Immune globulins Or immunoglobulins are extracted from the human plasma of an immune person. Immune globulins provide passive immunity and are effective in various diseases. In the recent pandemic of coronavirus infection, immune globulins have also been tried in the treatment of patients with COVID-19 infection. The convalescent plasma is taken from individuals who have recovered from the disease and made antibodies against the virus and are administered to seriously ill patients with COVID-19 infections.

Immune globulins Uses:

• Chronic inflammatory demyelinating polyneuropathy:

  • Gammaked, Gamunex-C, Hizentra, Privigen: For chronic inflammatory demyelinating polyneuropathy treatment.

• Chronic lymphocytic leukemia:

  • Gammagard S/D: For Prevention and prophylaxis of bacterial infection in patients with low levels of gamma globulin and/or repeated bacterial infections with B-cell chronic lymphocytic leukemia.

• Immune thrombocytopenia:

  • Carimune NF, Gammaked, Gamunex-C: acute immune thrombocytopenia (ITP) Treatment.
  • Carimune NF, Flebogamma DIF 10%, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam 10%, Panzyga, Privigen: Chronic ITP treatment.

• Immunodeficiency syndromes:

  • Bivigam, Asceniv, Carimune NF, Cutaquig, Gamunex-C, Gammagard S/D, Cuvitru, Flebogamma DIF, Gammaked, HyQvia, Gammagard Liquid, Gammaplex, Hizentra, Octagam 5%, Panzyga, Privigen, Xembify:
    • Treatment of primary humoral immunodeficiency syndromes like
      • congenital agammaglobulinemia,
      • severe combined immunodeficiency syndromes,
      • common variable immunodeficiency,
      • X-linked agammaglobulinemia,
      • Wiskott-Aldrich syndrome.

• Kawasaki syndrome:

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

• Multifocal motor neuropathy:

  • Gammagard Liquid: Treatment of multifocal motor neuropathy.

• Passive immunity:

  • GamaSTAN, GamaSTAN S/D: Administration of passive immunity in the following susceptible individuals:

• Hepatitis A:

  • Preexposure prophylaxis; postexposure: within 2 weeks and/or prior to manifestation of disease.

• Measles:

  • Use within 6 days of exposure in an non-vaccinated person who hasn't previously had measles.

  • ACIP recommendations:

    • The Advisory Committee on Immunization Practices (ACIP) recommends post-exposure prophylaxis with immune globulin (IG) to any non-immune person exposed to measles.
    • The following patient groups are at risk for developing severe measles complications and should get 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]).
    • NOTE:
      • Although prophylaxis may be given to any non-immune person, priority should be given to those who are at greatest risk for measles complications and also to persons exposed in settings with intense, prolonged, close contact (eg, households, daycare centers, classrooms).
      • 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.

• Rubella:

  • Postexposure prophylaxis to reduce the risk of infection and fetal damage in exposed pregnant women who are not willing to consider therapeutic abortion.

• Varicella:

  • For immunosuppressed patients when varicella-zoster immune globulin is not available.

• Off Label Use of Immune Globulin in Adults:

  • Acquired hypogammaglobulinemia secondary to malignancy
  • Antibody-mediated rejection (AMR) in cardiac transplantation (treatment)
  • Clostridioides (formerly Clostridium) difficile infection (severe, refractory, and recurrent)
  • Dermatomyositis/polymyositis (refractory)
  • Guillain-Barré syndrome
  • Hematopoietic cell transplantation with hypogammaglobulinemia (prevention of bacterial infection)
  • HIV-associated thrombocytopenia
  • Lambert-Eaton myasthenic syndrome
  • Myasthenia gravis (acute exacerbation)

Immune globulins dose in adults:

Note:

• Not all products are interchangeable with regards to the route of administration;
• consult manufacturers' labeling for additional information.
• Some clinicians may administer IVIG formulations FDA approved only for intravenous administration as a subcutaneous infusion based on clinical judgment and patient tolerability.
• Product-specific dosing is provided where applicable.
• Dosage expressed as mg/kg or mL/kg and is dependent upon the route of administration;
• use extra precaution to ensure accuracy.

Immune globulins Dose in the treatment of B-cell chronic lymphocytic leukemia with hypogammaglobulinemia, prevention of bacterial infections (Gammagard S/D):

• IV: 400 mg/kg every 3 to 4 weeks.

Immune globulins (bivigam) Dose in the treatment of Chronic inflammatory demyelinating polyneuropathy:

IV:

• Gammaked, Gamunex-C:

  • Loading dose: 2,000 mg/kg (in divided doses over 2 to 4 consecutive days);
  • Maintenance:
    • 1,000 mg/kg administered over 1 day every 3 weeks.
    • Alternatively, administer 500 mg/kg/day for 2 consecutive days every 3 weeks.
    • Note: Continued maintenance therapy beyond the initial 6 months may not be required to maintain therapeutic response.

• Privigen:

  • Loading dose: 2,000 mg/kg (in divided doses over 2 to 5 consecutive days);
  • Maintenance:
    • 1,000 mg/kg administered in a single infusion over 1 day or
    • divided into 2 doses over 2 consecutive days, every 3 weeks.
    • Note: Maintenance therapy beyond 6 months has not been studied.

SubCutaneous:

• Hizentra:
  • Maintenance:
    • Begin therapy 1 week after last IGIV infusion:
    • 200 to 400 mg/kg/week administered in 1 or 2 sessions over 1 or 2 consecutive days.
    • For worsening symptoms, consider restarting IGIV;
    • refer to manufacturer's labeling for additional information.

Immune globulins Dose in the treatment of Hepatitis A (GamaSTAN, GamaSTAN S/D): IM:

• Preexposure prophylaxis upon travel into endemic areas (hepatitis A vaccine preferred) (CDC 2017):

  • 1 mL/kg for anticipated risk of exposure less than 1 month.
  • 2 mL/kg for anticipated risk of exposure 1 to 2 months.
  • Repeat dose of 0.2 mL/kg every 2 months for anticipated risk of exposure ≥2 months.

• Postexposure prophylaxis:

  • 1 mL/kg given within 14 days of exposure and/or prior to the manifestation of disease;
  • not needed if at least 1 dose of hepatitis A vaccine was given at ≥1 month before exposure (CDC 2017).

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Immune globulins Dose in the treatment of Immune thrombocytopenia:

• 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 required to maintain platelet count ≥30,000/mm 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 a day for 2 consecutive days.

• Gammagard S/D:

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

• Gammaked, Gamunex-C:

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

• Gammaplex 5% and 10%, Octagam 10%, Privigen:

  • IV: 1,000 mg/kg/day for 2 consecutive days.

• Panzyga:

  • IV: 1,000 mg/kg/day for 2 consecutive days.

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American College of Obstetricians and Gynecologists Guidelines: IV:

• Immune thrombocytopenia in pregnancy:

  • Initial: 1,000 mg/kg as a one-time dose for pregnant women with immune thrombocytopenia (ITP) may be needed in following cases:
    • refractory to corticosteroids,
    • when significant side effects occur with corticosteroids, or
    • a more rapid platelet increase is necessary;
    • may repeat if necessary (ACOG 207 2019).

• Fetal and neonatal alloimmune thrombocytopenia:

  • 1,000 to 2,000 mg/kg per week administered to the mother, with or without corticosteroids.
  • Dose is according to gestational age and risk.

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American Society of Hematology Guidelines:

• Newly diagnosed ITP with platelets <30,000/mm :

  • First-line treatment:
    • IV: 1,000 mg/kg as a single dose, may repeat if necessary (Neunert 2011).

