Immune Globulin (Monograph)

Brand names: Asceniv, Bivigam, Carimune, Cutaquig, Cuvitru, ... show all 17 brands Flebogamma, Gammagard, GamaSTAN, Gammaked, Gammaplex, Gamunex-C, Hizentra, Hyqvia, Octagam, Panzyga, Privigen, Xembify
Drug class: Antitoxins and Immune Globulins
VA class: IM500
CAS number: 9007-83-4

Introduction

Immune globulin IM (IGIM), immune globulin IV (IGIV), and immune globulin subcutaneous; sterile, nonpyrogenic preparations of globulins containing many antibodies normally present in adult human blood.

Uses for Immune Globulin

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

IGIM (GamaSTAN) is used to provide short-term passive immunity to HAV infection for preexposure prophylaxis in certain susceptible individuals at risk of exposure to the virus.

Primary immunization with an age-appropriate schedule of hepatitis A vaccine is preferred for HAV preexposure prophylaxis in most adults, adolescents, children, and infants ≥12 months of age, unless contraindicated, since active immunization provides long-term protection.

IGIM can be used alone for HAV preexposure prophylaxis when the vaccine is unavailable or cannot be used (e.g., infants <12 months of age, individuals hypersensitive to vaccine components).

Combined passive immunization with IGIM and active immunization with hepatitis A vaccine should be used in those who require both immediate and long-term protection against HAV.

Travelers to areas with intermediate or high levels of endemic HAV are at substantial risk of acquiring the disease. Risk is highest for those who live in or visit rural areas, trek in back country areas, or frequently eat or drink in settings with poor sanitation. However, cases of travel-related HAV can occur in travelers who have standard tourist itineraries and accommodations and food consumption behaviors considered low risk. Consult CDC website ([Web]) for information regarding which countries have intermediate or high levels of HAV endemicity.

USPHS Advisory Committee on Immunization Practices (ACIP) and CDC recommend HAV preexposure prophylaxis in all susceptible individuals (i.e., unvaccinated, partially vaccinated, or never infected) traveling for any purpose, frequency, or duration to areas where HAV endemicity is intermediate or high. In addition, because of the complexity of determining HAV endemicity globally, some experts advise individuals traveling outside the US to consider HAV preexposure prophylaxis regardless of travel destination.

Hepatitis A vaccine is preferred for HAV preexposure prophylaxis in most travelers, unless contraindicated, and should be administered as soon as travel is considered. A single dose of hepatitis A vaccine administered before departure can provide adequate protection for most healthy travelers. For optimal protection in travelers at greatest risk for HAV (adults >40 years of age or individuals with altered immunocompetence, chronic liver disease or other chronic medical condition) who plan to depart in <2 weeks, a single dose of IGIM can be given concurrently with the initial dose of hepatitis A vaccine (at a different site).

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IGIM (GamaSTAN) is used to provide short-term passive immunity for postexposure prophylaxis of HAV in susceptible individuals with recent (within 2 weeks) exposure to the virus.

Although IGIM is 80–90% effective in preventing symptomatic HAV infection if administered within 2 weeks of exposure, monovalent hepatitis A vaccine appears to be as effective as IGIM for HAV postexposure prophylaxis in healthy individuals 1 through 40 years of age if administered within 2 weeks of exposure. The vaccine offers certain advantages over IGIM (e.g., induces active immunity and longer protection, more readily available, easier to administer, greater patient acceptance). However, if only IGIM or only hepatitis A vaccine is available at the time HAV postexposure prophylaxis is needed, either product can be administered, unless contraindicated.

Combined passive immunization with IGIM and active immunization with hepatitis A vaccine is recommended for postexposure prophylaxis of HAV in susceptible individuals ≥12 months of age who are immunocompromised or have chronic liver disease and may be considered in healthy adults >40 years of age since such individuals may have lower seroconversion rates after vaccination and are at increased risk of more severe manifestations of HAV.

HAV postexposure prophylaxis is not necessary in healthy individuals who have previously received hepatitis A vaccine according to the age-appropriate immunization schedule.

If HAV postexposure prophylaxis is indicated, administer hepatitis A vaccine and/or IGIM as appropriate as soon as possible (within 2 weeks of exposure). Data not available regarding efficacy of hepatitis A vaccine or IGIM administered for HAV postexposure prophylaxis >2 weeks after exposure. Routine serologic screening of contacts for markers of HAV infection prior to administration of HAV postexposure prophylaxis is not recommended since this would delay prophylaxis.

In individuals in whom IGIM is preferred for HAV postexposure prophylaxis, give a dose of hepatitis A vaccine concurrently (using different syringes and different injection sites) if the vaccine is indicated for other reasons (e.g., catch-up vaccination, preexposure vaccination in high-risk groups) and is not contraindicated.

Infants <12 months of age and whenever hepatitis A vaccine is contraindicated: IGIM recommended for HAV postexposure prophylaxis.

Healthy individuals 12 months through 40 years of age: Monovalent hepatitis A vaccine recommended for HAV postexposure prophylaxis.

Healthy adults >40 years of age: Monovalent hepatitis A vaccine recommended for HAV postexposure prophylaxis. Also consider concomitant use of IGIM (administered at a separate site) based on risk assessment.

Individuals ≥12 months of age who are immunocompromised or have chronic liver disease: Combined regimen of monovalent hepatitis A vaccine and IGIM (at separate sites) recommended for HAV postexposure prophylaxis.

Travelers not adequately immunized with hepatitis A vaccine exposed to HAV (within the past 2 weeks) should receive HAV postexposure prophylaxis.

Individuals not adequately immunized with hepatitis A vaccine who are household or sexual (heterosexual or homosexual) contacts (within the past 2 weeks) of an individual with serologically confirmed HAV should receive HAV postexposure prophylaxis.

Child-care center staff and attendees not adequately immunized with hepatitis A vaccine should receive HAV postexposure prophylaxis if ≥1 case of HAV is recognized in attendees or if HAV is recognized in ≥2 households of center attendees (within the past 2 weeks). If ≥1 case of HAV occurs among employees of a child-care center, consider HAV postexposure prophylaxis for other staff and for attendees based on duties, hygienic practices, and presence of symptoms in the index case while at work. In centers that do not provide care to children who wear diapers, HAV postexposure prophylaxis is indicated only in classroom contacts of the index patient.

School staff and attendees not adequately immunized with hepatitis A vaccine may receive HAV postexposure prophylaxis if transmission within the school setting is documented. Schoolroom exposure generally does not pose an appreciable risk of infection and HAV postexposure prophylaxis is not indicated if only a single case occurs and the source of infection is outside the school. However, HAV postexposure prophylaxis is recommended for susceptible close personal contacts of the index case if an epidemiologic investigation indicates that HAV transmission has occurred (e.g., among students in a school).

Individuals not adequately immunized with hepatitis A vaccine who are exposed to an infected food handler should receive HAV postexposure prophylaxis (within 2 weeks) if they are food handlers at the same establishment. Because common-source transmission to patrons is unlikely, HAV postexposure prophylaxis is not usually indicated for patrons, but may be considered if the food handler directly handled uncooked or cooked food and had diarrhea or poor hygienic practices and if patrons can be identified and given prophylaxis within 2 weeks after exposure. Settings where repeated HAV exposure might have occurred (e.g., institutional cafeterias) warrant stronger consideration of postexposure prophylaxis for patrons.

Healthcare personnel are not at substantially increased risk for HAV infection as the result of occupational exposures and healthcare-associated HAV transmission is rare. HAV postexposure prophylaxis within the healthcare setting should be considered on a case-by-case basis if the risk for HAV exposure is considered high.

Neonates of HAV-infected mothers do not usually need HAV postexposure prophylaxis since perinatal transmission of HAV is rare. Although efficacy not established, some experts suggest that the infant^{† [off-label]} receive HAV postexposure prophylaxis with IGIM if the mother's symptoms began between 2 weeks before and 1 week after delivery.

Measles

IGIM (GamaSTAN) and IGIV^{† [off-label]} are used to prevent or modify symptoms of measles (rubeola) in susceptible individuals exposed to the disease <6 days previously.

Individuals born before 1957 and individuals with documentation of adequate vaccination against measles at ≥12 months of age, laboratory evidence of measles immunity, or laboratory confirmation of prior measles infection have acceptable presumptive evidence of measles immunity. Consider other individuals susceptible to measles.

Postexposure vaccination (i.e., within 72 hours of exposure) with a vaccine containing measles virus vaccine live (e.g., measles, mumps, and rubella virus vaccine live; MMR) is recommended by ACIP and AAP and is preferred for postexposure prophylaxis against measles in most susceptible individuals ≥12 months of age who are exposed to measles in most settings (e.g., day-care facilities, schools, colleges, health-care facilities), provided the vaccine can be given within 72 hours of the exposure and is not contraindicated.

Postexposure prophylaxis with immune globulin (i.e., within 6 days of exposure) is recommended in certain individuals at risk for severe disease and complications from measles who cannot receive the vaccine, including infants <12 months of age, pregnant women without evidence of measles immunity, and severely immunocompromised patients.

When immune globulin is indicated for measles postexposure prophylaxis, ACIP and AAP recommend IGIM for such prophylaxis in infants <12 months of age and IGIV for such prophylaxis in susceptible pregnant women and severely immunocompromised individuals.

Because infants are at higher risk for severe measles and complications and are susceptible to measles if mothers are nonimmune or have low antibody titers, ACIP and AAP state that infants <12 months of age^{† [off-label]} should receive IGIM following exposure to measles. Alternatively, infants 6 through 11 months of age can receive postexposure vaccination with MMR, provided the vaccine can be administered within 72 hours of exposure.

In severely immunocompromised patients at increased risk for severe measles and complications (e.g., those with severe primary immunodeficiency, bone marrow transplant recipients, patients being treated for acute lymphocytic leukemia, HIV-infected patients with AIDS), ACIP and AAP recommend postexposure prophylaxis with IGIV within 6 days following exposure, regardless of vaccination status.

Because passive immunity to measles following administration of IGIM or IGIV is temporary (unless modified or typical measles occurs), initiate immunization with MMR 6 months after IGIM was given or 8 months after IGIV was given, providing the individual is ≥12 months of age and there are no contraindications to the vaccine.

Do not give MMR concurrently with immune globulin. (See Specific Drugs and Laboratory Tests under Interactions.)

Do not use immune globulin in an attempt to control measles outbreaks.

Mumps

Immune globulin, including IGIM, is not effective for prevention of mumps and should not be used for prophylaxis or treatment of mumps.

Poliomyelitis

IGIM is not indicated for and should not be used for prophylaxis or treatment of poliomyelitis.

Rubella

Immune globulin, including IGIM, has not been shown to prevent rubella and should not be used for that purpose.

IGIM (GamaSTAN) is labeled by FDA for use to modify symptoms of rubella in pregnant women who will not consider therapeutic abortion; do not use for routine prophylaxis of rubella in early pregnancy in women who have not been exposed.

Although some studies suggest that use of IGIM in susceptible pregnant women exposed to rubella may lessen the likelihood of rubella infection and associated adverse fetal effects, ACIP and AAP state do not use IGIM routinely for postexposure prophylaxis of rubella in early pregnancy or any other circumstance. These experts state that use of IGIM after rubella exposure will not prevent infection or viremia, but may modify or suppress symptoms and can create an unwarranted sense of security. Infants with congenital rubella syndrome have been born to women who received IGIM shortly after exposure to the disease.

Varicella

IGIV has been used and is recommended as an alternative to varicella-zoster immune globulin (VZIG) for postexposure prophylaxis of varicella^{† [off-label]} in susceptible individuals when VZIG is unavailable.

IGIM (GamaSTAN) is labeled by FDA for use to modify symptoms of varicella (chickenpox) in susceptible individuals; do not use for routine prophylaxis or treatment of varicella.

Although manufacturer states that IGIM may be considered an alternative to VZIG for postexposure prophylaxis of varicella in susceptible individuals who are immunocompromised, IGIV (not IGIM) is recommended when VZIG is unavailable.

VZIG is the preferred immune globulin for postexposure prophylaxis of varicella in individuals who do not have evidence of immunity (i.e., without a history of varicella or varicella vaccination) and are at high risk for severe disease and complications (e.g., HIV-infected or other immunocompromised individuals, pregnant women).

Clinical data demonstrating effectiveness of IGIV for postexposure prophylaxis of varicella not available. Commercially available IGIV preparations contain anti-varicella antibody titers, but the titer of any specific IGIV lot is uncertain since IGIV is not routinely tested for anti-varicella antibodies.

ACIP, AAP, CDC, NIH, and others state that HIV-infected adults, adolescents, or children or other individuals who are receiving IGIV replacement therapy (≥400 mg/kg given at regular intervals) and received a dose of IGIV within 3 weeks prior to exposure to wild-type varicella-zoster virus are likely to be protected and probably do not require postexposure prophylaxis with VZIG or IGIV.

Although VZIG or IGIV given shortly after exposure to varicella-zoster virus can prevent or modify the course of the disease, immune globulin is not effective once disease is established.

Primary Immunodeficiency Diseases

IGIV (i.e., Asceniv 10%, Bivigam 10%, Carimune NF, Flebogamma 5% DIF, Flebogamma 10% DIF, Gammagard S/D [IgA <1 mcg/mL], Gammagard 10%, Gammaked 10%, Gammaplex 5%, Gammaplex 10%, Gamunex-C 10%, Octagam 5%, Panzyga 10%, Privigen 10%) is used for replacement therapy to promote passive immunity in patients with primary humoral immunodeficiency who are unable to produce sufficient amounts of IgG antibodies. This includes, but is not limited to, patients with common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies (SCID).

Immune globulin subcutaneous (i.e., Cutaquig 16.5%, Cuvitru 20%, Gammagard Liquid 10%, Gammaked 10%, Gamunex-C 10%, Hizentra 20%, Xembify 20%) and immune globulin subcutaneous in conjunction with recombinant human hyaluronidase (Hyqvia; immune globulin subcutaneous 10% copackaged with recombinant human hyaluronidase) are used for replacement therapy in patients with primary humoral immunodeficiency. This includes, but is not limited to, patients with CVID, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and SCID.

IGIV and immune globulin subcutaneous are contraindicated in IgA-deficient individuals with antibodies against IgA and a history of hypersensitivity. (See Contraindications under Cautions and see IgA Deficiency under Cautions.)

Idiopathic Thrombocytopenic Purpura (ITP)

IGIV (i.e., Carimune NF, Flebogamma 10% DIF, Gammagard S/D [IgA <1 mcg/mL], Gammaked 10%, Gammaplex 5%, Gammaplex 10%, Gamunex-C 10%, Octagam 10%, Panzyga 10%, Privigen 10%) is used in the management of ITP (also known as immune thrombocytopenic purpura or immune thrombocytopenia). IGIV is designated an orphan drug by FDA for treatment of ITP.

IGIV is used to increase platelet counts to prevent and/or control bleeding in patients with ITP or to allow a patient with ITP to undergo surgery.

Individuals with B-cell Chronic Lymphocytic Leukemia (CLL)

IGIV (i.e., Gammagard S/D [IgA <1 mcg/mL]) is used for prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell CLL.

Kawasaki Disease

IGIV (i.e., Gammagard S/D [IgA <1 mcg/mL]) is used in conjunction with aspirin therapy for initial treatment of the acute phase of Kawasaki disease.

AAP, AHA, and American College of Chest Physicians (ACCP) state that combined therapy with IGIV and aspirin should be administered as soon as possible after Kawasaki disease is diagnosed or strongly suspected (optimally within 7–10 days of disease onset). In those with a delayed diagnosis (i.e., >10 days after disease onset), AAP and AHA suggest initiation of combined therapy with IGIV and aspirin if the patient has unexplained persistent fever or aneurysms and manifestations of ongoing systemic inflammation (elevated erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP >3 mg/dL]) or evolving CAD.

Approximately 10–20% of patients with Kawasaki disease fail to respond to initial treatment with IGIV and aspirin therapy and have persistent fever or recurrent fever after an initial afebrile period. In such situations, AHA and AAP state that IGIV retreatment and continued aspirin therapy is a reasonable option. Use of additional or alternative anti-inflammatory or immunosuppressive agents may be necessary in IGIV-resistant patients.

Coronary artery abnormalities develop in 15–25% of children with Kawasaki disease if they are not treated within 10 days of fever onset; approximately 2–4% of patients develop coronary artery abnormalities despite prompt treatment with IGIV and aspirin therapy. Long-term management of those who develop coronary abnormalities depends on the severity of coronary involvement and may include use of low-dose aspirin, anticoagulants, anti-thrombotic agents, and/or antiplatelet agents.

