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.^{125 154 263 265 266 280 282 292 294 308 324 325 326 327 331 332}

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.^{105 115 154 186 231}

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.^{105 115 186}

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).^{105 115 186}

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.^{105 115 186}

Travelers to areas with intermediate or high levels of endemic HAV are at substantial risk of acquiring the disease.^{115 186} 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.^{115 186} However, cases of travel-related HAV can occur in travelers who have standard tourist itineraries and accommodations and food consumption behaviors considered low risk.^{115 186} Consult CDC website ([Web]) for information regarding which countries have intermediate or high levels of HAV endemicity.¹¹⁵

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.^{115 186} 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.^{115 186}

Hepatitis A vaccine is preferred for HAV preexposure prophylaxis in most travelers, unless contraindicated, and should be administered as soon as travel is considered.^{115 186} A single dose of hepatitis A vaccine administered before departure can provide adequate protection for most healthy travelers.¹¹⁵ 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).^{105 115 186}

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.^{105 115 154 186}

Although IGIM is 80–90% effective in preventing symptomatic HAV infection if administered within 2 weeks of exposure,^{105 186} 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.^{105 287} The vaccine offers certain advantages over IGIM (e.g., induces active immunity and longer protection, more readily available, easier to administer, greater patient acceptance).¹⁸⁶ 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.¹⁸⁶

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.^{115 186}

HAV postexposure prophylaxis is not necessary in healthy individuals who have previously received hepatitis A vaccine according to the age-appropriate immunization schedule.¹⁸⁶

If HAV postexposure prophylaxis is indicated, administer hepatitis A vaccine and/or IGIM as appropriate as soon as possible (within 2 weeks of exposure).^{105 115 186} Data not available regarding efficacy of hepatitis A vaccine or IGIM administered for HAV postexposure prophylaxis >2 weeks after exposure.^{105 115} 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.^{105 186}

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.¹⁰⁵

Infants <12 months of age and whenever hepatitis A vaccine is contraindicated: IGIM recommended for HAV postexposure prophylaxis.^{105 186}

Healthy individuals 12 months through 40 years of age: Monovalent hepatitis A vaccine recommended for HAV postexposure prophylaxis.^{105 186}

Healthy adults >40 years of age: Monovalent hepatitis A vaccine recommended for HAV postexposure prophylaxis.¹⁸⁶ Also consider concomitant use of IGIM (administered at a separate site) based on risk assessment.¹⁸⁶

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.¹⁸⁶

Travelers not adequately immunized with hepatitis A vaccine exposed to HAV (within the past 2 weeks) should receive HAV postexposure prophylaxis.¹¹⁵

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.^{105 186}

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).^{105 186} 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.¹⁸⁶ 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.^{105 186}

School staff and attendees not adequately immunized with hepatitis A vaccine may receive HAV postexposure prophylaxis if transmission within the school setting is documented.¹⁰⁵ 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.^{105 186} 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).^{105 186}

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.¹⁸⁶ 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.¹⁸⁶ Settings where repeated HAV exposure might have occurred (e.g., institutional cafeterias) warrant stronger consideration of postexposure prophylaxis for patrons.¹⁸⁶

Healthcare personnel are not at substantially increased risk for HAV infection as the result of occupational exposures and healthcare-associated HAV transmission is rare.^{186 235} 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.¹⁸⁶

Neonates of HAV-infected mothers do not usually need HAV postexposure prophylaxis since perinatal transmission of HAV is rare.¹⁰⁵ 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.¹⁰⁵

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.^{105 133 154}

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.^{105 133} Consider other individuals susceptible to measles.¹³³

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.^{105 133}

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.^{105 133 154}

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.^{105 133}

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.^{105 133} 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.¹³³

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.^{105 133}

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.^{105 133}

Do not give MMR concurrently with immune globulin.^{105 133 134 154} (See Specific Drugs and Laboratory Tests under Interactions.)

Do not use immune globulin in an attempt to control measles outbreaks.¹³³

Mumps

Immune globulin, including IGIM, is not effective for prevention of mumps^{105 133} and should not be used for prophylaxis or treatment of mumps.^{133 154}

Poliomyelitis

IGIM is not indicated for and should not be used for prophylaxis or treatment of poliomyelitis.¹⁵⁴

Rubella

Immune globulin, including IGIM, has not been shown to prevent rubella and should not be used for that purpose.^{105 133}

IGIM (GamaSTAN) is labeled by FDA for use to modify symptoms of rubella in pregnant women who will not consider therapeutic abortion;¹⁵⁴ do not use for routine prophylaxis of rubella in early pregnancy in women who have not been exposed.¹⁵⁴

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,¹⁵⁴ ACIP and AAP state do not use IGIM routinely for postexposure prophylaxis of rubella in early pregnancy or any other circumstance.^{105 131} 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.^{105 131} Infants with congenital rubella syndrome have been born to women who received IGIM shortly after exposure to the disease.^{105 131}

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.^{105 156 268}

IGIM (GamaSTAN) is labeled by FDA for use to modify symptoms of varicella (chickenpox) in susceptible individuals;¹⁵⁴ do not use for routine prophylaxis or treatment of varicella.¹⁵⁴

Although manufacturer states that IGIM may be considered an alternative to VZIG for postexposure prophylaxis of varicella in susceptible individuals who are immunocompromised,¹⁵⁴ IGIV (not IGIM) is recommended when VZIG is unavailable.^{105 156 269}

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).^{105 146 155 156 269}

Clinical data demonstrating effectiveness of IGIV for postexposure prophylaxis of varicella not available.¹⁰⁵ 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.^{105 156}

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.^{105 146 155 156 269}

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.¹⁰⁵

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.^{125 263 265 266 274 275 276 280 282 292 308 324 325 332 337 338 339} 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).^{125 263 265 266 280 282 292 308 324 325 327 332 337 338 339}

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.^{265 266 294 327 331 332 340 341} This includes, but is not limited to, patients with CVID, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and SCID.^{265 266 294 327 331 332 340 341}

IGIV and immune globulin subcutaneous are contraindicated in IgA-deficient individuals with antibodies against IgA and a history of hypersensitivity.^{263 265 266 282 292 294 308 324 325 327 331 332 337 338 339 340 341} (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).^{125 138 139 265 280 292 308 325 326 332 335 337 339} IGIV is designated an orphan drug by FDA for treatment of ITP.¹⁴⁸

IGIV is used to increase platelet counts^{125 265 280 292 308 325 326 332 337 339} to prevent and/or control bleeding in patients with ITP^{265 280 326 332 339} or to allow a patient with ITP to undergo surgery.^{125 265 332}

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.^{144 145 153 157 280}

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.^{103 104 105 128 144 145 157 163 240 241 280 299 300}

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).^{105 299 300} 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.^{105 299}

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.^{105 299} In such situations, AHA and AAP state that IGIV retreatment and continued aspirin therapy is a reasonable option.^{105 299} Use of additional or alternative anti-inflammatory or immunosuppressive agents may be necessary in IGIV-resistant patients.^{105 299}

Coronary artery abnormalities develop in 15–25% of children with Kawasaki disease if they are not treated within 10 days of fever onset;^{105 299} approximately 2–4% of patients develop coronary artery abnormalities despite prompt treatment with IGIV and aspirin therapy.¹⁰⁵ 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.^{105 299 300}

Consult specialized references for additional information on management of Kawasaki disease, including long-term management in individuals with coronary abnormalities.^{299 300}

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.^{265 292 298 332}

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.³⁴³ Immune globulin subcutaneous is designated an orphan drug by FDA for treatment of CIDP.¹⁴⁸

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.^{305 306}

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);²⁶⁶ designated an orphan drug by FDA for this use.¹⁴⁸

Some clinicians recommend IGIV as a treatment of choice for MMN^{301 305 306 310 311} when disability is severe enough to warrant treatment.³¹¹

Other Neurologic and Neuromuscular Disorders

IGIV is used in the treatment of Guillain-Barré syndrome^† (GBS);^{165 219 301 304 305 306 310 312 317 318} designated an orphan drug by FDA for this use.¹⁴⁸ Although safety and efficacy not established, IGIV initiated within 2 weeks of symptom onset appears to be as effective as plasma exchange^{218 301 305 306 310 312 317} and is recommended by some clinicians as a treatment of choice for GBS in adults or children,^{218 301 305 306 310 312 318} especially if disease is severe.^{301 312} Additional study needed to determine whether IGIV is beneficial in patients with mild GBS or Miller Fischer syndrome.^{310 312 317}

IGIV has been used in the management of multiple sclerosis^† (MS).^{301 305 306 310 318} Benefits (e.g., reduced exacerbations, reduced disability scores) reported in some patients with relapsing-remitting MS,^{301 305 306 310 318} but these findings not confirmed with subsequent studies.^{333 334} Although some clinicians suggest that IGIV can be considered as a potentially effective second- or third-line treatment in patients with relapsing-remitting MS,^{306 310} others state IGIV not recommended for treatment of relapsing-remitting³³³ or secondary progressive MS^{310 333} or treatment of chronic symptoms of MS.³¹⁰

IGIV has been used with some success in the treatment of myasthenia gravis^{†108 110 217 301 304 305 306 310 312 318 319 320} and Lambert-Eaton myasthenic syndrome^† (LEMS).^{301 306 318 320 322} Designated an orphan drug by FDA for treatment of myasthenia gravis.¹⁴⁸ Efficacy and safety not established and further study needed.^{305 306 318 320} 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^{218 306 318 320} and also can be considered for second-line treatment of LEMS.^{306 320 322} Although there is some evidence that IGIV may be beneficial in patients with severe myasthenia gravis exacerbation,^{310 312 319 320} data insufficient regarding use of the drug (either alone or in conjunction with other agents) in those with stable or chronic myasthenia gravis.^{310 312 319 320}

IGIV may provide some benefits in the management of stiff person syndrome^† (Moersch-Woltmann syndrome);^{301 304 305 306 310 312 321} designated an orphan drug by FDA for this use.¹⁴⁸ 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.^{301 310}

IGIV has been used in a limited number of children with intractable epilepsy^†.^{218 306} There is some evidence that IGIV may be beneficial in some patients with Lennox-Gastaut syndrome^† or Rasmussen syndrome^†,^{306 310} but further study needed.^{145 157 165 218} 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,^{306 310} especially if they are otherwise candidates for surgical resection.³⁰⁶

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).^{130 139 144 145 156 157 175 176 177 178 179 180 181 184 216}

IGIV also has been used in an attempt to control or prevent infections in HIV-infected adults^†.^{130 144 145 157}

IGIV reduces incidence of recurrent bacterial infections and sepsis, including upper respiratory tract infections, in adults and children with symptomatic HIV infection.^{144 145 157 175 176 177 178 216}

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).¹⁵⁶ These experts also recommend IGIV as an alternative to co-trimoxazole for secondary prophylaxis of serious bacterial infections in certain HIV-infected children.¹⁵⁶

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).^{221 223 224 225 306}

Effect of IGIV on the incidence of cytomegalovirus (CMV) infection, other infections, or GVHD in patients undergoing allogeneic BMT is unclear.^{221 222 223 224 225 304 306} 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.²²¹

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.²²²

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.³⁰⁶ 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.³⁰⁶

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.²⁶²

Routine administration of IGIV in HSCT recipients >90 days after HSCT is not recommended in the absence of severe hypogammaglobulinemia.²⁶²

Infections in Low-birthweight Neonates

IGIV has been used for prophylaxis and treatment of infections in certain high-risk, preterm, low-birthweight neonates^†.^{130 137 144 145 157 162 167 168 169 170 171 172 214} However, use of IGIV for prophylaxis of infections in high-risk neonates is controversial.^{144 145 157 167 170 183 214} AAP does not recommend routine use of IGIV for prophylaxis of infections in preterm neonates.¹⁰⁵

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^†.^{130 138 140 145 157 164} May be beneficial in some patients,^{304 306} but unclear whether IGIV offers any advantage over corticosteroid therapy.³⁰⁶

IGIV has been used with variable results in patients with autoimmune hemolytic anemia^†.^{130 140 142 143 157} 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.³⁰⁶

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).^{346 347 348 349 350 352 354 355}

There is some evidence that commercially available IGIV may contain antibodies against some previously circulating coronaviruses,^{344 351} including antibodies that cross-react with SARS-CoV-2 antigens.³⁵¹ 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.^{346 351 353 354} 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.^{354 356}

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.^{355 356} 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.³⁵⁶

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.³⁵⁶ 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-19.³⁵⁶

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).³⁵⁷

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-19.³⁵⁶

Dermatomyositis and Polymyositis

IGIV has been used in the treatment of dermatomyositis^† and polymyositis^†.^{220 301 304 305 306 310 312 318} IGIV and immune globulin subcutaneous designated as orphan drugs for treatment of dermatomyositis.¹⁴⁸