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Immunoglobulins Dose in the treatment of Measles:

• Cutaquig: SubQ infusion:

  • Pre-exposure prophylaxis in patients with primary humoral immunodeficiency at risk of measles exposure:

    • If weekly dose <245 mg/kg: Increase dose to 245 mg/kg weekly.
    • If weekly dose ≥245 mg/kg: Maintain current dose.

  • Post-exposure prophylaxis in patients with primary humoral immunodeficiency:

    • Administer a dose of an IV immune globulin product as soon as possible and within 6 days of exposure, followed by resumption of prior SubQ infusion dosing schedule.

  • GamaSTAN, GamaSTAN S/D: IM:

    • Post-exposure prophylaxis:
      • 25 mL/kg given within 6 days of exposure.
      • CDC recommends 0.5 mL/kg (maximum dose: 15 mL) within 6 days of exposure.
      • If the patient >30 kg, the patient will have lower titers than what is recommended due to the maximum volume that can be administered (CDC 2013).

  • Gammaked, Gammaplex 5%, Gammaplex 10%, Gamunex-C, Flebogamma DIF 5%, Flebogamma DIF 10%, Octagam 5%, Privigen: IV:

    • Pre exposure prophylaxis in patients with primary humoral immunodeficiency (ONLY if routine dose is <400 mg/kg [or <530 mg/kg (Gammaplex 5%, Flebogamma DIF 5%, Flebogamma DIF 10%, and Privigen only)]):

      • ≥400 mg/kg (≥530 mg/kg for Gammaplex 5%, Flebogamma DIF 5%, Flebogamma DIF 10%, Privigen) immediately before expected exposure followed by resumption of prior dosing in 3 to 4 weeks.

    • Post-exposure prophylaxis in patients with primary humoral immunodeficiency:

      • 400 mg/kg administered as soon as possible after exposure followed by a 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:

  • Pre-exposure prophylaxis in patients with primary humoral immunodeficiency at risk of measles exposure (e.g, during an outbreak, travel to the endemic area):

    • Patients receiving weekly or more frequent dosing: Make sure the total weekly dose of ≥200 mg/kg for 2 consecutive weeks followed by continuation of prior dosing schedule.
    • Patients receiving biweekly dosing: Administer ≥400 mg/kg once followed by resumption of prior dosing schedule.

  • Post-exposure 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 a resumption of the prior dosing schedule.

• ACIP recommendations:

  • IGIV is recommended for pregnant women (without any evidence of measles immunity) and severely immunocompromised persons for post-exposure prophylaxis.
  • Following IG administration, any non-immune 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 getting 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 (CDC 2013).

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Immune globulins Dose in the treatment of Multifocal motor neuropathy (Gammagard Liquid):

• IV: 500 to 2400 mg/kg/month based upon response.

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Immunoglobulins Dose in the treatment of Primary humoral immunodeficiency disorders:

IV infusion dosing:

• Asceniv, Bivigam, Gammaplex 5% and 10%:

  • 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%, Panzyga:

  • 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 SubQ 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 drug 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 weeks) dosing, begin 1 or 2 weeks after the last IV infusion or 1 week after the last SubQ weekly infusion.
      • Note: The patient should have received an IV immune globulin routinely for at least 3 months before switching to SubQ.

  • Use the following equation to calculate the 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 grams) by 5.

Note:

Provided the total per week dose is maintained, any dosing interval from per day up to 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 drug labeling.

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SubQ infusion dosing of immunoglobulins:

• Cutaquig: SubQ:

  • Patients shifting from another IG SubQ product: SubQ infusion: Begin treatment 7 days after patient's last SubQ immune globulin.
    • Initial weekly dosing (grams): Use the same dose as the initial/earlier SubQ immune globulin therapy (grams).
    • Note: For subsequent dose adjustments, refer to drug labeling.
    • Patients shifting from IGIV therapy: SubQ infusion: Begin treatment 7 days after patient's last immune globulin IV.
    • Initial per week dosing (grams): Divide the prior immune globulin IV dose (grams) by the total number of weeks between IV doses, then multiply this by 1.4 (dose adjustment factor).
    • Frequent (2 to 7 times a week) dosing (grams): Divide the calculated per week dose by the required number of times per week.
    • Note: For subsequent dose adjustments, refer to drug labeling.

• Cuvitru: SubQ:

  • Patients shifting from another IG SubQ product: SubQ infusion:
    • Weekly dosing (grams): Weekly dose is the same as the earlier immune globulin subcutaneous dose per week.
    • Biweekly dosing (grams): Multiply the calculated per week dose by 2.
    • Frequent (2 to 7 times a week) dosing (grams): Divide the calculated per week dose by the required number of administration times per week.
    • Note: For subsequent dose adjustments, refer to drug labeling.
  • Patients shifting from IGIV therapy or Hyqvia: SubQ infusion: Begin treatment 7 days after the patient's last immune globulin IV or Hyqvia infusion.
    • Initial per week dosing (grams): Divide the previous immune globulin IV or Hyqvia dose (grams) by the total number of weeks between IV doses, then multiply this by 1.3 (dose adjustment factor).
    • Biweekly dosing (grams): Multiply the calculated per week dose by 2.
    • Frequent (2 to 7 times per week) dosing (grams): Divide the calculated per week dose by the required number of times per week.
    • Note: For subsequent dose adjustments, refer to drug labeling.

• HyQvia: SubQ:

  • See drug manufacturer's labeling for initial ramp-up schedule (starting treatment with a full monthly dose has not been evaluated);
  • dose adjustment is 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 7 days after the last infusion of previous treatment.
  • Patients naive to IgG therapy or shifting from IG SubQ therapy: SubQ infusion: 300 to 600 mg/kg every 21 to 28 days, after the initial dose ramp-up.
  • Patients shifting from IGIV therapy: SubQ infusion: Administer the same dose and frequency as the prior IGIV therapy after the initial dose ramp-up. For subsequent dose adjustments, refer to drug labeling.

• Xembify: SubQ:

  • Patients shifting from another IG SubQ product: SubQ infusion: Weekly dose is the same as the previous immune globulin subcutaneous weekly dose (grams).
  • Note: For subsequent dose adjustments, refer to drug labeling.
  • Patients shifting from IGIV therapy: SubQ infusion: Begin treatment 7 days after patient's last immune globulin IV.
    • Initial weekly dosing (grams): Divide the prior immune globulin IV dose (grams) by the total number of weeks between IV doses, then multiply this by 1.37 (dose adjustment factor).
    • Frequent (2 to 7 times per week) dosing (grams): Divide the calculated per week dose by the required number of times per week.
    • Note: For subsequent dose adjustments, refer to drug labeling.

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Rubella (GamaSTAN, GamaSTAN S/D): IM:

• Postexposure prophylaxis during pregnancy:55 mL/kg.

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Dose in the treatment of Varicella (GamaSTAN, GamaSTAN S/D): IM:

• Prophylaxis:
  • 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.

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Off-label uses: IV:

Immunoglobulins Dose in the treatment of Acquired hypogammaglobulinemia secondary to malignancy (off-label):

• 400 mg/kg/dose every 21 days; reevaluate every 4 to 6 months.

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Immunoglobulins Dose in the treatment of Antibody-mediated rejection in cardiac transplantation, treatment (off-label):

• Dose/frequency/duration of treatment varies greatly:
  • 100 to 2,000 mg/kg (into 2 or 4 divided doses) 1 to 3 times a week, often given after each session of plasmapheresis; maybe re-dosed every month, if re-dose required and based on response.

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Immune globulins (bivigam) Dose in the treatment of severe, refractory, and recurrent C. difficile infection (off-label):

• 150 to 400 mg/kg has been recommended for patients who don't respond to other therapies.
• In retrospective studies and case reports, most of the patients received single-dose therapy within the range previously cited, with a few patients receiving 2 doses (either on consecutive days or by a gap of ≥2 days) and 1 patient getting 6 doses.