Consult specialized references for additional information on management of Kawasaki disease, including long-term management in individuals with coronary abnormalities.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

IGIV (i.e., Gammaked 10%, Gamunex-C 10%, Privigen 10%) is used for the treatment of CIDP to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.

Immune globulin subcutaneous (i.e., Hizentra 20%) is used for the treatment of CIDP in adults as maintenance therapy to prevent relapse of neuromuscular disability and impairment. Immune globulin subcutaneous is designated an orphan drug by FDA for treatment of CIDP.

Some clinicians consider IGIV the preferred treatment for CIDP, especially in children^{† [off-label]}, patients with poor venous access that precludes use of plasma exchange, and in those susceptible to complications of long-term corticosteroid therapy.

Multifocal Motor Neuropathy

IGIV (i.e., Gammagard Liquid 10%) is used for maintenance treatment to improve muscle strength and disability in adults with multifocal motor neuropathy (MMN); designated an orphan drug by FDA for this use.

Some clinicians recommend IGIV as a treatment of choice for MMN when disability is severe enough to warrant treatment.

Other Neurologic and Neuromuscular Disorders

IGIV is used in the treatment of Guillain-Barré syndrome^† (GBS); designated an orphan drug by FDA for this use. Although safety and efficacy not established, IGIV initiated within 2 weeks of symptom onset appears to be as effective as plasma exchange and is recommended by some clinicians as a treatment of choice for GBS in adults or children, especially if disease is severe. Additional study needed to determine whether IGIV is beneficial in patients with mild GBS or Miller Fischer syndrome.

IGIV has been used in the management of multiple sclerosis^† (MS). Benefits (e.g., reduced exacerbations, reduced disability scores) reported in some patients with relapsing-remitting MS, but these findings not confirmed with subsequent studies. Although some clinicians suggest that IGIV can be considered as a potentially effective second- or third-line treatment in patients with relapsing-remitting MS, others state IGIV not recommended for treatment of relapsing-remitting or secondary progressive MS or treatment of chronic symptoms of MS.

IGIV has been used with some success in the treatment of myasthenia gravis^† and Lambert-Eaton myasthenic syndrome^† (LEMS). Designated an orphan drug by FDA for treatment of myasthenia gravis. Efficacy and safety not established and further study needed. Some clinicians suggest IGIV may be beneficial for second-line or adjunctive treatment of severe or worsening myasthenia gravis when other treatments unsuccessful or not tolerated and also can be considered for second-line treatment of LEMS. Although there is some evidence that IGIV may be beneficial in patients with severe myasthenia gravis exacerbation, data insufficient regarding use of the drug (either alone or in conjunction with other agents) in those with stable or chronic myasthenia gravis.

IGIV may provide some benefits in the management of stiff person syndrome^† (Moersch-Woltmann syndrome); designated an orphan drug by FDA for this use. Although efficacy and safety not established, some clinicians recommend use of IGIV as second-line treatment when other treatments have been unsuccessful or cannot be used.

IGIV has been used in a limited number of children with intractable epilepsy^†. There is some evidence that IGIV may be beneficial in some patients with Lennox-Gastaut syndrome^† or Rasmussen syndrome^†, but further study needed. Although efficacy and safety not established, some clinicians suggest IGIV can be considered in children with intractable epilepsy if they have not responded to antiepileptic agents and corticosteroids, especially if they are otherwise candidates for surgical resection.

Infections in HIV-infected Individuals

IGIV has been used in an attempt to control or prevent infections and improve immunologic parameters in children with symptomatic HIV infection^† who are immunosuppressed in association with AIDS or AIDS-related complex (ARC).

IGIV also has been used in an attempt to control or prevent infections in HIV-infected adults^†.

IGIV reduces incidence of recurrent bacterial infections and sepsis, including upper respiratory tract infections, in adults and children with symptomatic HIV infection.

AAP, CDC, NIH, and other experts state that HIV-infected children with hypogammaglobulinemia (IgG <400 mg/dL) should receive primary prophylaxis with IGIV (400 mg/kg once every 2–4 weeks) to prevent serious bacterial infections (e.g., those caused by Streptococcus pneumoniae or other invasive bacteria). These experts also recommend IGIV as an alternative to co-trimoxazole for secondary prophylaxis of serious bacterial infections in certain HIV-infected children.

Infections in Bone Marrow Transplant (BMT) Recipients

IGIV has been used in adults and children undergoing BMT^† to decrease the risk of infections (e.g., septicemia), interstitial pneumonia of infectious or idiopathic etiologies, and acute graft-versus-host disease (GVHD).

Effect of IGIV on the incidence of cytomegalovirus (CMV) infection, other infections, or GVHD in patients undergoing allogeneic BMT is unclear. IGIV prophylaxis in BMT patients does not appear to affect survival or risk of cancer relapse, and the long-term effects of such therapy remain to be determined.

Although efficacy and safety in BMT patients not established, some clinicians suggest that IGIV be used for prophylaxis in all allogeneic BMT patients, especially CMV-positive patients or those who have received a transplant from a CMV-positive donor.

Some clinicians suggest that, although there is a perceived benefit of IGIV prophylaxis in infants with severe combined immunodeficiency or other primary immunodeficiency diseases undergoing BMT, the effect of IGIV in these children is difficult to study since they generally are receiving IGIV for replacement therapy. These clinicians also state that use of IGIV appears to offer little benefit in patients with malignancies undergoing HLA-identical sibling BMT and that additional study is needed to determine whether the drug is beneficial in those undergoing HLA-matched unrelated BMT or cord blood transplants.

Infections in Hematopoietic Stem Cell Transplant (HSCT) Recipients

CDC, IDSA, and American Society of Blood and Marrow Transplantation (ASBMT) state that, although routine use of IGIV for prophylaxis is not recommended for autologous HSCT recipients, some clinicians recommend use of IGIV to prevent bacterial infections (e.g., S. pneumoniae sinopulmonary infections) in adult, adolescent, or pediatric allogeneic HSCT recipients^† who experience severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after transplant.

Routine administration of IGIV in HSCT recipients >90 days after HSCT is not recommended in the absence of severe hypogammaglobulinemia.

Infections in Low-birthweight Neonates

IGIV has been used for prophylaxis and treatment of infections in certain high-risk, preterm, low-birthweight neonates^†. However, use of IGIV for prophylaxis of infections in high-risk neonates is controversial. AAP does not recommend routine use of IGIV for prophylaxis of infections in preterm neonates.

Autoimmune Neutropenia and Autoimmune Hemolytic Anemia

IGIV has been used with some success in a limited number of adults and children for the treatment of autoimmune neutropenia^†. May be beneficial in some patients, but unclear whether IGIV offers any advantage over corticosteroid therapy.

IGIV has been used with variable results in patients with autoimmune hemolytic anemia^†. Some clinicians state IGIV should be used in the management of autoimmune hemolytic anemia only in those who fail to respond to other treatment options.

Coronavirus Disease 2019 (COVID-19)

IGIV is being investigated for and has been used in the treatment of COVID-19^† caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

There is some evidence that commercially available IGIV may contain antibodies against some previously circulating coronaviruses, including antibodies that cross-react with SARS-CoV-2 antigens. In addition, it has been suggested that the various immunomodulatory and anti-inflammatory effects of IGIV potentially could help combat the hyperinflammatory state and symptoms of cytokine release syndrome in patients with severe COVID-19. However, it is unclear whether IGIV contains clinically important titers of SARS-CoV-2 antibodies and additional study is needed to determine whether the general immunomodulatory effects of IGIV provide benefits in patients with COVID-19.

Specific SARS-CoV-2 immune globulin prepared using plasma obtained from individuals who have recovered from COVID-19 (not commercially available in US) also is being investigated for treatment of COVID-19. Such concentrated immune globulin (hyperimmune globulin) preparations containing antibodies specific to SARS-CoV-2 could potentially suppress the virus and modify the inflammatory response to COVID-19 infection.

NIH COVID-19 Treatment Guidelines Panel recommends against use of commercially available IGIV for treatment of COVID-19, except in the context of a clinical trial; this does not preclude use of IGIV when it is otherwise indicated for treatment of complications arising during the course of COVID-19 disease. NIH panel states that it is not known whether products derived from plasma of donors without confirmation of prior SARS-CoV-2 infection contain high titers of SARS-CoV-2 neutralizing antibodies and, although other blood components in IGIV may have general immunomodulatory effects, it is unclear whether these theoretical effects benefit patients with COVID-19.

Surviving Sepsis Campaign COVID-19 subcommittee (joint initiative of Society of Critical Care Medicine and European Society of Intensive Care Medicine) suggests against routine use of IGIV in critically ill adults with COVID-19 because efficacy data are not available, commercially available IGIV preparations unlikely to contain adequate titers of neutralizing antibodies against SARS-CoV-2, and IGIV can be associated with increased risk of severe adverse effects (e.g., anaphylaxis, aseptic meningitis, renal failure, thromboembolism, hemolytic reactions, transfusion-related lung injury).

NIH COVID-19 panel states that there are insufficient data to date to recommend either for or against use of investigational SARS-CoV-2 immune globulin for treatment of COVID-19.

Dermatomyositis and Polymyositis

IGIV has been used in the treatment of dermatomyositis^† and polymyositis^†. IGIV and immune globulin subcutaneous designated as orphan drugs for treatment of dermatomyositis.

IGIV has resulted in improvements (e.g., in muscle strength, neuromuscular symptoms, rash, scaling) in a limited number of patients with biopsy-proven, treatment-resistant dermatomyositis. Although efficacy and safety not established, it has been suggested that IGIV (usually in conjunction with corticosteroids) may be beneficial as second-line therapy in patients with dermatomyositis when other therapies are unsuccessful or cannot be used.

Graves’ Ophthalmopathy

IGIV has been used with some success in the management of Graves’ ophthalmopathy^†.

Some patients responded to IGIV with improvements in diplopia, proptosis, visual acuity, and intraocular pressure; response rate appeared similar to that obtained with corticosteroid treatment.

Systemic Lupus Erythematosus

IGIV has been used with some success in the treatment of systemic lupus erythematosus^† (SLE); efficacy and safety not definitely established and additional study needed.

Some clinicians suggest use of IGIV may be considered in patients with severe active SLE when other drugs have been ineffective or not tolerated; other clinicians recommend caution.

Tetanus

IGIV has been recommended as an alternative for the treatment of tetanus^† when tetanus immune globulin (TIG) is unavailable; TIG is the immune globulin of choice.

IGIV has been recommended as an alternative for postexposure prophylaxis of tetanus^† in individuals with tetanus-prone wounds when TIG is unavailable; TIG is the immune globulin of choice.

Toxic Shock Syndrome

IGIV has been used as an adjunct to anti-infectives and surgical intervention in the treatment of staphylococcal or streptococcal toxic shock syndrome^† or necrotizing fasciitis^† in severely ill patients.

Although data are limited and efficacy and safety not established, AAP and others suggest use of IGIV may be considered as an adjunct in the management of severe staphylococcal or streptococcal toxic shock syndrome^† or necrotizing fasciitis^† (e.g., when the infection is refractory to several hours of aggressive therapy, an undrainable focus is present, or the patient has persistent oliguria with pulmonary edema).

Immune Globulin Dosage and Administration

Administration

Administer IGIM only by IM injection; do not administer IV because of risk of serious reactions (e.g., renal dysfunction, acute renal failure, hemolysis, transfusion-related acute lung injury).

Administer IGIV by IV infusion; do not administer IM. Certain IGIV preparations can be given by IV infusion or sub-Q infusion for treatment of primary humoral immunodeficiency (i.e., Gammagard Liquid 10%, Gammaked 10%, Gamunex-C 10% ); administer all other IGIV preparations only by IV infusion.

Administer immune globulin subcutaneous (Cutaquig 16.5%, Cuvitru 20%, Hizentra 20%, Hyqvia, Xembify 20%) only by sub-Q infusion.

IM Administration

Administer IGIM by IM injection, preferably into deltoid muscle of upper arm or anterolateral aspect of thigh.

Do not administer routinely into gluteal muscle because of potential for injection-associated injury to the sciatic nerve.

Draw back syringe plunger before IGIM injection to ensure needle is not in a blood vessel.

Prior to administration of IGIM, ensure that patient is not volume depleted and is adequately hydrated.

Do not exceed recommended dosage in patients at increased risk of thrombosis.

IV Administration

General Considerations

Prior to initiation of IGIV infusion, ensure that patients are not volume depleted and are adequately hydrated.

Individualize IV infusion rate based on the specific preparation, indication, tolerability, and individual patient requirements.

In general, in patients receiving initial doses of IGIV or switching from one IGIV preparation to another, initiate IGIV using infusion rate at lower end of recommended range and slowly increase to maximum recommended rate only after patient has tolerated several infusions at an intermediate infusion rate.

If adverse reactions occur during the IGIV infusion, decrease IV infusion rate or stop the infusion until reactions subside.

Use minimum dose and minimum IV infusion rate practicable in patients at risk for renal dysfunction or thrombosis.

IV Administration of Asceniv 10%

Administer Asceniv 10% only by IV infusion.

Do not dilute; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Vials are for single use only.

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion bag using aseptic technique.

Administer at room temperature.

Rate of Administration

Primary immunodeficiency: Initiate IV infusions of Asceniv 10% at a rate of 0.5 mg/kg per minute (0.005 mL/kg per minute) for first 15 minutes. If tolerated, may gradually increase IV infusion rate every 15 minutes up to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute). If adverse effects related to infusion rate occur, slow or stop the infusion. If symptoms subside promptly, may resume IV infusion at a lower rate that is comfortable for the patient.

Patients at increased risk of thrombosis or renal dysfunction: Use minimum IV infusion rate practicable. Consider discontinuing if renal function deteriorates.

IV Administration of Bivigam 10%

Administer Bivigam 10% only by IV infusion.

Do not dilute; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Vials are for single use only.

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion bag using aseptic technique.

Discard any partially used vials.

Administer at room temperature.

Rate of Administration

Primary immunodeficiency: Initiate IV infusion of Bivigam 10% at a rate of 0.5 mg/kg per minute (0.005 mL/kg per minute) for first 10 minutes. If tolerated, may gradually increase IV infusion rate every 20 minutes by 0.8 mg/kg per minute to a maximum of 6 mg/kg per minute. If adverse effects related to infusion rate occur, symptoms may disappear if infusion is stopped or slowed. If symptoms subside promptly, may resume IV infusion at a lower rate that is comfortable for the patient.

Patients at risk for renal dysfunction or thrombosis (including those ≥65 years of age): Use minimum IV infusion rate practicable. Consider discontinuing if renal function deteriorates.

IV Administration of Carimune NF

Administer Carimune NF only by IV infusion.

Administer reconstituted solution through a separate IV line; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Administer at room temperature.

Manufacturer states that, although the drug may be filtered, filtering not required. If filter is used, those with pore sizes of ≥15 μm are less likely to slow the IV infusion, especially when higher concentrations given; antimicrobial filters (0.2 μm) may be used.

Reconstitution

Reconstitute Carimune NF according to the manufacturer’s directions with 0.9% sodium chloride injection, 5% dextrose injection, or sterile water for injection to prepare a solution containing 30, 60, 90, or 120 mg of protein per mL (3, 6, 9, or 12% solution, respectively). Consider patient’s fluid, electrolyte, and caloric requirements when selecting an appropriate diluent and concentration.

After diluent added, swirl vial vigorously to dissolve the drug; to avoid foaming, do not shake. Generally dissolves within a few minutes, but may take up to 20 minutes for complete dissolution.

Discard any partially used vials.

If large doses are to be administered, contents of several reconstituted vials of identical concentration and diluent may be pooled into an empty, sterile glass or plastic IV infusion container using aseptic technique.

If reconstituted outside of sterile laminar airflow conditions, promptly administer the reconstituted solution. If reconstituted in a sterile laminar flow hood using aseptic technique and reconstituted solution stored under refrigeration, initiate IV infusion within 24 hours after reconstitution.

Rate of Administration

Primary immunodeficiency in individuals with previously untreated agammaglobulinemia or hypogammaglobulinemia: Administer initial dose of Carimune NF as a 3% solution (30 mg/mL) at an initial IV infusion rate of 0.5 mg/kg per minute. After 30 minutes, may increase infusion rate to 1 mg/kg per minute for the next 30 minutes; thereafter, may gradually increase infusion rate in a stepwise manner up to a maximum of 3 mg/kg per minute as tolerated. If initial IV infusion well tolerated, higher concentrations may be used for subsequent infusions. (See Table 1.) Inflammatory reactions have occurred when initial IV infusion rate >2 mg/kg per minute was used in patients with agammaglobulinemia or hypogammaglobulinemia who had not previously received IGIV or had not received a dose within the last 8 weeks. (See Infusion Reactions under Cautions.)