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.²²⁰ 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.^{218 301 305 306 310 312 318}

Graves’ Ophthalmopathy

IGIV has been used with some success in the management of Graves’ ophthalmopathy^†.^{301 302 303 304 305 306}

Some patients responded to IGIV with improvements in diplopia, proptosis, visual acuity, and intraocular pressure;^{302 303} response rate appeared similar to that obtained with corticosteroid treatment.^{301 302 303 305}

Systemic Lupus Erythematosus

IGIV has been used with some success in the treatment of systemic lupus erythematosus^† (SLE);^{218 301 304 305 306} efficacy and safety not definitely established and additional study needed.^{305 306}

Some clinicians suggest use of IGIV may be considered in patients with severe active SLE when other drugs have been ineffective or not tolerated;²¹⁸ other clinicians recommend caution.³⁰⁶

Tetanus

IGIV has been recommended as an alternative for the treatment of tetanus^† when tetanus immune globulin (TIG) is unavailable;¹⁰⁵ TIG is the immune globulin of choice.¹⁰⁵

IGIV has been recommended as an alternative for postexposure prophylaxis of tetanus^† in individuals with tetanus-prone wounds when TIG is unavailable;¹⁰⁵ TIG is the immune globulin of choice.¹⁰⁵

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.^{105 201 306 323}

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).^{105 323}

Immune Globulin Dosage and Administration

Administration

Administer IGIM only by IM injection;¹⁵⁴ do not administer IV because of risk of serious reactions (e.g., renal dysfunction, acute renal failure, hemolysis, transfusion-related acute lung injury).¹⁵⁴

Administer IGIV by IV infusion;^{125 263 265 266 282 292} do not administer IM.^{263 265 266 308} Certain IGIV preparations can be given by IV infusion or sub-Q infusion for treatment of primary humoral immunodeficiency (i.e., Gammagard Liquid 10%,²⁶⁶ Gammaked 10%,³³² Gamunex-C 10%²⁶⁵ ); administer all other IGIV preparations only by IV infusion.^{125 263 280 282 292 308 324 325 326}

Administer immune globulin subcutaneous (Cutaquig 16.5%, Cuvitru 20%, Hizentra 20%, Hyqvia, Xembify 20%) only by sub-Q infusion.^{294 327 331 340 341}

IM Administration

Administer IGIM by IM injection, preferably into deltoid muscle of upper arm or anterolateral aspect of thigh.¹⁵⁴

Do not administer routinely into gluteal muscle because of potential for injection-associated injury to the sciatic nerve.¹⁵⁴

Draw back syringe plunger before IGIM injection to ensure needle is not in a blood vessel.¹⁵⁴

Prior to administration of IGIM, ensure that patient is not volume depleted and is adequately hydrated.¹⁵⁴

Do not exceed recommended dosage in patients at increased risk of thrombosis.¹⁵⁴

IV Administration

General Considerations

Prior to initiation of IGIV infusion, ensure that patients are not volume depleted and are adequately hydrated.^{125 263 265 266 282 292 308 324 325 326 332 337 338 339}

Individualize IV infusion rate based on the specific preparation, indication, tolerability, and individual patient requirements.^{165 263 265 266 280 282 324 325 326 332 337 338 339}

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.^{266 280 324 325 326 337 338 339}

If adverse reactions occur during the IGIV infusion, decrease IV infusion rate or stop the infusion until reactions subside.^{263 265 266 292 308 324 325 326 337 338 339}

Use minimum dose and minimum IV infusion rate practicable in patients at risk for renal dysfunction or thrombosis.^{125 263 265 266 280 282 292 308 324 325 326 332 337 338 339}

IV Administration of Asceniv 10%

Administer Asceniv 10% only by IV infusion.³³⁸

Do not dilute;³³⁸ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.³³⁸

Vials are for single use only.³³⁸

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion bag using aseptic technique.³³⁸

Administer at room temperature.³³⁸

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.³³⁸ 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).³³⁸ If adverse effects related to infusion rate occur, slow or stop the infusion.³³⁸ If symptoms subside promptly, may resume IV infusion at a lower rate that is comfortable for the patient.³³⁸

Patients at increased risk of thrombosis or renal dysfunction: Use minimum IV infusion rate practicable.³³⁸ Consider discontinuing if renal function deteriorates.³³⁸

IV Administration of Bivigam 10%

Administer Bivigam 10% only by IV infusion.³²⁴

Do not dilute;³²⁴ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.³²⁴

Vials are for single use only.³²⁴

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion bag using aseptic technique.³²⁴

Discard any partially used vials.³²⁴

Administer at room temperature.³²⁴

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.³²⁴ 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.³²⁴ If adverse effects related to infusion rate occur, symptoms may disappear if infusion is stopped or slowed.³²⁴ If symptoms subside promptly, may resume IV infusion at a lower rate that is comfortable for the patient.³²⁴

Patients at risk for renal dysfunction or thrombosis (including those ≥65 years of age): Use minimum IV infusion rate practicable.³²⁴ Consider discontinuing if renal function deteriorates.³²⁴

IV Administration of Carimune NF

Administer Carimune NF only by IV infusion.¹²⁵

Administer reconstituted solution through a separate IV line;¹²⁵ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.¹²⁵

Administer at room temperature.¹²⁵

Manufacturer states that, although the drug may be filtered, filtering not required.¹²⁵ If filter is used, those with pore sizes of ≥15 μm are less likely to slow the IV infusion, especially when higher concentrations given;¹²⁵ antimicrobial filters (0.2 μm) may be used.¹²⁵

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).¹²⁵ Consider patient’s fluid, electrolyte, and caloric requirements when selecting an appropriate diluent and concentration.¹²⁵

After diluent added, swirl vial vigorously to dissolve the drug;¹²⁵ to avoid foaming, do not shake.¹²⁵ Generally dissolves within a few minutes, but may take up to 20 minutes for complete dissolution.¹²⁵

Discard any partially used vials.¹²⁵

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.¹²⁵

If reconstituted outside of sterile laminar airflow conditions, promptly administer the reconstituted solution.¹²⁵ 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.¹²⁵

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.¹²⁵ 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.¹²⁵ If initial IV infusion well tolerated, higher concentrations may be used for subsequent infusions.¹²⁵ (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.¹²⁵ (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.¹²⁵ 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.¹²⁵ (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.¹²⁵

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.¹²⁵

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.²⁸²

Do not dilute;²⁸² do not mix with other drugs, IV infusion fluids, or other IGIV preparations.²⁸²

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion container using aseptic technique.²⁸²

Discard any partially used vials.²⁸²

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).²⁸² 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).²⁸²

Patients ≥65 years of age or at increased risk for renal dysfunction or thrombosis: Use minimum infusion rate practicable.²⁸² IV infusion rate in geriatric patients should be <0.06 mL/kg per minute (<3 mg/kg per minute).²⁸²

IV Administration of Flebogamma 10% DIF

Administer Flebogamma 10% DIF only by IV infusion.³²⁵

Do not dilute;³²⁵ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.³²⁵

If large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion container using aseptic technique.³²⁵

Discard any partially used vials and administration sets.³²⁵

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;³²⁵ if tolerated, may gradually increase IV infusion rate to 0.04 mL/kg per minute (4 mg/kg per minute).³²⁵ If tolerated, may gradually increase to a maximum rate of 0.08 mL/kg per minute (8 mg/kg per minute).³²⁵

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;³²⁵ if tolerated, may gradually increase IV infusion rate to 0.04 mL/kg per minute (4 mg/kg per minute).³²⁵ May gradually increase to a maximum rate of 0.08 mL/kg per minute (8 mg/kg per minute) if tolerated.³²⁵

Patients ≥65 years of age or at risk for renal dysfunction or thrombosis: Use minimum infusion rate practicable.³²⁵ IV infusion rate in geriatric patients should be <0.04 mL/kg per minute (<4 mg/kg per minute).³²⁵

IV Administration of Gammagard Liquid 10%

Administer Gammagard Liquid 10% by IV infusion.²⁶⁶ Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gammagard Liquid 10% under Dosage and Administration).²⁶⁶

Do not mix with other drugs or other IGIV preparations.²⁶⁶

Do not shake.²⁶⁶

Use of an in-line filter is optional.²⁶⁶ IV infusion line may be flushed with 0.9% sodium chloride injection.²⁶⁶

Administer at room temperature;²⁶⁶ do not warm in microwave.²⁶⁶

Vials are for single use only.²⁶⁶

Dilution

Available as a 10% solution.²⁶⁶ If necessary, may be diluted with 5% dextrose injection;²⁶⁶ do not use 0.9% sodium chloride as diluent.²⁶⁶ 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.²⁶⁶ 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).²⁶⁶

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).²⁶⁶ IV infusion rate may be increased (if tolerated) up to a maximum of 5.4 mL/kg per hour (9 mg/kg per minute).²⁶⁶

Patients >65 years of age or at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable.²⁶⁶ IV infusion rate in such patients should be <2 mL/kg per hour (<3.3 mg/kg per minute).²⁶⁶

IV Administration of Gammagard S/D

Administer Gammagard S/D only by IV infusion.²⁸⁰

Infuse via the administration set provided by the manufacturer, which contains an integral airway and a 15-µm filter;²⁸⁰ if this administration set not used, a similar filter must be used.²⁸⁰

Use the antecubital vein for IV infusion whenever possible, especially when a 10% solution used;²⁸⁰ this may reduce infusion site discomfort.²⁸⁰

Administer reconstituted Gammagard S/D through a separate IV line;²⁸⁰ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.²⁸⁰

Administer at room temperature.²⁸⁰

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).²⁸⁰

Prior to reconstitution, allow powder for injection and diluent to warm to room temperature.²⁸⁰

After diluent added, gently rotate vial to dissolve the drug;²⁸⁰ to avoid foaming, do not shake.²⁸⁰

When large doses are to be administered, contents of several vials may be pooled into an empty, sterile IV infusion container using aseptic technique.²⁸⁰

If reconstituted outside of sterile laminar airflow conditions, administer within 2 hours after reconstitution (preferably as soon as possible).²⁸⁰ 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).²⁸⁰

Discard any partially used vials.²⁸⁰

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;²⁸⁰ if tolerated, may gradually increase IV infusion rate of 5% solution to a maximum of 4 mL/kg per hour.²⁸⁰ 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;²⁸⁰ if tolerated, may gradually increase IV infusion rate of 10% solution to a maximum of 8 mL/kg per hour.²⁸⁰

Patients at increased risk for renal dysfunction or thrombosis: Use minimum rate practicable.²⁸⁰ 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).²⁸⁰ However, data not available to date to identify maximum safe concentration or IV infusion rate in patients at risk for renal dysfunction.²⁸⁰

IV Administration of Gammaked 10%

Administer Gammaked 10% by IV infusion.³³² Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gammaked 10% under Dosage and Administration).³³²

Prior to administration, allow to come to room temperature (may take ≥60 minutes);³³² should be clear to opalescent and colorless to pale yellow.³³²

Vials are for single use only.³³²

Do not shake.³³²

Penetrate the stopper of the 10-mL vial (containing 1 g of protein) with an 18-gauge needle;³³² 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.³³² Promptly use any vial that has been entered;³³² discard any partially used vials.³³²

Contents of full vials may be pooled under aseptic conditions into empty, sterile IV infusion bags and infused within 8 hours after pooling.³³²

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.³³² Do not flush infusion line with heparin because of potential for incompatibility between Gammaked 10% and heparin.³³²

Dilution

Available as a 10% solution.³³² If necessary, may be diluted with 5% dextrose injection;³³² do not use saline solutions as diluent.³³² 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.³³² If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).³³² If adverse effects related to IV infusion rate occur, symptoms may disappear if infusion is stopped or slowed.³³²

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.³³² If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).³³² If adverse effects related to IV infusion rate occur, symptoms may disappear if infusion is stopped or slowed.³³²

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]).³³²

IV Administration of Gammaplex 5%

Administer Gammaplex 5% only by IV infusion.³⁰⁸

Administer through a separate IV line;³⁰⁸ do not mix with other drugs or other IGIV preparations.³⁰⁸

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.³⁰⁸

When large doses are to be administered, contents of several bottles may be pooled using aseptic technique;³⁰⁸ begin IV infusion within 2 hours after pooling.³⁰⁸

Do not shake.³⁰⁸

Promptly use bottle after it has been entered;³⁰⁸ discard any partially used bottles.³⁰⁸

An infusion pump may be used to control IV infusion rate.³⁰⁸

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).³⁰⁸ 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).³⁰⁸

Patients at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable.³⁰⁸ Discontinue if renal function deteriorates.³⁰⁸

