

Renal: Increased blood urea nitrogen

<1% (Limited to important or life-threatening): Acute renal disease, acute renal failure, acute respiratory distress, agitation, allergic dermatitis, alopecia, anaphylactic shock, apnea, arterial thrombosis, aseptic meningitis, bradycardia, bullous dermatitis, cerebrovascular accident, chest tightness, circulatory shock, coma, cyanosis, deep vein thrombosis, disseminated intravascular coagulation (intravenous, subcutaneous, intramuscular; FDA Safety Communication, November 13, 2012), edema, epidermolysis, erythema multiforme, erythematous rash, exacerbation of autoimmune pure red cell aplasia, eye pain, facial edema, hematuria, hemoglobinuria, hemolysis (may be mild), hemolytic anemia (may be delayed), hepatic insufficiency, hepatitis (non-infectious), hypersensitivity, hyperventilation, hypervolemia, hypoxemia, jaundice, laryngospasm, leukopenia, loss of consciousness, lymphadenopathy, musculoskeletal pain, myocardial infarction, osmotic nephrosis, oxygen saturation decreased, palpitations, pancytopenia, paresthesia, peripheral vascular insufficiency, pharyngeal edema, phlebitis, photophobia, proximal tubular nephropathy, pulmonary edema, pulmonary embolism, renal failure, renal insufficiency, renal tubular necrosis, respiratory distress, respiratory failure, restlessness, retinal thrombosis, seizure, Stevens-Johnson syndrome, syncope, thromboembolism, thrombophlebitis, thrombosis, transfusion-related acute lung injury, transient ischemic attacks, tremor, urine discoloration, vena cava thrombosis

ALERT: U.S. Boxed Warning

Thrombosis:

Thrombosis may occur with immune globulin products. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. For patients at risk of thrombosis, administer at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Renal dysfunction and acute renal failure (excluding Hizentra, HyQvia, and Gammastan):

Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients with immune globulin intravenous (IGIV) products. Patients predisposed to renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. (Note: The following products do not contain sucrose: Bivigam, Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam 5%, Octagam 10%, and Privigen.) For patients at risk of renal dysfunction or acute renal failure, administer immune globulin IV products at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions can occur (some severe); patients with anti-IgA antibodies are at greater risk; a severe fall in blood pressure may rarely occur with anaphylactic reaction; discontinue therapy and institute immediate treatment (including epinephrine 1 mg/mL) should be available.

• Aseptic meningitis: Aseptic meningitis syndrome (AMS) has been reported with immune globulin administration; may occur with high doses (≥1 g/kg) and/or rapid infusion. Syndrome usually appears within several hours to 2 days following treatment; usually resolves within several days after product is discontinued. Patients with a migraine history may be at higher risk for AMS.

• Hematoma: Increased risk of hematoma formation when administered subcutaneously for the treatment of ITP.

• Hemolysis: Intravenous immune globulin has been associated with antiglobulin hemolysis (acute or delayed); monitor for signs of hemolytic anemia. Cases of hemolysis-related renal dysfunction/failure or disseminated intravascular coagulation (DIC) have been reported. Risk factors associated with hemolysis include high doses (≥2 g/kg) given either as a single administration or divided over several days, underlying associated inflammatory conditions, and non-O blood type (FDA, 2012).

• Hyperproteinemia: Hyperproteinemia, increased serum viscosity, and hyponatremia may occur; distinguish hyponatremia from pseudohyponatremia to prevent volume depletion, a further increase in serum viscosity and a higher risk of thrombotic events.

• Infusion reactions: Patients should be monitored for adverse events during and after the infusion. Stop administration with signs of infusion reaction (fever, chills, nausea, vomiting, and rarely shock). Risk may be increased with initial treatment, when switching brands of immune globulin, and with treatment interruptions of >8 weeks.

• Pulmonary edema: Monitor for transfusion-related acute lung injury (TRALI); noncardiogenic pulmonary edema has been reported with immune globulin use. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever in the presence of normal left ventricular function. Usually occurs within 1 to 6 hours after infusion.

• Renal impairment: [US Boxed Warning]: IV administration only: Acute renal dysfunction (increased serum creatinine, oliguria, acute renal failure, osmotic nephrosis) can rarely occur and has been associated with fatalities; usually within 7 days of use (more likely with products stabilized with sucrose). Use with caution in the elderly, patients with renal disease, diabetes mellitus, overweight, hypovolemia, volume depletion, sepsis, paraproteinemia, and nephrotoxic medications due to risk of renal dysfunction. In patients at risk of renal dysfunction, ensure adequate hydration prior to administration; the dose rate of infusion and concentration of solution should be minimized. Assess renal function prior to treatment and periodically thereafter. Discontinue if renal function deteriorates.

