Immune Globulin

Class: Serums
VA Class: IM500
CAS Number: 9007-83-4
Brands: Carimune, Flebogamma, Gammagard, GamaSTAN, Gammaplex, Gamunex, Hizentra, Octagam, Privigen

Warning(s)

  • Acute Renal Dysfunction and Failure
  • Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with use of IGIV in predisposed patients.125 151 249 263 265 266 282 292 308 (See Renal Effects under Cautions.)

  • Patients predisposed or at increased risk of acute renal failure include those with any degree of preexisting renal insufficiency, diabetes mellitus, age >65 years, volume depletion, sepsis, paraproteinemia, or concomitant therapy with nephrotoxic drugs.125 151 249 263 265 266 282 308

  • Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV preparations containing sucrose.125 151 263 265 266 282 292 308

  • In patients at risk of renal dysfunction or failure, administer IGIV at the minimum concentration available and at the minimum practicable infusion rate.125 151 249 263 265 266 282 292 308

Introduction

Immune globulin IM (IGIM), immune globulin IV (IGIV), and immune globulin subcutaneous; sterile, nonpyrogenic solutions of globulins containing many antibodies normally present in adult human blood.125 151 154 263 265 266 280 282 292 294 308

Uses for Immune Globulin

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 gravis108 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

Immune Globulin Dosage and Administration

Administration

Administer IGIM by IM injection; do not administer sub-Q, intradermally, or IV.154

Administer IGIV by IV infusion;125 151 263 265 266 282 292 do not administer IM.263 265 266 308 Certain IGIV preparations can be given by either IV or sub-Q infusion (i.e., Gamunex-C 10%,265 Gammagard Liquid 10%266 ); administer all other IGIV preparations only by IV infusion.125 151 263 282 292

Administer immune globulin subcutaneous by sub-Q infusion; do not administer IM.294

IM Administration

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

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

When the dose is >10 mL, divide and inject into several muscle sites to reduce local discomfort.154

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

IV Administration

General Considerations

Prior to initiation of IGIV infusion, ensure that patients are not volume depleted and are adequately hydrated.125 151 263 265 266 282 292 308

Individualize the rate of infusion based on the preparation and individual patient requirements.151

In general, in patients receiving initial doses of IGIV or switching from one IGIV preparation to another, initiate the infusion rate at the lower end of the recommended range and increase to the maximum recommended rate only after the patient has tolerated several infusions at an intermediate infusion rate.151

If an adverse reaction occurs during the IGIV infusion, decrease the rate of infusion or stop the infusion until the reaction subsides.263 265 266 292 308

Do not administer by rapid IV infusion in patients with or at risk for renal dysfunction or thrombotic events.151 282 292

IV Administration of Carimune NF

Administer Carimune NF only by IV infusion.125

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

Administer at room temperature.125

The manufacturer states that the drug may be filtered; however, filtering is not required.125 Filters with pore sizes of ≥15 μm are less likely to slow the infusion, especially with higher concentrations; may use antimicrobial filters (0.2 μm).125

Reconstitution

Reconstitute according to the manufacturer’s directions with 0.9% sodium chloride injection, 5% dextrose injection, or sterile water diluent to prepare a solution containing 30, 60, 90, or 120 mg of protein per mL (3, 6, 9, or 12% solution, respectively).125 Consider the patient’s fluid, electrolyte, and caloric requirements when selecting an appropriate diluent and concentration.125

Swirl the vial vigorously to dissolve the drug; do not shake since this may cause foaming.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, pool the contents of several reconstituted vials of identical concentration and diluent in 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 the reconstituted solution is stored under refrigeration, administer within 24 hours after reconstitution.125

Rate of Administration

Treatment of primary immunodeficiency in individuals with previously untreated agammaglobulinemia or hypogammaglobulinemia: Administer initial dose as a 3% solution (30 mg/mL) at an initial infusion rate of 0.5 mg/kg per minute.125 After 30 minutes, infusion rate may be increased to 1 mg/kg per minute for the next 30 minutes; thereafter, infusion rate may be gradually increased in a stepwise manner up to a maximum of 3 mg/kg per minute as tolerated.125 If initial infusion was well tolerated, higher concentrations may be used for subsequent infusions.125 (See Table 1.) Inflammatory reactions have occurred when an initial 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.)

Treatment of idiopathic thrombocytopenic purpura (ITP): A 6% solution (60 mg/mL) is recommended given at an initial infusion rate of 0.5 mg/kg per minute.125 After 30 minutes, infusion rate may be increased to 1 mg/kg per minute for the next 30 minutes; thereafter, infusion rate may be gradually increased 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): Infuse at a rate <2 mg/kg per minute.125 Maximum safe dose, concentration, and rate of infusion not determined to date for those at increased risk of acute renal failure.125

Patients at increased risk of thromboembolic events (e.g., those with history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity): Infuse at a rate of <2 mg/kg per minute.125

Maximum infusion rate for patients at risk of renal dysfunction or thromboembolic events.

For patients not at risk of renal dysfunction or thromboembolic events.