IV Administration of Gammaplex 10%

Administer Gammaplex 10% only by IV infusion.³³⁷

Administer through a separate IV line;³³⁷ do not mix with other drugs or other IGIV preparations.³³⁷

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.³³⁷

When large doses are to be administered, contents of several vials may be pooled using aseptic technique.³³⁷

Do not shake.³³⁷

Promptly use vial after it has been entered;³³⁷ discard any partially used vials.³³⁷

An infusion pump may be used to control IV infusion rate.³³⁷

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).³³⁷ 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).³³⁷

Patients at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable.³³⁷ Consider discontinuing if renal function deteriorates.³³⁷

IV Administration of Gamunex-C 10%

Administer Gamunex-C 10% by IV infusion.²⁶⁵ Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gamunex-C 10% under Dosage and Administration).²⁶⁵

Administer through a separate IV line;²⁶⁵ do not mix with other drugs or other IGIV preparations.²⁶⁵

Vials are for single use only.²⁶⁵

Administer at room temperature.²⁶⁵

Penetrate the stopper of the 10-mL vial (containing 1 g of protein) with an 18-gauge needle;²⁶⁵ 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.²⁶⁵ Promptly use any vial that has been entered;²⁶⁵ discard any partially used vials.²⁶⁵

Contents of full vials may be pooled under aseptic conditions into empty, sterile IV infusion bags and infused within 8 hours after pooling.²⁶⁵

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.²⁶⁵ Do not flush infusion line with heparin because of potential for incompatibility between Gamunex-C 10% and heparin.²⁶⁵

Dilution

Available as a 10% solution.²⁶⁵ If necessary, may dilute with 5% dextrose injection;²⁶⁵ do not use saline solutions as diluent.²⁶⁵ 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.²⁶⁵ If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).²⁶⁵ If adverse effects related to infusion rate occur, symptoms may disappear if infusion is stopped or slowed.²⁶⁵

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.²⁶⁵ If well tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).²⁶⁵ If adverse effects related to infusion rate occur, symptoms may disappear if infusion is stopped or slowed.²⁶⁵

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]).²⁶⁵

IV Administration of Octagam 5%

Administer Octagam 5% only by IV infusion.²⁶³

Do not dilute;²⁶³ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.²⁶³

Administer at room temperature.²⁶³

Penetrate the stopper of the single-use bottle with a 16-gauge or smaller needle;²⁶³ insert needle only once.²⁶³ Promptly use any single-use bottle that has been entered;²⁶³ discard partially used bottles.²⁶³

If necessary, contents of several single-use bottles may be pooled into a sterile IV infusion bag using aseptic technique;²⁶³ infuse within 8 hours after pooling.²⁶³

An infusion set is not provided with Octagam 5%;²⁶³ if an in-line filter is used (not mandatory), filter pore size should be 0.2–200 μm.²⁶³

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection before and after administration of Octagam 5%.²⁶³

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.²⁶³ 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.²⁶³ 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.²⁶³

Patients at risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable.²⁶³ 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).²⁶³ Discontinue if renal function deteriorates.²⁶³

IV Administration of Octagam 10%

Administer Octagam 10% only by IV infusion.³²⁶

Do not dilute;³²⁶ do not mix with other drugs, IV infusion fluids, or other IGIV preparations.³²⁶

Administer at room temperature.³²⁶

Penetrate the stopper of the single-use bottle with a 16-gauge or smaller needle;³²⁶ insert needle only once.³²⁶ Promptly use any single-use bottle that has been entered;³²⁶ discard partially used bottles.³²⁶

If necessary, contents of several single-use bottles may be pooled into a sterile IV infusion bag using aseptic technique;³²⁶ infuse within 8 hours after pooling.³²⁶

An infusion set is not provided with Octagam 10%;³²⁶ if an in-line filter is used (not mandatory), filter pore size should be 0.2–200 μm.³²⁶

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection before and after administration of Octagam 10%.³²⁶

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.³²⁶ 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).³²⁶ Maximum IV infusion rate is 720 mg/kg per hour (maximum 12 mg/kg per minute or 0.12 mL/kg per minute).³²⁶

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]).³²⁶ Discontinue if renal function deteriorates.³²⁶

IV Administration of Panzyga 10%

Administer Panzyga 10% only by IV infusion.³³⁹

Do not mix with other drugs, IV infusion fluids, or other IGIV preparations.³³⁹

Penetrate stopper of the single-use bottle using a 16-gauge or smaller needle;³³⁹ insert needle only once.³³⁹

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.³³⁹

Should be at room or body temperature before IV infusion.³³⁹

Administer using a filter with a pore size of 0.2–200 µm.³³⁹

After IV infusion, flush infusion line with 0.9% sodium chloride injection or 5% dextrose injection.³³⁹

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.³³⁹ 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.³³⁹ 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).³³⁹ 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.³³⁹ 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).³³⁹

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.³³⁹ 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.³³⁹

Patients at increased risk for renal dysfunction or thrombosis: Administer at minimum IV infusion rate practicable.³³⁹ Maximum IV infusion rate is 3.33 mg/kg per minute (0.03 mL/kg per minute).³³⁹ Discontinue if renal function deteriorates.³³⁹

IV Administration of Privigen 10%

Administer Privigen 10% only by IV infusion.²⁹²

Do not mix with other drugs, IV infusion fluids, or other IGIV preparations.²⁹²

Do not shake.²⁹²

Administer at room temperature (up to 25°C).²⁹²

Promptly use any vial that has been entered;²⁹² discard partially used vials.²⁹²

If large doses are to be administered, contents of several vials may be pooled using aseptic technique;²⁹² begin infusion within 8 hours after pooling.²⁹²

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.²⁹²

An infusion pump may be used to control IV infusion rate.²⁹²

Dilution

Available as 10% solution.²⁹² If necessary, may be diluted with 5% dextrose injection.²⁹² 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).²⁹² If tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).²⁹²

ITP: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute).²⁹² If tolerated, may gradually increase IV infusion rate to a maximum of 4 mg/kg per minute (0.04 mL/kg per minute).²⁹²

CIDP: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute).²⁹² If tolerated, may gradually increase IV infusion rate to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).²⁹²

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.²⁹² 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.²⁹²

Patients at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable.²⁹² Discontinue if renal function deteriorates.²⁹²

Sub-Q Administration

General Considerations

Prior to initiation of sub-Q infusion, ensure that patients are not volume depleted and are adequately hydrated.^{265 266 294 327 331 332 340 341}

Individualize sub-Q infusion rate based on the specific preparation, indication, tolerability, and other patient factors.^{265 266 294 327 331 332 340 341}

In general, initiate using lowest recommended sub-Q infusion rate and slowly increase to maximum recommended rate as tolerated.^{265 266 294 327 331 332 340 341}

If adverse reactions occur during sub-Q infusion, decrease rate of infusion or stop the infusion until reactions subside.^{265 266 294 327 331 332 340 341}

Use minimum dose and minimum sub-Q infusion rate practicable in patients at risk for thrombosis.^{265 266 294 327 331 332 340 341}

Sub-Q Administration of Cutaquig 16.5%

Administer Cutaquig 16.5% only by sub-Q infusion.³⁴⁰

May be self-administered in the home or other appropriate setting;³⁴⁰ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.³⁴⁰

Administer undiluted;³⁴⁰ do not mix with other drugs, IV infusion fluids, or other immune globulin preparations.³⁴⁰

Vials are for single use only;³⁴⁰ discard partially used vials.³⁴⁰

Make sub-Q infusions into abdomen, thighs, upper arms, and/or upper leg/hips using an infusion pump;³⁴⁰ avoid scars, tattoos, and any injured or inflamed areas.³⁴⁰

Dose may be divided and infused simultaneously in up to 6 different infusion sites that are ≥2 inches apart.³⁴⁰ For those who have not previously received immune globulin subcutaneous, maximum volume of Cutaquig 16.5% per infusion site is 25 mL;³⁴⁰ after first 5 doses, volume may be gradually increased to a maximum of 40 mL per infusion site as tolerated.³⁴⁰ Rotate sub-Q infusion sites for each subsequent dose.³⁴⁰

Consult manufacturer’s instructions provided with Cutaquig 16.5% and with the infusion pump for specific information regarding sub-Q administration.³⁴⁰

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.³⁴⁰ For subsequent sub-Q infusions, may increase infusion rate as tolerated to a maximum of 25 mL/hour at each infusion site.³⁴⁰

Sub-Q Administration of Cuvitru 20%

Administer Cuvitru 20% only by sub-Q infusion.³³¹

May be self-administered sub-Q in the home or other appropriate setting;³³¹ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.³³¹

Make sub-Q infusions into abdomen, thighs, upper arms, and/or lateral hip area;³³¹ avoid bony areas, visible blood vessels, scars, and any areas with inflammation (irritation) or infection.³³¹

Dose may be divided and infused simultaneously in up to 4 different infusion sites that are ≥4 inches apart;³³¹ use of a multi-needle administration set facilitates simultaneous sub-Q infusion at multiple sites.³³¹ Number of sites depends on volume of the dose;³³¹ calculate by dividing total volume to be infused by maximum volume per site.³³¹ 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;³³¹ maximum volume per site for subsequent infusions is 60 mL regardless of weight.³³¹

Rotate sub-Q infusion sites for each subsequent dose.³³¹

Consult manufacturer’s instructions provided with Cuvitru 20% and with the infusion pump for specific information regarding sub-Q administration.³³¹

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.³³¹ For subsequent sub-Q infusions, may increase infusion rate as tolerated to a maximum of 60 mL/hour at each infusion site.³³¹

Sub-Q Administration of Gammagard Liquid 10%

Gammagard Liquid 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency.²⁶⁶ Also may be administered by IV infusion (see IV Administration of Gammagard Liquid 10% under Dosage and Administration).²⁶⁶

May be self-administered sub-Q in the home or other appropriate setting;²⁶⁶ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.²⁶⁶

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lower back using an infusion pump;²⁶⁶ avoid bony prominences.²⁶⁶

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).²⁶⁶ Sites should be located ≥2 inches apart and should be changed for each weekly dose.²⁶⁶ Use a maximum of 8 simultaneous infusion sites.²⁶⁶

Discard any unused portions.²⁶⁶

Consult manufacturer’s instructions provided with Gammagard Liquid 10% and with the infusion pump for specific information regarding sub-Q administration.²⁶⁶

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.²⁶⁶ For maintenance doses, use a volume of 30 mL per site and an infusion rate of 20–30 mL/hour per site.²⁶⁶

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.²⁶⁶ For maintenance doses, use a volume of 20 mL per site and an infusion rate of 15–20 mL/hour per site.²⁶⁶

Sub-Q Administration of Gammaked 10%

Gammaked 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency.³³² Also may be administered by IV infusion (see IV Administration of Gammaked 10% under Dosage and Administration).³³²

May be self-administered sub-Q in the home or other appropriate setting;³³² provide patient and/or their caregiver with instructions and training regarding sub-Q administration.³³²

Prior to administration, allow to come to room temperature (may take ≥60 minutes);³³² should be clear to opalescent and colorless to pale yellow.³³²

Vials are for single use only.³³²

Do not shake.³³²

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hip using an infusion pump.³³²

Depending on total volume required, each dose of Gammaked 10% may be divided and infused into multiple sites.³³² Use a maximum of 8 simultaneous infusion sites in adults (4 infusion sites used simultaneously in most adults);³³² use a maximum of 6 simultaneous infusion sites in children.³³² Infusion sites should be located ≥2 inches apart.³³²

Does not contain preservatives;³³² discard any unused portions.³³²

Consult manufacturer’s instructions provided with Gammaked 10% and with the infusion pump for specific information regarding sub-Q administration.³³²

Rate of Administration

Primary immunodeficiency in adults: Administer Gammaked 10% sub-Q at an infusion rate of 20 mL/hour at each infusion site.³³²

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.³³² Infusion rate may then be increased to 20 mL/hour.³³²

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.³³²

Sub-Q Administration of Gamunex-C 10%

Gamunex-C 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency.²⁶⁵ Also may be administered by IV infusion (see IV Administration of Gamunex-C 10% under Dosage and Administration).²⁶⁵

May be self-administered sub-Q in the home or other appropriate setting;²⁶⁵ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.²⁶⁵

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.²⁶⁵

Do not shake.²⁶⁵

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hip using an infusion pump.²⁶⁵

Depending on total volume required, each dose of Gamunex-C 10% may be divided and infused into multiple sites.²⁶⁵ Use a maximum of 8 simultaneous infusion sites in adults (4 infusion sites used simultaneously in most adults);²⁶⁵ use a maximum of 6 simultaneous infusion sites in children.²⁶⁵ Infusion sites should be located ≥2 inches apart.²⁶⁵