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Immune globulins (bivigam) Dose in the treatment of refractory dermatomyositis/ polymyositis in combination with other agents:

• 2,000 mg/kg per treatment course were given in divided doses over 2 to FIVE consecutive days (eg, 400 mg/kg/day for 5 days);
• maximum (per treatment course): 2,000 mg/kg (Feasby 2007).

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Immune globulins (bivigam) Dose in the treatment of Guillain-Barré syndrome (off-label):

• A total dose of 2,000 mg/kg per treatment course, administered in divided doses over 2 to 5 consecutive days (eg, 400 mg/kg/day for FIVE days).
• European Federation of Neurological Societies guidelines recommends the treatment regimen of 5-days.

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Immune globulins Dose in the treatment of Hematopoietic cell transplantation (HCT) with hypogammaglobulinemia (IgG <400 mg/dL), prevention of bacterial infection (off-label):

Note: Increase dose or frequency to maintain IgG concentration >400 mg/dL.

• ≤100 days post-HCT: 500 mg/kg/dose once a week (Tomblyn 2009).
• >100 days post-HCT: 500 mg/kg per dose every 21 to 28 days.

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Immune globulins (bivigam) Dose in the treatment of HIV-associated thrombocytopenia (off-label):

• 1,000 mg/kg/day for 2 days (Anderson 2007).

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Immune globulins Dose in the treatment of Lambert-Eaton myasthenic syndrome (LEMS) (off-label):

• 1,000 mg/kg per day for 2 days.

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Immune globulins Dose in the treatment of acute exacerbation of myasthenia gravis (off-label):

• Adjunctive therapy:
  • 2,000 mg/kg per treatment course, given in divided doses over 2 to 5 consecutive days (eg, 400 mg/kg/day for FIVE days).
• Note: A single dose of 1,000 mg/kg may have the same efficacy to 1,000 mg/kg given on consecutive 2 days.

Immune globulins dose in childrens:

Note:

• Not all products are interchangeable with regards to route of administration;
• consult manufacturers' labeling for additional information.
• Product-specific dosing is provided where applicable;
• some clinicians consider ideal body weight or adjusted ideal body weight in morbidly-obese patients For IVIG dose calculation.
• Dosage mentioned as mg/kg or mL/kg and depend upon the route of administration;
• use extra precaution to ensure accuracy.

Immune globulins Dose in the treatment of acute disseminated encephalomyelitis (ADEM):

• Children and Adolescents:

  • IV: 1,000 mg/kg/dose once a day for 2 days

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Immune globulins Dose in the treatment of Colitis due to Clostridioides (formerly Clostridium) difficile, chronic: 

• Infants and Children:

  • IV: 400 mg/kg/dose every 3 weeks lead to resolution of colitis symptoms during therapy; duration of treatment was unclear (n=5; age range: 6 to 37 months)

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Immune globulins Dose in the treatment of refractory Dermatomyositis:

• Children:

  • IV: 1,000 mg/kg/dose once daily for 2 days;
  • Note: If maintenance therapy is needed, the dose and frequency should be according to clinical response, and doses should not exceed 2,000 mg/kg per treatment course.

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Immune globulins Dose in the treatment of Guillain-Barré syndrome:

Various regimens have been used: Limited data available:

• Children:

  • IV:
    • 1,000 mg/kg/dose once a day for 2 days
    • or 400 mg/kg/dose once a day for 5 days

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Immune globulins (bivigam) Dose in the treatment of Hematopoietic cell transplantation (HCT) with hypogammaglobulinemia (IgG <400 mg/dL), prevention of bacterial infection:

Note: Increase dose or frequency to maintain IgG concentration >400 mg/dL.

• Within the first 100 days after HCT:

  • Infants and Children (Allogeneic HCT recipients):

    • IV: 400 mg/kg/dose once a month

  • Adolescents:

    • IV: 500 mg/kg/dose once a week

• >100 days after HCT:

  • Infants, Children, and Adolescents:

    • IV: 500 mg/kg/dose every 3 to 4 weeks

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Immunoglobulins Dose in the prophylaxis of Hepatitis A:

• Infants, Children, and Adolescents:

Note: Hepatitis A vaccine preferred for patients 1 year to 40 years: Note:

• In adults, total dose volumes of >10 mL should be divided into multiple injections administered at different sites;
• in pediatric patients, consider splitting doses <10 mL based on patient size.

  • Pre-exposure prophylaxis upon travel into endemic areas (CDC 2017):

    • Anticipated duration of risk ≤1 month: IM: 0.1 mL/kg/dose as a single dose
    • Anticipated duration of risk 1 to 2 months: IM: 0.2 mL/kg/dose
    • Anticipated duration of risk ≥2 months: IM: 0.2 mL/kg/dose every 2 months

  • Postexposure prophylaxis:

    • IM:
      • 0.1 mL/kg/dose as a single dose given within 14 days of exposure and prior to the manifestation of disease;
      • not needed if at least 1 dose of hepatitis A vaccine was given at ≥1 month before exposure (CDC 2006; CDC 2007; CDC 2017)

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Immune globulins Dose in the treatment of HIV infection:

• Infants and Children:

  • Primary prophylaxis for serious bacterial infection in patients with hypogammaglobulinemia (IgG <400 mg/dL):

    • IV: 400 mg/kg/dose every 2 to 4 weeks

  • Secondary prophylaxis for invasive bacterial infections:

    • Should only be used if subsequent infections are frequent severe infections (>2 infections during a 1-year period):
    • IV: 400 mg/kg/dose every 2 to 4 weeks

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Immune globulins Dose in the treatment of Immune thrombocytopenia (ITP):

General dosing:

Note: Dosing regimens variable, consult product specific information if available:

• Infants, Children, and Adolescents:

  • Acute therapy:

    • IV: 400 to 1,000 mg/kg/dose once daily for 2 to 5 consecutive days for a total cumulative dose of 2,000 mg/kg;
    • in some cases, cumulative doses up to 3,000 mg/kg have been used

  • Chronic therapy:

    • IV: 400 to 1,000 mg/kg/dose every 3 to 6 weeks based on clinical response and platelet count

Manufacturer's labeling:

• Carimune NF: Infants, Children, and Adolescents:

  • Acute therapy:

    • IV:
      • 400 mg/kg/dose once daily for 2 to 5 days to maintain platelet count ≥30,000/mm and/or to control significant bleeding.
      • If platelet response is adequate (30,000 to 50,000/mm ) after the first 2 doses, then may discontinue therapy.

  • Chronic therapy:

    • IV: 400 mg/kg/dose as a single infusion; may increase to 800 to 1,000 mg/kg/dose to maintain platelet count ≥30,000/mm and/or to control significant bleeding

• Flebogamma DIF 10%: Children ≥2 years and Adolescents:

  • Chronic therapy:

    • IV: 1,000 mg/kg/dose once daily for 2 consecutive days

• Gammaked: Infants, Children, and Adolescents:

  • Acute or chronic therapy:

    • IV: 400 to 1,000 mg/kg/dose once daily for 2 to 5 consecutive days for a total cumulative dose of 2,000 mg/kg; if an adequate platelet response is observed after the initial 1,000 mg/kg/dose, then the subsequent dose may be held

• Gamunex-C: Infants, Children, and Adolescents:

  • Acute or chronic therapy:

    • IV: 1,000 mg/kg/dose once daily for 1 to 2 days based on patient response and/or platelet response or for fluid-restricted patients or other conditions sensitive to volume: 400 mg/kg once daily for 5 days

• Privigen: Adolescents ≥15 years:

  • Chronic therapy:

    • IV: 1,000 mg/kg/dose once daily for 2 days

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Immune globulins (bivigam) Dose in the treatment of Kawasaki disease:

• Infants and Children:

  • IV:
    • 2,000 mg/kg as a single dose over 10 to 12 hours;
    • usually given within 10 days of disease onset;
    • however, may be given >10 days from the onset in patients with a delayed diagnosis or with persistent symptoms of systemic inflammation with persistent fever and/or coronary artery aneurysms;
    • must be used in combination with aspirin;
    • if signs and symptoms persist ≥36 hours after completion of the infusion, retreatment with a second 2,000 mg/kg infusion may be considered with or without corticosteroids.
    • Note: Corticosteroids may be added for primary treatment in patients identified as high risk for the development of coronary artery aneurysms (AHA [McCrindle 2017]).