ITP: Administer initial dose of Carimune NF as a 6% solution (60 mg/mL) at an initial IV infusion rate of 0.5 mg/kg per minute. After 30 minutes, may increase infusion rate to 1 mg/kg per minute for the next 30 minutes; thereafter, may gradually increase infusion rate in a stepwise manner up to a maximum of 3 mg/kg per minute as tolerated. (See Table 1.)

Patients at risk of developing renal dysfunction (e.g., adults >65 years of age, individuals receiving nephrotoxic drugs, individuals with diabetes mellitus, volume depletion, paraproteinemia, or sepsis): Use IV infusion rate ≤2 mg/kg per minute.

Patients at increased risk of thrombosis (e.g., those with cardiovascular risk factors, advanced age, prolonged periods of immobilization, hypercoagulable disorders, history of venous or arterial thrombosis, use of estrogen-containing preparations, indwelling central vascular catheters, and/or hyperviscosity): Use IV infusion rate ≤2 mg/kg per minute.

Maximum IV infusion rate for patients at risk of renal dysfunction or thrombosis.

Maximum IV infusion rate for patients not at risk of renal dysfunction or thrombosis.

IV Administration of Flebogamma 5% DIF

Administer Flebogamma 5% DIF only by IV infusion.

Do not dilute; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion container using aseptic technique.

Discard any partially used vials.

Rate of Administration

Primary immunodeficiency: Administer Flebogamma 5% DIF at an initial IV infusion rate of 0.01 mL/kg per minute (0.5 mg/kg per minute). If tolerated for first 30 minutes, may gradually increase IV infusion rate to a maximum of 0.1 mL/kg per minute (5 mg/kg per minute).

Patients ≥65 years of age or at increased risk for renal dysfunction or thrombosis: Use minimum infusion rate practicable. IV infusion rate in geriatric patients should be <0.06 mL/kg per minute (<3 mg/kg per minute).

IV Administration of Flebogamma 10% DIF

Administer Flebogamma 10% DIF only by IV infusion.

Do not dilute; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion container using aseptic technique.

Discard any partially used vials and administration sets.

Rate of Administration

Primary immunodeficiency: Administer Flebogamma 10% DIF at an initial IV infusion rate of 0.01 mL/kg per minute (1 mg/kg per minute) for 30 minutes; if tolerated, may gradually increase IV infusion rate to 0.04 mL/kg per minute (4 mg/kg per minute). If tolerated, may gradually increase to a maximum rate of 0.08 mL/kg per minute (8 mg/kg per minute).

ITP: Administer Flebogamma 10% DIF at an initial IV infusion rate of 0.01 mL/kg per minute (1 mg/kg per minute) for 30 minutes; if tolerated, may gradually increase IV infusion rate to 0.04 mL/kg per minute (4 mg/kg per minute). May gradually increase to a maximum rate of 0.08 mL/kg per minute (8 mg/kg per minute) if tolerated.

Patients ≥65 years of age or at risk for renal dysfunction or thrombosis: Use minimum infusion rate practicable. IV infusion rate in geriatric patients should be <0.04 mL/kg per minute (<4 mg/kg per minute).

IV Administration of Gammagard Liquid 10%

Administer Gammagard Liquid 10% by IV infusion. Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gammagard Liquid 10% under Dosage and Administration).

Do not mix with other drugs or other IGIV preparations.

Do not shake.

Use of an in-line filter is optional. IV infusion line may be flushed with 0.9% sodium chloride injection.

Administer at room temperature; do not warm in microwave.

Vials are for single use only.

Dilution

Available as a 10% solution. If necessary, may be diluted with 5% dextrose injection; do not use 0.9% sodium chloride as diluent. For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary humoral immunodeficiency: Administer Gammagard Liquid 10% at an initial IV infusion rate of 0.5 mL/kg per hour (0.8 mg/kg per minute) for 30 minutes. IV infusion rate may be increased every 30 minutes (if tolerated) up to a maximum of 5 mL/kg per hour (8 mg/kg per minute).

Maintenance treatment of MMN: Administer Gammagard Liquid 10% at an initial IV infusion rate of 0.5 mL/kg per hour (0.8 mg/kg per minute). IV infusion rate may be increased (if tolerated) up to a maximum of 5.4 mL/kg per hour (9 mg/kg per minute).

Patients >65 years of age or at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable. IV infusion rate in such patients should be <2 mL/kg per hour (<3.3 mg/kg per minute).

IV Administration of Gammagard S/D

Administer Gammagard S/D only by IV infusion.

Infuse via the administration set provided by the manufacturer, which contains an integral airway and a 15-µm filter; if this administration set not used, a similar filter must be used.

Use the antecubital vein for IV infusion whenever possible, especially when a 10% solution used; this may reduce infusion site discomfort.

Administer reconstituted Gammagard S/D through a separate IV line; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Administer at room temperature.

Reconstitution

Reconstitute Gammagard S/D according to the manufacturer’s directions with the sterile water for injection diluent and transfer device provided to prepare a solution containing 50 or 100 mg of protein per mL (5 or 10% solution, respectively).

Prior to reconstitution, allow powder for injection and diluent to warm to room temperature.

After diluent added, gently rotate vial to dissolve the drug; to avoid foaming, do not shake.

When large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion container using aseptic technique.

If reconstituted outside of sterile laminar airflow conditions, administer within 2 hours after reconstitution (preferably as soon as possible). If reconstituted in a sterile laminar flow hood using aseptic technique and reconstituted solution stored under constant refrigeration (2–8°C), administer within 24 hours after reconstitution (preferably as soon as possible).

Discard any partially used vials.

Rate of Administration

Administer Gammagard S/D initially as a 5% solution at an initial IV infusion rate of 0.5 mL/kg per hour; if tolerated, may gradually increase IV infusion rate of 5% solution to a maximum of 4 mL/kg per hour. If further tolerated, may administer subsequent doses as a 10% solution given initially at an IV infusion rate of 0.5 mL/kg per hour; if tolerated, may gradually increase IV infusion rate of 10% solution to a maximum of 8 mL/kg per hour.

Patients at increased risk for renal dysfunction or thrombosis: Use minimum rate practicable. Manufacturer recommends maximum IV infusion rate of <3.3 mg/kg per minute (<4 mL/kg per hour as a 5% solution or <2 mL/kg per hour as a 10% solution). However, data not available to date to identify maximum safe concentration or IV infusion rate in patients at risk for renal dysfunction.

IV Administration of Gammaked 10%

Administer Gammaked 10% by IV infusion. Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gammaked 10% under Dosage and Administration).

Prior to administration, allow to come to room temperature (may take ≥60 minutes); should be clear to opalescent and colorless to pale yellow.

Vials are for single use only.

Do not shake.

Penetrate the stopper of the 10-mL vial (containing 1 g of protein) with an 18-gauge needle; when 25-, 50-, 100-, or 200-mL vials (containing 2.5, 5, 10, or 20 g of protein, respectively) are used, use only 16-gauge needles or dispensing pins to penetrate the vial stopper. Promptly use any vial that has been entered; discard any partially used vials.

Contents of full vials may be pooled under aseptic conditions into empty, sterile IV infusion bags and infused within 8 hours after pooling.

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection. Do not flush infusion line with heparin because of potential for incompatibility between Gammaked 10% and heparin.

Dilution

Available as a 10% solution. If necessary, may be diluted with 5% dextrose injection; do not use saline solutions as diluent. For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary immunodeficiency or ITP: Administer Gammaked 10% at an initial IV infusion rate of 1 mg/kg per minute (0.01 mL/kg per minute) for first 30 minutes. If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute). If adverse effects related to IV infusion rate occur, symptoms may disappear if infusion is stopped or slowed.

CIDP: Administer Gammaked 10% at an initial IV infusion rate of 2 mg/kg per minute (0.02 mL/kg per minute) for first 30 minutes. If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute). If adverse effects related to IV infusion rate occur, symptoms may disappear if infusion is stopped or slowed.

Patients at increased risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable (<8 mg/kg per minute [<0.08 mL/kg per minute]).

IV Administration of Gammaplex 5%

Administer Gammaplex 5% only by IV infusion.

Administer through a separate IV line; do not mix with other drugs or other IGIV preparations.

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.

When large doses are to be administered, contents of several bottles may be pooled using aseptic technique; begin IV infusion within 2 hours after pooling.

Do not shake.

Promptly use bottle after it has been entered; discard any partially used bottles.

An infusion pump may be used to control IV infusion rate.

Rate of Administration

Primary immunodeficiency or ITP: Administer Gammaplex 5% at an initial IV infusion rate of 0.5 mg/kg per minute (0.01 mL/kg per minute). If well tolerated for first 15 minutes, may gradually increase IV infusion rate every 15 minutes to a maximum of 4 mg/kg per minute (0.08 mL/kg per minute).

Patients at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable. Discontinue if renal function deteriorates.

IV Administration of Gammaplex 10%

Administer Gammaplex 10% only by IV infusion.

Administer through a separate IV line; do not mix with other drugs or other IGIV preparations.

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.

When large doses are to be administered, contents of several vials may be pooled using aseptic technique.

Do not shake.

Promptly use vial after it has been entered; discard any partially used vials.

An infusion pump may be used to control IV infusion rate.

Rate of Administration

Primary immunodeficiency or ITP: Administer Gammaplex 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute). If well tolerated for first 15 minutes, may gradually increase IV infusion rate every 15 minutes to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).

Patients at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable. Consider discontinuing if renal function deteriorates.

IV Administration of Gamunex-C 10%

Administer Gamunex-C 10% by IV infusion. Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gamunex-C 10% under Dosage and Administration).

Administer through a separate IV line; do not mix with other drugs or other IGIV preparations.

Vials are for single use only.

Administer at room temperature.

Penetrate the stopper of the 10-mL vial (containing 1 g of protein) with an 18-gauge needle; when 25-, 50-, 100-, 200, or 400-mL vials (containing 2.5, 5, 10, 20, or 40 g of protein, respectively) are used, use only 16-gauge needles or dispensing pins to penetrate the vial stopper. Promptly use any vial that has been entered; discard any partially used vials.

Contents of full vials may be pooled under aseptic conditions into empty, sterile IV infusion bags and infused within 8 hours after pooling.

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection. Do not flush infusion line with heparin because of potential for incompatibility between Gamunex-C 10% and heparin.

Dilution

Available as a 10% solution. If necessary, may dilute with 5% dextrose injection; do not use saline solutions as diluent. For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary immunodeficiency or ITP: Administer Gamunex-C 10% at an initial IV infusion rate of 1 mg/kg per minute (0.01 mL/kg per minute) for first 30 minutes. If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute). If adverse effects related to infusion rate occur, symptoms may disappear if infusion is stopped or slowed.

CIDP: Administer Gamunex-C 10% at an initial IV infusion rate of 2 mg/kg per minute (0.02 mL/kg per minute) for first 30 minutes. If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute). If adverse effects related to infusion rate occur, symptoms may disappear if infusion is stopped or slowed.

Patients at increased risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable (<8 mg/kg per minute [<0.08 mL/kg per minute]).

IV Administration of Octagam 5%

Administer Octagam 5% only by IV infusion.

Do not dilute; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Administer at room temperature.

Penetrate the stopper of the single-use bottle with a 16-gauge or smaller needle; insert needle only once. Promptly use any single-use bottle that has been entered; discard partially used bottles.

If necessary, contents of several single-use bottles may be pooled into a sterile IV infusion bag using aseptic technique; infuse within 8 hours after pooling.

An infusion set is not provided with Octagam 5%; if an in-line filter is used (not mandatory), filter pore size should be 0.2–200 μm.

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection before and after administration of Octagam 5%.

Rate of Administration

Primary immunodeficiency: Administer Octagam 5% at an initial IV infusion rate of 30 mg/kg per hour (0.5 mg/kg per minute or 0.01 mL/kg per minute) for first 30 minutes. If tolerated, may increase IV infusion rate to 60 mg/kg per hour (1 mg/kg per minute or 0.02 mL/kg per minute) for second 30 minutes and, if further tolerated, to 120 mg/kg per hour (2 mg/kg per minute or 0.04 mL/kg per minute) for third 30 minutes. IV infusion rate can be increased to and maintained at 200 mg/kg per hour (maximum 3.33 mg/kg per minute or 0.07 mL/kg per minute) if tolerated.

Patients at risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable. Maximum IV infusion rate in those at risk for renal dysfunction is 200 mg/kg per hour (3.33 mg/kg per minute or 0.07 mL/kg per minute). Discontinue if renal function deteriorates.

IV Administration of Octagam 10%

Administer Octagam 10% only by IV infusion.

Do not dilute; do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Administer at room temperature.

Penetrate the stopper of the single-use bottle with a 16-gauge or smaller needle; insert needle only once. Promptly use any single-use bottle that has been entered; discard partially used bottles.

If necessary, contents of several single-use bottles may be pooled into a sterile IV infusion bag using aseptic technique; infuse within 8 hours after pooling.

An infusion set is not provided with Octagam 10%; if an in-line filter is used (not mandatory), filter pore size should be 0.2–200 μm.

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection before and after administration of Octagam 10%.

Rate of Administration

ITP: Administer Octagam 10% at an initial IV infusion rate of 60 mg/kg per hour (1 mg/kg per minute or 0.01 mL/kg per minute) for first 30 minutes. If tolerated, increase to 120 mg/kg per hour (2 mg/kg per minute or 0.02 mL/kg per minute) for second 30 minutes and, if further tolerated, to 240 mg/kg per hour (4 mg/kg per minute or 0.04 mL/kg per minute) for third 30 minutes, and if further tolerated, to 480 mg/kg per hour (8 mg/kg per minute or 0.08 mL/kg per minute). Maximum IV infusion rate is 720 mg/kg per hour (maximum 12 mg/kg per minute or 0.12 mL/kg per minute).

Patients at risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable (maximum IV infusion rate 200 mg/kg per hour [3.33 mg/kg per minute or 0.03 mL/kg per minute]). Discontinue if renal function deteriorates.

IV Administration of Panzyga 10%

Administer Panzyga 10% only by IV infusion.

Do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Penetrate stopper of the single-use bottle using a 16-gauge or smaller needle; insert needle only once.

If necessary, contents of several single-use bottles may be pooled into a sterile IV infusion bag using aseptic technique and infused within 8 hours after pooling.

Should be at room or body temperature before IV infusion.

Administer using a filter with a pore size of 0.2–200 µm.

After IV infusion, flush infusion line with 0.9% sodium chloride injection or 5% dextrose injection.

Rate of Administration

Primary immunodeficiency: Administer Panzyga 10% at an initial IV infusion rate of 1 mg/kg per minute (0.01 mL/kg per minute) for first 30 minutes. In those who are receiving IGIV for first time or received a dose of IGIV >8 weeks previously, may gradually increase IV infusion rate every 15–30 minutes to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute) as tolerated. Manufacturer recommends that IV infusion rate in such patients be ramped up using sequential infusion rates of 1, 2, 4, and 8 mg/kg per minute (0.01, 0.02, 0.04, and 0.08 mL/kg per minute). In those who are IGIV-experienced (i.e., previously received more than 3–6 IGIV infusions), may gradually increase IV infusion rate to a maximum of 12 or 14 mg/kg per minute (0.12 or 0.14 mL/kg per minute) as tolerated. Manufacturer recommends that IV infusion rate in IGIV-experienced patients be ramped up using sequential infusion rates of 1, 4, 8, and 12 or 14 mg/kg per minute (0.01, 0.04, 0.08, and 0.12 or 0.14 mL/kg per minute).

ITP: Administer Panzyga 10% using an initial IV infusion rate of 1 mg/kg per minute (0.01 mL/kg per minute) for first 30 minutes. May gradually increase IV infusion rate every 15–30 minutes to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute) as tolerated.

Patients at increased risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable. Maximum IV infusion rate is 3.33 mg/kg per minute (0.03 mL/kg per minute). Discontinue if renal function deteriorates.

IV Administration of Privigen 10%

Administer Privigen 10% only by IV infusion.

Do not mix with other drugs, IV infusion fluids, or other IGIV preparations.

Do not shake.

Administer at room temperature (up to 25°C).

Promptly use any vial that has been entered; discard partially used vials.

If large doses are to be administered, contents of several vials may be pooled using aseptic technique; begin infusion within 8 hours after pooling.

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.

An infusion pump may be used to control IV infusion rate.

Dilution

Available as 10% solution. If necessary, may be diluted with 5% dextrose injection. For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary immunodeficiency: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute). If tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).