Table 1. Carimune NF Concentrations and Infusion Rates125

Concentration

Initial Infusion Rate: 0.5 mg/kg per minute

1 mg/kg per minute

2 mg/kg per minute

Maximum Infusion Rate: 3 mg/kg per minute

3%

0.0167 mL/kg per minute

0.033 mL/kg per minute

0.067 mL/kg per minute

0.10 mL/kg per minute

6%

0.008 mL/kg per minute

0.0167 mL/kg per minute

0.033 mL/kg per minute

0.05 mL/kg per minute

9%

0.006 mL/kg per minute

0.011 mL/kg per minute

0.022 mL/kg per minute

0.033 mL/kg per minute

12%

0.004 mL/kg per minute

0.008 mL/kg per minute

0.016 mL/kg per minute

0.025 mL/kg per minute

IV Administration of Flebogamma 5% DIF

Administer Flebogamma 5% DIF only by IV infusion.282

Administer through a separate IV line; do not mix with other drugs, IV infusion fluids, or IGIV preparations from other manufacturers.282

If large doses are to be administered, pool the contents of several vials into an empty sterile IV solution container using aseptic technique.282

Discard any partially used vials.282

Manufacturer recommends use of an inline filter with pore size of 15–20 μm.282 Antibacterial filters (0.2 μm) may be used, but may slow the infusion.282

Dilution

Do not dilute with IV fluids.282

Rate of Administration

Available as a 5% solution.282 Administer as a 5% solution at an initial rate of 0.01 mL/kg per minute (0.5 mg/kg per minute).282 If tolerated for the first 30 minutes, gradually increase to a maximum rate of 0.1 mL/kg per minute (5 mg/kg per minute).282

In patients at increased risk for renal dysfunction or thrombotic complications, manufacturer recommends a maximum infusion rate of <0.06 mL/kg per minute (<3 mg/kg per minute).282 However, data are not available to date to identify maximum safe dose, concentration, and rate of infusion in patients at risk for renal dysfunction.282

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

Vials are for single use only.266

Do not mix with other drugs or with IGIV preparations from other manufacturers.266 Infusion line may be flushed with 0.9% sodium chloride injection.266

Do not shake.266

Administer at room temperature;266 do not microwave.266

Use of an in-line filter is optional.266

Dilution

Available as a 10% solution.266 If necessary, dilute with 5% dextrose injection; do not use 0.9% sodium chloride as a diluent.266 For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Initially, administer at a rate of 0.5 mL/kg per hour (0.8 mg/kg per minute) for 30 minutes.266 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

In patients >65 years of age or at risk for renal dysfunction or thrombotic complications, use the minimum infusion rate practicable.266 Maximum 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.151

Administer through a separate IV line; do not mix with other drugs, IV infusion fluids, or IGIV preparations from other manufacturers.151

Administer at room temperature.151

Infuse via the administration set provided by the manufacturer, which contains an integral airway and a 15-mcm filter; if this administration set is not used, use a similar filter.151

When the 10% reconstituted solution is used, infuse through antecubital vein, if possible, to reduce infusion site discomfort.151

Reconstitution

Reconstitute 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).151

Prior to reconstitution, warm the powder for injection and diluent to room temperature.151

Gently rotate vial to dissolve the drug; do not shake.151 Avoid foaming.151

When large doses are to be administered, contents of several vials may be pooled into an empty sterile IV solution container using aseptic technique.151

If reconstituted outside of sterile laminar airflow conditions, administer within 2 hours after reconstitution (preferably as soon as possible).151 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).151

Discard any partially used vials.151

Rate of Administration

Initially, administer as a 5% solution at an infusion rate of 0.5 mL/kg per hour (0.4 mg/kg per minute); if tolerated, gradually increase the infusion rate to a maximum of 4 mL/kg per hour (3.3 mg/kg per minute).151 If further tolerated, may administer subsequent doses as a 10% solution, initially at a rate of 0.5 mL/kg per hour (0.8 mg/kg per minute);151 if tolerated, gradually increase the infusion rate to a maximum of 8 mL/kg per hour (13.3 mg/kg per minute).151

In patients at increased risk for renal dysfunction or thrombotic complications, manufacturer recommends a maximum infusion rate of <3.3 mg/kg per minute (<4 mL/kg per hour as a 5% solution; <2 mL/kg per hour as a 10% solution).151 However, data are not available to date to identify maximum safe concentration or rate of infusion in patients at risk for renal dysfunction.151

IV Administration of Gammaplex 5% Liquid

Administer Gammaplex 5% Liquid only by IV infusion.308

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

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

For large doses, several bottles may be pooled using aseptic technique;308 begin IV infusion within 2 hours after pooling.308

Do not shake.308

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

An infusion pump may be used to control rate of administration.308 Use an IV infusion set that preferably has an in-line filter with pore size of 15–20 mcm.308

Rate of Administration

For primary immunodeficiency, initial infusion rate is 0.5 mg/kg per minute (0.01 mL/kg per minute).308 If this rate is well tolerated for the first 15 minutes, rate may be gradually increased every 15 minutes to a maximum of 4 mg/kg per minute (0.08 mL/kg per minute).308

In patients at risk for renal dysfunction or thrombotic events, use the minimum infusion rate practicable and discontinue if renal function deteriorates.308

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; do not mix with other drugs or with IGIV preparations from other manufacturers.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-, 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.265 Promptly use any vial that has been entered; 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

Dilution

Available as a 10% solution.265 If necessary, dilute with 5% dextrose injection; do not use saline solutions as diluents.265 For solution compatibility information, see Compatibility under Stability.