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Immune globulins (bivigam) Dose in the Prophylaxis of Measles:

• Pre-exposure prophylaxis (eg, during an outbreak, travel to the endemic area):

  • Manufacturer's labeling: Patients with primary humoral immunodeficiency:

    • IV: Gammaked, Gamunex-C (Infants, Children, and Adolescents), Octagam 5% (Children and Adolescents, 6 to 16 years): ≥400 mg/kg per dose urgently prior to expected exposure;
    • Note: Only give to patients whose routine dose is <400 mg/kg/dose.

    • SubQ infusion: Hizentra: Children ≥2 years and Adolescents:

      • Weekly dosing: ≥200 mg/kg/dose once weekly for 2 consecutive weeks
      • Biweekly dosing: ≥400 mg/kg for 1 dose

  • Alternate dosing: ACIP recommendations (CDC 2013): Immunocompromised patients: Infants, Children, and Adolescents:

    • • IV: ≥400 mg/kg/dose within 3 weeks before anticipated exposure
      • SubQ:
        • 200 mg/kg/dose once weekly for 2 consecutive weeks prior to anticipated exposure (CDC 2013);
        • Note:
          • Not all immune globulin preparations may be administered by the SubQ route;
          • Hizentra is the only product currently approved for this indication that may be administered SubQ;
          • consult product labeling for additional information as market availability may change

• Post-exposure prophylaxis:

  • Manufacturer's labeling: Patients with primary humoral immunodeficiency:

    • • IV: Gammaked, Gamunex-C (Infants, Children, and Adolescents), Octagam 5% (Children and Adolescent, 6 to 16 years): 400 mg/kg/dose administered as soon as possible after exposure
      • SubQ infusion: Hizentra: Children ≥2 years and Adolescents:
        • • Weekly dosing: ≥200 mg/kg/dose as soon as possible following exposure
          • Biweekly dosing: ≥400 mg/kg as soon as possible following exposure

  • Alternate dosing: ACIP guidelines (CDC 2013): Any person without evidence of measles immunity:

    • Infants, Children, and Adolescents:

      • • IM:
          • 0.5 mL/kg/dose;
          • maximum dose: 15 mL within 6 days of exposure;
          • in adults, doses >10 mL should be split into multiple injections and administered at different sites;
          • in pediatric patients, may also split doses <10 mL based on patient size.
          • Note:
            • Not all immune globulin preparations may be administered by the IM route; of the products currently available on the market, GamaSTAN S/D may be given IM;
            • consult product labeling for additional information as market availability may change.
            • GamaSTAN S/D manufacturer labeling suggests a lower IM dose of 0.25 mL/kg; however, this dosing was based on previous immune globulin donor potency concentrations; recent data indicates that potency from current donor populations has decreased (ie, measles immunity now from vaccinations instead of immunity from disease) requiring a higher IM immune globulin dose (0.5 mL/kg) in all patients without evidence of measles immunity to ensure adequate serum titers.
        • IV: 400 mg/kg/dose within 6 days of exposure

---

Immune globulins (bivigam) Dose in the treatment of Multiple sclerosis (relapsing-remitting, when other therapies cannot be used): 

• Children and Adolescents:

  • Dosage regimen variable; optimal dose not established: IV: 1,000 mg/kg/dose once a month, with or without induction of 400 mg/kg/day for 5 days.

---

Immune globulins (bivigam) Dose in the treatment of severe exacerbation of Myasthenia gravis: Limited data available:

• Children:

  • IV:
    • 400 to 1,000 mg/kg/dose once daily over 2 to 5 days for a total dose of 2,000 mg/kg;
    • if additional therapy required, the dose should be based on clinical response and titrated to minimum effective dose (Feasby 2007)

---

Immune globulins Dose in the treatment of acute Myocarditis:

• Infants, Children, and Adolescents:

  • IV: 2000 mg/kg as a single dose.
  • A cohort study of 21 children showed improvement in LVF recovery and survival at 1 year as compared to the untreated historical cohort (Drucker 1994);
  • efficacy results are variable
  • the largest data analysis did not show clear clinical benefits nor a positive impact on survival.

Immune globulins Dose in the treatment of Primary immunodeficiency disorders:

Adjust dose/frequency based on desired IgG concentration and clinical response; a trough IgG concentration of ≥500 mg/dL has been recommended by some experts; consult product-specific labeling for appropriate age groups.

• ---

  General dosing (IV):

  • Infants, Children, and Adolescents:

    • 200 to 800 mg/kg/dose every 3 to 4 weeks

• ---

  Manufacturer's labeling:

  • Carimune NF: Infants, Children, and Adolescents:

    • 400 to 800 mg/kg/dose every 3 to 4 weeks

  • Flebogamma DIF 5%, Gammagard Liquid, Gammagard S/D (Children ≥2 years and Adolescents), Gammaked, Gamunex-C (Infants, Children, and Adolescents), Octagam 5% (Children and Adolescents 6 to 16 years):

    • 300 to 600 mg/kg/dose every 3 to 4 weeks

  • Bivigam (Children ≥6 years and Adolescents), Gammaplex 5% (Children ≥2 years and Adolescents):

    • 300 to 800 mg/kg/dose every 3 to 4 weeks

  • Privigen: Children ≥3 years and Adolescents:

    • 200 to 800 mg/kg/dose every 3 to 4 weeks

---

SubQ infusion:

• Cuvitru: Children ≥2 years and Adolescents:

  • Patients switching from IGIV therapy: Begin 1 week after last immune globulin IV dose. Use the following equations to calculate the initial dose:

    • Initial weekly dosing: Dose (grams) = (IV dose [grams] divided by IV dose interval [weeks]), then multiply this dose by 1.3 (dose adjustment factor)
    • Biweekly dosing (grams): Multiply the calculated weekly dose by 2
    • Frequent dosing (2 to 7 times per week) (grams): Divide the calculated weekly dose by the desired number of times per week
    • Note: For subsequent dose adjustments, refer to drug labeling.

  • 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 dosing (2 to 7 times per week) (grams): Divide the calculated weekly dose by the desired number of administration times per week
    • Note: For subsequent dose adjustments, refer to drug labeling.

  • ---

    Gammagard Liquid, Gammaked, Gamunex-C: Children ≥2 years and Adolescents:

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

      • Initial weekly dose: Dose (grams) = (1.37 x IV dose [grams]) divided by (IV dose interval [weeks]); Note: For subsequent doses, refer to product labeling.

  • Hizentra: Children ≥2 years and Adolescents:

    • For weekly dosing or frequent (up to daily), begin 1 week after last IV or SubQ infusion.
    • For biweekly dosing, begin 1 or 2 weeks after the 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 the initial dose:
      • Initial weekly dose: Dose (grams) = (Previous IV dose [grams]) divided by (IV dose interval [weeks]) then multiply by 1.37; if switching from a different SubQ formulation to Hizentra, maintain previous weekly SubQ dose initially. Note: To convert the dose (in grams) to mL, multiply the calculated dose (in grams) by 5.
• Note:
  • Provided the total per week dose is maintained, any dosing interval from per day up to every 2 weeks may be used.
  • Use the following calculations to calculate frequent or biweekly dosing:
    • • 2 weekly dose (grams): Dose = Calculated or prior weekly SubQ dose (grams) multiplied by 2
      • Frequent (2 to 7 times per week) dosing: Dose (grams) = Calculated or prior weekly dose (grams) divided by the total number of times per week (eg, for 3 times per week dosing, divide weekly dose by 3)

Note: For subsequent doses refer to product labeling.

