Immune Globulin

Immune Globulin (Human) — BayGam™ (immune globulin) treated with solvent/detergent is a sterile solution of immune globulin for intramuscular administration; it contains no preservative. BayGam is prepared by cold ethanol fractionation from human plasma. The immune globulin is isolated from solubilized Cohn fraction II. The fraction II solution is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate. After the addition of solvent (TNBP) and detergent (sodium cholate), the solution is heated to 30°C and maintained at that temperature for not less than 6 hours. After the viral inactivation step, the reactants are removed by precipitation, filtration and finally ultrafiltration and diafiltra-tion. BayGam (immune globulin) is formulated as a 15–18% protein solution at a pH of 6.4–7.2 in 0.21–0.32 M glycine. BayGam (immune globulin) is then incubated in the final container for 21–28 days at 20–27°C.

The removal and inactivation of spiked model enveloped and non-enveloped viruses during the manufacturing process for BayGam (immune globulin) has been validated in laboratory studies. Human Immunodeficiency Virus, Type 1 (HIV-1), was chosen as the relevant virus for blood products; Bovine Viral Diarrhea Virus (BVDV) was chosen to model Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model Hepatitis B virus and the Herpes viruses; and Reo virus type 3 (Reo) was chosen to model non-enveloped viruses and for its resistance to physical and chemical inactivation. Significant removal of model enveloped and non-enveloped viruses is achieved at two steps in the Cohn fractionation process leading to the collection of Cohn Fraction II:the precipitation and removal of Fraction III in the processing of Fraction II + IIIW suspension to Effluent IIIand the filtration step in the processing of Effluent III to Filtrate III. Significant inactivation of enveloped viruses is achieved at the time of treatment of solubilized Cohn Fraction II with TNBP/sodium cholate.

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

IGIM is used to provide passive immunity to HAV infection for preexposure prophylaxis in certain susceptible individuals who are at risk of exposure to the virus.105 154 186 105 286

Preexposure passive immunization with IGIM is recommended if hepatitis A vaccine cannot be used because it is contraindicated or unavailable and short-term protection against HAV is needed.105 115 186 191 192 193 286 In addition, for optimal protection, use of IGIM for passive immunization may be considered in conjunction with active immunization with hepatitis A vaccine in certain individuals.115 286

Travelers to areas with intermediate or high levels of endemic HAV are at risk of exposure to the disease.115 186 286 Risk of acquiring HAV while traveling varies with living conditions, length of stay, and incidence of HAV infection in the area visited.115 Consider that many cases of HAV occur in travelers to developing countries with standard tourist itineraries, accommodations, and food consumption behaviors.115 CDC website () has information regarding which countries have high or intermediate levels of HAV endemicity.115

USPHS Advisory Committee on Immunization Practices (ACIP), CDC, WHO, and others recommend preexposure vaccination against HAV for all susceptible individuals traveling to areas with intermediate or high levels of endemic HAV.115 186 189 193 286 291 Although active immunization with hepatitis A vaccine is preferred since it provides long-term protection, if the vaccine is contraindicated or cannot be used (e.g., in children <1 year of age, individuals hypersensitive to vaccine components) or the traveler chooses not to receive the vaccine, passive immunization with IGIM is recommended.115 186 231 286 291

For optimal protection in travelers at greatest risk for HAV (older adults or individuals with altered immunocompetence, chronic liver disease, or other chronic medical condition) who plan to depart in <2 weeks, the ACIP and CDC recommend that a single dose of IGIM be given concomitantly with the initial dose of hepatitis A vaccine (at a different site).115 286

A single 0.02-mL/kg dose of IGIM confers short-term protection (up to 3 months) against HAV and a single 0.06-mL/kg dose confers longer-term protection (3–5 months).115 186 286 291

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IGIM is used for postexposure prophylaxis of HAV in susceptible individuals with recent (within 2 weeks) exposure to the virus.105 154 186 286

The choice of active immunization with hepatitis A vaccine and/or passive immunization with IGIM should take into account the magnitude of risk associated with the exposure and characteristics of the patient that may be associated with more severe manifestations of HAV (e.g., older age, chronic liver disease).105 107 186 286