Rate of Administration

For primary immunodeficiency diseases and ITP, administer as a 10% solution at a rate of 1 mg/kg per minute (0.01 mL/kg per minute) for the first 30 minutes.265 For treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), administer as a 10% solution at an initial rate of 2 mg/kg per minute (0.02 mL/kg per minute).265 If well tolerated, rate may be gradually increased to a maximum rate of 8 mg/kg per minute (0.08 mL/kg per minute).265 If adverse effects related to the rate of infusion occur, symptoms may disappear if the infusion is stopped or slowed.265

In patients at increased risk for renal dysfunction or thrombotic complications, administer at minimum 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 or mix with other drugs, IV infusion fluids, or IGIV preparations from other manufacturers.263 Flush the infusion line before and after administration with either 0.9% sodium chloride injection or 5% dextrose injection.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; discard partially used bottles.263

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

An infusion set is not provided with Octagam 5%; if an in-line filter is used, use a filter with pore size 0.2–200 μm.263

Rate of Administration

Administer as a 5% solution at a rate of 30 mg/kg per hour (0.5 mg/kg per minute or 0.01 mL/kg per minute) for the first 30 minutes.263 If tolerated, increase to 60 mg/kg per hour (1 mg/kg per minute or 0.02 mL/kg per minute) for the 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 the third 30 minutes.263 Thereafter, maintain at an infusion rate up to a maximum of 200 mg/kg per hour (maximum 3.33 mg/kg per minute or 0.07 mL/kg per minute).263

In patients at risk for renal dysfunction or thrombotic events, administer using the minimum infusion rate practicable (maximum infusion rate 200 mg/kg per hour [3.33 mg/kg per minute or 0.07 mL/kg per minute]).263

IV Administration of Privigen 10% Liquid

Administer Privigen 10% Liquid only by IV infusion.292

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

Do not shake.292

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

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

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

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.292

An infusion pump may be used to control the rate of administration.292

Dilution

Available as 10% solution.292 If necessary, dilute with 5% dextrose injection.292

Rate of Administration

For primary immunodeficiency, initially administer at a rate of 0.5 mg/kg per minute (0.005 mL/kg per minute).292 If tolerated, rate may be gradually increased to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).292

For chronic ITP, initially administer at a rate of 0.5 mg/kg per minute (0.005 mL/kg per minute).292 If tolerated, rate may be gradually increased to a maximum of 4 mg/kg per minute (0.04 mL/kg per minute).292

Patients who have not previously received Privigen 10% Liquid (or another 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 may be at risk of developing inflammatory reactions if a rapid infusion rate (e.g., >4 mg/kg per minute [>0.04 mL/kg per minute]) is used.292 Initiate Privigen in such patients using a slow infusion rate (e.g., ≤0.5 mg/kg per minute [≤0.005 mL/kg per minute]) and increase rate gradually up to the maximum rate tolerated.292

In patients at risk for renal dysfunction or thrombotic events, manufacturer recommends using the minimum infusion rate practicable.292

Sub-Q Administration of Gammagard Liquid 10%

Gammagard Liquid 10% may be administered by sub-Q infusion for 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; 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; avoid bony prominences.266

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

To determine number of infusion sites needed, 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

Does not contain preservatives; discard any unused portions.266

Rate of Administration

Primary immunodeficiency in patients weighing ≥40 kg: For initial sub-Q infusion, 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, 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 Gamunex-C 10%

Gamunex-C 10% may be administered by sub-Q infusion for 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; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.265

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

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

Depending on the total volume required, each dose of Gamunex-C 10% may be divided and infused into multiple sites.265 A maximum of 8 different administration sites may be used simultaneously; sites should be located ≥2 inches apart.265

Does not contain preservatives; discard any unused portions.265

Rate of Administration

Primary immunodeficiency: Infuse sub-Q at a rate of 20 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; provide patient and/or their caregiver with instructions and training regarding sub-Q administration.294

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

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

Depending on total volume required, each dose may be divided and infused into multiple infusion sites.294 Maximum of 4 different administration sites may be used simultaneously; if more sites are needed for the full dose, sites can be used consecutively.294 Sites should be located ≥2 inches apart and should be changed for each weekly dose.294

Does not contain preservatives; discard any unused portions.294

Rate of Administration

Primary immunodeficiency: For initial sub-Q infusion, use a maximum volume of 15 mL at a maximum infusion rate of 15 mL/hour at each administration site.294 For subsequent infusions, infusion rate may be increased to a maximum of 25 mL/hour per site as tolerated;294 maximum flow rate should not exceed a total of 50 mL/hour for all sites combined at any time.294 After the fourth infusion, volume at each infusion site may be increased to 20 mL and then increased to a maximum volume of 25 mL per site as tolerated.294

Dosage

Dosage varies depending on the formulation, route of administration, and minimum serum IgG concentrations necessary for protection in patients.151 263 266 282 308

Pediatric Patients

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)
Travelers to Areas with Intermediate or High Levels of Endemic HAV
IM

Primary immunization with the usually recommended initial and additional (booster) doses of hepatitis A vaccine before an expected exposure to HAV ensures the highest level of protection.115 186 286 Those who have received at least 1 dose given 1 month prior to exposure probably will be protected.115 186 286 For most healthy children, a single dose of monovalent hepatitis A vaccine will provide adequate protection regardless of the scheduled departure date.286