Does not contain preservatives; discard any unused portions.²⁶⁵

Consult manufacturer’s instructions provided with Gamunex-C 10% and with the infusion pump for specific information regarding sub-Q administration.²⁶⁵

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.²⁶⁵

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.²⁶⁵ Infusion rate may then be increased to 20 mL/hour.²⁶⁵

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.²⁶⁵

Sub-Q Administration of Hizentra 20%

Administer Hizentra 20% only by sub-Q infusion.²⁹⁴

May be self-administered in the home or other appropriate setting;²⁹⁴ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.²⁹⁴

Prefilled syringes and vials are for single use only and should not be shaken;²⁹⁴ discard partially used syringes and vials.²⁹⁴

Consult manufacturer’s instructions for specific information on preparing and using the single-use prefilled syringes and vials.²⁹⁴

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hips using an infusion pump.²⁹⁴

Depending on total volume required, each dose may be divided and infused into multiple infusion sites.²⁹⁴ Use a maximum of 8 simultaneous infusion sites; more than one infusion device may be used simultaneously.²⁹⁴ Sites should be located ≥2 inches apart and should be changed for each weekly dose.²⁹⁴

Consult manufacturer’s instructions provided with Hizentra 20% and with the infusion pump for specific information regarding sub-Q administration.²⁹⁴

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.²⁹⁴ 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.²⁹⁴

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.²⁹⁴ 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.²⁹⁴

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.³²⁷ Administer both components only by sub-Q infusion sequentially at same infusion site.³²⁷

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.³²⁷ 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.³²⁷

Do not mix recombinant human hyaluronidase component and immune globulin subcutaneous 10% component together in same container;³²⁷ do not mix or administer the individual components with other drugs or infusion fluids.³²⁷

May be self-administered in the home or other appropriate setting;³²⁷ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.³²⁷

Make sub-Q infusions into the abdomen and/or thighs using an infusion pump.³²⁷ Avoid bony prominences or scarred, infected, or inflamed areas.³²⁷

In patients weighing ≥40 kg, maximum volume at each sub-Q infusion site is 600 mL.³²⁷ In patients weighing <40 kg, maximum volume at each site is 300 mL.³²⁷

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.³²⁷ When 2 sites are used, also divide the dose of recombinant human hyaluronidase and administer half at each site.³²⁷

Rotate administration sites on opposite sides of the body between successive infusions.³²⁷

Consult manufacturer’s instructions provided with Hyqvia and with the infusion pump for specific information regarding sub-Q administration.³²⁷

Rate of Administration

Recombinant human hyaluronidase component of Hyqvia: Administer sub-Q at an infusion rate of 1–2 mL/minute or as tolerated.³²⁷

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).³²⁷ Adjust time intervals and number of rate changes if full dose and maximum rate are tolerated.³²⁷

Consult manufacturer’s instructions provided with Hyqvia for specific information on recommended sub-Q infusion rates and time intervals during the ramp-up period.³²⁷

Sub-Q Administration of Xembify 20%

Administer Xembify 20% only by sub-Q infusion.³⁴¹

May be self-administered in the home or other appropriate setting;³⁴¹ provide patient and/or their caregiver with instructions and training regarding sub-Q administration.³⁴¹

Administer undiluted; do not mix with other drugs, IV infusion fluids, or other immune globulin preparations.³⁴¹

Vials are for single use only;³⁴¹ discard partially used vials.³⁴¹

Make sub-Q infusions of Xembify 20% into abdomen, thigh, upper arm, side, back, and/or upper lateral hip area using an infusion pump;³⁴¹ avoid bony areas, scars, blood vessels, and any areas with inflammation or superficial infection.³⁴¹

Dose may be divided and infused simultaneously in up to 6 different infusion sites that are ≥2 inches apart.³⁴¹ Maximum volume per infusion site is 25 mL.³⁴¹ Rotate sub-Q infusion sites for each subsequent dose.³⁴¹

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.³⁴¹

Consult manufacturer’s instructions provided with Xembify 20% and with the infusion pump for specific information regarding sub-Q administration.³⁴¹

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.^{115 154 186} If period of exposure in such areas will be ≥2 months, give 0.2 mL/kg once every 2 months.^{115 154 186}

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.^{115 186}

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).¹¹⁵

The above IGIM dosage is higher than previously recommended.¹⁸⁶ 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).¹⁸⁶

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).^{105 115 154 186}

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.^{105 115 186}

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).¹⁸⁶

Efficacy of IGIM for HAV postexposure prophylaxis not established if given >2 weeks.^{115 186}

The above IGIM dosage is higher than previously recommended.¹⁸⁶ 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).¹⁸⁶

Measles

Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.25 mL/kg of IGIM given within 6 days after exposure in susceptible individuals.¹⁵⁴ If susceptible child is immunocompromised, manufacturer recommends single dose of 0.5 mL/kg (up to 15 mL) given immediately after the exposure.¹⁵⁴

ACIP and AAP recommend single dose of 0.5 mL/kg (up to 15 mL) of IGIM given within 6 days after exposure.^{105 133} ACIP states optimal dose needed to provide protection against measles unknown.¹³³

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.^{105 133} (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.^{105 133}

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.³³² 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.³³²

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.²⁶⁵ 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.²⁶⁵

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.²⁶³ If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg as soon as possible after the exposure.²⁶³

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).²⁹⁴ If a biweekly regimen is being used, give a single dose of at least 400 mg/kg.²⁹⁴ 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.²⁹⁴

Varicella

Alternative to VZIG for Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.6–1.2 mL/kg of IGIM given promptly.¹⁵⁴

IGIV (not IGIM) usually recommended when VZIG unavailable.^{105 156} (See Varicella under Uses.)

IV^†

Single dose of 400 mg/kg of IGIV (ideally within 96 hours after exposure).^{105 156}

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.^{105 146 155 156 269}

Primary Immunodeficiency Diseases

Replacement Therapy

IV

Minimum serum IgG concentration necessary for protection varies among patients;²⁶⁶ there is considerable interindividual variation in half-life of IgG in patients with primary humoral immunodeficiency.^{263 265 266 282 308 324 337 339} Monitor clinical response and adjust IGIV dosage to achieve desired trough serum IgG concentrations and/or clinical response.^{263 265 266 282 308 324 337 338 339}

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.^{263 282 292 308 325 337 339} 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.^{105 133}

Asceniv 10% (adolescents ≥12 years of age): 300–800 mg/kg IV once every 3–4 weeks.³³⁸ Starting with second IV infusion, adjust dosage proportionately and target a trough IgG concentration of ≥600 mg/dL.³³⁸ 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.³³⁸

Bivigam 10% (children ≥6 years of age): 300–800 mg/kg IV once every 3–4 weeks.³²⁴ Starting with second IV infusion, adjust dosage over time to achieve and maintain trough serum IgG concentrations >600 mg/dL.³²⁴ 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.³²⁴

Carimune NF: 400–800 mg/kg IV once every 3–4 weeks.¹²⁵

Flebogamma 5% DIF (children ≥2 years of age): 300–600 mg/kg IV once every 3–4 weeks.²⁸² Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response;²⁸² data not available to determine optimum target trough IgG concentrations.²⁸²

Gammagard Liquid 10% (children ≥2 years of age): Usually, 300–600 mg/kg IV once every 3–4 weeks.²⁶⁶ Adjust dosage to achieve desired trough serum IgG concentration and clinical response;²⁶⁶ data not available to determine optimum target trough IgG concentrations.²⁶⁶

Gammagard S/D (children ≥2 years of age): 300–600 mg/kg IV once every 3–4 weeks.²⁸⁰ Adjust dosage to achieve desired trough serum IgG concentration and clinical response;²⁸⁰ data not available to determine optimum target trough IgG concentrations.²⁸⁰

Gammaked 10% (children ≥2 years of age): 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks.³³² Adjust dosage over time to achieve desired trough serum IgG concentrations and clinical response.³³²

Gammaplex 5% (children ≥2 years of age): 300–800 mg/kg (6–16 mL/kg) IV once every 3–4 weeks.³⁰⁸ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.³⁰⁸ If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.³⁰⁸

Gammaplex 10% (children ≥2 years of age): 300–800 mg/kg (3–8 mL/kg) IV once every 3–4 weeks.³³⁷ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.³³⁷ If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.³³⁷

Gamunex-C 10% (children ≥2 years of age): 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks.²⁶⁵ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.²⁶⁵

Octagam 5%: 300–600 mg/kg (6–12 mL/kg) IV once every 3–4 weeks.²⁶³ Adjust dosage to achieve desired trough serum IgG concentration and clinical response.²⁶³ If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.²⁶³

Panzyga 10% (children ≥2 years of age): 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks.³³⁹ Adjust dosage to achieve desired trough serum IgG concentration and clinical response.³³⁹

Privigen 10% (children ≥3 years of age): 200–800 mg/kg (2–8 mL/kg) IV once every 3 to 4 weeks.²⁹² Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.²⁹² If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.²⁹²

Sub-Q

Monitor clinical response and individualize dosage of immune globulin subcutaneous based on clinical response and trough serum IgG concentrations.^{265 266 294 327 331 332 340 341}

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.^{105 133}

Cuvitru 20% (children ≥2 years of age): Give at regular intervals ranging from once daily up to once every 2 weeks (biweekly).³³¹ Calculate initial sub-Q dose based on monthly dose of prior immune globulin regimen.³³¹ 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.³³¹ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.³³¹

Gammagard Liquid 10% (children ≥2 years of age): Administer sub-Q once weekly.²⁶⁶ Give initial dose approximately 1 week after last IGIV dose.²⁶⁶ 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 1.37.²⁶⁶ Base maintenance sub-Q doses on clinical response and target trough IgG concentrations.²⁶⁶ Consult manufacturer’s literature for specific information regarding how to adjust sub-Q dosage based on trough serum IgG concentrations.²⁶⁶

Gammaked 10% (children ≥2 years of age): Administer sub-Q once weekly.³³² Give initial dose 1 week after last IGIV dose.³³² 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 1.37.³³² Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.³³² 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%.³³²

Gamunex-C 10% (children ≥2 years of age): Administer sub-Q once weekly.²⁶⁵ Give initial dose 1 week after last IGIV dose.²⁶⁵ 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 1.37.²⁶⁵ Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.²⁶⁵ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.²⁶⁵

Hizentra 20% (children ≥2 years of age): Administer sub-Q at regular intervals ranging from once daily up to once every 2 weeks (biweekly).²⁹⁴ Use only in patients who have been receiving IGIV for ≥3 months before being switched to Hizentra 20%;²⁹⁴ give initial dose 1 week after last IGIV dose.²⁹⁴ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.²⁹⁴

Xembify 20% (children ≥2 years of age): Administer sub-Q once weekly;³⁴¹ alternatively, may divide weekly dose and give in 2–7 doses during the week.³⁴¹ 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.³⁴¹ 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.³⁴¹ Base subsequent doses on clinical response and target trough IgG concentrations.³⁴¹ Consult manufacturer’s literature for specific information regarding how to adjust sub-Q dosage based on trough serum IgG concentrations.³⁴¹

Idiopathic Thrombocytopenic Purpura (ITP)

IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg IV once daily for 2–5 consecutive days.¹²⁵ 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.¹²⁵ 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.¹²⁵ If adequate response does not occur, increase maintenance dose to 800–1000 mg/kg given as a single infusion.¹²⁵

Flebogamma 10% DIF (children ≥2 years of age): 1 g/kg IV once daily for 2 consecutive days for chronic ITP.³²⁵

Gammaked 10%: 1 g/kg (10 mL/kg) IV on 2 consecutive days (total dose 2 g/kg);³³² if increase in platelet count adequate 24 hours after initial dose, second dose may be withheld.³³² Alternatively, give 400 mg/kg (4 mL/kg) on 5 consecutive days (total dose 2 g/kg).³³² 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.³³²

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.²⁶⁵ Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg).²⁶⁵ 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.²⁶⁵

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.²⁹² 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.²⁹²

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).^{105 299 300} 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).^{299 300}

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.^{105 299} Use of additional or alternative anti-inflammatory or immunosuppressive agents may be necessary in IGIV-resistant patients.^{105 299} Consult specialized references for additional information on management of such individuals.²⁹⁹

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.²⁸⁰ Used in conjunction with appropriate aspirin therapy.²⁸⁰

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),²⁴⁰ 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.²⁴⁰

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.¹⁵⁶ Discontinue if hypogammaglobulinemia resolves.¹⁵⁶

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.²⁶² 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).²⁶²

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.²⁶² 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).²⁶²

Tetanus†

Treatment of Tetanus†

IV

200–400 mg/kg of IGIV has been recommended as an alternative when TIG not available.¹⁰⁵ (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.¹⁰⁵ Optimal dosage regimen not established.¹⁰⁵