Although IGIM is 80–90% effective if administered within 2 weeks of exposure186 286 and was traditionally the recommended regimen for HAV postexposure prophylaxis,105 186 286 there is some evidence that monovalent hepatitis A vaccine administered within 2 weeks of exposure may be as effective as IGIM in preventing symptomatic HAV infection in susceptible contacts 2–40 years of age.105 286 287 The vaccine also offers certain advantages over IGIM (e.g., induces active immunity and longer protection, more readily available, easier to administer, greater patient acceptance).286 287

For HAV postexposure prophylaxis in healthy individuals 12 months to 40 years of age, ACIP and AAP prefer use of monovalent hepatitis A vaccine.105 286 In adults >40 years of age, IGIM is preferred since data are not available to date regarding efficacy of the vaccine for postexposure prophylaxis in this age group and these individuals are at risk for more severe manifestations of HAV; the vaccine can be used if IGIM cannot be obtained.105 286 Use IGIM for HAV postexposure prophylaxis in children <12 months of age, immunocompromised individuals, individuals with chronic liver disease, and whenever the vaccine is contraindicated.105 286

In individuals in whom IGIM is preferred for HAV postexposure prophylaxis, administer a dose of hepatitis A vaccine simultaneously (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.105 286 If a dose of hepatitis A vaccine is used (with or without IGIM) for HAV postexposure prophylaxis, administer an additional (booster) dose of the vaccine according to the usually recommended schedule to ensure long-term protection.105 186 286

If HAV postexposure prophylaxis is indicated, administer as soon as possible (within 2 weeks of exposure).105 186 286 Data not available regarding efficacy of HAV postexposure prophylaxis administered >2 weeks after exposure.286 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

HAV postexposure prophylaxis is indicated in all previously unvaccinated individuals who have had household or sexual (heterosexual or homosexual) contact (within the past 2 weeks) with an individual with serologically confirmed HAV.286 Also consider HAV postexposure prophylaxis for individuals exposed (within the past 2 weeks) through other types of ongoing, close personal contact (e.g., regular babysitting).286

Contacts who have shared illicit drugs (within the past 2 weeks) with an individual with serologically confirmed HAV should receive HAV postexposure prophylaxis.286

Administer HAV postexposure prophylaxis to all previously unvaccinated staff and attendees of child-care centers or homes if ≥1 case of HAV is recognized in children or employees or if HAV is recognized in ≥2 households of center attendees (within the past 2 weeks).286 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.286 If an outbreak occurs (i.e., HAV in ≥3 families), also consider HAV postexposure prophylaxis for members of households that have diapered children attending the center.286

If HAV is diagnosed in a food handler, ACIP recommends HAV postexposure prophylaxis (within 2 weeks) for other food handlers at the same establishment.286 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.186 286 Settings where repeated HAV exposure might have occurred (e.g., institutional cafeterias) warrant stronger consideration of postexposure prophylaxis for patrons.186 286

HAV postexposure prophylaxis is not usually indicated after a common-source HAV outbreak if cases have begun to occur because the 2-week period when such prophylaxis is known to be effective will have been exceeded.286

When an individual with HAV is admitted to a hospital, health-care personnel do not need to receive routine HAV postexposure prophylaxis; careful hygienic practices should be emphasized in such situations.105 107 182 186 286

If an epidemiologic investigation indicates that HAV transmission has occurred among students in a school or among hospital patients and/or hospital staff, ACIP recommends HAV postexposure prophylaxis in individuals who have close contact with index patients.286

Routine HAV postexposure prophylaxis is not indicated when a single HAV case occurs in an elementary or secondary school or an office or other work setting and the source case is outside the school or work setting.286

Hepatitis B Virus (HBV) Infection

IGIM is not effective for postexposure prophylaxis of HBV infection since concentrations of anti-HBs in IGIM are too low.105

Hepatitis B immune globulin (HBIG) is the only immune globulin recommended by ACIP and AAP for passive immunization for postexposure prophylaxis of HBV.100 105 126 182