Immunoglobulins Dose in the postexposure Prophylaxis of Rubella during pregnancy:

• GamaSTAN S/D: Adolescents:

  • IM: 0.55 mL/kg per dose as a single dose within 3 days of exposure.
  • Note:
    • Not recommended for routine use;
    • may reduce, but not eliminate, the risk for rubella.
    • In adults, total dose volumes of >10 mL should be divided into multiple injections given at different sites.

Dose in the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN):

• Infants, Children, and Adolescents:

  • IV: Usual dose: 1500 to 2000 mg/kg total dose as a single dose or divided over 2 to 4 days; dosing based on retrospective reviews and case reports;
  • efficacy results are variable.

Immune globulins dose for the postexposure prophylaxis of Varicella-zoster (independent of HIV-status):

• Infants, Children, and Adolescents:

Note: Use only if varicella-zoster immune globulin is not available.

• • IV: 400 mg/kg as a single infusion as soon as possible and within 10 days of exposure; ideally within 96 hours of exposure.
  • IM: GamaSTAN S/D: 0.6 to 1.2 mL/kg per dose as a single dose within 3 days of exposure
  • Note:
    • In adults, injections of >10 mL should be divided into multiple injections given at different sites;
    • in pediatric patients, consider splitting doses <10 mL based on patient size.

 

Pregnancy Risk Category: C

• Placental transfer is affected by the IgG subclass as well as the gestational year. This trend generally increases with every pregnancy.
• The lowest possible exposure should be expected during the period of organogenesis.
• Two women were involved in the study to test exogenous immunoglobulin, a treatment for common variable immune deficiency. It was found that it crossed the placenta at levels similar to those of endogenous.
• It has been recommended to use IV immune globulin for the treatment of fetal and neonatal immune thrombocytopenias (FNAIT) as well as pregnancy-associated immuno thrombocytopenias.
• Patients who have severe side effects or are refractory to treatment should consider ITP.
• Intravenous immune globulin is recommended to prevent measles in pregnant mothers who aren't immune.
• It can also be used to prevent rubella infection in post-exposure prophylaxis. This is for pregnant women who do not want to have therapeutic abortion.
• IV immunoglobulin is an option for myasthenia gravis patients who need immediate treatment during pregnancy.

Use of immunoglobulins while breastfeeding

• Immune globulin is usually found in breast milk.
• Two women received IV immunoglobulin, (IVIG) for common variable immunodeficiency. One mother suffering from IgA deficiency received colostrum, which provided the same IgA immunological protection as mothers without any deficiencies.
• According to the manufacturer, therapy should be considered when deciding whether to stop or continue breastfeeding.
• Breastfeeding can be done with immunoglobulin.

 

Immunoglobulins Dose in Kidney Disease:

• 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.

 

Immunoglobulins Dose in Liver disease:

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

 

Common Side Effects of Immune globulins:

• Cardiovascular:

  • Hypotension
  • Tachycardia
  • Decreased Diastolic Blood Pressure
  • Decreased Heart Rate

• Central Nervous System:

  • Headache
  • Fatigue
  • Chills
  • Pain
  • Rigors
  • Dizziness

• Dermatologic:

  • Injection Site Pruritus

• Gastrointestinal:

  • Sore Throat
  • Abdominal Pain
  • Diarrhea
  • Vomiting
  • Viral Gastroenteritis
  • Nausea
  • Upper Abdominal Pain

• Hematologic & Oncologic:

  • Positive Direct Coombs Test
  • Hemorrhage
  • Anemia

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Hyperbilirubinemia

• Immunologic:

  • Antibody Development

• Local:

  • Infusion Site Reaction
  • Erythema At Injection Site
  • Pain At Injection Site

• Neuromuscular And Skeletal:

  • Arthralgia
  • Limb Pain
  • Muscle Cramps
  • Back Pain

• Otic:

  • Otalgia

• Renal:

  • Nephrolithiasis

• Respiratory:

  • Cough
  • Nasal Congestion
  • Sinusitis
  • Pharyngitis
  • Asthma
  • Upper Respiratory Tract Infection
  • Rhinitis
  • Epistaxis
  • Bronchitis
  • Nasopharyngitis
  • Rhinorrhea
  • Paranasal Sinus Congestion
  • Nasal Mucosa Swelling
  • Wheezing

• Miscellaneous:

  • Fever
  • Accidental Injury

Less Common Side Effects of Immune globulins:

• Cardiovascular:

  • Chest Pain
  • Hypertension
  • Peripheral Edema
  • Heart Murmur
  • Chest Discomfort
  • Flushing
  • Thrombosis

• Central Nervous System:

  • Insomnia
  • Myasthenia
  • Migraine
  • Depression
  • Lethargy
  • Fibromyalgia Syndrome
  • Falling
  • Malaise
  • Vertigo

• Dermatologic:

  • Skin Rash
  • Xeroderma
  • Dermatitis
  • Cellulitis
  • Urticaria
  • Excoriation Of Skin
  • Hyperhidrosis
  • Allergic Dermatitis
  • Erythema Of Skin
  • Pruritus
  • Eczema

• Endocrine & Metabolic:

  • Thyroiditis
  • Ketonuria
  • Dehydration
  • Increased Lactate Dehydrogenase

• Gastrointestinal:

  • Dyspepsia
  • Clostridioides Difficile Colitis
  • Gastroenteritis
  • Gastritis
  • Stomach Discomfort
  • Abdominal Distress

• Genitourinary:

  • Vulvovaginal Candidiasis
  • Urinary Tract Infection
  • Cystitis
  • Dysuria

• Hematologic & Oncologic:

  • Bruise
  • Hematoma

• Hepatic:

  • Increased Serum Aspartate Aminotransferase
  • Decreased Serum Alkaline Phosphatase

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Fungal Infection
  • Influenza
  • Infection
  • Viral Infection

• Local:

  • Infusion Site Pain
  • Local Swelling
  • Local Inflammation

• Neuromuscular & Skeletal:

  • Asthenia
  • Myalgia
  • Muscle Spasm
  • Joint Effusion
  • Joint Swelling

• Ophthalmic:

  • Conjunctivitis
  • Eye Discharge
  • Eye Irritation

• Otic:

  • Otitis Media

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Exacerbation Of Asthma
  • Viral Upper Respiratory Tract Infection
  • Tonsil Disease
  • Dyspnea
  • Pharyngolaryngeal Pain
  • Pneumonia
  • Oropharyngeal Pain
  • Post-Nasal Drip
  • Throat Irritation
  • Flu-Like Symptoms

Side effects of immunoglobulins (Frequency Not known):

• Cardiovascular:

  • Facial flushing

• Central nervous system:

  • Drowsiness

• Local:

  • Localized tenderness
  • Local pain

• Neuromuscular & skeletal:

  • Lower limb cramp

• Ophthalmic:

  • Blurred vision

• Renal:

  • Increased blood urea nitrogen
  • Renal insufficiency

 

Contraindications to Immune globulins:

• Hypersensitivity to immunoglobulins and any other component of this formulation
• IgA deficiency (with anti IgA antibodies and history hypersensitivity [exclusively Gammagard S/D]);
• Hyperprolinemia (Hizentra, Privigen);
• Severe thrombocytopenia (GamaSTAN), and coagulation disorders are reasons not to use IM injections.
• Hypersensitivity to corn (Octagam 5%)
• Genetic intolerance to fructose (Gammaplex 5%)
• Infants/neonates not tolerating sucrose/fructose (Gammaplex 5%)
• Hypersensitivity to hyaluronidase, humanalbumin or any other component of the hyaluronidase formulation (HyQvia).
• Cross-reactivity between allergens and immune globulins is unlikely. Cross-sensitivity can be caused by similarities in chemical structure and pharmacologic effects.