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.^{115 154 186} If period of exposure in such areas will be ≥2 months, give 0.2 mL/kg once every 2 months.^{115 154 186}

Primary immunization with an age-appropriate schedule of hepatitis A vaccine before an expected exposure to HAV is preferred, unless contraindicated.^{115 186}

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).¹¹⁵

The above IGIM dosage is higher than previously recommended.¹⁸⁶ 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).¹⁸⁶

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).^{115 154 186}

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.^{115 186}

Immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: Give single dose of 0.1 mL/kg of IGIM^{154 186} as soon as possible after exposure (ideally within 2 weeks).¹⁸⁶

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).^{186 194}

Efficacy of IGIM for HAV postexposure prophylaxis not established if given >2 weeks after exposure.^{115 186}

The above IGIM dosage is higher than previously recommended.¹⁸⁶ 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).¹⁸⁶

Measles

Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.25 mL/kg of IGIM given within 6 days after exposure in susceptible individuals.¹⁵⁴

ACIP recommends single dose of 0.5 mL/kg (up to 15 mL) of IGIM given within 6 days after exposure.¹³³ ACIP states optimal dose needed to provide protection against measles infection unknown.¹³³

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.¹³³ (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.¹³³

IV†

ACIP recommends a single dose of 400 mg/kg given within 6 days after exposure.^{105 133}

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.^{263 282 292 308 325 337 339} 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.^{263 282 292 308 325 337 339}

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.³³² 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.³³²

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.²⁶⁵ 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.²⁶⁵

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.²⁶³ If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg as soon as possible after the exposure.²⁶³

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.³⁴⁰

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.²⁹⁴ If a biweekly sub-Q regimen is being used, give a single dose of at least 400 mg/kg.²⁹⁴ 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.²⁹⁴

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.¹⁵⁴ Routine use not recommended.^{105 131 154} (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.¹⁵⁴

IGIV (not IGIM) usually recommended when VZIG is unavailable.¹⁵⁶

IV^†

Single dose of 400 mg/kg of IGIV (ideally within 96 hours after varicella exposure).^{105 156}

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.^{105 146 155 156}

Primary Immunodeficiency Diseases

Replacement Therapy

IV

Minimum serum IgG concentration necessary for protection varies among patients;²⁶⁶ there is considerable interindividual variation in half-life of IgG in patients with primary humoral immunodeficiency.^{263 265 266 282 308 324 337 339} Monitor clinical response and adjust IGIV dosage to achieve desired trough serum IgG concentrations and/or clinical response.^{125 263 265 266 282 292 308 324 325 332 337 338 339}

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.^{263 282 292 308 325 337 339} 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.^{105 133}

Asceniv 10%: 300–800 mg/kg IV once every 3–4 weeks.³³⁸ Starting with second infusion, adjust dosage proportionately, targeting a trough IgG concentration of ≥600 mg/dL.³³⁸ 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.³³⁸

Bivigam 10%: 300–800 mg/kg IV once every 3–4 weeks.³²⁴ Starting with second infusion, adjust dosage over time to achieve and maintain trough serum IgG concentrations >600 mg/dL.³²⁴ 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.³²⁴

Carimune NF: 400–800 mg/kg IV once every 3–4 weeks.¹²⁵

Flebogamma 5% DIF: 300–600 mg/kg IV once every 3–4 weeks.²⁸² Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response;²⁸² data not available to determine optimum target trough serum IgG concentrations.²⁸²

Flebogamma 10% DIF: 300–600 mg/kg IV once every 3–4 weeks.³²⁵ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response;³²⁵ data not available to determine optimum target trough serum IgG concentrations.³²⁵

Gammagard Liquid 10%: Usually, 300–600 mg/kg IV once every 3–4 weeks.²⁶⁶ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response;²⁶⁶ data not available to determine optimum target trough serum IgG concentrations.²⁶⁶

Gammagard S/D (IgA <1 mcg/mL): Usually, 300–600 mg/kg IV once every 3–4 weeks.²⁸⁰ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response;²⁸⁰ data not available to determine optimum target trough serum IgG concentrations.²⁸⁰

Gammaked 10%: 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks.³³² Adjust dosage over time to achieve desired trough serum IgG concentrations and clinical response.³³²

Gammaplex 5%: 300–800 mg/kg (6–16 mL/kg) IV once every 3–4 weeks.³⁰⁸ Adjust dosage to achieve desired trough serum IgG concentration and clinical response.³⁰⁸ If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.³⁰⁸

Gammaplex 10%: 300–800 mg/kg (3–8 mL/kg) IV once every 3–4 weeks.³³⁷ Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.³³⁷ If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.³³⁷

Gamunex-C 10%: 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks.²⁶⁵ Adjust dosage to achieve desired trough serum IgG concentration and clinical response.²⁶⁵

Octagam 5%: 300–600 mg/kg (6–12 mL/kg) IV once every 3–4 weeks.²⁶³ Adjust dosage to achieve desired trough serum IgG concentration and clinical response.²⁶³ If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.²⁶³

Panzyga 10%: 300–600 mg/kg (3–6 mL/kg) IV once every 3–4 weeks.³³⁹ Adjust dosage to achieve desired trough serum IgG concentration and clinical response.³³⁹

Privigen 10%: 200–800 mg/kg (2–8 mL/kg) IV once every 3–4 weeks.²⁹² Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.²⁹² If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.²⁹²

Sub-Q

Monitor clinical response and individualize dosage of immune globulin subcutaneous based on clinical response and trough serum IgG concentrations.^{265 266 294 327 331 332 340 341}

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.¹³³

Cutaquig 16.5%: Administer sub-Q once weekly.³⁴⁰ 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.³⁴⁰ Calculate initial dose of Cutaquig 16.5% based on prior immune globulin dosage.³⁴⁰ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage of Cutaquig 16.5%.³⁴⁰

Cuvitru 20%: Give at regular intervals ranging from once daily up to once every 2 weeks (biweekly).³³¹ Calculate initial sub-Q dose based on monthly dose of prior immune globulin regimen.³³¹ 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.³³¹ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.³³¹

Gammagard Liquid 10%: Administer sub-Q once weekly.²⁶⁶ Give initial dose approximately 1 week after last IGIV dose.²⁶⁶ 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 1.37.²⁶⁶ Base maintenance sub-Q doses on clinical response and target trough IgG concentrations.²⁶⁶ Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations.²⁶⁶

Gammaked 10%: Administer sub-Q once weekly.³³² Give initial dose 1 week after last IGIV dose.³³² 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 1.37.³³² Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.³³² 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%.³³²

Gamunex-C 10%: Administer sub-Q once weekly.²⁶⁵ Give initial dose 1 week after last IGIV dose.²⁶⁵ 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 1.37.²⁶⁵ Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.²⁶⁵ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.²⁶⁵

Hizentra 20%: Administer sub-Q at regular intervals ranging from once daily up to once every 2 weeks (biweekly).²⁹⁴ Use only in patients who have been receiving IGIV for ≥3 months before being switched to Hizentra 20%;²⁹⁴ give initial dose 1 week after last IGIV dose.²⁹⁴ Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.²⁹⁴

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.³²⁷ Consult manufacturer's literature for specific information on the ramp-up schedule, including specific doses and dosing intervals for sub-Q administration.³²⁷

Xembify 20%: Administer sub-Q once weekly;³⁴¹ alternatively, may divide weekly dose and give in 2–7 doses during the week.³⁴¹ 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.³⁴¹ 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.³⁴¹ Base subsequent doses on clinical response and target trough IgG concentrations.³⁴¹ Consult manufacturer’s literature for specific information regarding how to adjust sub-Q dosage based on trough serum IgG concentrations.³⁴¹

Idiopathic Thrombocytopenic Purpura (ITP)

IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg IV once daily for 2–5 consecutive days.¹²⁵ 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.¹²⁵ If adequate response does not occur, increase maintenance dose to 800–1000 mg/kg given as a single infusion.¹²⁵

Flebogamma 10% DIF: 1 g/kg IV once daily for 2 consecutive days for chronic ITP.³²⁵

Gammagard S/D (IgA <1 mcg/mL): Single dose of 1 g/kg IV for chronic ITP.²⁸⁰ Determine need for additional doses based on clinical response and platelet count.²⁸⁰ If required, up to 3 doses may be given on alternate days.²⁸⁰

Gammaked 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg);³³² if increase in platelet count adequate 24 hours after first dose, second dose may be withheld.³³² Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg).³³² 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.³³²

Gammaplex 5%: 1 g/kg (20 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg).³⁰⁸ 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.³⁰⁸ Adequate data not available regarding platelet response to a lower-dose regimen (i.e., 400 mg/kg daily for 5 consecutive days).³⁰⁸

Gammaplex 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg).³³⁷ 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.³³⁷ Adequate data not available regarding platelet response to a lower-dose regimen (i.e., 400 mg/kg daily for 5 consecutive days).³³⁷

Gamunex-C 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg);²⁶⁵ if increase in platelet count adequate 24 hours after first dose, second dose may be withheld.²⁶⁵ Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg).²⁶⁵ 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.²⁶⁵

Octagam 10%: For chronic ITP, 1 g/kg IV once daily for 2 consecutive days (total dose 2 g/kg).³²⁶

Panzyga 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg).³³⁹

Privigen 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg) for chronic ITP.²⁹² 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.²⁹²

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.²⁸⁰

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.³³² 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.³³²

Gamunex-C 10%: Loading dose of 2 g/kg (20 mL/kg) IV given in divided doses over 2–4 consecutive days.²⁶⁵ 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.²⁶⁵ Has been continued for up to 48 weeks in clinical studies in patients with CIDP.²⁹⁸

Privigen 10%: Loading dose of 2 g/kg (20 mL/kg) IV given in divided doses over 2–5 consecutive days.²⁹² 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.²⁹² Has not been studied for durations >6 months.²⁹² After response is obtained during initial treatment period, not all patients require indefinite maintenance therapy to remain free of CIDP symptoms.²⁹² Assess patient's response and demonstrated need for continued Privigen 10% therapy beyond 6 months.²⁹²

Sub-Q

Hizentra 20% for maintenance treatment to prevent relapse: Give initial dose sub-Q 1 week after last IGIV dose.²⁹⁴ 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.²⁹⁴ 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.²⁹⁴ If CIDP symptoms worsen, consider discontinuing Hizentra 20% and reinitiating IGIV.²⁹⁴ 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.²⁹⁴ If CIDP symptoms worsen on the 0.4 g/kg weekly dose, consider discontinuing Hizentra 20% and reinitiating IGIV.²⁹⁴ Maintenance therapy with Hizentra 20% has been studied for a duration of 6 months and for an additional 12 months of follow-up.²⁹⁴ Use for maintenance therapy for a longer duration should be individualized based on patient's response and need for continued therapy.²⁹⁴

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.^{310 311} 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;^{310 311} frequency of maintenance therapy should be guided by response.^{310 311}

Gammagard Liquid 10%: Manufacturer recommends maintenance dosage ranging from 500 mg/kg to 2.4 g/kg IV once every month.²⁶⁶ Adjust dosage to achieve desired clinical response and avoid worsening of muscle weakness.²⁶⁶

Guillain-Barré Syndrome† (GBS)

IV

Although safety and efficacy and optimum dosage not established,^{312 317 318} EFNS and others recommend 0.4 g/kg of IGIV daily for 5 days.^{301 310 312} Unclear whether IGIV is effective when initiated more than 2 weeks after symptom onset.³¹⁷

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.³¹⁰ Retreatment also can be considered in those who do not respond to initial regimen,³¹⁰ but other clinicians state it is unclear whether retreatment is beneficial in such patients.^{305 318}

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.²⁶²

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).²⁶²

Tetanus†

Treatment of Tetanus†

IV

200–400 mg/kg of IGIV has been recommended as an alternative when TIG not available.¹⁰⁵ (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.¹⁰⁵ Optimal dosage regimen not established.¹⁰⁵

Prescribing Limits

Pediatric Patients

Measles

Postexposure Prophylaxis

IM

Maximum single IGIM dose: 15 mL.^{105 133 154}

Adults

Measles

Postexposure Prophylaxis

IM

Maximum single IGIM dose: 15 mL.^{105 133 154}

Special Populations

Renal Impairment

IGIV: Reduce dose, concentration, and/or rate of administration; maximum safe dose, concentration, and rate of administration not established.^{125 249 263 265 266 282} Ensure that patients are not volume depleted and are well hydrated; administer at the minimum concentration available and minimum infusion rate practicable.^{125 249 263 265 266 280 282 292 308 324 325 326 332 337 338 339} (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Immune globulin subcutaneous: Consider lower, more frequent dosing.^{294 327 331 340 341} Ensure that patients are not volume depleted and are adequately hydrated.^{265 266 294 327 331 332 340 341}

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.^{125 249 280 263 265 266 282} Administer IGIV and immune globulin subcutaneous at minimum infusion rate practicable.^{125 249 263 265 266 280 282 292 294 308 324 325 326 331 332 337 339} (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;^{340 341} administer at minimum infusion rate practicable.^{265 266 331 332}

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.^{125 154 263 265 266 282 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

• IGIM, IGIV, immune globulin subcutaneous: IgA-deficient individuals with antibodies against IgA and history of hypersensitivity.^{154 263 265 266 282 292 294 308 324 325 327 331 332 337 338 339 340 341} (See IgA Deficiency under Cautions.)