Hepatitis C Virus (HCV) Infection

IGIM has been used in attempt to prevent HCV† infection or other parenterally transmitted non-A, non-B hepatitis†.107 182

ACIP and AAP state that available data indicate that immune globulin is not effective for, and not recommended for, postexposure prophylaxis of HCV, including following occupational exposures to HCV.105 107 246 Manage occupational exposures through early identification of the disease in exposed individuals and appropriate antiviral therapy if indicated.100

ACIP states that immune globulin is not recommended for postexposure prophylaxis in infants born to HCV-positive women.246

Hepatitis E Virus (HEV) Infection

No evidence that IGIM is effective for postexposure prophylaxis of HEV infection.182 230 Travelers who received IGIM for protection against HAV should not assume they are protected against HEV.182 230 Consult CDC website () for information regarding where HEV is endemic.115

Measles

IGIM is used to prevent or modify symptoms of measles (rubeola) in susceptible individuals exposed to the disease <6 days previously.105 115 154

Postexposure vaccination (i.e., within 72 hours of exposure) generally is preferred to postexposure prophylaxis with IGIM for 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), and is acceptable for susceptible individuals ≥6 months of age who are household contacts of measles patients.133 ACIP and AAP recommend that susceptible individuals receive vaccination against measles within 72 hours after exposure, unless the vaccine is contraindicated.101 105 133 If measles is not recognized within this time frame, postexposure prophylaxis with IGIM is recommended (if administered within 6 days of exposure), especially for susceptible household contacts for whom the risk of measles complications is high (e.g., contacts ≤12 months of age, pregnant women, immunocompromised individuals).105 133

If measles is diagnosed in a mother, unvaccinated children of all ages in the household who lack evidence of measles immunity should receive IGIM.133

Postexposure prophylaxis with IGIM is not indicated for household contacts who have received a dose of vaccine containing measles virus vaccine live on or after 12 months of age, unless they are immunocompromised.105 133

When postexposure prophylaxis is indicated in a pregnant woman with documented measles exposure, administer IGIM within 6 days of exposure.105 115

Passive immunity to measles following IGIM administration is temporary (unless modified or typical measles occurs); 5–6 months after IGIM administration, initiate immunization with vaccine containing measles virus vaccine live in individuals ≥12 months of age who have no contraindications to the vaccine.115 133 Do not administer the vaccine and IGIM concurrently.115 133 (See Specific Drugs and Laboratory Tests under Interactions.)

Do not use IGIM to control measles outbreaks.101 133

IGIM is used following measles exposure in children and young adults with symptomatic HIV infection and immunosuppression associated with AIDS or other clinical manifestations of HIV infection, regardless of vaccination status;105 132 133 however, IGIM may not be necessary if the patient has been receiving IGIV (100–400 mg/kg) at regular intervals and received the last dose within 2–3 weeks of exposure to measles.105 133 150

IGIM (given within 6 days of exposure) can be used to prevent or modify measles infection in asymptomatic HIV-infected children.150 In addition, administer IGIM to measles-susceptible household contacts of asymptomatic HIV-infected children, particularly contacts <1 year of age and pregnant women.105 150

Consider preexposure prophylaxis with immune globulin in susceptible individuals with severe immunosuppression (e.g., HIV-infected individuals) who are planning travel to measles-endemic areas; vaccines containing measles virus vaccine live are not recommended for severely immunocompromised individuals.155

Mumps

IGIM is not effective for and should not be used for postexposure prophylaxis of mumps infection.105 133 154

Poliomyelitis

IGIM should not be used for postexposure prophylaxis of poliomyelitis.154

Rubella

Although some studies suggest that use of IGIM in susceptible women exposed to rubella during the first trimester of pregnancy† may lessen the likelihood of infection and adverse fetal effects, ACIP states that use of IGIM after exposure to rubella will not prevent infection or viremia but may modify or suppress symptoms and can create an unwarranted sense of security.131 133