Precautions and warnings

• Anaphylaxis and hypersensitivity reactions

  • Anaphylactic reactions and hypersensitivity may occur, some very serious. Patients with antibodies against IgA are at greater risk. It is rare for blood pressure to drop dramatically.
  • Stop using any medication.
  • You should immediately seek treatment (including epinephrine 1, mg/mL).

• Aseptic meningitis

  • Aseptic meningitis syndrome, also known as AMS, can be caused by immune globulin administration in high doses (>=1 g/kg) and/or rapid infusion.
  • Symptoms typically appear within one to two days.
  • Most problems resolve within days of the product being discontinued.
  • Patients who have had migraines in the past or patients who are female may be at greater risk for developing AMS.

• Hematoma

  • Subcutaneous treatment of immune thrombocytopenia is not recommended due to the potential for hematoma formation.

• Hemolysis

  • Intravenous immune globulin was linked to antiglobulin hemolysis.
  • Hemolysis-related renal impairment/failure has been reported.
  • High hemolysis doses (>=2g/kg) that are administered in one or multiple administrations over several days can pose a risk factor. 
  • You may also have underlying conditions such as inflammatory disorders and non-O blood types.
  • Risk factors that could increase include an underlying inflammation condition such as high C-reactive protein or erythrocyte separation rate.
  • Patients suffering from hemolytic anemia need to be closely monitored, particularly if they have a history of anemia or are experiencing cardiovascular or pulmonary complications.

• Inheritable fructose intolerance

  • It is possible that sorbitol may be found in immunoglobulins.
  • HFI sufferers who have been affected by sorbitol could be at risk.
  • One in 20,000 babies can develop HFI. It is usually diagnosed when sucrose and fructose are added to the diet.
  • Common signs include persistent vomiting, stomach pain, hypoglycemia and stomach cramps.
  • Patients with HFI shouldn't be given immunoglobulin containingsorbitol.

• Hyperproteinemia

  • Hyperproteinemia, elevated serum viscosity, and hyponatremia are all possible causes of hyponatremia. Hyponatremia must not be confused with pseudo hyponatremia in order to avoid volume depletion.

• Hypertension

  • Infusions of Panzyga and Privigen resulted in blood pressure elevations (systolic >=180mmHg and/or dialystolic>120mmHg), which were treated with observation or oral antihypertensive treatment.

• Infusion reactions

  • Monitor patients for adverse reactions before and after infusions.
  • Stop administering the infusion if you feel severe symptoms (fever, chills, nausea).
  • Two possible ways to increase your risk are first treatment with an alternative brand of immunoglobulin, and second treatment interruptions lasting longer than 8 weeks.

• Pulmonary edema

  • Monitor for transfusion-related acute lung injury (TRALI).
  • It has been reported that non-cardiogenic pulmonary embolism can be caused by immune globulin.
  • TRALI can be described by severe respiratory distress, hypoxemia, pulmonary embolism and fever even though left-ventricular function is normal.
  • It typically occurs between 1 to 6 hours after infusion.

• Acute renal failure and kidney dysfunction: [US Boxed Warn]

  • IV Administration is only:Although rare, acute renal dysfunction (increased creatinine and oliguria) can lead to fatalities in predisposed people.
  • Patients at high risk for kidney dysfunction include those over 65, those who have kidney problems, diabetics and people who are dehydrated.
  • Patients who are treated with sucrose-containing IGIV products have a higher risk of developing acute renal failure or renal dysfunction.

NotificationThe following IV preparations do not contain sucrose

• Asceniv
• Bivigam
• Flebogamma DIF
• Gammagard Liquid
• Gammagard S/D
• Gammaked
• Gammaplex
• Gamunex-C
• Octagam 5%
• Octagam 10%
• Panzyga can be described as:
• Privigen.
  • Patients at risk of acute renal failure and renal derangement need to be hydrated. Patients at higher risk should have the dose, rate, or concentration of the solution decreased.
  • Assess your kidney function before starting treatment. Then, check it again periodically.
  • Stop using if your renal function is declining

• [US Boxed Warning] Thromboembolic Events

  • Even if there are not any risk factors, immune globulin products can cause thrombosis.
  • High-risk individuals include people who are immobile, elderly, hypercoagulable, and have a history or use of estrogens. 
  • They should also be administered the lowest possible dose and infusion rate.
  • Make sure you are hydrated before you start administering.
  • Assess blood viscosity in patients at high risk of hypervisibility, such as those who have cryoglobulins, severe hypertriglyceridemia/fasting chylomicronemia or monoclonal Gammopathies.

• Fluid overload

  • Patients suffering from fluid overload or who are concerned about fluid volume should avoid high-dose regimens (up to 2 days) of 1g/kg.

• IgA deficiency

  • Patients with anti-IgA antibodies are at greater risk for hypersensitivity/allergy.
  • Patients with IgA deficiency (with antibodies against IgA or a history of hypersensitivity) and patients with isolated IgA deficiencies should not be treated.

• Renal impairment

  • Use caution when administering this medication. Before you can take this medication, it is important to hydrate.
  • It is important to maintain a low solution concentration and infusion rate

 

Monitoring parameters:

• Renal function (before initial infusion and at appropriate intervals),
• urine output,
• IgG concentrations,
• hemoglobin and hematocrit,
• platelets (in patients with ITP);
• infusion- or injectionrelated adverse reactions,
• anaphylaxis,
• signs and symptoms of thrombosis,
• 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;
• blood pressure (prior to, during, and following infusion);
• clinical response.
• Note:
  • 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 before and 36 to 96 hours post-infusion and again at 7 to 10 days after infusion.

• SubQ infusion:

  • For the treatment of primary humoral immunodeficiency, 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.

 

How to administer Immune globulins?

Notice: After the plasmapheresis session is completed, administer immune globulin to the patient.

Injecting immunoglobulins intramuscularly:

• Apply IM to the anterolateral areas of the upper thigh and deltoid muscles of the upper arms.
• Avoid the gluteal area as it could cause injury to the sciatic nerve.
• Divide doses greater than 10 mL and inject them at multiple locations.

GamaSTAN and GamaSTANS/D are only for IM routes.

---

Intravenous infusion of immunoglobulins:

• Allow to infuse for between 2 and 24 hours
• Infusions should be administered separately from any other medications.
• If you are using primary line, flush the system with D5W or NS before administering.
• Persons at high risk of developing renal failure may need to be given a lower dose, a lower rate and/or a lower concentration of infusions.
• To relieve certain adverse effects, such as flushing, pulse rate changes, or changes in blood pressure, it may be beneficial to reduce the infusion rate or stop the infusion.
• Epinephrine should always be available during administration.
• Infusions should be administered at a slower or lower rate for patients with advanced disease, as well as those who are receiving treatment initially.
• Each IVIG product has a unique initial rate and titration.
• Before infusion, the refrigerated product must be brought to room temperature.
• Filtration is required for certain products. Refer to the individual product labeling.
• To avoid discomfort at the injection site, antecubital veins should not be used in concentrations greater than 10%

Asceniv: 

• Primary humoral immunodeficiency
  • Initial (15 minutes): 0.5 mg/kg/minute (0.3mL/kg/hour).
  • Maintenance: If tolerated, titrate every 15 minutes up to 8 mg/kg/minute (4.8mL/kg/hour).