• Flebogamma 5% DIF and Flebogamma 10% DIF: Hereditary fructose intolerance;^{282 325} contains sorbitol, which presents a risk to individuals with hereditary fructose intolerance.^{282 325}

• Gammaplex 5%: Hereditary fructose intolerance and neonates and infants for whom sucrose or fructose tolerance not established;³⁰⁸ contains sorbitol.³⁰⁸

• Hizentra 20%, Privigen 10%: Hyperprolinemia (type I or II);^{292 294} contain l-proline as a stabilizer.^{292 294}

• Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Known systemic hypersensitivity to human albumin (contained in the recombinant human hyaluronidase component).³²⁷

• Octagam 5%: Acute hypersensitivity reactions to corn;²⁶³ contains maltose derived from corn.²⁶³ (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.^{125 154 252 253 254 255 256 257 258 259 263 265 266 282 292 294 308 324 325 326 327 328 329 332 337 338 339 340 341}

Etiology for thrombosis in patients receiving immune globulin not fully determined;^{252 253 255 256 259 260 329} 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.^{252 253 256 260 329}

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.^{125 263 265 266 292 294 308 324 325 326 327 328 329 337 338 339 340 341} Thrombosis may occur in patients without known risk factors.^{125 154 263 265 266 282 292 294 308 324 325 326 327 328 337 338 339 340 341}

Weigh potential risks and benefits of immune globulin against those of alternative therapies in all patients in whom immune globulin is being considered.^{125 263 265 266 292 308}

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).^{125 252 253 255 256 257 259 260 263 308 324 325 326 327 328 329 337 338 340}

In patients at risk for thrombosis, use minimum dose and minimum infusion rate practicable and monitor closely for signs and symptoms of thrombosis.^{125 154 263 265 266 282 292 294 308 324 325 326 327 328 329 331 332 337 338 339 340 341} In addition, ensure that all patients are adequately hydrated prior to administration of immune globulin.^{125 154 263 265 266 282 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

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).^{125 263 265 266 282 292 294 308 324 325 326 327 328 329 331 332 337 338 339 340 341}

Renal Effects

Renal dysfunction, acute renal failure, osmotic nephrosis, and death reported in patients receiving immune globulin.^{125 249 251 263 265 266 282 292 308 324 325 326 327 332 337 338 339 340 341}

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.^{125 249 263 265 266 282 308 327 337 338 339 340 341}

IGIV preparations stabilized with sucrose (e.g., Carimune NF) have been associated with renal dysfunction more frequently than other IGIV preparations;^{125 249 263 265 266 282 308} weigh benefits of these preparations against potential risk of renal dysfunction.²⁴⁹ Maximum infusion rate of 3 mg of sucrose/kg per minute recommended.^{125 249 261}

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.^{125 249 251 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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.^{125 249 263 265 266 282 294 308 337 338 339 340 341}

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.^{125 249 263 265 266 282 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

If renal dysfunction occurs, consider discontinuing immune globulin therapy.^{125 249 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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.^{125 282 292 325}

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.^{265 266 282} 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.¹²⁵

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%).²⁹² 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.²⁹²

Closely monitor for adverse reactions throughout the infusion^{125 282 292} since these reactions may rarely lead to shock.^{125 282}

If flushing, changes in BP or pulse, or other infusion reactions occur, slow or temporarily stop the infusion.^{125 266} In some cases when symptoms subside promptly, the infusion may be resumed at a rate that is comfortable for the patient.^{125 266 292} Stop infusion immediately if anaphylaxis or other severe reactions occur.¹²⁵ (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.^{125 154 263 265 266 292 294 308 324 325 326 327 337 338 339 340 341}

If a severe hypersensitivity reaction occurs, discontinue immune globulin immediately and institute appropriate therapy as indicated.^{154 263 265 292 294 308 324 325 326 327 331 332 337 338 339 340 341} Epinephrine and antihistamines should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.^{125 263 265 266 282 292 308 331 332 337 338 339 340}

Use IGIM with caution in patients with a history of systemic allergic reactions to immune globulin preparations.¹⁵⁴

The manufacturer of IGIM states that intradermal sensitivity testing should not be performed;¹⁵⁴ 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.¹⁵⁴

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.^{125 263 265 266 282 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

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.^{125 154 263 265 266 280 282 292 294 337 338 339 340 341} Potential for severe hypersensitivity (e.g., anaphylactic) reactions to IgA in such patients.^{125 154 263 265 266 280 282 292 294 308 327 337 338 339 340 341}

Administer only in a setting where supportive care is available for treating life-threatening reactions.^{266 282} If a hypersensitivity reaction occurs, consider alternative therapy.^{266 280}

All commercially available preparations of IGIV contain trace amounts of IgA, but the amount varies among the different preparations.^{262 263 265 266 280 292} Concentration of IgA that will not provoke a reaction to IgA not known.²⁸⁰

Asceniv 10%: ≤200 mcg/mL of IgA.³³⁸

Bivigam 10%: ≤200 mcg/mL of IgA.³²⁴

Carimune NF: Trace amounts of IgA.¹²⁵

Cutaquig 16.5% : ≤600 mcg/mL of IgA.³⁴⁰

Cuvitru 20%: Average of 80 mcg/mL of IgA.³³¹

Flebogamma 5% DIF: <50 mcg/mL of IgA.²⁸²

Flebogamma 10% DIF: <32 mcg/mL of IgA.³²⁵

Gammagard Liquid 10%: Average of 37 mcg/mL of IgA.²⁶⁶

Gammagard S/D: <1 mcg/mL of IgA.²⁸⁰

Gammaked 10%: Average of 46 mcg/mL of IgA.³³²

Gammaplex 5%: Trace amounts of IgA (<10 mcg/mL).³⁰⁸

Gammaplex 10%: Trace amounts of IgA (<20 mcg/mL).³³⁷

Gamunex-C 10%: Average of 46 mcg/mL of IgA.²⁶⁵

Hizentra 20%: ≤50 mcg/mL of IgA.²⁹⁴

Hyqvia 10%: Average of 37 mcg/mL of IgA.³²⁷

Octagam 5%: ≤200 mcg/mL of IgA.²⁶³

Octagam 10%: Average of 106 mcg/mL of IgA.³²⁶

Panzyga 10%: Average of 100 mcg/mL of IgA.³³⁹

Privigen 10%: ≤25 mcg/mL of IgA.²⁹²

Xembify 20%: Contains IgA (amount not specified).³⁴¹

Corn Allergy

Octagam 5% and Octagam 10% contain maltose, a disaccharide sugar derived from corn.^{263 326} Hypersensitivity reactions may occur if these preparations are used in patients with corn allergy.^{263 326} Manufacturer states avoid Octagam 5% in patients with known corn allergies;²⁶³ contraindicated in those with acute hypersensitivity reactions to corn.²⁶³

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.^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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.^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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).^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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.^{263 265 266 282 292 308 325 326 332 337 339} If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit occur, perform additional confirmatory laboratory tests.^{263 265 266 282 292 308 325 326 332 337 338 339 340 341}

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.^{263 265 266 282 292 294 308 325 326 332 337 338 339}

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (noncardiogenic pulmonary edema) reported in patients receiving IGIV^{125 263 265 266 282 292 308 324 325 326 337 338 339} and could also occur in patients receiving immune globulin subcutaneous.^{294 327 340 341} 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.^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339}

Monitor patients receiving immune globulin for adverse pulmonary reactions.^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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.^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341} Manage using oxygen therapy with adequate ventilatory support.^{125 263 265 266 282 292 294 308 324 325 326 327 337 338 339 340 341}

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.^{125 211 263 265 266 282 292 294 308 324 325 326 332 337 338 339 340 341} 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.^{125 211 212 263 265 266 282 292 308 337 338 339 340 341}

In patients exhibiting such symptoms, perform a thorough neurologic examination, including CSF studies, to rule out other causes of meningitis.^{125 263 265 266 282 294 308 324 332 337 338 339 340 341} 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,^{125 211 212 263 265 266 282 294 308 324 332} but negative culture results.^{265 266 292 324 332 337 338 339 340 341}

Syndrome has resolved without sequelae within several days following discontinuance of the immune globulin.^{125 211 212 263 265 266 282 294 308 324 332 337 338 339 340 341}

Hyperproteinemia, Increased Viscosity, and Hyponatremia

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV.^{263 265 280 282 292 308 324 325 326 337 338 339} The hyponatremia is likely to be pseudohyponatremia, as demonstrated by decreased calculated serum osmolality or elevated osmolar gap.^{263 265 266 292 308 325 337 338 339}

If hyponatremia occurs, it is critical to distinguish true hyponatremia from pseudohyponatremia.^{263 265 266 292 308 324 325 326 332 337 338 339} 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.^{263 265 266 292 308 324 332 337 338 339} (See Thrombosis under Cautions.)

Gammagard S/D (IgA <1 mcg/mL) contains approximately 8.5 mg of sodium chloride per mL;²⁸⁰ consider this amount when determining dietary sodium in patients on a low-sodium diet since hypernatremia may occur.²⁸⁰

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.^{292 308 337}

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.^{265 332}

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).^{125 154 210 263 265 266 280 282 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

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.^{154 263 265 266 280 282 292 294 308 324 325 326 327 331 332} Despite such stringent procedures, a risk of transmission still remains.^{125 154 227 263 265 266 282 292 324 325 326 337 338 339 340 341}

Report all infections thought possibly to have been transmitted by immune globulin preparations to the appropriate manufacturer.^{125 154 227 263 265 266 280 282 292 294 308 324 325 326 337 338 339 340 341}

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.³²⁷ Clinical importance unknown.³²⁷

Animal studies indicate that antibodies to recombinant human hyaluronidase cross the placenta and are transferred to offspring during lactation.³²⁷ These antibodies could potentially cross-react with endogenous human hyaluronidase (expressed in adult male testes, epididymis, and sperm).³²⁷

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.^{263 267 326 340} (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.^{125 154 263 265 266 280 282 292 294 308 324 325 326 327 331 332 337 338 340 341}

Some manufacturers state use immune globulin during pregnancy only when clearly needed.^{125 265 266 280 282 292 294 308 324 325 326 327 331 332 337}

ACIP states there are no known risks associated with immune globulins used for passive immunization in pregnant women.¹³⁴

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.³²⁷ Not known whether these anti-recombinant human hyaluronidase antibodies interfere with human fertility.³²⁷

Lactation

Not evaluated in nursing women.^{265 280 282 292 294 308 324 325 327 331 332 337 338 340 341}

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.^{154 263 265 266 280 281 282 325 326 332}

Use with caution in nursing women.²⁶⁶ 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.^{154 263 265 325 266 280 282 292 294 325 327 331 332 338 340 341}

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Animal studies indicate maternal antibodies bound to recombinant human hyaluronidase are transferred to nursing offspring;³²⁷ no adverse effects on pregnancy or offspring development associated with these antibodies reported.³²⁷ Data not available regarding use in nursing women;³²⁷ possible effects of antibodies to recombinant human hyaluronidase that may be transferred to infants unknown.³²⁷

Pediatric Use

GamaSTAN: Manufacturer states safety and efficacy of IGIM not established in pediatric patients;¹⁵⁴ however, passive immunization with IGIM is recommended by ACIP and AAP in pediatric patients under certain circumstances using same dosages recommended for adults.^{105 133 186 231} (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;³³⁸ safety, efficacy, and pharmacokinetic profiles in adolescents were comparable to adults.³³⁸ Data insufficient regarding safety, efficacy, and pharmacokinetics in pediatric patients <12 years of age;³³⁸ safety and efficacy not studied in those <3 years of age.³³⁸

Bivigam 10%: Safety and efficacy not established in children <6 years of age.³²⁴ Only limited data regarding efficacy and safety in pediatric patients.³²⁴

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.¹²⁵

Cutaquig 16.5%: Only limited number of pediatric patients were included in clinical study evaluating use for treatment of primary immunodeficiency.³⁴⁰ Safety and efficacy not established in pediatric patients <17 years of age.³⁴⁰