ACIP and AAP state that IGIM should not be used routinely for postexposure prophylaxis of rubella in early pregnancy or any other circumstance.105 131 133 The only instance in which IGIM might be considered for postexposure prophylaxis of rubella is in a susceptible pregnant woman who is exposed to a confirmed case of rubella early in the pregnancy and who will not consider terminating the pregnancy under any circumstances.105 131 133 Administration within 72 hours of exposure might reduce, but will not eliminate, risk for rubella.131 133

Varicella

ACIP, AAP, and others state that varicella-zoster immune globulin (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 individuals).105 155 156 269 272

IGIV is recommended as an alternative to VZIG for postexposure prophylaxis of varicella† in susceptible individuals when VZIG is unavailable (e.g., cannot be obtained within 96 hours of exposure).105 156 268 269 272 ACIP and others state that IGIV may be used (if VZIG is unavailable) in immunocompromised patients (including HIV-infected patients),156 269 neonates whose mothers develop signs and symptoms of varicella around the time of delivery (within 5 days before to 2 days after delivery),269 premature infants exposed during the neonatal period whose mothers do not have evidence of varicella immunity,269 or premature infants exposed during the neonatal period who were born at <28 weeks’ gestation or with a birthweight of ≤1 kg (regardless of maternal history of varicella).269

ACIP, AAP, CDC, National Institutes of Health (NIH), and other experts state that HIV-infected children, adolescents, or adults 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 should be protected and should not require postexposure prophylaxis with VZIG.105 146 155 156 269

IGIV may prolong the incubation period; therefore, closely observe the patient for signs or symptoms of varicella for 28 days following exposure.269

IGIM has been used as an alternative to VZIG for postexposure prophylaxis of varicella in susceptible individuals,154 but IGIV (not IGIM) is recommended when VZIG is unavailable.105 156 268 269 272

If the exposed patient does not develop varicella, administer varicella virus vaccine live at a later date, unless contraindicated.269 (See Specific Drugs and Laboratory Tests under Interactions.)

Primary Immunodeficiency Diseases

Immune globulins (IGIM, IGIV, immune globulin subcutaneous) are used as replacement therapy to promote passive immunity in patients with primary humoral immunodeficiency diseases.125 263 265 266 274 275 276 280 292 294 308

IGIV and immune globulin subcutaneous are used in patients with IgG and other antibody-deficiency diseases, including congenital agammaglobulinemia, common variable hypogammaglobulinemia, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.125 151 263 265 266 282 292 294 308

Prophylactic IGIM therapy, especially against infections caused by encapsulated bacteria, is often effective in Bruton-type, sex-linked congenital agammaglobulinemia, agammaglobulinemia associated with thymoma, and acquired agammaglobulinemia.154 IGIM may not prevent chronic infections of the external secretory tissues (e.g., respiratory and GI tracts).154

IGIV (not IGIM) may be preferred in patients who require an immediate or large increase in intravascular immunoglobulin concentrations, in patients with small muscle mass, and in patients with bleeding tendencies in whom IM injections are contraindicated.125 280 282

Self-administration of immune globulin subcutaneous (at home) may result in improved quality of life and treatment satisfaction compared with use of IGIV (administered in the hospital or clinician’s office).275 276

IGIM, IGIV, and immune globulin subcutaneous should not be used in individuals with selective IgA deficiency151 154 266 280 282 and should not be used in IgA-deficient individuals125 151 154 263 265 266 280 282 292 294 308 with antibodies against IgA.125 263 265 266 292 294 308 (See Contraindications under Cautions and see IgA Deficiency under Cautions.)