To ensure protection in immunocompromised individuals and those with chronic liver disease or other chronic medical conditions who plan to depart within 2 weeks, give a single 0.02-mL/kg dose of IGIM simultaneously with the initial hepatitis A vaccine dose (using different syringes and different injection sites).115 286

Travelers who are <12 months of age, choose not to receive hepatitis A vaccine, or are allergic to the vaccine, should receive IGIM.115 286 A single 0.02-mL/kg dose of IGIM provides effective protection for up to 3 months.115 286 If period of exposure will be >2 months, usual dose is 0.06 mL/kg once every 4–6 months.101 105 115 154 186 286

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)
IM

Children <12 months of age, immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: 0.02 mL/kg of IGIM as a single dose as soon as possible after exposure.105 107 154 186 286 Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure.105 107 154 186 286

Healthy children and adolescents 12 months to 18 years of age: ACIP prefers use of monovalent hepatitis A vaccine since it provides long-term protection.286

In individuals receiving IGIM for HAV postexposure prophylaxis and in whom hepatitis A vaccine also is recommended for other reasons, administer the first dose of hepatitis A vaccine concurrently with IGIM (using different syringes and different injection sites).101 186 194 286

Individuals who have received at least one hepatitis A vaccine dose at least 1 month prior to the current HAV exposure do not need to receive postexposure prophylaxis with IGIM.186

Measles
Postexposure Prophylaxis
IM

Usually, 0.2–0.25 mL/kg (maximum 15 mL) of IGIM as a single dose within 6 days after exposure.101 105 133 154 At 5–6 months after IGIM administration, initiate active immunization with a vaccine containing measles virus vaccine live in individuals ≥12 months of age unless contraindicated.105 133 185 (See Specific Drugs and Laboratory Tests under Interactions.)

In exposed individuals with immunosuppression (known or suspected leukemia, lymphoma, generalized malignancy, or immunodeficiency disorder, or therapy with corticosteroids or other immunosuppressive therapy such as antimetabolites, alkylating agents, radiation therapy), the usual IGIM dose is 0.5 mL/kg (maximum 15 mL) as a single dose.101 105 133 154

Individuals receiving replacement therapy with IGIM or those who have received IGIV (≥100 mg/kg) within 3 weeks prior to measles exposure do not need to receive additional prophylaxis with IGIM.105 133

Varicella
Alternative to VZIG for Postexposure Prophylaxis
IM

0.6–1.2 mL/kg of IGIM as a single dose recommended by manufacturer.154 However, IGIV (not IGIM) is recommended when VZIG is unavailable.105 268 269 272

IV

400 mg/kg of IGIV as a single dose up to 96 hours after exposure.156 269 272 Use IGIV only when VZIG is unavailable.155 156 269 272

May not be necessary in patients (e.g., HIV-infected individuals) receiving 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
IM

0.66 mL/kg (≥100 mg/kg) once every 3–4 weeks;154 some individuals may require more frequent injections.154 IGIM may prevent serious infections if serum IgG concentrations maintained at >200 mg/dL.154 Do not exceed a single dose of 20–30 mL in infants and small children.a

IV

Minimum serum IgG concentration necessary for protection varies among patients; not established in controlled clinical studies.151 266 Adjust dosage to achieve desired trough serum IgG concentration and/or clinical response.263 266 282 308 Some clinicians suggest a target trough serum IgG concentration (i.e., prior to the next dose) of ≥500 mg/dL.265

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

Gammagard Liquid 10% (children ≥2 years of age): Usually, 300–600 mg/kg once every 3–4 weeks.266 Dosage may be adjusted to achieve desired trough serum IgG concentration and clinical response;266 no data to date to determine optimum target trough concentration.266

Gammagard S/D: Usually, 300–600 mg/kg once every 3–4 weeks.151 280 Dosage may be adjusted to achieve desired trough serum IgG concentration and clinical response;151 280 no data to date to determine optimum target trough concentration.151 280 282

Gammaplex 5% Liquid: 300–800 mg/kg (6–16 mL/kg) 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 every 3 or 4 weeks as applicable.308

Gamunex-C 10%: 300–600 mg/kg (3–6 mL/kg) once every 3–4 weeks.265 Adjust dosage to achieve desired trough serum IgG concentration and clinical response.265 If a dosage <400 mg/kg once every 3–4 weeks is being used in a patient 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 patient has been exposed to measles, a dose of 400 mg/kg should be administered as soon as possible after exposure.265

Octagam 5%: 300–600 mg/kg (6–12 mL/kg) once every 3–4 weeks.263 Adjust dosage to achieve desired trough serum IgG concentration and clinical response.263 If patient misses a dose, give the missed dose as soon as possible; resume scheduled doses every 3 or 4 weeks as applicable.263 If a dosage <400 mg/kg once every 3–4 weeks is being used in a patient at risk of measles exposure (i.e., measles outbreak in US or susceptible traveler to area outside US where measles is endemic), increase dosage to at least 400 mg/kg.263 If patient has been exposed to measles, administer the dose as soon as possible after exposure.263