Cuvitru 20%: Safety and efficacy not established in pediatric patients <2 years of age.³³¹

Flebogamma 5% DIF: Safety and efficacy not established in pediatric patients <2 years of age.²⁸²

Flebogamma 10% DIF: Safety and efficacy not established for treatment of primary immunodeficiency in pediatric patients.³²⁵ Evaluated in a limited number of children and adolescents with chronic ITP;³²⁵ safety and efficacy not established for treatment of chronic ITP in children <2 years of age.³²⁵

Gammagard Liquid 10%: Safety and efficacy for treatment of primary immunodeficiency not established in children <2 years of age.²⁶⁶ Safety and efficacy for treatment of MMN not established in pediatric patients of any age.²⁶⁶

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.²⁸⁰ Safety and efficacy not established for treatment of ITP in pediatric patients.²⁸⁰ Safety and efficacy established for treatment of Kawasaki disease in pediatric patients;²⁸⁰ majority of patients in clinical studies were <5 years of age.²⁸⁰

Gammaked 10%: Safety and efficacy of IV route established for treatment of primary immunodeficiency in pediatric patients;³³² safety and efficacy of sub-Q route not established for treatment of primary immunodeficiency in pediatric patients <2 years of age.³³² Safety and efficacy of IV (not sub-Q) route established for treatment of ITP in pediatric patients.³³² Safety and efficacy not established for treatment of CIDP in pediatric patients.³³²

Gammaplex 5%: Safety and efficacy for treatment of primary immunodeficiency not established in children <2 years of age.³⁰⁸ Clinical studies in patients with ITP included only limited number of children;³⁰⁸ data insufficient to determine whether efficacy in pediatric patients with ITP differs from that in adults.³⁰⁸

Gammaplex 10%: Evaluated in limited number of pediatric patients 3–15 years of age for treatment of primary immunodeficiency;³³⁷ pediatric-specific dosage not required to achieve desired serum IgG concentrations in this age group.³³⁷ Safety and pharmacokinetics in pediatric patients ≥3 years of age similar to adults.³³⁷ Safety and efficacy not established for treatment of ITP in pediatric patients.³³⁷

Gamunex-C 10%: Safety and efficacy of IV route established for treatment of primary immunodeficiency in pediatric patients;²⁶⁵ safety and efficacy of sub-Q route not established for treatment of primary immunodeficiency in pediatric patients <2 years of age.²⁶⁵ Safety and efficacy of IV (not sub-Q) route established for treatment of ITP in pediatric patients.²⁶⁵ Safety and efficacy not established for treatment of CIDP in pediatric patients.²⁶⁵

Hizentra 20%: Safety and efficacy for treatment of primary immunodeficiency not established in pediatric patients <2 years of age.²⁹⁴ Safety and efficacy established for replacement therapy in pediatric patients 2–16 years of age with primary immunodeficiency;²⁹⁴ no differences in safety and efficacy profiles in pediatric patients compared with adults;²⁹⁴ pediatric-specific dosage not required to achieve desired serum IgG concentrations.²⁹⁴ Safety and efficacy not established for treatment of CIDP in pediatric patients <18 years of age.²⁹⁴

Hyqvia 10%: Safety not established in pediatric patients.³²⁷

Octagam 5%: Evaluated in a limited number of children 6–16 years of age;²⁶³ no apparent differences in pharmacokinetics, efficacy, or safety compared with adults.²⁶³ Pediatric-specific dosage not required to achieve desired serum IgG concentrations.²⁶³

Octagam 10%: Safety and efficacy not established in pediatric patients.³²⁶

Panzyga 10%: Evaluated in limited number of pediatric patients 2–15 years of age for treatment of primary immunodeficiency.³³⁹ Pharmacokinetics, efficacy, and safety in these pediatric patients similar to adults; pediatric-specific dosage not required to achieve targeted serum IgG concentrations.³³⁹ Safety and efficacy not established for treatment of ITP in pediatric patients.³³⁹

Privigen 10%: Safety and efficacy for treatment of primary immunodeficiency not established in pediatric patients <3 years of age.²⁹² Has been evaluated in a limited number of children and adolescents with primary immunodeficiency;²⁹² no apparent differences in safety and efficacy compared with adults; pediatric-specific dosage not required to achieve desired serum IgG concentrations.²⁹² Safety and efficacy not established for treatment of chronic ITP in pediatric patients <15 years of age.²⁹² Safety and efficacy not established for treatment of CIDP in pediatric patients <18 years of age.²⁹²

Geriatric Use

Patients >65 years of age are at increased risk for acute renal failure or thrombotic event during immune globulin therapy.^{125 263 265 266 282 292 294 308 324 325 326 332 337 338 339 340 341}

IGIM: Safety and efficacy not established in geriatric patients.¹⁵⁴

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.^{263 265 266 280 282 292 308 324 325 326 332 337 338 339} Other reported clinical experience has not identified differences in responses between geriatric and younger patients.^{263 338}

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.^{340 341} Only limited number of patients ≥65 years of age were included in clinical studies of Cuvitru 20%,³³¹ Gammagard Liquid 10%,²⁶⁶ Hizentra 20%,²⁹⁴ or Hyqvia;³²⁷ no overall differences in safety or efficacy were observed compared with younger patients.^{266 294 331}

Use with caution;^{125 265 282 292 308 324 325 332 337} do not exceed recommended dosage;^{125 265 266 280 282 292 308 324 325 326 331 337 339} administer at minimum concentration available and minimum practicable infusion rate.^{263 265 266 280 282 292 308 324 325 326 331 332 337 339} (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.^{125 249 263 265 266 282 292 294 308 324 325 326 327 331 332 337 338 339 340 341} 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.^{125 249 263 265 266 282 292 308 324 325 326 332 337 338 339 340 341} (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).¹⁵⁴

IGIV: Infusion site reactions (pain, irritation);^{265 266 280 282 292} chest, hip, joint, back, or extremity pain;^{263 265 266 282 308} arthralgia^{125 263 265 282} or myalgia;^{125 308} GI effects (diarrhea,^{265 266 282} nausea,^{263 265 266 282 292 308} vomiting);^{263 265 266 282 308} chills;^{263 266 282 292 308} fever/hyperthermia;^{263 265 266 282 292 308} asthenia;²⁶⁵ malaise;²⁸² fatigue;^{266 282 292 308} insomnia;³⁰⁸ dizziness;^{263 265 266} headache;^{263 265 266 282 292 308} migraine headache;²⁶⁶ immediate anaphylactoid and hypersensitivity reactions;¹²⁵ allergic and cutaneous reactions^{263 282} such as rash,^{125 266} erythema,¹²⁵ pruritus,^{125 265 266} urticaria,^{125 265 266} eczema,¹²⁵ or dermatitis;¹²⁵ hypertension or fluctuations in BP;^{263 308} palpitations;²⁸² tachycardia;^{266 282} increased liver function test results;^{263 265 282} asthma;^{265 282} wheezing;²⁸² otic pain;²⁶⁵ upper respiratory tract infection;³⁰⁸ cough (increased or productive);^{265 266 282} bronchitis;²⁸² rhinitis/nasal congestion;^{265 308} sinusitis;^{282 308} pharyngitis.²⁶⁵

IGIV for treatment of ITP: Headache,^{125 265 265 292 308 325 332 339} fever,^{265 292 308 325 332 339} chills,³²⁵ GI effects (nausea,^{265 292 308 325 332 339} vomiting,^{265 292 325 332 339} diarrhea,³²⁵ dyspepsia^{265 332} ), dizziness,^{325 339} hypotension,³²⁵ hypertension,³²⁵ increased heart rate,³²⁵ pain (abdominal or back),^{265 325 332} dehydration,³⁰⁸ rash,^{265 332} pruritus,³⁰⁸ ecchymosis,^{265 332} anemia.^{292 339}

IGIV for treatment of CIDP: Headache,^{265 292 332} fever,^{265 332} chills,^{265 332} nausea,^{265 292 332} hypertension,^{265 292 332} pain (extremity),²⁹² arthralgia,^{265 332} influenza-like illness,²⁹² leukopenia,²⁹² rash,^{265 292 332} asthenia.^{265 292 332}

Immune globulin subcutaneous: Infusion site reactions (e.g., erythema, pain, swelling, induration, edema, pruritus, heat, bruising, hematoma, nodule, scab),^{265 266 294 327 331 340 341} headache,^{265 266 294 327 331 332 340} migraine headache,^{265 266 294 332} fever,^{265 266 327 332 340} fatigue,^{265 266 294 327 331 332} cough,^{294 341} upper respiratory tract infection,^{265 294 332} asthma,^{266 340} GI effects (e.g., nausea, vomiting, diarrhea, upper abdominal pain, stomatitis),^{265 266 294 327 331 332 340 341} increased heart rate,²⁶⁶ increased systolic BP,²⁶⁶ pain (back pain, extremity pain),^{266 294 332} arthralgia,^{265 332} cough,²⁹⁴ dermatitis,³⁴⁰ rash,²⁹⁴ pruritus.²⁹⁴

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;^{105 125 134 154 263 265 292 294 308 324 325 326 327 331 332 337 338 339 340 341} 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).^{105 134} (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.^{105 134}

Specific Drugs and Laboratory Tests

Immune Globulin Pharmacokinetics

Absorption

Bioavailability

Following IM administration of IGIM, serum concentrations of IgG peak within 2 days.¹⁵⁴

Following IV administration of IGIV, there is an immediate post-infusion peak in serum IgG concentrations followed by a biphasic decline.^{125 263 265 266 280}

Following sub-Q administration of immune globulin, peak serum IgG concentrations are lower than those attained with IGIV, but trough concentrations generally are higher.^{265 266 294} In contrast to the biphasic IgG concentrations reported with IGIV, sub-Q immune globulin given once weekly results in relatively stable IgG concentrations.^{265 294} Peak serum IgG concentrations in patients receiving sub-Q immune globulin generally occur 2.9 days (range: 0–7 days) after a dose.^{266 294}

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.³²⁷ In addition, AUC of IgG is 20% higher than that attained with immune globulin subcutaneous given without recombinant human hyaluronidase.³²⁷ Peak serum IgG concentrations in patients receiving Hyqvia generally occur 5 days (range 3.3–5.1 days) after a dose.³²⁷

Distribution

Extent

IgG present in IGIM or IGIV is rapidly and evenly distributed between intravascular and extravascular spaces.^{125 263 266 280}

Intact immune globulins cross the placenta in increasing amounts after 30 weeks’ gestation.^{125 265 266 292 325 331}

Not known whether immune globulin is distributed into milk following IM, IV, or sub-Q administration.^{265 266 281 292}

Elimination

Half-life

IGIV undergoes biphasic elimination;^{125 263 265 266 280} rapid initial decline in serum IgG concentrations associated with equilibration between plasma and extravascular space, followed by slower elimination phase.^{125 263 265 266 280}

High IgG concentrations and hypermetabolism associated with fever and infection have been reported to coincide with shortened IgG half-life.^{263 266 280}

Half-life of IgG in individuals with normal serum IgG concentrations: 18–25 days.^{154 266}

Half-life of IGIV preparations in patients with immunodeficiencies: 12–59 days.^{263 266 280 282 292 308 324 325 338}

Stability

Storage

Parenteral

Injection for IM Use

GamaSTAN: 2–8°C.¹⁵⁴ Do not freeze.¹⁵⁴

Injection for IV Infusion

Asceniv 10%: 2–8°C.³³⁸ Do not freeze or heat;³³⁸ discard if frozen or heated.³³⁸

Bivigam 10%: 2–8°C.³²⁴ Do not freeze or heat;³²⁴ discard if frozen or heated.³²⁴ Promptly use vials that have been entered.³²⁴ Discard partially used vials.³²⁴

Flebogamma 5% DIF: 2–25°C;²⁸² stable for up to 24 months as indicated by expiration date on outer carton and container label.²⁸² Do not freeze;²⁸² discard if frozen.²⁸² Protect from light by storing in original carton.²⁸² Discard partially used vials.²⁸²

Flebogamma 10% DIF: 2–25°C;³²⁵ stable for up to 24 months as indicated by expiration date on outer carton and container label.³²⁵ Do not freeze;³²⁵ discard if frozen.³²⁵ Protect from light by storing in original carton.³²⁵ Discard partially used vials.³²⁵

Gammaplex 5% and Gammaplex 10%: 2–25°C for up to 36 months after date of manufacture.^{308 337} Do not freeze;^{308 337} discard if frozen.^{308 337} Protect from light by storing in original carton.^{308 337} Promptly use bottles or vials that have been entered;^{308 337} discard partially used bottles or vials.^{308 337}

Octagam 5%: 2–25°C for 24 months after date of manufacture.²⁶³ Do not freeze;²⁶³ discard if frozen.²⁶³ Promptly use bottles that have been entered;²⁶³ discard partially used bottles.²⁶³