• Thromboembolic events: [US Boxed Warning]: Thrombosis may occur with immune globulin products even in the absence of risk factors for thrombosis. For patients at risk of thrombosis (eg, advanced age, history of atherosclerosis, impaired cardiac output, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors), administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity such as those with cryoglobulins, fasting chylomicronemia/severe hypertriglyceridemia, or monoclonal gammopathies.

Disease-related concerns:

• Fluid overload: High-dose regimens (1 g/kg for 1 to 2 days) are not recommended for individuals with fluid overload or where fluid volume may be of concern.

• Hypovolemia: Patients should not be volume depleted prior to initiation of therapy.

• IgA deficiency: Increased risk of hypersensitivity, especially in patients with anti-IgA antibodies; use is contraindicated in patients with IgA deficiency (with antibodies against IgA and history of hypersensitivity) or isolated IgA deficiency (GamaSTAN S/D).

• ITP, chronic: Consider risk versus benefit for high-dose regimen in patients with increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

• Renal impairment: Use with caution; ensure adequate hydration prior to administration; the rate of infusion and concentration of solution should be minimized.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly; may be at increased risk for renal dysfunction/failure and thromboembolic events.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease, including unknown or emerging viruses and other pathogens. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.

• Latex: Packaging of some products may contain natural latex/natural rubber.

• L-proline: Hizentra and Privigen contain the stabilizer L-proline and are contraindicated in patients with hyperprolinemia.

• Maltose: Some products may contain maltose, which may result in falsely elevated blood glucose readings. Maltose-containing products may be contraindicated with patients with corn allergy.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.

• Skin testing: Skin testing should not be performed with GamaSTAN S/D as local irritation can occur and be misinterpreted as a positive reaction.

• Sodium: Some products may contain sodium.

• Sorbitol: Some products may contain sorbitol; do not use immune globulin in patients with fructose intolerance.

• Subcutaneous administration: Some clinicians may administer intravenous immune globulin products as a subcutaneous infusion based on patient tolerability and clinical judgment. SubQ infusion should begin 1 week after the last IV dose; dose should be individualized based on clinical response and serum IgG trough concentrations. Consider premedicating with acetaminophen and diphenhydramine.

• Sucrose: Some products may contain sucrose.

Other warnings/precautions:

• Administration: Patients should be adequately hydrated prior to therapy.

• Vaccinations: Response to live vaccinations may be impaired.

Monitoring Parameters

Renal function, urine output, IgG concentrations, hemoglobin and hematocrit, platelets (in patients with ITP); infusion- or injection-related adverse reactions, anaphylaxis, signs and symptoms of hemolysis; blood viscosity (in patients at risk for hyperviscosity); presence of antineutrophil antibodies (if TRALI is suspected); volume status; neurologic symptoms (if AMS suspected); pulmonary adverse reactions; clinical response

For patients at high risk of hemolysis (dose ≥2 g/kg, given as a single dose or divided over several days, and non-O blood type): Hemoglobin or hematocrit prior to and 36 to 96 hours postinfusion.

SubQ infusion: Monitor IgG trough levels every 2 to 3 months before/after conversion from IV; subcutaneous infusions provide more constant IgG levels than usual IV immune globulin treatments.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Immune globulins cross the placenta in increased amounts after 30 weeks gestation. Intravenous immune globulin has been recommended for use in fetal-neonatal alloimmune thrombocytopenia and pregnancy-associated ITP (Anderson, 2007). Intravenous immune globulin is recommended to prevent measles in nonimmune women exposed during pregnancy (CDC, 2013). May also be used in postexposure prophylaxis for rubella to reduce the risk of infection and fetal damage in exposed pregnant women who will not consider therapeutic abortion (per GamaSTAN S/D product labeling; use for postexposure rubella prophylaxis is not currently recommended [CDC, 2013]).

HyQvia: Women who become pregnant during treatment are encouraged to enroll in the HyQvia Pregnancy Registry (1-866-424-6724).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, diarrhea, back pain, pharyngitis, rhinitis, flushing, or cramps. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood), chills, skin discoloration, severe loss of strength and energy, seizures, bloating, confusion, edema, severe dizziness, passing out, abnormal heartbeat, bruising, bleeding, mood changes, joint pain, muscle pain, change in speech, vision changes, blurred vision, tremors, sweating a lot, severe abdominal pain, dark urine, jaundice, severe injection site irritation, signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), or signs of aseptic meningitis (headache, fever, chills, severe nausea or vomiting, stiff neck, rash, sensitivity to lights, fatigue, or confusion) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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