ITP: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute). If tolerated, may gradually increase IV infusion rate to a maximum of 4 mg/kg per minute (0.04 mL/kg per minute).

CIDP: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute). If tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).

Patients who have not previously received Privigen 10% (or other immune globulin preparation), patients who have not received the drug within the past 8 weeks, and patients switching from another immune globulin preparation to Privigen 10%: May be at risk of developing inflammatory reactions if rapid IV infusion rate (e.g., >4 mg/kg per minute [>0.04 mL/kg per minute]) used. Initiate Privigen10% in such patients using a slow IV infusion rate (e.g., ≤0.5 mg/kg per minute [≤0.005 mL/kg per minute]) and increase rate gradually to maximum rate tolerated.

Patients at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable. Discontinue if renal function deteriorates.

Sub-Q Administration

General Considerations

Prior to initiation of sub-Q infusion, ensure that patients are not volume depleted and are adequately hydrated.

Individualize sub-Q infusion rate based on the specific preparation, indication, tolerability, and other patient factors.

In general, initiate using lowest recommended sub-Q infusion rate and slowly increase to maximum recommended rate as tolerated.

If adverse reactions occur during sub-Q infusion, decrease rate of infusion or stop the infusion until reactions subside.

Use minimum dose and minimum sub-Q infusion rate practicable in patients at risk for thrombosis.

Sub-Q Administration of Cutaquig 16.5%

Administer Cutaquig 16.5% only by sub-Q infusion.

May be self-administered in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Administer undiluted; do not mix with other drugs, IV infusion fluids, or other immune globulin preparations.

Vials are for single use only; discard partially used vials.

Make sub-Q infusions into abdomen, thighs, upper arms, and/or upper leg/hips using an infusion pump; avoid scars, tattoos, and any injured or inflamed areas.

Dose may be divided and infused simultaneously in up to 6 different infusion sites that are ≥2 inches apart. For those who have not previously received immune globulin subcutaneous, maximum volume of Cutaquig 16.5% per infusion site is 25 mL; after first 5 doses, volume may be gradually increased to a maximum of 40 mL per infusion site as tolerated. Rotate sub-Q infusion sites for each subsequent dose.

Consult manufacturer’s instructions provided with Cutaquig 16.5% and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Primary immunodeficiency: Administer first 6 sub-Q infusions of Cutaquig 16.5% at an infusion rate of 15–20 mL/hour at each infusion site. For subsequent sub-Q infusions, may increase infusion rate as tolerated to a maximum of 25 mL/hour at each infusion site.

Sub-Q Administration of Cuvitru 20%

Administer Cuvitru 20% only by sub-Q infusion.

May be self-administered sub-Q in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Make sub-Q infusions into abdomen, thighs, upper arms, and/or lateral hip area; avoid bony areas, visible blood vessels, scars, and any areas with inflammation (irritation) or infection.

Dose may be divided and infused simultaneously in up to 4 different infusion sites that are ≥4 inches apart; use of a multi-needle administration set facilitates simultaneous sub-Q infusion at multiple sites. Number of sites depends on volume of the dose; calculate by dividing total volume to be infused by maximum volume per site. For first 2 sub-Q infusions, maximum volume per site is 20 mL in those weighing <40 kg or 60 mL in those weighing ≥40 kg; maximum volume per site for subsequent infusions is 60 mL regardless of weight.

Rotate sub-Q infusion sites for each subsequent dose.

Consult manufacturer’s instructions provided with Cuvitru 20% and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Primary immunodeficiency: Administer first 2 sub-Q infusions of Cuvitru 20% at an infusion rate of 10–20 mL/hour at each infusion site. For subsequent sub-Q infusions, may increase infusion rate as tolerated to a maximum of 60 mL/hour at each infusion site.

Sub-Q Administration of Gammagard Liquid 10%

Gammagard Liquid 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency. Also may be administered by IV infusion (see IV Administration of Gammagard Liquid 10% under Dosage and Administration).

May be self-administered sub-Q in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lower back using an infusion pump; avoid bony prominences.

To determine number of infusion sites needed for Gammagard Liquid 10%, divide weekly dose (in mL) by 30 or 20 (i.e., divide by recommended volume per site based on patient weight). Sites should be located ≥2 inches apart and should be changed for each weekly dose. Use a maximum of 8 simultaneous infusion sites.

Discard any unused portions.

Consult manufacturer’s instructions provided with Gammagard Liquid 10% and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Primary immunodeficiency in patients weighing ≥40 kg: For initial sub-Q infusion of Gammagard Liquid 10%, use a volume of 30 mL per site and an infusion rate of 20 mL/hour per site. For maintenance doses, use a volume of 30 mL per site and an infusion rate of 20–30 mL/hour per site.

Primary immunodeficiency in patients weighing <40 kg: For initial sub-Q infusion of Gammagard Liquid 10%, use a volume of 20 mL per site and an infusion rate of 15 mL/hour per site. For maintenance doses, use a volume of 20 mL per site and an infusion rate of 15–20 mL/hour per site.

Sub-Q Administration of Gammaked 10%

Gammaked 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency. Also may be administered by IV infusion (see IV Administration of Gammaked 10% under Dosage and Administration).

May be self-administered sub-Q in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Prior to administration, allow to come to room temperature (may take ≥60 minutes); should be clear to opalescent and colorless to pale yellow.

Vials are for single use only.

Do not shake.

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hip using an infusion pump.

Depending on total volume required, each dose of Gammaked 10% may be divided and infused into multiple sites. Use a maximum of 8 simultaneous infusion sites in adults (4 infusion sites used simultaneously in most adults); use a maximum of 6 simultaneous infusion sites in children. Infusion sites should be located ≥2 inches apart.

Does not contain preservatives; discard any unused portions.

Consult manufacturer’s instructions provided with Gammaked 10% and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Primary immunodeficiency in adults: Administer Gammaked 10% sub-Q at an infusion rate of 20 mL/hour at each infusion site.

Primary immunodeficiency in pediatric patients ≥2 years of age weighing ≥25 kg: Administer Gammaked 10% sub-Q at an initial infusion rate of 15 mL/hour at each infusion site. Infusion rate may then be increased to 20 mL/hour.

Primary immunodeficiency in pediatric patients ≥2 years of age weighing <25 kg: Administer Gammaked 10% sub-Q at an infusion rate of 10 mL/hour at each infusion site.

Sub-Q Administration of Gamunex-C 10%

Gamunex-C 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency. Also may be administered by IV infusion (see IV Administration of Gamunex-C 10% under Dosage and Administration).

May be self-administered sub-Q in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.

Do not shake.

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hip using an infusion pump.

Depending on total volume required, each dose of Gamunex-C 10% may be divided and infused into multiple sites. Use a maximum of 8 simultaneous infusion sites in adults (4 infusion sites used simultaneously in most adults); use a maximum of 6 simultaneous infusion sites in children. Infusion sites should be located ≥2 inches apart.

Does not contain preservatives; discard any unused portions.

Consult manufacturer’s instructions provided with Gamunex-C 10% and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Primary immunodeficiency in adults: Administer Gamunex-C 10% sub-Q at an infusion rate of 20 mL/hour at each infusion site.

Primary immunodeficiency in pediatric patients ≥2 years of age weighing ≥25 kg: Administer Gamunex-C 10% sub-Q at an initial infusion rate of 15 mL/hour at each infusion site. Infusion rate may then be increased to 20 mL/hour.

Primary immunodeficiency in pediatric patients ≥2 years of age weighing <25 kg: Administer Gamunex-C 10% sub-Q at an infusion rate of 10 mL/hour at each infusion site.

Sub-Q Administration of Hizentra 20%

Administer Hizentra 20% only by sub-Q infusion.

May be self-administered in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Prefilled syringes and vials are for single use only and should not be shaken; discard partially used syringes and vials.

Consult manufacturer’s instructions for specific information on preparing and using the single-use prefilled syringes and vials.

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hips using an infusion pump.

Depending on total volume required, each dose may be divided and infused into multiple infusion sites. Use a maximum of 8 simultaneous infusion sites; more than one infusion device may be used simultaneously. Sites should be located ≥2 inches apart and should be changed for each weekly dose.

Consult manufacturer’s instructions provided with Hizentra 20% and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Primary immunodeficiency: For initial sub-Q infusion of Hizentra 20%, use a maximum volume of 15 mL at each infusion site and a maximum infusion rate of 15 mL/hour at each infusion site. For subsequent infusions, the volume may be increased up to 25 mL at each infusion site and infusion rate may be increased up to a maximum of 25 mL/hour at each infusion site as tolerated.

CIDP: For initial sub-Q infusions of Hizentra 20%, use a maximum volume of 20 mL at each infusion site and a maximum infusion rate of 20 mL/hour at each infusion site. For subsequent infusions, the volume may be increased up to 50 mL at each infusion site and infusion rate may be increased up to a maximum of 50 mL/hour at each infusion site as tolerated.

Sub-Q Administration of Hyqvia (Immune Globulin Subcutaneous 10% with Recombinant Human Hyaluronidase)

Hyqvia is commercially available as a kit containing a vial of immune globulin subcutaneous 10% copackaged with a vial of recombinant human hyaluronidase. Administer both components only by sub-Q infusion sequentially at same infusion site.

For each dose of Hyqvia, administer entire contents of vial containing recombinant human hyaluronidase component (acts locally to temporarily increase permeability of sub-Q tissue to increase dispersion and absorption of the immune globulin component) first. Within approximately 10 minutes after completion of sub-Q infusion of recombinant human hyaluronidase component, administer appropriate dose of the immune globulin subcutaneous 10% component using same sub-Q infusion site and same needle set.

Do not mix recombinant human hyaluronidase component and immune globulin subcutaneous 10% component together in same container; do not mix or administer the individual components with other drugs or infusion fluids.

May be self-administered in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Make sub-Q infusions into the abdomen and/or thighs using an infusion pump. Avoid bony prominences or scarred, infected, or inflamed areas.

In patients weighing ≥40 kg, maximum volume at each sub-Q infusion site is 600 mL. In patients weighing <40 kg, maximum volume at each site is 300 mL.

Depending on total volume required and tolerability, each dose of immune globulin subcutaneous 10% may be divided and administered using 2 infusion sites on opposite sides of the body. When 2 sites are used, also divide the dose of recombinant human hyaluronidase and administer half at each site.

Rotate administration sites on opposite sides of the body between successive infusions.

Consult manufacturer’s instructions provided with Hyqvia and with the infusion pump for specific information regarding sub-Q administration.

Rate of Administration

Recombinant human hyaluronidase component of Hyqvia: Administer sub-Q at an infusion rate of 1–2 mL/minute or as tolerated.

Immune globulin subcutaneous 10% component of Hyqvia: Administer first 4 or 5 sub-Q infusions using increasing infusion rate and a variable infusion rate (ramp-up period). Adjust time intervals and number of rate changes if full dose and maximum rate are tolerated.

Consult manufacturer’s instructions provided with Hyqvia for specific information on recommended sub-Q infusion rates and time intervals during the ramp-up period.

Sub-Q Administration of Xembify 20%

Administer Xembify 20% only by sub-Q infusion.

May be self-administered in the home or other appropriate setting; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.

Administer undiluted; do not mix with other drugs, IV infusion fluids, or other immune globulin preparations.

Vials are for single use only; discard partially used vials.

Make sub-Q infusions of Xembify 20% into abdomen, thigh, upper arm, side, back, and/or upper lateral hip area using an infusion pump; avoid bony areas, scars, blood vessels, and any areas with inflammation or superficial infection.

Dose may be divided and infused simultaneously in up to 6 different infusion sites that are ≥2 inches apart. Maximum volume per infusion site is 25 mL. Rotate sub-Q infusion sites for each subsequent dose.

Rate of Administration

Primary immunodeficiency: Sub-Q infusions of Xembify 20% should be given at a maximum rate of 25 mL/hour at each infusion site.

Consult manufacturer’s instructions provided with Xembify 20% and with the infusion pump for specific information regarding sub-Q administration.

Dosage

Pediatric Patients

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

Travelers to Areas with Intermediate or High Levels of Endemic HAV

IM

Children^†: Single dose of 0.1 or 0.2 mL/kg of IGIM in those staying in such areas for up to 1 or 2 months, respectively. If period of exposure in such areas will be ≥2 months, give 0.2 mL/kg once every 2 months.

Primary immunization with an age-appropriate schedule of hepatitis A vaccine before an expected exposure to HAV is preferred in children and infants ≥12 months of age, unless contraindicated.

To ensure protection in travelers who are immunocompromised or have chronic liver disease or other chronic medical conditions and plan to depart within 2 weeks, give single dose of IGIM simultaneously with initial dose of hepatitis A vaccine (using different syringes and different injection sites).

The above IGIM dosage is higher than previously recommended. This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IM

Infants <12 months of age^†, immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: Give single dose of 0.1 mL/kg of IGIM as soon as possible after exposure (ideally within 2 weeks).

Individuals ≥12 months of age: ACIP, CDC, and AAP prefer active immunization with an age-appropriate schedule of hepatitis A vaccine since it provides long-term protection.

In individuals receiving IGIM for HAV postexposure prophylaxis and in whom hepatitis A vaccine also recommended for other reasons, give single dose of IGIM concurrently with first dose of hepatitis A vaccine (using different syringes and different injection sites).

Efficacy of IGIM for HAV postexposure prophylaxis not established if given >2 weeks.

The above IGIM dosage is higher than previously recommended. This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).

Measles

Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.25 mL/kg of IGIM given within 6 days after exposure in susceptible individuals. If susceptible child is immunocompromised, manufacturer recommends single dose of 0.5 mL/kg (up to 15 mL) given immediately after the exposure.

ACIP and AAP recommend single dose of 0.5 mL/kg (up to 15 mL) of IGIM given within 6 days after exposure. ACIP states optimal dose needed to provide protection against measles unknown.

Individuals ≥12 months of age: Initiate active immunization with a vaccine containing measles virus vaccine live (e.g., MMR) 6 months after the IGIM dose, unless the vaccine is contraindicated. (See Specific Drugs and Laboratory Tests under Interactions.)

Individuals currently receiving immune globulin therapy who received IGIV (≥400 mg/kg) within 3 weeks prior to measles exposure or received immune globulin subcutaneous (≥200 mg/kg) for 2 consecutive weeks prior to measles exposure should be sufficiently protected against measles.

IV

Gammaked 10% (children ≥2 years of age): If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to expected measles exposure. If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.

Gamunex-C 10% (children ≥2 years of age): If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to measles exposure. If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.

Octagam 5%: If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area, measles outbreak in US), increase dosage to at least 400 mg/kg just prior to measles exposure. If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg as soon as possible after the exposure.

Sub-Q

Hizentra 20% (children ≥2 years of age): Use minimum total weekly dose of 200 mg/kg for 2 consecutive weeks in those at risk of measles exposure (e.g., susceptible traveler to measles endemic area, measles outbreak in US). If a biweekly regimen is being used, give a single dose of at least 400 mg/kg. If a susceptible individual has been exposed to measles, give a dose of at least 400 mg/kg as soon as possible after the exposure.

Varicella

Alternative to VZIG for Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.6–1.2 mL/kg of IGIM given promptly.

IGIV (not IGIM) usually recommended when VZIG unavailable. (See Varicella under Uses.)

IV^†

Single dose of 400 mg/kg of IGIV (ideally within 96 hours after exposure).

May not be necessary in patients already receiving immune globulin replacement therapy with IGIV (≥400 mg/kg given at regular intervals) if the last dose was administered within 3 weeks prior to exposure.

Primary Immunodeficiency Diseases

Replacement Therapy

IV

Minimum serum IgG concentration necessary for protection varies among patients; there is considerable interindividual variation in half-life of IgG in patients with primary humoral immunodeficiency. Monitor clinical response and adjust IGIV dosage to achieve desired trough serum IgG concentrations and/or clinical response.

Individuals with primary immunodeficiency who are exposed to measles or are at increased risk of measles exposure: Some manufacturers state it may be prudent to administer an extra IGIV dose or increase the IGIV dose, respectively. ACIP and AAP state that those currently receiving immune globulin replacement therapy who received an IGIV dose of ≥400 mg/kg within 3 weeks prior to measles exposure or received immune globulin subcutaneous in a dosage of ≥200 mg/kg for 2 consecutive weeks prior to measles exposure should be sufficiently protected against measles.

Asceniv 10% (adolescents ≥12 years of age): 300–800 mg/kg IV once every 3–4 weeks. Starting with second IV infusion, adjust dosage proportionately and target a trough IgG concentration of ≥600 mg/dL. Dosage adjustment may be required in those who fail to maintain trough serum IgG concentrations ≥500 mg/dL with a target of 600 mg/dL.