Octagam 10%: 2–8°C for 24 months after date of manufacture.³²⁶ 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.³²⁶ Do not freeze;³²⁶ discard if frozen.³²⁶ Promptly use bottles that have been entered;³²⁶ discard partially used bottles.³²⁶

Panzyga 10%: 2–8°C for up to 24 months after date of manufacture.³³⁹ 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.³³⁹ Do not freeze;³³⁹ discard if frozen.³³⁹

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.²⁹² Do not freeze;²⁹² discard if frozen.²⁹² Protect from light.²⁹²

Powder for Injection, for IV Infusion

Carimune NF: Room temperature (≤30°C);¹²⁵ may be stored until expiration date indicated on vial label.¹²⁵ Use promptly if reconstituted outside of sterile laminar airflow conditions;¹²⁵ use within 24 hours if reconstituted in a sterile laminar flow hood using aseptic technique and stored under refrigeration.¹²⁵ Do not freeze reconstituted solution.¹²⁵ Discard partially used vials.¹²⁵

Gammagard S/D (IgA <1 mcg/mL): ≤25°C;²⁸⁰ do not freeze.²⁸⁰ 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.²⁸⁰ Discard partially used vials.²⁸⁰

Injection for Sub-Q Infusion

Cutaquig 16.5%: 2–8°C for up to 24 months after date of manufacture.³⁴⁰ 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.³⁴⁰ To protect from light, store in original carton until used.³⁴⁰ Do not freeze; discard if frozen.³⁴⁰

Cuvitru 20%: 2–8°C for up to 36 months.³³¹ Alternatively, store at room temperature (≤25°C) for up to 12 months;³³¹ do not return to refrigeration.³³¹ Do not freeze.³³¹ To protect from light, store in original carton until used.³³¹ Discard partially used vials.³³¹

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.²⁹⁴ Do not freeze;²⁹⁴ discard if frozen.²⁹⁴ To protect from light, store in original carton until used.²⁹⁴ Discard partially used vials.²⁹⁴

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.³²⁷ Alternatively, may be stored for up to 3 months at room temperature (≤25°C) during first 24 months from date of manufacture;³²⁷ do not return to refrigeration.³²⁷ Do not freeze.³²⁷ To protect from light, store in original carton until used.³²⁷ Discard partially used vials.³²⁷

Xembify 20%: 2–8°C.³⁴¹ 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.³⁴¹ Do not freeze;³⁴¹ discard if frozen.³⁴¹

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.²⁶⁶ Alternatively, may be stored at ≤25°C for up to 24 months as indicated by expiration date on outer carton and container label.²⁶⁶ Do not freeze.²⁶⁶ Vials are for single use only.²⁶⁶ Discard partially used vials.²⁶⁶

Gammaked 10%: 2–8°C for 36 months after date of manufacture.³³² 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.³³² Do not freeze;³³² discard if frozen.³³² Promptly use vials that have been entered;³³² discard partially used vials.³³²

Gamunex-C 10%: 2–8°C for 36 months after date of manufacture.²⁶⁵ 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.²⁶⁵ Do not freeze.²⁶⁵ Promptly use vials that have been entered;²⁶⁵ discard partially used vials.²⁶⁵

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.^{125 263 265 266 282 292 294 308 324 325 327 331 332 337 338 339 340 341}

• 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.¹⁰⁵

• Mechanism of action in the treatment of primary humoral immunodeficiency not fully elucidated.^{263 265 282 292 294 308 324 325 331 332 337 338 339 340 341}

• Mechanism by which IGIV increases platelet counts in the treatment of ITP not fully elucidated.^{125 130 139 140 142 265 292 308 325 326 332 337 339} May saturate Fc (crystallizable fragment) receptors on cells of the reticuloendothelial system, resulting in decreased Fc-mediated phagocytosis of antibody-coated cells.^{130 139 142} Altered Fc-receptor affinity for IgG or suppression of antiplatelet antibody production may be involved.^{139 140 142}

• Mechanism by which IGIV reduces the incidence of acute GVHD following BMT not determined.²²¹

• Mechanism of action of IGIV in the treatment of chronic inflammatory demyelinating polyneuropathy not fully elucidated.²⁶⁵

• Mechanism of action of IGIV in the treatment of Kawasaki disease is not known,²⁹⁹ 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.²⁹⁹ IGIV and aspirin appear to have additive anti-inflammatory effects in the treatment of Kawasaki disease.²⁹⁹

• Asceniv 10%: Contains ≥96% IgG.³³⁸ Contains glycine and polysorbate 80 as stabilizers.³³⁸

• Bivigam 10%: Contains ≥96% IgG.³²⁴ Contains glycine and polysorbate 80 as stabilizers.³²⁴

• Carimune NF: Following reconstitution, contains 30–120 mg of protein per mL.¹²⁵ 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.¹²⁵ Distribution of IgG subclasses corresponds to that of normal serum.¹²⁵ Contains sucrose as stabilizing agent.¹²⁵

• Cutaquig 16.5%: Contains ≥96% IgG.³⁴⁰ Distribution of IgG subclasses is approximately 70% IgG₁, 25% IgG₂, 3% IgG₃, and 2% IgG₄.³⁴⁰ Contains maltose.³⁴⁰

• Cuvitru 20%: Contains 20% protein, of which ≥98% is IgG.³³¹ Distribution of IgG subclasses is similar to that of normal plasma.³³¹ Fc and Fab functions are maintained.³³¹ Contains glycine as stabilizing and buffering agent.³³¹

• Flebogamma 5% DIF: Contains ≥97% IgG and trace amounts of IgA (typically <50 mcg/mL) and IgM.²⁸² Distribution of IgG subclasses is approximately 66.6% IgG₁, 28.5% IgG₂, 2.7% IgG₃, and 2.2% IgG₄.²⁸² Contains sorbitol as stabilizing agent, polyethylene glycol, and trace amounts of sodium.²⁸²

• Flebogamma 10% DIF: Contains ≥97% IgG.³²⁵ Distribution of IgG subclasses is approximately 66.6% IgG₁, 27.9% IgG₂, 3.0% IgG₃, and 2.5% IgG₄.³²⁵ Contains sorbitol as stabilizing agent, polyethylene glycol, and trace amounts of sodium.³²⁵

• GamaSTAN: Contains 15–18% protein.¹⁵⁴

• Gammagard Liquid 10%: Contains ≥98% IgG, IgA (average 37 mcg/mL), and trace amounts of IgM.²⁶⁶ Distribution of IgG subclasses is similar to that of normal serum.²⁶⁶ Fc and Fab functions are maintained.²⁶⁶ Contains glycine as stabilizing and buffering agent.²⁶⁶

• 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.²⁸⁰ Distribution of IgG subclasses is similar to that of normal serum.²⁸⁰ Fc portion is maintained intact.²⁸⁰ Contains glycine, dextrose, polyethylene glycol, polysorbate 80, and human albumin.²⁸⁰

• Gammaked 10%: Contains 9–11% protein stabilized in 0.16–0.24 M glycine;³³² ≥98% of protein content has the electrophoretic mobility of IgG.³³² Distribution of IgG subclasses is similar to that of normal serum;³³² contains trace amounts of fragments, IgA (average 46 mcg/mL), and IgM.³³²

• Gammaplex 5%: Contains ≥95% IgG and <10 mcg/mL of IgA.³⁰⁸ The IgG subclass distribution is approximately 64% IgG₁, 30% IgG₂, 5% IgG₃, and 1% IgG₄.³⁰⁸ Contains sorbitol, glycine, and polysorbate 80 as stabilizers.³⁰⁸

• Gammaplex 10%: Contains ≥98% IgG and <20 mcg/mL of IgA.³³⁷ The IgG subclass distribution reflects that of normal serum.³³⁷ Contains glycine and polysorbate 80 as stabilizers.³³⁷

• Gamunex-C 10%: Contains 9–11% protein stabilized in 0.16–0.24 M glycine;²⁶⁵ ≥98% of the protein content has the electrophoretic mobility of IgG.²⁶⁵ Contains trace amounts of fragments, IgA (average 46 mcg/mL), and IgM.²⁶⁵ Distribution of IgG subclasses is similar to that of normal serum.²⁶⁵ Fc and Fab functions are maintained, but do not activate complement or pre-Kallikrein activity in unspecific manner.²⁶⁵

• Hizentra 20%: Contains 200 mg of protein per mL, of which ≥98% is IgG.²⁹⁴ The Fc and Fab functions of the IgG molecule are retained.²⁹⁴ Distribution of IgG subclasses is similar to that of normal plasma.²⁹⁴ Contains trace amounts of IgA (≤50 mcg/mL).²⁹⁴ 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.²⁹⁴

• 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;³²⁵ distribution of IgG subclasses is similar to that of normal serum.³²⁷ Fab and Fc portions maintained intact and prekallikrein activity not detectable.³²⁵ Contains glycine as stabilizing and buffering agent.³²⁵ Recombinant human hyaluronidase component is a polysaccharide containing 447 amino acids prepared from mammalian cells using recombinant DNA technology.³²⁷ Recombinant human hyaluronidase acts locally to temporarily increase permeability of sub-Q tissue to increase dispersion and absorption of the immune globulin subcutaneous component.³²⁷

• 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%).²⁶³ Distribution of IgG subclasses is approximately 65% IgG₁, 30% IgG₂, 3% IgG₃, and 2% IgG₄ (similar to that of normal serum).²⁶³ Contains trace amounts of IgA (≤200 mcg/mL) and IgM (≤100 mcg/mL).²⁶³ Fc portion is maintained intact.²⁶³

• Octagam 10%: Contains approximately 100 mg of protein per mL, of which ≥96% is IgG;³²⁶ contains aggregates (≤3%), monomers and dimers (≥94%), and fragments (≤3%).³²⁶ Distribution of IgG subclasses is approximately 65% IgG₁, 30% IgG₂, 3% IgG₃, and 2% IgG₄ (similar to that of normal serum).³²⁶ Contains trace amounts of IgA (approximately 106 mcg/mL) and IgM.³²⁶ Fc portion is maintained intact.³²⁶

• 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%);³³⁹ Fc portion is maintained intact.³³⁹ Distribution of IgG subclasses is approximately 65% IgG₁, 28% IgG₂, 3% IgG₃, and 4% IgG₄.³³⁹ Contains glycine as a stabilizer.³³⁹

• Privigen 10%: Contains ≥98% IgG; Fc and Fab functions of IgG molecule are retained.²⁹² Distribution of IgG subclasses reflects that of normal plasma.²⁹² Contains ≤25 mcg/mL of IgA.²⁹² Also contains 250 mmol/L (range 210–290 mmol/L) of l-proline (a nonessential amino acid) as a stabilizer.²⁹²

• Xembify 20%: Contains ≥98% IgG.³⁴¹ Distribution of IgG subclasses is similar to that of normal serum.³⁴¹ Contains glycine and polysorbate 80.³⁴¹

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.^{125 263 265 266 292 294 308 324 325 326 327 332 337 338 339 340 341}

• 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.^{265 266 294 326 327 331 332 340 341}

• 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.^{125 154 263 265 266 282 294 308 324 325 326 327 328 331 332 337 338 339 340 341}

• 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.^{125 249 263 265 266 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

• 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.^{263 265 266 294 308 324 325 326 327 337 338 339 340 341}

• 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.^{263 265 266 292 294 308 324 325 326 327 331 332 337 338 339 340 341}

• 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.^{263 265 292 294 308 327 332 337 338 339 340 341}

• 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).^{263 265 266 292 294 308 324 325 326 327 331 332} Advise patients that such effects typically occur within 1–6 hours following infusion.^{263 265 266 294 308 324 325 326 327 331 337 338 339 340 341}

• Advise patients that immune globulin is prepared from pooled human plasma.^{263 265 266 292 294 308 324 325 326 327 332 337 338 339 340 341} 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.^{125 154 227 263 265 266 294 308 324 325 326 327 332 337 338 339 340 341} Importance of reporting any infection believed to have been transmitted by the immune globulin preparation.^{125 263 265 266 282 292 308 332 337 338 339 340 341}

• 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.^{154 265 266 280 282 292 324 325 326 327 331 337 338 339 340 341}

• 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.^{263 267 340} Importance of using glucose-specific test methods not affected by maltose.^{263 267 340}

• 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.^{125 263 265 266 280 282 292 294 308 327 331 332 337 338 339 340 341}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{125 263 265 266 292 308 332 337 338 339 340 341}

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.^{125 337 338 339 340 341}

• Importance of informing patients of other important precautionary information.^{125 263 265 266 280 282 292 294 308 332 337 338 339 340 341} (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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