Idiopathic Thrombocytopenic Purpura (ITP)

IGIV (i.e., Carimune NF, Gammagard S/D, Gamunex-C 10%, Privigen 10% Liquid) is used for the treatment of acute or chronic (e.g., >6 months duration) ITP (also known as immune thrombocytopenic purpura).125 138 139 151 265 292

In patients in whom an IGIV response is obtained, the rise in platelet count is generally rapid (within 1–5 days) and transient (usually lasting from several days to 2–4 weeks)125 130 139 151 but rarely may last 4–12 months or longer.125 130 138

Chronic Inflammatory Demyelinating Polyneuropathy

IGIV (i.e., Gamunex-C 10%) is used for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.265

Some clinicians consider IGIV the preferred treatment for CIDP, especially in children, patients with poor venous access that precludes use of plasma exchange, and in those susceptible to complications of long-term corticosteroid therapy.305 306

Kawasaki Disease

IGIV (i.e., Gammagard S/D) is used in conjunction with aspirin therapy for initial treatment of the acute phase of Kawasaki disease.103 104 105 128 144 145 151 157 163 237 238 240 241 299 300

Concomitant use of IGIV and high-dose aspirin therapy initiated within 10 days of the onset of fever is more effective than aspirin alone in preventing or reducing the occurrence of coronary artery abnormalities associated with Kawasaki disease and may result in more rapid resolution of fever and other manifestations of acute inflammation.104 105 128 151 280 299

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 that combined therapy with IGIV and aspirin should be initiated 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]) or evolving CAD.105 237 238 299

Approximately ≥10% 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 Retreatment with IGIV (within 24–48 hours of persistent or recrudescent fever) and continued aspirin therapy usually is recommended for these patients.105 237 299

Coronary artery abnormalities develop in 15–25% of children with Kawasaki disease if they are not treated within 10 days of fever onset;105 299 300 2–4% of patients develop coronary artery abnormalities despite prompt treatment with IGIV and aspirin.105 Long-term management of those who develop coronary abnormalities depends on the severity of coronary involvement and may include low-dose aspirin (with or without clopidogrel or dipyridamole), anticoagulant therapy with warfarin or low molecular weight heparin, or a combination of antiplatelet and anticoagulant therapy (usually low-dose aspirin and warfarin).105 299 300 Consult specialized references for additional information on long-term management of Kawasaki disease in individuals with coronary abnormalities.299 300

B-cell Chronic Lymphocytic Leukemia (CLL)

IGIV (i.e., Gammagard S/D) is used for prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell CLL.144 145 151 153 157

Prevention of Serious Bacterial Infections in HIV-infected Individuals

IGIV has been used in children with symptomatic HIV infection† who are immunosuppressed in association with AIDS or AIDS-related complex (ARC) in an attempt to control or prevent infections and improve immunologic parameters.130 139 144 145 156 157 173 174 175 176 177 178 179 180 181 184 216

IGIV also has been used in HIV-infected adults†.130 144 145 157

IGIV reduces the 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

The ACIP, AAP, CDC, NIH, HIV Medicine Association of the IDSA, Pediatric Infectious Diseases Society, and other experts state that HIV-infected infants and children with hypogammaglobulinemia (IgG <400 mg/dL) should receive IGIV (400 mg/kg once every 2–4 weeks) to prevent serious bacterial infections.156 These experts state that use of IGIV is no longer recommended for routine primary prevention of serious bacterial infections in HIV-infected infants and children; IGIV should only be used for prevention of serious bacterial infections if hypogammaglobulinemia is present or functional antibody deficiency is demonstrated by either poor specific antibody titers or recurrent bacterial infections.156

Bone Marrow Transplantation (BMT)

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 have not been 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

Hematopoietic Stem Cell Transplant (HSCT) Recipients

CDC, IDSA, and 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., Streptococcus 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†.130 137 144 145 157 166 167 168 169 170 171 172 214 However, until further data are available, do not use IGIV routinely for prophylaxis or treatment of nosocomial infections in preterm, low-birthweight infants.105 144 167 170 171 172 214

Toxic Shock Syndrome

Some clinicians suggest that IGIV may be considered as an adjunct in the treatment of staphylococcal or streptococcal toxic shock syndrome† or necrotizing fasciitis† in severely ill patients.105 201 306

Although efficacy and safety have not been established, AAP suggests that IGIV may be considered in the management of severe staphylococcal or streptococcal toxic shock syndrome† 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