Bivigam 10% (children ≥6 years of age): 300–800 mg/kg IV once every 3–4 weeks. Starting with second IV infusion, adjust dosage over time to achieve and maintain trough serum IgG concentrations >600 mg/dL. If trough serum IgG concentrations cannot be maintained at ≥500 mg/dL, adjust dosage to achieve target trough serum IgG concentration of 600 mg/dL.

Carimune NF: 400–800 mg/kg IV once every 3–4 weeks.

Flebogamma 5% DIF (children ≥2 years of age): 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough IgG concentrations.

Gammagard Liquid 10% (children ≥2 years of age): Usually, 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough IgG concentrations.

Gammagard S/D (children ≥2 years of age): 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough IgG concentrations.

Gammaked 10% (children ≥2 years of age): 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentrations and clinical response.

Gammaplex 5% (children ≥2 years of age): 300–800 mg/kg (6–16 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Gammaplex 10% (children ≥2 years of age): 300–800 mg/kg (3–8 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Gamunex-C 10% (children ≥2 years of age): 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.

Octagam 5%: 300–600 mg/kg (6–12 mL/kg) IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Panzyga 10% (children ≥2 years of age): 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response.

Privigen 10% (children ≥3 years of age): 200–800 mg/kg (2–8 mL/kg) IV once every 3 to 4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Sub-Q

Monitor clinical response and individualize dosage of immune globulin subcutaneous based on clinical response and trough serum IgG concentrations.

Individuals with primary immunodeficiency who are exposed to measles or are at increased risk of measles exposure: ACIP and AAP state that those currently receiving immune globulin replacement therapy who received an IGIV dose of ≥400 mg/kg within 3 weeks prior to measles exposure or received immune globulin subcutaneous in a dosage of ≥200 mg/kg for 2 consecutive weeks prior to measles exposure should be sufficiently protected against measles.

Cuvitru 20% (children ≥2 years of age): Give at regular intervals ranging from once daily up to once every 2 weeks (biweekly). Calculate initial sub-Q dose based on monthly dose of prior immune globulin regimen. If switching from IGIV or immune globulin subcutaneous 10% with recombinant human hyaluronidase (Hyqvia), give initial dose 1 week after last dose of the other immune globulin. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.

Gammagard Liquid 10% (children ≥2 years of age): Administer sub-Q once weekly. Give initial dose approximately 1 week after last IGIV dose. To calculate initial weekly sub-Q dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37. Base maintenance sub-Q doses on clinical response and target trough IgG concentrations. Consult manufacturer’s literature for specific information regarding how to adjust sub-Q dosage based on trough serum IgG concentrations.

Gammaked 10% (children ≥2 years of age): Administer sub-Q once weekly. Give initial dose 1 week after last IGIV dose. To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37. Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response. Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations and for information regarding dosage requirements for patients switching from another immune globulin subcutaneous preparation to Gammaked 10%.

Gamunex-C 10% (children ≥2 years of age): Administer sub-Q once weekly. Give initial dose 1 week after last IGIV dose. To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37. Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.

Hizentra 20% (children ≥2 years of age): Administer sub-Q at regular intervals ranging from once daily up to once every 2 weeks (biweekly). Use only in patients who have been receiving IGIV for ≥3 months before being switched to Hizentra 20%; give initial dose 1 week after last IGIV dose. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.

Xembify 20% (children ≥2 years of age): Administer sub-Q once weekly; alternatively, may divide weekly dose and give in 2–7 doses during the week. When switching from IGIV, calculate initial weekly dose of Xembify 20% based on previous IGIV monthly (or every 3 weeks) dosage and give first dose of Xembify 20% 1 week after last IGIV dose. When switching from a different immune globulin subcutaneous preparation, initial weekly dose of Xembify 20% should be the same as weekly dose of prior immune globulin subcutaneous treatment. Base subsequent doses on clinical response and target trough IgG concentrations. Consult manufacturer’s literature for specific information regarding how to adjust sub-Q dosage based on trough serum IgG concentrations.

Idiopathic Thrombocytopenic Purpura (ITP)

IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg IV once daily for 2–5 consecutive days. For treatment of acute childhood ITP, if an initial platelet count response to first 2 doses is adequate (30,000–50,000/mm³), discontinue therapy after second day of the 5-day regimen. For treatment of chronic ITP, if platelet count decreases to <30,000/mm³ and/or clinically important bleeding becomes apparent following initial induction therapy, administer 400 mg/kg as a single maintenance infusion. If adequate response does not occur, increase maintenance dose to 800–1000 mg/kg given as a single infusion.

Flebogamma 10% DIF (children ≥2 years of age): 1 g/kg IV once daily for 2 consecutive days for chronic ITP.

Gammaked 10%: 1 g/kg (10 mL/kg) IV on 2 consecutive days (total dose 2 g/kg); if increase in platelet count adequate 24 hours after initial dose, second dose may be withheld. Alternatively, give 400 mg/kg (4 mL/kg) on 5 consecutive days (total dose 2 g/kg). High-dose regimen (1 g/kg for 1 or 2 doses) not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.

Gamunex-C 10%: 1 g/kg (10 mL/kg) IV on 2 consecutive days (total dose 2 mg/kg); if increase in platelet count adequate 24 hours after initial dose, second dose may be withheld. Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg). High-dose regimen (1 g/kg for 1 or 2 doses) not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.

Privigen 10% (adolescents ≥15 years of age): 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg) for chronic ITP. Carefully consider potential benefits versus risks before using this high-dose regimen in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

Kawasaki Disease

IV

For initial treatment of acute phase, AAP, AHA, and ACCP recommend a single dose of 2 g/kg of IGIV given by IV infusion (usually over 10–12 hours) as soon as possible (optimally within 7–10 days of disease onset). Used in conjunction with appropriate aspirin therapy (e.g., 80–100 mg/kg daily continued for up to 14 days and/or until patient has been afebrile for 48–72 hours; may be followed by low-dose aspirin therapy).

If no response (i.e., fever persists or recurs ≥36 hours after the IGIV dose), AHA and AAP state that retreatment with a second IGIV dose of 2 g/kg and continued aspirin therapy is a reasonable option. Use of additional or alternative anti-inflammatory or immunosuppressive agents may be necessary in IGIV-resistant patients. Consult specialized references for additional information on management of such individuals.

Gammagard S/D (IgA <1 mcg/mL): Manufacturer recommends a single dose of 1 g/kg IV beginning within 7 days of onset of fever or, alternatively, 400 mg/kg once daily for 4 consecutive days beginning within 7 days of onset of fever. Used in conjunction with appropriate aspirin therapy.

In one study evaluating IGIV and aspirin therapy, a single 2-g/kg IGIV dose was as effective or more effective in preventing coronary artery abnormalities than a 4-day regimen (400 mg/kg daily for 4 days), and the single IGIV dose was associated with more rapid defervescence, shorter duration of fever, and more rapid return to normal of clinical measures of inflammation.

Prevention of Infections in HIV-infected Individuals†

IV

Infants and children with hypogammaglobulinemia (IgG <400 mg/dL): AAP, CDC, NIH, and other experts recommend 400 mg/kg of IGIV once every 2–4 weeks. Discontinue if hypogammaglobulinemia resolves.

Prevention of Infections in Hematopoietic Stem Cell Transplant (HSCT) Recipients†

IV

Preadolescent children with severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after allogeneic HSCT^†: 400 mg/kg of IGIV once monthly has been used. Individualize dosage to maintain trough serum IgG concentrations exceeding 400–500 mg/dL; monitor trough serum IgG concentrations regularly (e.g., approximately every 2 weeks).

Adolescents with severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after allogeneic HSCT^†: 500 mg/kg of IGIV once weekly has been used. Individualize dosage to maintain trough serum IgG concentrations exceeding 400–500 mg/dL; monitor trough serum IgG concentrations regularly (e.g., approximately every 2 weeks).

Tetanus†

Treatment of Tetanus†

IV

200–400 mg/kg of IGIV has been recommended as an alternative when TIG not available. (See Tetanus under Uses.)

Toxic Shock Syndrome†

Staphylococcal or Streptococcal Toxic Shock Syndrome†

IV

150–400 mg/kg of IGIV once daily for 5 days or, alternatively, a single dose of 1–2 g/kg has been used. Optimal dosage regimen not established.

Adults

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

Travelers to Areas with Intermediate or High Levels of Endemic HAV

IM

Single dose of 0.1 or 0.2 mL/kg of IGIM in those staying in such areas for up to 1 or 2 months, respectively. If period of exposure in such areas will be ≥2 months, give 0.2 mL/kg once every 2 months.

Primary immunization with an age-appropriate schedule of hepatitis A vaccine before an expected exposure to HAV is preferred, unless contraindicated.

To ensure protection in travelers who are older adults, immunocompromised, or have chronic liver disease or other chronic medical conditions and plan to depart within 2 weeks, give single dose of IGIM concurrently with first dose of hepatitis A vaccine (using different syringes and different injection sites).

The above IGIM dosage is higher than previously recommended. This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IM

Adults >40 years of age who have not previously received hepatitis A vaccine: Give single dose of 0.1 mL/kg of IGIM as soon as possible after exposure (ideally within 2 weeks).

Adults ≤40 years of age who have not previously received hepatitis A vaccine: ACIP and CDC prefer active immunization with an age-appropriate schedule of hepatitis A vaccine since it provides long-term protection.

Immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: Give single dose of 0.1 mL/kg of IGIM as soon as possible after exposure (ideally within 2 weeks).

In individuals receiving IGIM for HAV postexposure prophylaxis and in whom hepatitis A vaccine also is recommended, give IGIM dose concurrently with first dose of hepatitis A vaccine (using different syringes and different injection sites).

Efficacy of IGIM for HAV postexposure prophylaxis not established if given >2 weeks after exposure.

The above IGIM dosage is higher than previously recommended. This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).

Measles

Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.25 mL/kg of IGIM given within 6 days after exposure in susceptible individuals.

ACIP recommends single dose of 0.5 mL/kg (up to 15 mL) of IGIM given within 6 days after exposure. ACIP states optimal dose needed to provide protection against measles infection unknown.

Initiate active immunization with a vaccine containing measles virus vaccine live (e.g., MMR) 6 months after the IGIM dose, unless the vaccine is contraindicated. (See Specific Drugs and Laboratory Tests under Interactions.)

Individuals currently receiving immune globulin therapy who received IGIV (≥400 mg/kg) within 3 weeks prior to measles exposure or immune globulin subcutaneous (≥2 mg/kg) for 2 consecutive weeks prior to measles exposure should be sufficiently protected and do not need IGIM for postexposure prophylaxis.

IV†

ACIP recommends a single dose of 400 mg/kg given within 6 days after exposure.

If patient with primary immunodeficiency is receiving IGIV replacement therapy and is exposed to measles, some manufacturers state that it may be prudent to administer an extra IGIV dose as soon as possible and within 6 days after exposure; a dose of 400 mg/kg should provide serum levels of measles antibody that are >240 mIU/mL for at least 2 weeks. These manufacturers state that if a patient with primary immunodeficiency is receiving IGIV in a dosage <530 mg/kg once every 3–4 weeks and is at risk of measles exposure, increase the dose to at least 530 mg/kg since this should provide serum levels of measles antibody that are 240 mIU/mL for at least 22 days after the IGIV dose.

Gammaked 10%: If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to expected measles exposure. If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.

Gamunex-C 10%: If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to measles exposure. If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.

Octagam 5%: If a patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area, measles outbreak in US), increase dosage to at least 400 mg/kg just prior to measles exposure. If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg as soon as possible after the exposure.

Sub-Q

Cutaquig 16.5%: If patient with primary immunodeficiency is at risk of measles exposure and is receiving a weekly dosage <245 mg/kg, manufacturer states the weekly dosage should be increased to ≥245 mg/kg.

Hizentra 20%: If patient with primary immunodeficiency is at risk of measles exposure (e.g., susceptible traveler to measles endemic area, measles outbreak in US), manufacturer recommends minimum total weekly dose of 200 mg/kg for 2 consecutive weeks. If a biweekly sub-Q regimen is being used, give a single dose of at least 400 mg/kg. If a susceptible individual has been exposed to measles, give a dose of at least 400 mg/kg as soon as possible after the exposure.

Rubella

Postexposure Prophylaxis in Pregnant Women

IM

Manufacturer recommends single dose of 0.55 mL/kg of IGIM to modify rubella in susceptible pregnant women exposed to the disease. Routine use not recommended. (See Rubella under Uses.)

Varicella

Alternative to VZIG for Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.6–1.2 mL/kg of IGIM given promptly.

IGIV (not IGIM) usually recommended when VZIG is unavailable.

IV^†

Single dose of 400 mg/kg of IGIV (ideally within 96 hours after varicella exposure).

May not be necessary in patients already receiving immune globulin replacement therapy with IGIV (≥400 mg/kg given at regular intervals) if the last dose was administered within 3 weeks prior to varicella exposure.

Primary Immunodeficiency Diseases

Replacement Therapy

IV

Minimum serum IgG concentration necessary for protection varies among patients; there is considerable interindividual variation in half-life of IgG in patients with primary humoral immunodeficiency. Monitor clinical response and adjust IGIV dosage to achieve desired trough serum IgG concentrations and/or clinical response.

Individuals with primary immunodeficiency who are exposed to measles or are at increased risk of measles exposure: Some manufacturers state it may be prudent to administer an extra IGIV dose or increase the IGIV dose, respectively. ACIP and AAP state that those currently receiving immune globulin replacement therapy who received an IGIV dose of ≥400 mg/kg within 3 weeks prior to measles exposure or received immune globulin subcutaneous in a dosage of ≥200 mg/kg for 2 consecutive weeks prior to measles exposure should be sufficiently protected against measles.

Asceniv 10%: 300–800 mg/kg IV once every 3–4 weeks. Starting with second infusion, adjust dosage proportionately, targeting a trough IgG concentration of ≥600 mg/dL. Dosage adjustment may be required in those who fail to maintain trough serum IgG concentrations ≥500 mg/dL with a target of 600 mg/dL.

Bivigam 10%: 300–800 mg/kg IV once every 3–4 weeks. Starting with second infusion, adjust dosage over time to achieve and maintain trough serum IgG concentrations >600 mg/dL. If trough serum IgG concentrations cannot be maintained at ≥500 mg/dL, adjust dosage to achieve a target trough serum IgG concentration of 600 mg/dL.

Carimune NF: 400–800 mg/kg IV once every 3–4 weeks.

Flebogamma 5% DIF: 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough serum IgG concentrations.

Flebogamma 10% DIF: 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough serum IgG concentrations.

Gammagard Liquid 10%: Usually, 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough serum IgG concentrations.

Gammagard S/D (IgA <1 mcg/mL): Usually, 300–600 mg/kg IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response; data not available to determine optimum target trough serum IgG concentrations.

Gammaked 10%: 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentrations and clinical response.

Gammaplex 5%: 300–800 mg/kg (6–16 mL/kg) IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Gammaplex 10%: 300–800 mg/kg (3–8 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Gamunex-C 10%: 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response.

Octagam 5%: 300–600 mg/kg (6–12 mL/kg) IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Panzyga 10%: 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks. Adjust dosage to achieve desired trough serum IgG concentration and clinical response.

Privigen 10%: 200–800 mg/kg (2–8 mL/kg) IV once every 3–4 weeks. Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response. If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.

Sub-Q

Monitor clinical response and individualize dosage of immune globulin subcutaneous based on clinical response and trough serum IgG concentrations.

Individuals with primary immunodeficiency who are exposed to measles: ACIP states that those currently receiving immune globulin replacement therapy who received an IGIV dose of ≥400 mg/kg within 3 weeks prior to measles exposure or received immune globulin subcutaneous in a dosage ≥200 mg/kg for 2 consecutive weeks prior to measles exposure should be sufficiently protected against measles.

Cutaquig 16.5%: Administer sub-Q once weekly. When switching from IGIV or a different immune globulin subcutaneous preparation, initiate in those who have received ≥3 months of prior treatment and give first dose of Cutaquig 16.5% 1 week after last dose of prior immune globulin. Calculate initial dose of Cutaquig 16.5% based on prior immune globulin dosage. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage of Cutaquig 16.5%.

Cuvitru 20%: Give at regular intervals ranging from once daily up to once every 2 weeks (biweekly). Calculate initial sub-Q dose based on monthly dose of prior immune globulin regimen. If switching from IGIV or immune globulin subcutaneous 10% with recombinant human hyaluronidase (Hyqvia), give initial dose 1 week after last dose of the other immune globulin. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.