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

Sub-Q

Gammagard Liquid 10% (children ≥2 years of age): Administer once weekly.266 Give initial dose approximately 1 week after last IGIV dose.266 To calculate initial 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 by a dose adjustment factor of 1.37.266 Base maintenance doses on clinical response and target trough IgG concentrations;266 consult manufacturer’s literature for specific information.266

Hizentra 20% (children ≥2 years of age): Administer once weekly.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 To calculate initial weekly dose, divide previous IGIV dose (in g) by the number of weeks between IGIV doses (e.g., divide by 3 or 4 depending on whether patient was receiving IGIV every 3 or 4 weeks), then multiply this by a dose adjustment factor of 1.53;294 convert this dose to mL by multiplying calculated dose (in g) by 5.294 May need to adjust weekly dose over time to achieve desired clinical response and trough serum IgG concentrations;294 consult manufacturer’s literature for specific information.294

Idiopathic Thrombocytopenic Purpura (ITP)
IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg once daily for 2–5 consecutive days.125 In acute childhood ITP, if an initial platelet count response to the first 2 doses is adequate (30,000–50,000/mm3), discontinue therapy after the 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 an adequate response does not occur, increase the maintenance dose to 800–1000 mg/kg given as a single infusion.125

Gammagard S/D: Usually, 1 g/kg as a single dose.151 280 Determine need for additional doses based on clinical response and platelet count.151 280 If required, up to 3 doses may be given on alternate days.151 280

Gamunex-C 10%: 1 g/kg (10 mL/kg) once daily for 2 consecutive days (total dose of 2 g/kg); if an adequate increase in platelet count is obtained 24 hours after the initial 1-g/kg dose, the second 1-g/kg dose may be withheld.265 Alternatively, 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose of 2 g/kg).265 In patients with expanded fluid volumes or when fluid volume may be a concern, the regimen of 1 g/kg once daily for 1 or 2 doses is not recommended.265

Privigen 10% Liquid: In adolescents ≥15 years of age, 1 g/kg (10 mL/kg) once daily for 2 consecutive days (total of 2 g/kg).292 This dosage not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.292

Kawasaki Disease
IV

For initial treatment of acute phase, AHA, AAP, and ACCP recommend a single dose of 2 g/kg of IGIV given in conjunction with aspirin (80–100 mg/kg daily for up to 14 days, then 1–5 mg/kg once daily for 6–8 weeks); initiate as soon as possible (optimally within 7–10 days of disease onset).105 299 300 If there is no response (i.e., fever persists or recurs ≥36 hours after initial IGIV dose), retreatment with another single dose of 2 g/kg of IGIV (given within 24–48 hours of persistent or recrudescent fever) and continued aspirin therapy is recommended.105 299

Gammagard S/D: Manufacturer recommends a single dose of 1 g/kg beginning within seven days of the onset of fever or, alternatively, 400 mg/kg once daily for 4 consecutive days beginning within 7 days of the onset of fever.151 280

In one study, a single 2-g/kg IGIV infusion was at least as effective as a 4-day regimen of 400 mg/kg daily in preventing coronary artery abnormalities,238 240 and a single infusion was associated with more rapid defervescence, shorter duration of fever, and more rapid return to normal of clinical measures of inflammation.237 238 240

Prevention of Serious Infections in HIV-infected Individuals
IV

Infants and children with hypogammaglobulinemia (IgG <400 mg/dL): ACIP, AAP, CDC, NIH, and other experts recommend 400 mg/kg of IGIV once every 2–4 weeks.156

Hematopoietic Stem Cell Transplant (HSCT) Recipients
Bacterial Infection Prophylaxis
IV

Preadolescent children with severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after allogeneic HSCT: 400 mg/kg 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 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

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

Tetanus
Treatment of Tetanus
IV

200–400 mg/kg of IGIV has been recommended as an alternative when tetanus immune globulin (TIG) is not available.105 (See Tetanus under Uses.)

Adults

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)
Travelers to Areas with Intermediate or High Levels of Endemic HAV
IM

Primary immunization with the usually recommended initial and additional (booster) doses of hepatitis A vaccine before an expected exposure to HAV ensures the highest level of protection.115 186 286 Those who have received at least one dose of vaccine given 1 month prior to exposure probably will be protected.186 286 For most healthy adults ≤40 years of age, a single dose of monovalent hepatitis A vaccine will provide adequate protection regardless of the scheduled departure date.115 286

To ensure protection in older adults, immunocompromised individuals, and those with chronic liver disease or other chronic medical conditions who plan to depart within 2 weeks, give a single 0.02-mL/kg dose of IGIM simultaneously with the initial hepatitis A vaccine dose (using different syringes and different injection sites).115 286

Travelers who choose not to receive hepatitis A vaccine or are allergic to the vaccine should receive IGIM.115 286 A single 0.02-mL/kg dose of IGIM provides effective protection for up to 3 months.115 286 If period of exposure will be >2 months, usual dose is 0.06 mL/kg administered once every 4–6 months.101 105 115 154 186 286

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)
IM

Adults >40 years of age who have not previously received hepatitis A vaccine: 0.02 mL/kg of IGIM as a single dose as soon as possible after exposure.105 107 154 186 286 Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure.105 107 154 186 286 If IGIM cannot be obtained, monovalent hepatitis A vaccine may be used.286

Adults ≤40 years of age who have not previously received hepatitis A vaccine: ACIP prefers active immunization with monovalent hepatitis A vaccine since it provides long-term protection.286

Immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: 0.02 mL/kg of IGIM as a single dose as soon as possible after exposure.105 107 154 186 286 Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure.105 107 154 186 286

In individuals receiving IGIM for HAV postexposure prophylaxis and in whom hepatitis A vaccine also is recommended for other reasons, administer the first dose of hepatitis A vaccine concurrently with IGIM (using different syringes and different injection sites).101 186 194 286

Individuals who have received at least one dose of hepatitis A vaccine at least 1 month prior to the current HAV exposure do not need to receive postexposure prophylaxis with IGIM.186

Measles
Postexposure Prophylaxis
IM

0.2–0.25 mL/kg (maximum 15 mL) of IGIM as a single dose within 6 days after exposure.101 105 133 154 At 5–6 months after IGIM administration, initiate active immunization with a vaccine containing measles virus vaccine live unless contraindicated.105 133 185 (See Specific Drugs and Laboratory Tests under Interactions.)

In exposed individuals with immunosuppression (e.g., known or suspected leukemia, lymphoma, generalized malignancy, or immunodeficiency disorder, or exposed individuals receiving therapy with corticosteroids or other immunosuppressive therapy such as antimetabolites, alkylating agents, radiation therapy), the usual IGIM dose is 0.5 mL/kg (maximum 15 mL) as a single dose.101 105 133 154

Individuals receiving replacement therapy with IGIM or those who have received IGIV (≥100 mg/kg) within 3 weeks prior to measles exposure do not need to receive additional prophylaxis with IGIM.105 133

Rubella
Postexposure Prophylaxis in Pregnant Women
IM

0.55 mL/kg of IGIM as a single dose within 72 hours of exposure.154 However, routine use not recommended.105 131 133

Varicella
Alternative to VZIG for Postexposure Prophylaxis
IM

0.6–1.2 mL/kg of IGIM as a single dose.154 However, IGIV (not IGIM) is recommended when VZIG is unavailable.268 269 272

IV

400 mg/kg of IGIV as a single dose up to 96 hours after varicella exposure.105 269 272 Use IGIV only when VZIG is unavailable.105 269 272

May not be necessary in patients receiving 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
IM

0.66 mL/kg (≥100 mg/kg) once every 3–4 weeks;154 some individuals may require more frequent injections.154 IGIM may prevent serious infections if serum IgG concentrations maintained at >200 mg/dL.154 Do not exceed a single dose of 30–50 mL.a

IV

Minimum serum IgG concentration necessary for protection varies among patients; not established in controlled clinical studies.151 266 Adjust dosage to achieve desired trough serum IgG concentration and clinical response.263 266 282

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

Flebogamma 5% DIF: Usually, 300–600 mg/kg once every 3–4 weeks.282 Dosage may be adjusted to achieve desired trough serum IgG concentration and clinical response;282 no data to date to determine an optimum target trough concentration.282

Gammagard Liquid 10% or Gammagard S/D: Usually, 300–600 mg/kg once every 3–4 weeks.151 266 Dosage may be adjusted to achieve desired trough serum IgG concentration and clinical response;151 266 280 no data to date to determine an optimum target trough concentration.151 266 280

Gammaplex 5% Liquid: 300–800 mg/kg (6–16 mL/kg) 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 every 3 or 4 weeks as applicable.308

Gamunex-C 10%: 300–600 mg/kg (3–6 mL/kg) once every 3–4 weeks.265 Adjust dosage to achieve desired trough serum IgG concentration and clinical response.265 If a dosage <400 mg/kg once every 3–4 weeks is being used in a patient 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 patient has been exposed to measles, a dose of 400 mg/kg should be administered as soon as possible after exposure.265

Octagam 5%: 300–600 mg/kg (6–12 mL/kg) once every 3–4 weeks.263 Adjust dosage to achieve desired trough serum IgG concentration and clinical response.263 If patient misses a dose, give the missed dose as soon as possible; resume scheduled doses every 3 or 4 weeks as applicable.263 If a dosage <400 mg/kg once every 3–4 weeks is being used in a patient at risk of measles exposure (i.e., measles outbreak in US or susceptible traveler to area outside US where measles is endemic), increase dosage to at least 400 mg/kg.263 If patient has been exposed to measles, administer the dose as soon as possible after exposure.263

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

Sub-Q

Gammagard Liquid 10%: Administer once weekly.266 Give initial dose approximately 1 week after last IGIV dose.266 To calculate initial 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 by a dose adjustment factor of 1.37.266 Base maintenance doses on clinical response and target trough IgG concentrations;266 consult manufacturer’s literature for specific information.266

Gamunex-C 10%: Administer once weekly.265 Give initial dose 1 week after last IGIV dose.265 To calculate initial 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 by a dose adjustment factor of 1.37;265 convert this dose to mL by multiplying calculated dose (in g) by 10.265 May need to adjust weekly dose over time to achieve desired clinical response and trough serum IgG concentrations;265 consult manufacturer’s literature for specific information.265

Hizentra 20%: Administer once weekly.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 To calculate initial weekly dose, divide previous IGIV dose (in g) by the number of weeks between IGIV doses (e.g., divide by 3 or 4 depending on whether patient was receiving IGIV every 3 or 4 weeks), then multiply this by a dose adjustment factor of 1.53;294 convert this dose to mL by multiplying calculated dose (in g) by 5.294 May need to adjust weekly dose over time to achieve desired clinical response and trough serum IgG concentrations;294 consult manufacturer’s literature for specific information.294