Bivigam 10%: 

• Primary humoral immunodeficiency
  • Initial (10 minutes): 0.5 mg/kg/minute (0.3mL/kg/hour).
  • Maintenance: If tolerated, increase every 20 minutes by 0.8 mg/kg/minute (0.48 mg/kg/hour) 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 (0.66 mL/kg/hour).
  • Maintenance: If tolerated, slowly increase the dosage to 5 mg/kg/minute (6mL/kg/hour).

Flebogamma DIF 10%: 

• Primary immunodeficiency (or immune thrombocytopenia):
  • Initial: 1 mg/kg/minute (0.66 mL/kg/hour);
  • Maintenance: If tolerated, slowly increase the rate of titration to 8 mg/kg/minute (4.8mL/kg/hour).

Gammagard Liquid 10%:

• Multifocal motor neuropathy
  • Initial: 0.8 mg/kg/minute (0.5mL/kg/hour);
  • Maintenance: If tolerated, increase gradually to 9 mg/kg/minute (5.4mL/kg/hour).
• Primary humoral immunodeficiency
  • Initial (30 minutes): 0.8 mg/kg/minute (0.5mL/kg/hour).
  • Maintenance: Increase every 30 min (if tolerated). Maximum 8 mg/kg/minute (5mL/kg/hour).

Gammagard S/D: 5% solution: 

• Initial: 0.5 mg/kg/hour. May increase, if tolerated, to a maximum rate 4 mL/kg/hour.
• If the maximum tolerated rate of 5% solution is reached, you may be able to administer 10% solution at a rate of 0.5mL/kg/hour.
• You may increase the dose (if tolerated), to 8 mL/kg/hour.

Gammaked 10%:

• CIDP
  • Initial (30 minutes): 2 mg/kg/minute (1.2mL/kg/hour).
  • Maintenance: Keep the dose at a maximum of 8 mg/kg/minute (4.8mL/kg/hour).
• Primary humoral immunodeficiency (ITP) or immune thrombocytopenia
  • Initial (30 minutes): 1 mg/kg/minute (6.6 mL/kg/hour).
  • Maintenance: Keep the dose at a maximum of 8 mg/kg/minute (4.8mL/kg/hour).

Gammaplex 5%: 

• Primary humoral immunodeficiency (or ITP):
  • Initial (15 minutes): 0.5 mg/kg/minute (0.6mL/kg/hour).
  • Maintenance: Increase once every 15 minutes (if tolerated), up to 4 mg/kg/minute (44.8 mL/kg/hour).

Gammaplex 10%: 

• Primary humoral immunodeficiency (or ITP):
  • Initial (15 minutes): 0.5 mg/kg/minute (0.3mL/kg/hour).
  • Maintenance: If tolerated, titrate every 15 minutes up to 8 mg/kg/minute (4.8mL/kg/hour).

Gamunex-C 10%:

• CIDP
  • Initial (30 minutes): 2 mg/kg/minute (1.2mL/kg/hour).
  • Maintenance: Keep the dose at a maximum of 8 mg/kg/minute (4.8mL/kg/hour)
• Primary humoral immunodeficiency (or ITP):
  • Initial (30 minutes): 1 mg/kg/minute (6.6 mL/kg/hour).
  • Maintenance: Keep the dose at a maximum of 8 mg/kg/minute (4.8mL/kg/hour).

Octagam 5%:

• Primary humoral immunodeficiency
  • Initial (30 minutes): 0.5 mg/kg/minute (0.6mL/kg/hour).
  • Maintenance: Increase the infusion rate if necessary, up to a maximum rate at 3.33 mg/kg/minute (4.2mL/kg/hour).

Octagam 10%:

• ITP:
  • Initial (30 minutes):1 mg/kg/minute (0.6mL/kg/hour).
  • Maintenance: Increase the infusion rate if necessary, up to a maximum of 12 mg/kg/minute (7.2mL/kg/hour).

Panzyga:

• ITP:
  • Initial (30 minutes): 1 mg/kg/minute (6.6 mL/kg/hour).
  • Maintenance: May be increased gradually (if tolerated), every 15-30 minutes to up to 8 mg/kg/minute (44.8 mL/kg/hour).
• Primary humoral immunodeficiency
  • Initial (30 minutes): 1 mg/kg/minute (6.6 mL/kg/hour).
  • Maintenance: May be increased gradually (if tolerated), every 15-30 minutes up to 8 mg/kg/minute (4.8 mL/kg/hour in treatment-naive people) or up to 12-14 mg/kg/minute (7.8 to 8.4 mg/kg/hour in treatment-experienced persons).

Privigen 10%:

• ITP:
  • Initial: 0.5 mg/kg/minute (0.33 mL/kg/hour).
  • Maintenance: If tolerated, increase gradually to 4 mg/kg/minute (2.4mL/kg/hour).
• CIDP/Primary Humoral Immunodeficiency
  • Initial: 0.5 mg/kg/minute (0.33 mL/kg/hour).
  • Maintenance: If tolerated, increase gradually to 8 mg/kg/minute (4.8mL/kg/hour).

---

SubQ infusion of Immunoglobulins:

• It is important to administer the initial dose in a setting that can provide monitoring and treatment for hypersensitivity.
• Follow the instructions of the manufacturer for filling the reservoir, and preparing your pump using an aseptic method.
• Prime the needle and remove any air from the administration set.
• Once the administration sites have dried, insert a subcutaneous needle to prime the administration set.
• Attach a sterilize needle to the administration set. Gently pull back on syringe until blood vessels are not inadvertently accessed.
• For each injection site, repeat the process.
• Follow the instructions on the infusion device to administer the dose.
• Alternate infusions to rotate the area.
• In the event of no adverse reactions, treatment may be transferred to the home/homecare setting.

Cutaquig:

• Injection sites
  • Abdomen, hip, thigh, upper arm and/or upper leg/hip. =6 simultaneous injections sites (spaced at least 2 inches apart).
• Maximum infusion rate
  • Initial 6 infusions: 20mL/hour at each injection site, or 30mL/hour at all sites.
  • Seventh and subsequent infusions: 25 mL/hour for each injection site. The initial maximum rate for all injection sites is 50 mL/hour. If tolerated, it may rise to 80 mL/hour. In the future, 100 mL/hour.
• Maximum infusion volume
  • Initial 6 Infusions: 25mL per Injection Site
  • After the seventh infusion, 40 mL per injection site.

Cuvitru: 

 

Notice: Siliconized syringes can cause particles to form. The manufacturer suggests that administration be completed within two hours.

• Injection sites
  • Abdomen, thigh and upper arm; =4 simultaneous injections sites (spaced >=4 inches apart).
• Maximum infusion rate
  • For the first 2 infusions, 10-20 mL/hour are recommended for each injection site. The rate may be increased to 60 mg/hour for subsequent injections if tolerated.
• Maximum infusion volume
  • Patients under 40 kg
    • 20 mL per injection site (2nd and 3rd infusions); can increase to 60 mg per site for the subsequent infusions.
  • Patients >=40kg:
    • 60 mL per injection site

Gammagard Liquid:

• Injection sites
  • Abdomen, thigh and upper arm; =8 simultaneous injections sites (spaced >=2 inches apart).
• Initial infusion rate
  • 40 kg
    • 15 mL/hour for each injection site (maximum volume 20 mL for each injection site).
  • >=40 kg
    • 20 mL/hour for each injection site (maximum volume 30 mL/injection site).
• Rate of maintenance infusion:
  • 40 kg
    • 15 to 20mL/hour for each injection site (maximum volume 20mL per injection station).
  • >=40 kg
    • 20-30 mL/hour for each injection site (maximum volume 30 mL/site).