Gammagard Liquid 10%: Administer sub-Q once weekly. Give initial dose approximately 1 week after last IGIV dose. To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37. Base maintenance sub-Q doses on clinical response and target trough IgG concentrations. Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations.

Gammaked 10%: Administer sub-Q once weekly. Give initial dose 1 week after last IGIV dose. To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37. Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response. Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations and for information regarding dosage requirements for patients switching from another immune globulin subcutaneous preparation to Gammaked 10%.

Gamunex-C 10%: Administer sub-Q once weekly. Give initial dose 1 week after last IGIV dose. To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37. Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.

Hizentra 20%: Administer sub-Q at regular intervals ranging from once daily up to once every 2 weeks (biweekly). Use only in patients who have been receiving IGIV for ≥3 months before being switched to Hizentra 20%; give initial dose 1 week after last IGIV dose. Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Administer sub-Q once every 3 to 4 weeks after an initial ramp-up period that incrementally changes the dosage regimen from a 1-week regimen to a 3- or 4-week regimen and allows the patient to become accustomed to the large volumes required for a full monthly dose. Consult manufacturer's literature for specific information on the ramp-up schedule, including specific doses and dosing intervals for sub-Q administration.

Xembify 20%: Administer sub-Q once weekly; alternatively, may divide weekly dose and give in 2–7 doses during the week. When switching from IGIV, calculate initial weekly dose of Xembify 20% based on previous IGIV monthly (or every 3 weeks) dosage and give first dose of Xembify 20% 1 week after last IGIV dose. When switching from a different immune globulin subcutaneous preparation, initial weekly dose of Xembify 20% should be the same as weekly dose of prior immune globulin subcutaneous treatment. Base subsequent doses on clinical response and target trough IgG concentrations. Consult manufacturer’s literature for specific information regarding how to adjust sub-Q dosage based on trough serum IgG concentrations.

Idiopathic Thrombocytopenic Purpura (ITP)

IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg IV once daily for 2–5 consecutive days. If platelet count decreases to <30,000/mm³ and/or clinically important bleeding becomes apparent following initial induction therapy, administer 400 mg/kg as a single maintenance infusion. If adequate response does not occur, increase maintenance dose to 800–1000 mg/kg given as a single infusion.

Flebogamma 10% DIF: 1 g/kg IV once daily for 2 consecutive days for chronic ITP.

Gammagard S/D (IgA <1 mcg/mL): Single dose of 1 g/kg IV for chronic ITP. Determine need for additional doses based on clinical response and platelet count. If required, up to 3 doses may be given on alternate days.

Gammaked 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg); if increase in platelet count adequate 24 hours after first dose, second dose may be withheld. Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg). High-dose regimen (1 g/kg for 1 or 2 doses) not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.

Gammaplex 5%: 1 g/kg (20 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg). Carefully consider risks and benefits of this high-dose regimen before using in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload. Adequate data not available regarding platelet response to a lower-dose regimen (i.e., 400 mg/kg daily for 5 consecutive days).

Gammaplex 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg). Carefully consider risks and benefits of this high-dose regimen before using in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload. Adequate data not available regarding platelet response to a lower-dose regimen (i.e., 400 mg/kg daily for 5 consecutive days).

Gamunex-C 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg); if increase in platelet count adequate 24 hours after first dose, second dose may be withheld. Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg). High-dose regimen (1 g/kg for 1 or 2 doses) not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.

Octagam 10%: For chronic ITP, 1 g/kg IV once daily for 2 consecutive days (total dose 2 g/kg).

Panzyga 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg).

Privigen 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg) for chronic ITP. Carefully consider potential benefits versus risks before using this high-dose regimen in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

Individuals with B-cell Chronic Lymphocytic Leukemia (CLL)

Prevention of Bacterial Infections in Those with Hypogammaglobulinemia and/or Recurrent Bacterial Infections

IV

Gammagard S/D (IgA <1 mcg/mL): 400 mg/kg IV once every 3–4 weeks.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

IV

Gammaked 10%: Loading dose of 2 g/kg (20 mL/kg) IV given in divided doses over 2–4 consecutive days. Then, maintenance dosage of 1 g/kg (10 mL/kg) given as a single dose once every 3 weeks or, alternatively, 2 doses of 0.5 g/kg (5 mL/kg) given on 2 consecutive days once every 3 weeks.

Gamunex-C 10%: Loading dose of 2 g/kg (20 mL/kg) IV given in divided doses over 2–4 consecutive days. Then, maintenance dosage of 1 g/kg (10 mL/kg) given as a single dose once every 3 weeks or, alternatively, 2 doses of 0.5 g/kg (5 mL/kg) given on 2 consecutive days once every 3 weeks. Has been continued for up to 48 weeks in clinical studies in patients with CIDP.

Privigen 10%: Loading dose of 2 g/kg (20 mL/kg) IV given in divided doses over 2–5 consecutive days. Then, maintenance dosage of 1 g/kg (10 mL/kg) given as a single dose once every 3 weeks or, alternatively, as 2 doses given on 2 consecutive days once every 3 weeks. Has not been studied for durations >6 months. After response is obtained during initial treatment period, not all patients require indefinite maintenance therapy to remain free of CIDP symptoms. Assess patient's response and demonstrated need for continued Privigen 10% therapy beyond 6 months.

Sub-Q

Hizentra 20% for maintenance treatment to prevent relapse: Give initial dose sub-Q 1 week after last IGIV dose. Weekly dosage of Hizentra 20% is 0.2 g/kg (1 mL/kg) given sub-Q in 1 or 2 sessions over 1 or 2 consecutive days. Clinical study data evaluating use of Hizentra 20% for maintenance therapy in CIDP patients transitioning from IGIV indicate that a weekly dose of 0.4 g/kg (2 mL/kg) also is safe and effective when used to prevent CIDP relapse. If CIDP symptoms worsen, consider discontinuing Hizentra 20% and reinitiating IGIV. If improvement and stabilization are observed during IGIV retreatment, consider discontinuing IGIV and reinitiating Hizentra 20% using a weekly dose of 0.4 g/kg sub-Q given in 2 sessions over 1 or 2 consecutive days. If CIDP symptoms worsen on the 0.4 g/kg weekly dose, consider discontinuing Hizentra 20% and reinitiating IGIV. Maintenance therapy with Hizentra 20% has been studied for a duration of 6 months and for an additional 12 months of follow-up. Use for maintenance therapy for a longer duration should be individualized based on patient's response and need for continued therapy.

Multifocal Motor Neuropathy (MMN)

IV

Although optimum dosage not established, if IGIV used when disability is severe enough to warrant treatment, the European Federation of Neurological Societies (EFNS) and Peripheral Nerve Society (PNS) suggest an initial IGIV dosage of 2 g/kg given in divided doses over 2–5 consecutive days. If initial regimen is effective, these clinicians state that maintenance therapy can be considered using 1 g/kg once every 2–4 weeks or 2 g/kg every 1–2 months; frequency of maintenance therapy should be guided by response.

Gammagard Liquid 10%: Manufacturer recommends maintenance dosage ranging from 500 mg/kg to 2.4 g/kg IV once every month. Adjust dosage to achieve desired clinical response and avoid worsening of muscle weakness.

Guillain-Barré Syndrome† (GBS)

IV

Although safety and efficacy and optimum dosage not established, EFNS and others recommend 0.4 g/kg of IGIV daily for 5 days. Unclear whether IGIV is effective when initiated more than 2 weeks after symptom onset.

If relapse occurs after an initial response, EFNS states that retreatment with a dosage of 2 g/kg of IGIV given in divided doses over 2–5 consecutive days can be considered. Retreatment also can be considered in those who do not respond to initial regimen, but other clinicians state it is unclear whether retreatment is beneficial in such patients.

Prevention of Infections in Hematopoietic Stem Cell Transplant (HSCT) Recipients†

IV

Patients with severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after allogeneic HSCT^†: 500 mg/kg of IGIV once weekly has been used.

Individualize dosage to maintain trough serum IgG concentrations exceeding 400–500 mg/dL; monitor trough serum IgG concentrations regularly (e.g., approximately every 2 weeks).

Tetanus†

Treatment of Tetanus†

IV

200–400 mg/kg of IGIV has been recommended as an alternative when TIG not available. (See Tetanus under Uses.)

Toxic Shock Syndrome†

Staphylococcal or Streptococcal Toxic Shock Syndrome†

IV

150–400 mg/kg of IGIV once daily for 5 days or, alternatively, a single dose of 1–2 g/kg has been used. Optimal dosage regimen not established.

Prescribing Limits

Pediatric Patients

Measles

Postexposure Prophylaxis

IM

Maximum single IGIM dose: 15 mL.

Adults

Measles

Postexposure Prophylaxis

IM

Maximum single IGIM dose: 15 mL.

Special Populations

Renal Impairment

IGIV: Reduce dose, concentration, and/or rate of administration; maximum safe dose, concentration, and rate of administration not established. Ensure that patients are not volume depleted and are well hydrated; administer at the minimum concentration available and minimum infusion rate practicable. (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Immune globulin subcutaneous: Consider lower, more frequent dosing. Ensure that patients are not volume depleted and are adequately hydrated.

Geriatric Patients

IGIV: Reduce dose, concentration, and/or rate of infusion in patients >65 years of age; maximum safe dose, concentration, and rate of administration not established. Administer IGIV and immune globulin subcutaneous at minimum infusion rate practicable. (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Immune globulin subcutaneous: Select dosage with caution, usually starting at low end of dosage range; administer at minimum infusion rate practicable.

Cautions for Immune Globulin

Contraindications

• IGIM, IGIV, immune globulin subcutaneous: History of anaphylactic or severe systemic hypersensitivity reaction to immune globulin or any ingredient in the formulation.

• IGIM, IGIV, immune globulin subcutaneous: IgA-deficient individuals with antibodies against IgA and history of hypersensitivity. (See IgA Deficiency under Cautions.)

• Flebogamma 5% DIF and Flebogamma 10% DIF: Hereditary fructose intolerance; contains sorbitol, which presents a risk to individuals with hereditary fructose intolerance.

• Gammaplex 5%: Hereditary fructose intolerance and neonates and infants for whom sucrose or fructose tolerance not established; contains sorbitol.

• Hizentra 20%, Privigen 10%: Hyperprolinemia (type I or II); contain l-proline as a stabilizer.

• Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Known systemic hypersensitivity to human albumin (contained in the recombinant human hyaluronidase component).

• Octagam 5%: Acute hypersensitivity reactions to corn; contains maltose derived from corn. (See Corn Allergy under Cautions.)

Warnings/Precautions

Warnings

Thrombosis

Thrombotic events (e.g., chest pain, MI, CHF, cerebral infarction, ischemic encephalopathy, severe headache requiring hospitalization, pulmonary embolism, retinal vein occlusion, peripheral venous thrombosis), including some fatalities, reported in patients receiving immune globulin.

Etiology for thrombosis in patients receiving immune globulin not fully determined; immune globulin-induced alterations of blood rheology (e.g., platelet activation, increased blood viscosity, elevated levels of activated coagulation factor XI [XIa]) and infusion-related hypertensive effects appear to contribute to development of thrombotic complications.

Patients at risk for thrombotic events may include those with a history of atherosclerosis, cardiovascular risk factors, impaired cardiac output, coagulation or hypercoagulable disorders (e.g., factor V Leiden), prolonged periods of immobilization, advanced age, acquired or inherited thrombotic disorder, previous thrombotic or thromboembolic event, known or suspected hyperviscosity, indwelling central vascular catheters, and/or treatment with estrogen-containing preparations. Thrombosis may occur in patients without known risk factors.

Weigh potential risks and benefits of immune globulin against those of alternative therapies in all patients in whom immune globulin is being considered.

Prior to immune globulin therapy, carefully evaluate patients with thrombotic risk factors (e.g., those with a history of atherosclerosis, cardiovascular risk factors, impaired cardiac output, coagulation or hypercoagulable disorders [e.g., factor V Leiden], prolonged periods of immobilization, advanced age, acquired or inherited thrombotic disorder, history of venous or arterial thrombosis, known or suspected hyperviscosity, indwelling central vascular catheters, and/or treatment with estrogen-containing preparations).

In patients at risk for thrombosis, use minimum dose and minimum infusion rate practicable and monitor closely for signs and symptoms of thrombosis. In addition, ensure that all patients are adequately hydrated prior to administration of immune globulin.

Because of potential increased risk of thrombosis, consider baseline assessment of blood viscosity in patients at risk for hyperviscosity (e.g., those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], or monoclonal gammopathies).

Renal Effects

Renal dysfunction, acute renal failure, osmotic nephrosis, and death reported in patients receiving immune globulin.

Patients at increased risk for acute renal failure include, but are not limited to, those with any degree of preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, or paraproteinemia; those receiving concomitant nephrotoxic drugs; and/or those >65 years of age.

IGIV preparations stabilized with sucrose (e.g., Carimune NF) have been associated with renal dysfunction more frequently than other IGIV preparations; weigh benefits of these preparations against potential risk of renal dysfunction. Maximum infusion rate of 3 mg of sucrose/kg per minute recommended.

To reduce risk of acute renal failure, ensure that patients are not volume depleted and are adequately hydrated prior to administration of IGIV or immune globulin subcutaneous and use lowest effective dosage.

Administer IGIV or immune globulin subcutaneous at the minimum concentration available and the minimum infusion rate practicable, especially in patients at increased risk for acute renal failure.

Assess urine output and renal function (BUN, S_cr) prior to and at appropriate intervals during therapy with IGIV or immune globulin subcutaneous, especially in patients considered at increased risk for acute renal failure.

If renal dysfunction occurs, consider discontinuing immune globulin therapy.

Infusion Reactions

Increased risk of infusion reactions (e.g., fever, chills, nausea, vomiting) when immune globulin administered by IV or sub-Q infusion in patients who have not previously received immune globulin therapy, in patients being switched to a different immune globulin preparation, and in those who have not received immune globulin within the preceding 8 weeks.

IGIV may cause a precipitous fall in BP and clinical manifestations of anaphylaxis, which appear to be related to the rate of IGIV infusion; do not exceed the recommended rate of infusion. These reactions generally appear 0.5–1 hour after initiation of the infusion and include facial flushing, chest tightness, chills, fever, dizziness, nausea, vomiting, diaphoresis, and hypotension or hypertension.

Hypertensive urgency with elevated systolic BP (≥180 mm Hg) and/or elevated diastolic BP (≥120 mm Hg) reported during and/or shortly following infusion of IGIV (Privigen 10%). BP elevations were reported more often among patients with a history of hypertension and resolved or significantly improved within hours with either observation alone or changes in oral antihypertensive therapy.

Closely monitor for adverse reactions throughout the infusion since these reactions may rarely lead to shock.

If flushing, changes in BP or pulse, or other infusion reactions occur, slow or temporarily stop the infusion. In some cases when symptoms subside promptly, the infusion may be resumed at a rate that is comfortable for the patient. Stop infusion immediately if anaphylaxis or other severe reactions occur. (See Sensitivity Reactions under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Severe hypersensitivity reactions, including anaphylaxis, reported rarely following administration of IGIV, IGIM, or immune globulin subcutaneous.

If a severe hypersensitivity reaction occurs, discontinue immune globulin immediately and institute appropriate therapy as indicated. Epinephrine and antihistamines should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.

Use IGIM with caution in patients with a history of systemic allergic reactions to immune globulin preparations.

The manufacturer of IGIM states that intradermal sensitivity testing should not be performed; intradermal injection of concentrated buffered immune globulin solution frequently causes localized chemical irritation, which may be misinterpreted as evidence of hypersensitivity and result in needed therapy being withheld.

IgA Deficiency

IGIM, IGIV, and immune globulin subcutaneous should not be used in IgA-deficient individuals with antibodies against IgA and a history of hypersensitivity.

Individuals with selective IgA deficiency or individuals in whom IgA deficiency exists as a component of an immunodeficiency disease may have serum antibodies to IgA or may develop such antibodies following administration of immune globulin or other blood products containing IgA. Potential for severe hypersensitivity (e.g., anaphylactic) reactions to IgA in such patients.

Administer only in a setting where supportive care is available for treating life-threatening reactions. If a hypersensitivity reaction occurs, consider alternative therapy.

All commercially available preparations of IGIV contain trace amounts of IgA, but the amount varies among the different preparations. Concentration of IgA that will not provoke a reaction to IgA not known.

Asceniv 10%: ≤200 mcg/mL of IgA.

Bivigam 10%: ≤200 mcg/mL of IgA.

Carimune NF: Trace amounts of IgA.

Cutaquig 16.5% : ≤600 mcg/mL of IgA.