Tetanus

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

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

Other Bacterial or Viral Infections

IGIV has been used alone or in conjunction with appropriate anti-infective therapy to prevent or modify acute bacterial or viral infections (e.g., CMV infections) in patients with iatrogenically induced or disease-associated immunosuppression† (e.g., patients undergoing major surgery [e.g., cardiac transplants]; patients with hematologic malignancies, extensive burns, or collagen-vascular diseases).130 136 141 144 145 157

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

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 is needed.305 306 Some clinicians suggest use of IGIV can be considered in patients with severe active SLE when other drugs have been ineffective or not tolerated;218 other clinicians recommend caution.306

Neurologic and Neuromuscular Disorders

IGIV has been used in the treatment of Guillain-Barré syndrome† (GBS).165 219 301 304 305 306 310 312 317 318 Although safety and efficacy have not been established, IGIV initiated within 2 weeks of symptom onset appears to be as effective as plasma exchange218 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 multifocal motor neuropathy† (MMN) and may provide benefits (e.g., improved muscle strength) in some patients.301 304 305 306 310 311 312 313 314 315 316 Although efficacy and safety have not been established, some clinicians recommend IGIV as a treatment of choice for MMN301 305 306 310 311 when severe disability warrants treatment.311

IGIV has been used in the management of multiple sclerosis† (MS) and has provided benefits (e.g., reduced exacerbations, reduced disability scores) in some patients with relapsing-remitting MS.301 305 306 310 318 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 that additional study is needed to further evaluate potential benefits and role of the drug in this disease.301 305 306 310 318 Not recommended for treatment of secondary progressive MS or for 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 Efficacy and safety have not been established and further study is needed.305 306 318 320 Some clinicians suggest that IGIV may be beneficial for second-line or adjunctive treatment of severe or worsening myasthenia gravis when other treatments have been unsuccessful or are not tolerated218 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 are 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 Although efficacy and safety have not been 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 is needed.145 157 165 218 Although efficacy and safety have not been established, some clinicians suggest that 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

Dermatomyositis and Polymyositis

IGIV has been used in the treatment of dermatomyositis† and polymyositis†.220 301 304 305 306 310 312 318 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 have not been 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

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

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

Injectable, Intramuscular [preservative free]:

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

Kit, Subcutaneous:

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

Solution, Injection [preservative free]:

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

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

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

Solution, Intravenous [preservative free]:

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

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

Gammaplex: 5 g/50 mL (50 mL); 5 g/100 mL (100 mL) [contains polysorbate 80]

Gammaplex: 10 g/100 mL (100 mL)

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

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

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

Solution, Subcutaneous [preservative free]:

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

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

Solution Reconstituted, Intravenous [preservative free]:

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

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

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

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

Children and Adolescents:

Hepatitis A: Refer to adult dosing.

Immune thrombocytopenia (ITP):

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

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

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

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

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

Kawasaki syndrome: IV:

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

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

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

Measles: Refer to adult dosing.

Primary humoral immunodeficiency disorders:

IV infusion dosing:

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

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

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

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

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

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

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

Panzyga [Canadian product]: IV: Children ≥2 years and Adolescents: 200 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response.

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

Switching to weekly subcutaneous infusion dosing:

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

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

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

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

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

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

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

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

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

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

SubQ infusion dosing:

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

Secondary immunodeficiency: Panzyga [Canadian product]: IV: Children ≥2 years and Adolescents: 200 to 800 mg/kg every 3 to 4 weeks; dose adjusted based on monitored trough serum IgG concentrations and clinical response.

Varicella: Refer to adult dosing.

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

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

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

≤100 days post-HCT:

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

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

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

HIV infection [prophylaxis of bacterial infection in patients with hypogammaglobulinemia (IgG <400 mg/dL)] (off-label use): Infants and Children: IV:

Primary prophylaxis for serious bacterial infections: 400 mg/kg/dose every 2 to 4 weeks (DHHS [pediatric] 2013)

Secondary prophylaxis for invasive bacterial infections: Should only be used if subsequent infections are frequent severe infections (>2 infections during a 1-year period): 400 mg/kg/dose every 2 to 4 weeks (DHHS [pediatric] 2013)

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