Gammaked, Gamunex-C:

• Injection sites
  • Abdomen, thigh and upper arm; =8 simultaneous injectable sites (spaced >=2 inches apart).
• Infusion rate recommended:
  • 20 mL/hour for each infusion site

Hizentra:

• Injection sites
  • Abdomen, thigh and upper arm; =8 simultaneous injectable sites in parallel (spaced =2 inches apart).
• Maximum infusion rate
  • First infusion
    • 15 mL/hour for injection sites (primary humoral immune deficiency) and 20 mL/hour for injection sites (CIDP).
  • The next infusions:
    • 25 mL/hour for injection sites (primary humoral immune deficiency), or 50 mL/hour for injection sites (CIDP).
• Maximum infusion volume
  • First infusion
    • 15 mL per injection (primary humoral immune deficiency) or 20 mg per injection (CIDP).
  • The next infusions:
    • 25 mL per injection (primary humoral immune deficiency) and 50 mL each injection site (CIDP).

HyQvia:

• In order to administer HyQvia, the components (immunoglobulin and Hyaluronidase), in a sequence.
• Do not use each component by itself.
• An infusion pump that can infuse rates of up to 300mL/hour/site, is required. It must also be able to adjust the flow rate.
• You should use a 24 gauge subcutaneous needle set that is marked for high flow rates.
• Leakage can occur at the Infusion site. Consider using longer needles (14mm or 12mm) and/or more that one infusion site.
• Within 10 minutes of hyaluronidase injection, infuse the entire dose of immune globulin using the same subcutaneous needle.
• Infuse every vial of immunoglobulin, whether it is full or part of it.
• You can use a second site based on tolerance and total volume. If you do choose to use a second site, administer half the volume of the hyaluronidase at each site.
• If necessary, flush the IV line with D5W or NS.
• Injection sites
  • The middle to upper abdomen and thighs should be avoided.
  • Two sites can be used simultaneously. The infusion sites must be located on opposite sides of the body.
• Volume per site
  • 40 kg
    • =300mL per injection site
  • >=40 kg
    • 600 mL per injection site
• Infusion rate
  • Hyaluronidase: 1 - 2 mL/minute or as tolerated

Immune globulin

• Infusions 2:
  • 40 kg
    • 5 mL/hour, 5 to 15, minutes; 10 to 15 mins; 20 to 30 mL/hour, 5 to 15, minutes; 40 to 60 mL/hour, 5 to 15. minutes; 80 to 80 mL/hour to complete the infusion.
  • >=40 kg
    • For 5 to 15, minutes, 10 mL/hour; 30 mL/hour; 60 mL/hour; 5 to15 minutes; 60mL/hour; 120mL/hour; 5 to15 minutes; 5 to15 minutes; and 5 to15 minutes; then, 240mL/hour to complete the infusion.
• Next 2 to 3 infusions
  • 40 kg
    • For 5 to 15, minutes, 10 mL/hour; 20 mL/hour; 40 mL/hour (5 to 15 min); 80 mL/hour (5 to 15 min); 160 mL/hour (remaining infusion)
  • >=40 kg
    • For 5 to 15, minutes, 10 mL/hour; 30 mL/hour; 120mL/hour (5 to 15 min); 240mL/hour (5 to 15 min); 300mL/hour (remaining infusion)

Xembify:

Notice: Siliconized syringes can cause particles to form. The manufacturer suggests that administration be completed within two hours.

• Injection sites
  • Abdomen, thigh and upper arm; sides, back, lateral hip.
• Maximum infusion rate
  • 25 mL/hour for each injection site
• Maximum infusion volume
  • 25 mL per injection site

 

Mechanism of action of Immune globulins (bivigam):

• Treatment for secondary and first immunodeficiencies, IgG antibodies to bacteria and viruses, parasitic and mycoplasma.
• Interference with Fc receptors in cells of the reticuloendothelial systems to cause autoimmune Cytopenias, ITP and other conditions
• Passive immunity can be achieved by raising the antibody titer or antigen-antibody reaction pot.

Onset of action: IV: Instantaneous antibody levels

• Immune thrombocytopenia - Initial response is 1 to 3 days. Peak response is 2 to 7 days

Time of action IM, IV:

• Immune effects: 3 to 4 Weeks (variable).
• Healthy subjects have an intravascular portion of 41% to 57%. Patients with congenital immunodeficiencies (CHI) are at 70%.

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 has coincided with a shortened half-life.

Time to peak:

• Plasma: SubQ: Cutaquig: ~2 days;
• Cuvitru: ~4.4 days;
• Gammagard Liquid: 2.9 days;
• Hizentra: 2.9 days;
• HyQvia: ~5 days;
• Xembify: ~3 days.
• Serum: IM: ~48 hours.

 

International Brands of Immune globulins:

• Asceniv
• Bivigam
• Carimune NF
• Cutaquig
• Cuvitru
• Flebogamma DIF
• GamaSTAN
• GamaSTAN S/D
• Gammagard
• Gammagard S/D Less IgA
• Gammaked
• Gammaplex
• Gamunex-C
• Hizentra
• Hyqvia
• Octagam
• Panzyga
• Privigen
• Xembify
• Cutaquig
• Cuvitru
• Gamastan S/D
• Gammagard
• Gammagard S/D
• Gamunex
• Hizentra
• IGIVnex
• Iveegam Immuno
• Octagam
• Panzyga
• Privigen
• Allerglobuline
• Aragam
• Aunativ
• Beriglobin
• Beriglobin P
• Beriglobina
• Beriglobina P
• Endobulin
• Flebogamma
• Gamastan
• Gamastan Immune Globulin
• Gamimune
• Gamma 16
• Gamma I.V.
• Gammagard
• Gammagard S/D
• Gammanorm
• Gammaplex
• Gammonativ
• Gamunex
• Gamunex C
• Gamunex-C
• Globuman Berna
• Hizentra
• Humaglobin
• Humoglob
• V.-Globulin SN
• IG Gamma
• IG Vena
• Ig Vena NIV
• Immunorel
• Intragam P
• Intraglobin
• Intraglobin F
• Intratect
• IV Globulin-S
• Kiovig
• Klovig
• Octagam
• Pentaglobin
• Privigen
• Sandoglobulin
• Sandoglobulina
• Subcuvia
• Subgam
• Tegeline
• Vena IG
• Vigam

 

Immune Globulins Brand Names in Pakistan:

Immune Globulins Injection 2 % w/v
Atg Fresenius	Universal Enterprises

 

Immune Globulins Injection 5 % w/v
Biaven	Amson Vaccines & Pharma (Pvt) Ltd.
Gama Globlin	Genesis Pharmaceuticals (Pvt) Ltd.
Gamimune- N	Popular International (Pvt) Ltd., Bayer Biological Division
Gamma Venin P	Hakimsons Impex (Pvt) Ltd.
Globulin I.V	Genesis Pharmaceuticals (Pvt) Ltd.
Intraglobin	Nabiqasim Industries (Pvt) Ltd.
Octagam	Hakimsons Impex (Pvt) Ltd.
Pentaglobin-Iv	The Eastern Trade & Distribution Co. (Pvt) Ltd.

 

Immune Globulins Injection 16 % w/v
Globuman	Hakimsons Impex (Pvt) Ltd.

 

Immune Globulins Injection 2.5 g
Gammaraas	Navegal Laboratories

 

Immune Globulins Injection 95 % w/v
Pentaglobin	Nabiqasim Industries (Pvt) Ltd.

 

Immune Globulins Injection 2.5 g/ml
Higlobin	Hi-Warble Pharmaceutical (Pvt) Ltd