Cuvitru 20%: Average of 80 mcg/mL of IgA.

Flebogamma 5% DIF: <50 mcg/mL of IgA.

Flebogamma 10% DIF: <32 mcg/mL of IgA.

Gammagard Liquid 10%: Average of 37 mcg/mL of IgA.

Gammagard S/D: <1 mcg/mL of IgA.

Gammaked 10%: Average of 46 mcg/mL of IgA.

Gammaplex 5%: Trace amounts of IgA (<10 mcg/mL).

Gammaplex 10%: Trace amounts of IgA (<20 mcg/mL).

Gamunex-C 10%: Average of 46 mcg/mL of IgA.

Hizentra 20%: ≤50 mcg/mL of IgA.

Hyqvia 10%: Average of 37 mcg/mL of IgA.

Octagam 5%: ≤200 mcg/mL of IgA.

Octagam 10%: Average of 106 mcg/mL of IgA.

Panzyga 10%: Average of 100 mcg/mL of IgA.

Privigen 10%: ≤25 mcg/mL of IgA.

Xembify 20%: Contains IgA (amount not specified).

Corn Allergy

Octagam 5% and Octagam 10% contain maltose, a disaccharide sugar derived from corn. Hypersensitivity reactions may occur if these preparations are used in patients with corn allergy. Manufacturer states avoid Octagam 5% in patients with known corn allergies; contraindicated in those with acute hypersensitivity reactions to corn.

Other Warnings and Precautions

Hemolysis

IGIV and immune globulin subcutaneous may contain blood group antibodies that can act as hemolysins and induce in vivo coating of RBCs with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis.

Delayed hemolytic anemia can develop subsequent to immune globulin therapy due to enhanced RBC sequestration, and acute hemolysis consistent with intravascular hemolysis has been reported.

Monitor for clinical signs and symptoms of hemolysis (e.g., increased heart rate, swelling, fatigue, difficulty breathing, yellowing of skin or eyes, dark-colored urine).

In higher risk patients, consider performing appropriate laboratory testing (e.g., hemoglobin or hematocrit) prior to IGIV infusion and within approximately 36–96 hours after infusion. If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit occur, perform additional confirmatory laboratory tests.

If a blood transfusion is indicated for a patient who developed hemolysis with clinically compromising anemia after receiving immune globulin, adequate cross-matching should be performed to avoid exacerbating on-going hemolysis.

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (noncardiogenic pulmonary edema) reported in patients receiving IGIV and could also occur in patients receiving immune globulin subcutaneous. Typically occurs within 1–6 hours after the infusion and is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever.

Monitor patients receiving immune globulin for adverse pulmonary reactions.

If transfusion-related acute lung injury suspected, perform appropriate tests for the presence of antineutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the product and patient serum. Manage using oxygen therapy with adequate ventilatory support.

Aseptic Meningitis Syndrome

Aseptic meningitis syndrome reported in patients receiving immune globulin, especially in those receiving high doses (e.g., >1 g/kg) and/or rapid infusions. Symptoms (e.g., severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, vomiting) may occur within several hours to 2 days following administration.

In patients exhibiting such symptoms, perform a thorough neurologic examination, including CSF studies, to rule out other causes of meningitis. CSF analysis frequently reveals elevated protein levels (up to several hundred mg/dL) and pleocytosis (up to several thousand cells per mm³), predominantly from the granulocytic series, but negative culture results.

Syndrome has resolved without sequelae within several days following discontinuance of the immune globulin.

Hyperproteinemia, Increased Viscosity, and Hyponatremia

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV. The hyponatremia is likely to be pseudohyponatremia, as demonstrated by decreased calculated serum osmolality or elevated osmolar gap.

If hyponatremia occurs, it is critical to distinguish true hyponatremia from pseudohyponatremia. Treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and may predispose to thromboembolic events. (See Thrombosis under Cautions.)

Gammagard S/D (IgA <1 mcg/mL) contains approximately 8.5 mg of sodium chloride per mL; consider this amount when determining dietary sodium in patients on a low-sodium diet since hypernatremia may occur.

Volume Overload

Because of risk of volume overload, manufacturers of Gammaplex 5%, Gammaplex 10%, and Privigen 10% state carefully consider relative risks and benefits before using high-dose IGIV regimens (1 g/kg daily for 1–2 days) for treatment of chronic ITP in patients at increased risk of volume overload.

Manufacturers of Gammaked 10% and Gamunex-C 10% state high-dose IGIV regimens (1 g/kg daily for 1–2 days) not recommended for treatment of chronic ITP in individuals with expanded fluid volumes or when fluid volume may be a concern.

Risk of Transmissible Agents in Plasma-derived Preparations

Because immune globulin preparations are prepared from pooled human plasma, they may carry a risk of transmitting human viruses (e.g., HAV, HBV, HCV, HIV) and theoretically may carry a risk of transmitting the causative agents of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).

Risk for transmission of recognized blood-borne viruses is considered to be low because plasma donors are screened for certain viruses (HBV, HCV, HIV, human parvovirus [B19V]) and viral reduction/inactivation procedures used in immune globulin production reduce the risk of transmission. Despite such stringent procedures, a risk of transmission still remains.

Report all infections thought possibly to have been transmitted by immune globulin preparations to the appropriate manufacturer.

Immunogenicity of Recombinant Human Hyaluronidase

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): In clinical studies, nonneutralizing antibodies to recombinant human hyaluronidase developed in 18% of patients. Clinical importance unknown.

Animal studies indicate that antibodies to recombinant human hyaluronidase cross the placenta and are transferred to offspring during lactation. These antibodies could potentially cross-react with endogenous human hyaluronidase (expressed in adult male testes, epididymis, and sperm).

Blood Glucose Testing

Immune globulin preparations that contain maltose (e.g., Cutaquig 16.5%, Octagam 5%, Octagam 10%) may cause falsely elevated results in blood glucose determinations with tests that use nonspecific methods based on glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye oxidoreductase. (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Populations

Pregnancy

Animal reproduction studies not performed with IGIM, IGIV, or immune globulin subcutaneous, and it is not known whether immune globulins can cause fetal harm when administered to pregnant women.

Some manufacturers state use immune globulin during pregnancy only when clearly needed.

ACIP states there are no known risks associated with immune globulins used for passive immunization in pregnant women.

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Some patients receiving this preparation have developed antibodies to recombinant human hyaluronidase and these antibodies potentially could cross-react with endogenous human hyaluronidase, which is expressed in adult male testes, epididymis, and sperm. Not known whether these anti-recombinant human hyaluronidase antibodies interfere with human fertility.

Lactation

Not evaluated in nursing women.

Not known whether immune globulin is distributed into milk following IM, IV, or sub-Q administration, affects milk production, or affects the breast-fed infant.

Use with caution in nursing women. Consider benefits of breast-feeding and importance of immune globulin to the woman as well as potential adverse effects on breast-fed infant from the drug or from underlying maternal condition.

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Animal studies indicate maternal antibodies bound to recombinant human hyaluronidase are transferred to nursing offspring; no adverse effects on pregnancy or offspring development associated with these antibodies reported. Data not available regarding use in nursing women; possible effects of antibodies to recombinant human hyaluronidase that may be transferred to infants unknown.

Pediatric Use

GamaSTAN: Manufacturer states safety and efficacy of IGIM not established in pediatric patients; however, passive immunization with IGIM is recommended by ACIP and AAP in pediatric patients under certain circumstances using same dosages recommended for adults. (See Hepatitis A Virus [HAV]) Infection [Preexposure Prophylaxis], Hepatitis A Virus [HAV] Infection [Postexposure Prophylaxis], and Measles, under Uses.)

Asceniv 10%: Evaluated in limited number of pediatric patients 6–16 years of age for treatment of primary immunodeficiency; safety, efficacy, and pharmacokinetic profiles in adolescents were comparable to adults. Data insufficient regarding safety, efficacy, and pharmacokinetics in pediatric patients <12 years of age; safety and efficacy not studied in those <3 years of age.

Bivigam 10%: Safety and efficacy not established in children <6 years of age. Only limited data regarding efficacy and safety in pediatric patients.

Carimune NF: Studies using high doses in pediatric patients with acute or chronic ITP did not reveal any specific differences in safety in pediatric patients versus adults.

Cutaquig 16.5%: Only limited number of pediatric patients were included in clinical study evaluating use for treatment of primary immunodeficiency. Safety and efficacy not established in pediatric patients <17 years of age.

Cuvitru 20%: Safety and efficacy not established in pediatric patients <2 years of age.

Flebogamma 5% DIF: Safety and efficacy not established in pediatric patients <2 years of age.

Flebogamma 10% DIF: Safety and efficacy not established for treatment of primary immunodeficiency in pediatric patients. Evaluated in a limited number of children and adolescents with chronic ITP; safety and efficacy not established for treatment of chronic ITP in children <2 years of age.

Gammagard Liquid 10%: Safety and efficacy for treatment of primary immunodeficiency not established in children <2 years of age. Safety and efficacy for treatment of MMN not established in pediatric patients of any age.

Gammagard S/D (IgA <1 mcg/mL): Clinical studies in patients with primary immunodeficiency did not include sufficient numbers of pediatric patients ≤16 years of age to determine whether they respond differently than adults. Safety and efficacy not established for treatment of ITP in pediatric patients. Safety and efficacy established for treatment of Kawasaki disease in pediatric patients; majority of patients in clinical studies were <5 years of age.

Gammaked 10%: Safety and efficacy of IV route established for treatment of primary immunodeficiency in pediatric patients; safety and efficacy of sub-Q route not established for treatment of primary immunodeficiency in pediatric patients <2 years of age. Safety and efficacy of IV (not sub-Q) route established for treatment of ITP in pediatric patients. Safety and efficacy not established for treatment of CIDP in pediatric patients.

Gammaplex 5%: Safety and efficacy for treatment of primary immunodeficiency not established in children <2 years of age. Clinical studies in patients with ITP included only limited number of children; data insufficient to determine whether efficacy in pediatric patients with ITP differs from that in adults.

Gammaplex 10%: Evaluated in limited number of pediatric patients 3–15 years of age for treatment of primary immunodeficiency; pediatric-specific dosage not required to achieve desired serum IgG concentrations in this age group. Safety and pharmacokinetics in pediatric patients ≥3 years of age similar to adults. Safety and efficacy not established for treatment of ITP in pediatric patients.

Gamunex-C 10%: Safety and efficacy of IV route established for treatment of primary immunodeficiency in pediatric patients; safety and efficacy of sub-Q route not established for treatment of primary immunodeficiency in pediatric patients <2 years of age. Safety and efficacy of IV (not sub-Q) route established for treatment of ITP in pediatric patients. Safety and efficacy not established for treatment of CIDP in pediatric patients.

Hizentra 20%: Safety and efficacy for treatment of primary immunodeficiency not established in pediatric patients <2 years of age. Safety and efficacy established for replacement therapy in pediatric patients 2–16 years of age with primary immunodeficiency; no differences in safety and efficacy profiles in pediatric patients compared with adults; pediatric-specific dosage not required to achieve desired serum IgG concentrations. Safety and efficacy not established for treatment of CIDP in pediatric patients <18 years of age.

Hyqvia 10%: Safety not established in pediatric patients.

Octagam 5%: Evaluated in a limited number of children 6–16 years of age; no apparent differences in pharmacokinetics, efficacy, or safety compared with adults. Pediatric-specific dosage not required to achieve desired serum IgG concentrations.

Octagam 10%: Safety and efficacy not established in pediatric patients.

Panzyga 10%: Evaluated in limited number of pediatric patients 2–15 years of age for treatment of primary immunodeficiency. Pharmacokinetics, efficacy, and safety in these pediatric patients similar to adults; pediatric-specific dosage not required to achieve targeted serum IgG concentrations. Safety and efficacy not established for treatment of ITP in pediatric patients.

Privigen 10%: Safety and efficacy for treatment of primary immunodeficiency not established in pediatric patients <3 years of age. Has been evaluated in a limited number of children and adolescents with primary immunodeficiency; no apparent differences in safety and efficacy compared with adults; pediatric-specific dosage not required to achieve desired serum IgG concentrations. Safety and efficacy not established for treatment of chronic ITP in pediatric patients <15 years of age. Safety and efficacy not established for treatment of CIDP in pediatric patients <18 years of age.

Geriatric Use

Patients >65 years of age are at increased risk for acute renal failure or thrombotic event during immune globulin therapy.

IGIM: Safety and efficacy not established in geriatric patients.

IGIV: Clinical studies of IGIV did not include a sufficient number of patients ≥65 years of age to determine whether geriatric individuals respond differently than younger patients. Other reported clinical experience has not identified differences in responses between geriatric and younger patients.

Immune globulin subcutaneous: Clinical studies of Cutaquig 16.5% and Xembify 20% did not include a sufficient number of patients ≥65 years of age to determine whether geriatric individuals respond differently than younger patients. Only limited number of patients ≥65 years of age were included in clinical studies of Cuvitru 20%, Gammagard Liquid 10%, Hizentra 20%, or Hyqvia; no overall differences in safety or efficacy were observed compared with younger patients.

Use with caution; do not exceed recommended dosage; administer at minimum concentration available and minimum practicable infusion rate. (See Renal Effects under Cautions and see Geriatric Patients under Dosage and Administration.)

Renal Impairment

Patients receiving immune globulin who have any degree of preexisting renal insufficiency are at increased risk for acute renal failure. Ensure that such patients are not volume depleted and are well hydrated and administer immune globulin at the minimum concentration available and minimum practicable rate of infusion. (See Renal Effects under Cautions and see Renal Impairment under Dosage and Administration.)

Common Adverse Effects

IGIM: Fatigue, headache, nausea, fever, injection site reactions (pain, tenderness).

IGIV: Infusion site reactions (pain, irritation); chest, hip, joint, back, or extremity pain; arthralgia or myalgia; GI effects (diarrhea, nausea, vomiting); chills; fever/hyperthermia; asthenia; malaise; fatigue; insomnia; dizziness; headache; migraine headache; immediate anaphylactoid and hypersensitivity reactions; allergic and cutaneous reactions such as rash, erythema, pruritus, urticaria, eczema, or dermatitis; hypertension or fluctuations in BP; palpitations; tachycardia; increased liver function test results; asthma; wheezing; otic pain; upper respiratory tract infection; cough (increased or productive); bronchitis; rhinitis/nasal congestion; sinusitis; pharyngitis.

IGIV for treatment of ITP: Headache, fever, chills, GI effects (nausea, vomiting, diarrhea, dyspepsia ), dizziness, hypotension, hypertension, increased heart rate, pain (abdominal or back), dehydration, rash, pruritus, ecchymosis, anemia.

IGIV for treatment of CIDP: Headache, fever, chills, nausea, hypertension, pain (extremity), arthralgia, influenza-like illness, leukopenia, rash, asthenia.

Immune globulin subcutaneous: Infusion site reactions (e.g., erythema, pain, swelling, induration, edema, pruritus, heat, bruising, hematoma, nodule, scab), headache, migraine headache, fever, fatigue, cough, upper respiratory tract infection, asthma, GI effects (e.g., nausea, vomiting, diarrhea, upper abdominal pain, stomatitis), increased heart rate, increased systolic BP, pain (back pain, extremity pain), arthralgia, cough, dermatitis, rash, pruritus.

Drug Interactions

Live Vaccines

Antibodies present in immune globulin preparations may interfere with immune response to some live virus vaccines, including MMR and varicella virus vaccine live; no evidence of interference with immune responses to influenza virus vaccine live intranasal, rotavirus vaccine live oral, typhoid vaccine live oral, yellow fever virus vaccine live, zoster vaccine live, or poliovirus vaccine live oral (OPV; no longer commercially available in US). (See Specific Drugs and Laboratory Tests under Interactions.)

Inactivated Vaccines and Toxoids

ACIP and AAP state that administration of inactivated vaccines and toxoids simultaneously with (at different sites) or at any interval before or after administration of immune globulin preparations should not have clinically important effects on immune responses to the vaccines or toxoids.

Specific Drugs and Laboratory Tests

Immune Globulin Pharmacokinetics

Absorption

Bioavailability

Following IM administration of IGIM, serum concentrations of IgG peak within 2 days.

Following IV administration of IGIV, there is an immediate post-infusion peak in serum IgG concentrations followed by a biphasic decline.

Following sub-Q administration of immune globulin, peak serum IgG concentrations are lower than those attained with IGIV, but trough concentrations generally are higher. In contrast to the biphasic IgG concentrations reported with IGIV, sub-Q immune globulin given once weekly results in relatively stable IgG concentrations. Peak serum IgG concentrations in patients receiving sub-Q immune globulin generally occur 2.9 days (range: 0–7 days) after a dose.