Idiopathic Thrombocytopenic Purpura (ITP)
IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg 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 an adequate response does not occur, increase the maintenance dose to 800–1000 mg/kg given as a single infusion.125

Gammagard S/D: Usually, 1 g/kg as a single dose.151 Determine need for additional doses based on clinical response and platelet count.151 If required, up to 3 doses may be given on alternate days.151

Gamunex-C 10%: Usually, 1 g/kg (10 mL/kg) once daily for 2 consecutive days (total dose of 2 g/kg); if an adequate increase in platelet count is obtained 24 hours after the initial 1-g/kg dose, the second 1-g/kg dose may be withheld.265 Alternatively, 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose of 2 g/kg).265 In patients with expanded fluid volumes or when fluid volume may be a concern, the regimen of 1 g/kg for 1 or 2 doses is not recommended.265

Privigen 10% Liquid: 1 g/kg (10 mL/kg) once daily for 2 consecutive days (total of 2 g/kg).292 This dosage not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.292

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
IV

Gamunex-C 10%: Loading dose of 2 g/kg (20 mL/kg) given in divided doses over 2–4 consecutive days.265 Then, maintenance dosage of 1 g/kg (10 mL/kg) once every 3 weeks given either as single doses of 1 g/kg (10 mL/kg) once very 3 weeks or 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

B-cell Chronic Lymphocytic Leukemia (CLL)
Hypogammaglobulinemia and/or Recurrent Bacterial Infections
IV

Gammagard S/D: 400 mg/kg once every 3–4 weeks.151 280

Hematopoietic Stem Cell Transplant (HSCT) Recipients
Bacterial Infection Prophylaxis
IV

Patients with severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after allogeneic HSCT: 500 mg/kg 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

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

Tetanus
Treatment of Tetanus
IV

200–400 mg/kg of IGIV has been recommended as an alternative when TIG is not available.105 (See Tetanus under Uses.)

Guillain-Barré Syndrome (GBS)
IV

Although safety and efficacy and optimum dosage not established,312 317 318 European Federation of Neurological Societies (EFNS) and others recommend 0.4 g/kg 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 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

Multifocal Motor Neuropathy (MMN)
IV

Although safety and efficacy and optimum dosage have not been established, if used when disability is severe enough to warrant treatment, EFNS and Peripheral Nerve Society (PNS) suggest an initial 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 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

Prescribing Limits

Pediatric Patients

Measles
Postexposure Prophylaxis
IM

Maximum single dose of IGIM: 15 mL.101 105 133 154

Primary Immunodeficiency Diseases
Replacement Therapy
IM

Infants and small children: Maximum single dose of IGIM: 20–30 mL.a

Adults

Measles
Postexposure Prophylaxis
IM

Maximum single dose of IGIM: 15 mL.101 105 133 154

Primary Immunodeficiency Diseases
Replacement Therapy
IM

Maximum single dose of IGIM: 30–50 mL.a

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.151

Renal Impairment

Reduce IGIV dose, concentration, and/or rate of administration; maximum safe dose, concentration, and rate of administration not established.125 151 249 263 265 266 282 Ensure that patients are not volume depleted and are well hydrated; administer at the minimum concentration available and minimum practicable rate of infusion.125 151 249 263 265 266 282 292 308 (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Geriatric Patients

Reduce IGIV dose, concentration, and/or rate of infusion in patients >65 years of age; maximum safe dose, concentration, and rate of administration not established.125 151 249 263 265 266 282 Administer at the minimum concentration available and at the minimum practicable rate of infusion.125 151 249 263 265 266 282 308 (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Cautions for Immune Globulin

Contraindications

  • History of anaphylactic or severe hypersensitivity reaction to immune globulin or any ingredient in the formulation.125 263 265 266 282 292 294 308

  • Selective IgA deficiency151 154 265 266 280 282 or IgA deficiency125 151 154 263 265 266 280 282 292 294 308 with antibodies against IgA125 263 265 292 294 308 and history of hypersensitivity.263 265 266 292 294 308 (See IgA Deficiency under Cautions.)

  • Octagam 5%: Acute hypersensitivity reaction to corn; this product contains maltose derived from corn.263 (See Corn Allergy under Cautions.)

  • Hizentra 20%, Privigen 10% Liquid: Hyperprolinemia; these products contain l-proline as a stabilizer.292 294

  • GamaSTAN S/D: Severe thrombocytopenia or any coagulation disorder that would contraindicate IM injections.154 (See Individuals with Bleeding Disorders under Cautions.)

Warnings/Precautions

Warnings

Infusion Reactions

Risk of reactions including fever, chills, nausea, and vomiting upon sub-Q or IV infusion in patients who have not previously received immune globulin therapy, patients who are being switched to another preparation of immune globulin, and those who have not received immune globulin within the preceding 8 weeks.125 265 266 282 These reactions generally appear 30 minutes to 1 hour after initiation of the infusion and include flushing of the face, tightness in the chest, chills, fever, dizziness, nausea, vomiting, diaphoresis, and hypotension or hypertension.125 Closely monitor for adverse reactions throughout the infusion125 282 292 since these reactions may rarely lead to shock.125 282

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 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.)