Following sub-Q administration of immune globulin with recombinant human hyaluronidase (Hyqvia), peak serum IgG concentrations are lower than those attained with IGIV, but trough IgG concentrations generally are comparable. In addition, AUC of IgG is 20% higher than that attained with immune globulin subcutaneous given without recombinant human hyaluronidase. Peak serum IgG concentrations in patients receiving Hyqvia generally occur 5 days (range 3.3–5.1 days) after a dose.

Distribution

Extent

IgG present in IGIM or IGIV is rapidly and evenly distributed between intravascular and extravascular spaces.

Intact immune globulins cross the placenta in increasing amounts after 30 weeks’ gestation.

Not known whether immune globulin is distributed into milk following IM, IV, or sub-Q administration.

Elimination

Half-life

IGIV undergoes biphasic elimination; rapid initial decline in serum IgG concentrations associated with equilibration between plasma and extravascular space, followed by slower elimination phase.

High IgG concentrations and hypermetabolism associated with fever and infection have been reported to coincide with shortened IgG half-life.

Half-life of IgG in individuals with normal serum IgG concentrations: 18–25 days.

Half-life of IGIV preparations in patients with immunodeficiencies: 12–59 days.

Stability

Storage

Parenteral

Injection for IM Use

GamaSTAN: 2–8°C. Do not freeze.

Injection for IV Infusion

Asceniv 10%: 2–8°C. Do not freeze or heat; discard if frozen or heated.

Bivigam 10%: 2–8°C. Do not freeze or heat; discard if frozen or heated. Promptly use vials that have been entered. Discard partially used vials.

Flebogamma 5% DIF: 2–25°C; stable for up to 24 months as indicated by expiration date on outer carton and container label. Do not freeze; discard if frozen. Protect from light by storing in original carton. Discard partially used vials.

Flebogamma 10% DIF: 2–25°C; stable for up to 24 months as indicated by expiration date on outer carton and container label. Do not freeze; discard if frozen. Protect from light by storing in original carton. Discard partially used vials.

Gammaplex 5% and Gammaplex 10%: 2–25°C for up to 36 months after date of manufacture. Do not freeze; discard if frozen. Protect from light by storing in original carton. Promptly use bottles or vials that have been entered; discard partially used bottles or vials.

Octagam 5%: 2–25°C for 24 months after date of manufacture. Do not freeze; discard if frozen. Promptly use bottles that have been entered; discard partially used bottles.

Octagam 10%: 2–8°C for 24 months after date of manufacture. Alternatively, may be stored at room temperature (≤25°C) for up to 9 months at any time during first 12 months from date of manufacture, but then must be used immediately or discarded. Do not freeze; discard if frozen. Promptly use bottles that have been entered; discard partially used bottles.

Panzyga 10%: 2–8°C for up to 24 months after date of manufacture. May be stored at room temperature (≤25°C) for up to 9 months at any time during the 24 months from date of manufacture, but then must be used immediately or discarded. Do not freeze; discard if frozen.

Privigen 10%: Room temperature (≤25ºC) for up to 36 months after date of manufacture as indicated by expiration date on outer carton and vial label. Do not freeze; discard if frozen. Protect from light.

Powder for Injection, for IV Infusion

Carimune NF: Room temperature (≤30°C); may be stored until expiration date indicated on vial label. Use promptly if reconstituted outside of sterile laminar airflow conditions; use within 24 hours if reconstituted in a sterile laminar flow hood using aseptic technique and stored under refrigeration. Do not freeze reconstituted solution. Discard partially used vials.

Gammagard S/D (IgA <1 mcg/mL): ≤25°C; do not freeze. If reconstituted outside of sterile laminar airflow conditions, use within 2 hours; if reconstituted in a sterile laminar flow hood using aseptic technique, may be stored at 2–8°C for up to 24 hours. Discard partially used vials.

Injection for Sub-Q Infusion

Cutaquig 16.5%: 2–8°C for up to 24 months after date of manufacture. May be stored at room temperature (≤25°C) for up to 6 months at any time during the 24 months, but then must be used immediately or discarded. To protect from light, store in original carton until used. Do not freeze; discard if frozen.

Cuvitru 20%: 2–8°C for up to 36 months. Alternatively, store at room temperature (≤25°C) for up to 12 months; do not return to refrigeration. Do not freeze. To protect from light, store in original carton until used. Discard partially used vials.

Hizentra 20%: Room temperature (≤25°C) for up to 30 months as indicated by expiration date on outer carton of prefilled syringe or vial label. Do not freeze; discard if frozen. To protect from light, store in original carton until used. Discard partially used vials.

Hyqvia (kit containing immune globulin subcutaneous 10% with recombinant human hyaluronidase): 2–8°C for up to 36 months as indicated by expiration date on outer carton and vial label. Alternatively, may be stored for up to 3 months at room temperature (≤25°C) during first 24 months from date of manufacture; do not return to refrigeration. Do not freeze. To protect from light, store in original carton until used. Discard partially used vials.

Xembify 20%: 2–8°C. May be stored at room temperature (≤25°C) for up to 6 months at any time prior to expiration date, but then must be used immediately or discarded. Do not freeze; discard if frozen.

Injection for IV or Sub-Q Infusion

Gammagard Liquid 10%: 2–8°C for ≤36 months as indicated by expiration date on outer carton and container label. Alternatively, may be stored at ≤25°C for up to 24 months as indicated by expiration date on outer carton and container label. Do not freeze. Vials are for single use only. Discard partially used vials.

Gammaked 10%: 2–8°C for 36 months after date of manufacture. May be stored at room temperature (≤25°C) for up to 6 months at any time during the 36 months, but then must be used immediately or discarded. Do not freeze; discard if frozen. Promptly use vials that have been entered; discard partially used vials.

Gamunex-C 10%: 2–8°C for 36 months after date of manufacture. May be stored at room temperature (≤25°C) for up to 6 months at any time during the 36 months, but then must be used immediately or discarded. Do not freeze. Promptly use vials that have been entered; discard partially used vials.

Compatibility

Parenteral

Solution Compatibility (Carimune NF)125

Solution Compatibility (Gammagard Liquid 10%)266

Solution Compatibility (Gammaked)332

Solution Compatibility (Gamunex-C 10%)265

Solution Compatibility (Privigen 10%)292

Actions

• Provides a broad spectrum of opsonic and neutralizing IgG antibodies against a wide variety of bacterial and viral agents.

• IgG antibodies contained in immune globulin provide passive immunity by increasing an individual’s antibody titer and antigen-antibody reaction potential and prevent or modify certain infectious diseases in susceptible individuals.

• Mechanism of action in the treatment of primary humoral immunodeficiency not fully elucidated.

• Mechanism by which IGIV increases platelet counts in the treatment of ITP not fully elucidated. May saturate Fc (crystallizable fragment) receptors on cells of the reticuloendothelial system, resulting in decreased Fc-mediated phagocytosis of antibody-coated cells. Altered Fc-receptor affinity for IgG or suppression of antiplatelet antibody production may be involved.

• Mechanism by which IGIV reduces the incidence of acute GVHD following BMT not determined.

• Mechanism of action of IGIV in the treatment of chronic inflammatory demyelinating polyneuropathy not fully elucidated.

• Mechanism of action of IGIV in the treatment of Kawasaki disease is not known, but possibly may include modulation of cytokine production, neutralization of bacterial superantigens or other etiologic agents, augmentation of T-cell suppressor activity, suppression of antibody synthesis, and provision of anti-idiotypic antibodies. IGIV and aspirin appear to have additive anti-inflammatory effects in the treatment of Kawasaki disease.

• Asceniv 10%: Contains ≥96% IgG. Contains glycine and polysorbate 80 as stabilizers.

• Bivigam 10%: Contains ≥96% IgG. Contains glycine and polysorbate 80 as stabilizers.

• Carimune NF: Following reconstitution, contains 30–120 mg of protein per mL. Contains ≥96% IgG; most of the immunoglobulins are monomeric (7S) IgG; the remainder are dimeric IgG, small amounts of polymeric IgG, traces of IgA and IgM, and immunoglobulin fragments. Distribution of IgG subclasses corresponds to that of normal serum. Contains sucrose as stabilizing agent.

• Cutaquig 16.5%: Contains ≥96% IgG. Distribution of IgG subclasses is approximately 70% IgG₁, 25% IgG₂, 3% IgG₃, and 2% IgG₄. Contains maltose.

• Cuvitru 20%: Contains 20% protein, of which ≥98% is IgG. Distribution of IgG subclasses is similar to that of normal plasma. Fc and Fab functions are maintained. Contains glycine as stabilizing and buffering agent.

• Flebogamma 5% DIF: Contains ≥97% IgG and trace amounts of IgA (typically <50 mcg/mL) and IgM. Distribution of IgG subclasses is approximately 66.6% IgG₁, 28.5% IgG₂, 2.7% IgG₃, and 2.2% IgG₄. Contains sorbitol as stabilizing agent, polyethylene glycol, and trace amounts of sodium.

• Flebogamma 10% DIF: Contains ≥97% IgG. Distribution of IgG subclasses is approximately 66.6% IgG₁, 27.9% IgG₂, 3.0% IgG₃, and 2.5% IgG₄. Contains sorbitol as stabilizing agent, polyethylene glycol, and trace amounts of sodium.

• GamaSTAN: Contains 15–18% protein.

• Gammagard Liquid 10%: Contains ≥98% IgG, IgA (average 37 mcg/mL), and trace amounts of IgM. Distribution of IgG subclasses is similar to that of normal serum. Fc and Fab functions are maintained. Contains glycine as stabilizing and buffering agent.

• Gammagard S/D: Following reconstitution, contains approximately 50 mg of protein per mL. Contains ≥90% IgG and trace amounts of IgA (<1 mcg/mL) and IgM. Distribution of IgG subclasses is similar to that of normal serum. Fc portion is maintained intact. Contains glycine, dextrose, polyethylene glycol, polysorbate 80, and human albumin.

• Gammaked 10%: Contains 9–11% protein stabilized in 0.16–0.24 M glycine; ≥98% of protein content has the electrophoretic mobility of IgG. Distribution of IgG subclasses is similar to that of normal serum; contains trace amounts of fragments, IgA (average 46 mcg/mL), and IgM.

• Gammaplex 5%: Contains ≥95% IgG and <10 mcg/mL of IgA. The IgG subclass distribution is approximately 64% IgG₁, 30% IgG₂, 5% IgG₃, and 1% IgG₄. Contains sorbitol, glycine, and polysorbate 80 as stabilizers.

• Gammaplex 10%: Contains ≥98% IgG and <20 mcg/mL of IgA. The IgG subclass distribution reflects that of normal serum. Contains glycine and polysorbate 80 as stabilizers.

• Gamunex-C 10%: Contains 9–11% protein stabilized in 0.16–0.24 M glycine; ≥98% of the protein content has the electrophoretic mobility of IgG. Contains trace amounts of fragments, IgA (average 46 mcg/mL), and IgM. Distribution of IgG subclasses is similar to that of normal serum. Fc and Fab functions are maintained, but do not activate complement or pre-Kallikrein activity in unspecific manner.

• Hizentra 20%: Contains 200 mg of protein per mL, of which ≥98% is IgG. The Fc and Fab functions of the IgG molecule are retained. Distribution of IgG subclasses is similar to that of normal plasma. Contains trace amounts of IgA (≤50 mcg/mL). Also contains approximately 250 mmol/L (range 210–290 mmol/L) of l-proline (a nonessential amino acid) as a stabilizer, polysorbate 80 (8–30 mg/L), and trace amounts of sodium.

• Hyqvia (kit containing immune globulin subcutaneous 10% with recombinant human hyaluronidase): Immune globulin subcutaneous component contains ≥98% IgG and trace amounts of IgA (average 37 mcg/mL) and IgM; distribution of IgG subclasses is similar to that of normal serum. Fab and Fc portions maintained intact and prekallikrein activity not detectable. Contains glycine as stabilizing and buffering agent. Recombinant human hyaluronidase component is a polysaccharide containing 447 amino acids prepared from mammalian cells using recombinant DNA technology. Recombinant human hyaluronidase acts locally to temporarily increase permeability of sub-Q tissue to increase dispersion and absorption of the immune globulin subcutaneous component.

• Octagam 5%: Contains approximately 50 mg of protein per mL, of which ≥96% is IgG; contains aggregates (≤3%), monomers and dimers (≥90%), and fragments (≤3%). Distribution of IgG subclasses is approximately 65% IgG₁, 30% IgG₂, 3% IgG₃, and 2% IgG₄ (similar to that of normal serum). Contains trace amounts of IgA (≤200 mcg/mL) and IgM (≤100 mcg/mL). Fc portion is maintained intact.

• Octagam 10%: Contains approximately 100 mg of protein per mL, of which ≥96% is IgG; contains aggregates (≤3%), monomers and dimers (≥94%), and fragments (≤3%). Distribution of IgG subclasses is approximately 65% IgG₁, 30% IgG₂, 3% IgG₃, and 2% IgG₄ (similar to that of normal serum). Contains trace amounts of IgA (approximately 106 mcg/mL) and IgM. Fc portion is maintained intact.

• Panzyga 10%: Contains approximately 100 mg of protein per mL, of which ≥96% is IgG; contains aggregates (≤3%), monomers and dimers (≥90%), and fragments (≤3%); Fc portion is maintained intact. Distribution of IgG subclasses is approximately 65% IgG₁, 28% IgG₂, 3% IgG₃, and 4% IgG₄. Contains glycine as a stabilizer.

• Privigen 10%: Contains ≥98% IgG; Fc and Fab functions of IgG molecule are retained. Distribution of IgG subclasses reflects that of normal plasma. Contains ≤25 mcg/mL of IgA. Also contains 250 mmol/L (range 210–290 mmol/L) of l-proline (a nonessential amino acid) as a stabilizer.

• Xembify 20%: Contains ≥98% IgG. Distribution of IgG subclasses is similar to that of normal serum. Contains glycine and polysorbate 80.

Advice to Patients

• Importance of patients understanding potential risks (e.g., thrombosis, hypersensitivity reactions, renal effects, possible transmission of infectious agents) and benefits of immune globulin.

• If the patient and/or caregiver are considered competent to safely administer immune globulin subcutaneous in the home or other appropriate setting, ensure that they receive instructions and training regarding proper dosage and administration.

• Advise patients of the importance of immediately informing a clinician if symptoms of thrombosis occur, including pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, unexplained rapid pulse, chest pain or discomfort that worsens on deep breathing, numbness or weakness on one side of the body, changes in mental status/confusion, numbness in the face or extremities, weakness or paralysis, severe headache, and/or visual disturbances.

• Instruct patients receiving immune globulin to immediately report symptoms of decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (which may suggest renal damage) to their clinician.

• Advise patients about the early signs of hypersensitivity (e.g., hives, generalized urticaria, chest tightness, wheezing, hypotension, anaphylaxis) and the importance of immediately contacting clinician if allergic symptoms occur.

• Importance of immediately informing clinician if severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, or nausea and vomiting occur since these are possible signs and symptoms of aseptic meningitis syndrome.

• Importance of immediately informing clinician if increased heart rate, fatigue, yellowing of skin or eyes, or dark-colored urine occurs since these are possible signs and symptoms of hemolytic anemia.

• Importance of immediately informing clinician if trouble breathing, severe respiratory distress, chest pain, pulmonary edema, hypoxemia, blue lips or extremities, lightheadedness, decreased BP, or fever occurs since these are possible signs and symptoms of transfusion-related acute lung injury (noncardiogenic pulmonary edema). Advise patients that such effects typically occur within 1–6 hours following infusion.

• Advise patients that immune globulin is prepared from pooled human plasma. Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, a risk of transmission of human viruses or other pathogens still remains. Importance of reporting any infection believed to have been transmitted by the immune globulin preparation.

• Advise patients with selective IgA deficiency that IGIV, IGIM, and immune globulin subcutaneous contain trace amounts of IgA and potentially could result in life-threatening allergic reactions if used in patients who have developed antibodies to IgA.

• Advise patients receiving Cutaquig or Octagam that these preparations contain maltose and may cause falsely-elevated glucose readings when blood glucose monitoring systems based on GDH-PQQ are used; this could result in inappropriate administration of insulin and life-threatening hypoglycemia or could mask true hypoglycemia. Importance of using glucose-specific test methods not affected by maltose.

• Advise patients that immune globulin may interfere with the immune response to certain live viral vaccines (e.g., MMR, MMRV, varicella virus vaccine live); importance of informing clinician administering vaccines about current or recent immune globulin therapy.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Medical Disclaimer