Renal Effects

Renal dysfunction, acute renal failure, osmotic nephrosis, and death reported in patients receiving immune globulin.125 151 249 251 263 265 266 282 292 308

Patients at increased risk for acute renal failure include 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.125 151 249 263 265 266 282 308

IGIV preparations stabilized with sucrose (e.g., Carimune NF) have been associated with renal dysfunction more frequently than other IGIV preparations;125 249 261 263 265 266 282 308 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 minimize 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.125 249 251 265 266 282 294 308

Administer IGIV or immune globulin subcutaneous at the minimum concentration available and at the minimum practicable rate of infusion, especially in patients at increased risk for acute renal failure.125 151 249 263 265 266 282 294 308

Assess urine output and renal function (BUN, Scr) 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.125 151 249 263 265 266 282 292 294 308

If renal dysfunction occurs, consider discontinuing immune globulin therapy.125 151 249 263 265 266 282 292 294 308

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 infectious agents, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).125 151 154 210 263 265 266 282 292 294 308

Risk for transmission of recognized blood-borne viruses is considered to be low because plasma donors are screened for certain viruses (HBV, HCV, HIV) and viral reduction/inactivation procedures used in immune globulin production reduce the risk of transmission.151 154 263 265 266 282 292 294 308 Despite such stringent procedures, a risk of transmission still remains.125 151 154 227 263 265 266 282 292

Solvent/detergent inactivation processes apparently can inactivate lipid-enveloped viruses (e.g., HBV, HCV, HIV-1, HIV-2) but are less effective against viruses that do not have a lipid envelope (e.g., HAV, parvovirus B19).151 The manufacturing processes for some immune globulin preparations (e.g., Carimune NF, Hizentra 20%, Privigen 10% Liquid) include treatment with pepsin at pH 4 to inactivate enveloped viruses125 292 and/or virus filtration procedures that use size exclusion to remove both enveloped and nonenveloped viruses.125 292 294 In addition, plasma used for some immune globulin preparations (e.g., Gammaplex 5% Liquid, Hizentra 20%, Privigen 10% Liquid) is tested for parvovirus B19 (B19V).292 294 308

The manufacturing process for some immune globulin preparations (e.g., Carimune NF, Hizentra 20%) also includes several steps shown to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE).125 294 The TSE reduction steps (e.g., precipitation, octanoic acid fractionation, depth filtration, nanofiltration) provide reasonable assurance that low levels of CJD or vCJD agents present in the starting material would be removed during the manufacturing process.125 294

Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be inactivated by the manufacturing process or various treatment procedures used, carefully weigh risk of pathogen transmission against the benefits of immune globulin therapy.125 151 154 227 263 265 266 292

Report all infections thought possibly to have been transmitted by immune globulin preparations to the appropriate manufacturer.125 151 154 227 263 265 266 282 292 294 308

Blood Glucose Testing

IGIV preparations that contain maltose (e.g., Octagam 5%) 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 (See Specific Drugs and Laboratory Tests under Interactions.)

Sensitivity Reactions

Sensitization Reactions

Repeated IGIM injections, especially in allergic individuals, may result in sensitization, which is usually manifested as fever, chills, and sweating.a

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

Epinephrine and antihistamines should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.125 151 263 265 266 282 292 308 If a severe hypersensitivity reaction occurs, discontinue immune globulin immediately and institute appropriate therapy as indicated.154 263 265 292 294 308

Use IGIM with caution in patients with a history of systemic allergic reactions to immune globulin preparations.154 Inadvertent IV administration of IGIM may result in severe hypersensitivity reactions.154 a

The manufacturer of IGIM states that intradermal sensitivity testing should not be performed; intradermal injection of concentrated buffered immune globulin solution frequently causes localized chemical irritation, which may be misinterpreted as evidence of hypersensitivity and result in needed therapy being withheld.154

IgA Deficiency

IGIM, IGIV, and immune globulin subcutaneous should not be used in individuals with selective IgA deficiency125 151 154 263 265 266 280 282 292 294 308 and should not be used in IgA-deficient individuals with antibodies against IgA125 263 265 266 292 294 308 and history of hypersensitivity.263 265 266 292 294 308

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 IGIV, IGIM, or other blood products containing IgA.125 151 154 263 265 266 280 282 292 294 Potential for severe hypersensitivity (e.g., anaphylactic) reactions to IgA in such patients.125 151 154 263 265 266 280 282 292 294 308

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 There is some evidence that IGIV preparations depleted of IgA (0.4–2.9 mcg/mL of IgA) may be better tolerated in patients who react to IGIV preparations containing higher IgA concentrations.151 However, concentration of IgA that will not provoke a reaction to IgA is not known.151 280 All IGIV preparations carry the risk of inducing an anaphylactic reaction to IgA;151 280 risk of anaphylaxis may exist despite use of preparations containing only trace amounts of IgA.151

Carimune NF: Trace amounts of IgA.125

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

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

Gammagard S/D: Available in a formulation containing <2.2 mcg/mL151 and a formulation containing <1 mcg/mL of IgA.280 Clinical studies were conducted using the formulation containing <2.2 mcg/mL of IgA; no clinical studies specifically conducted using formulation containing <1 mcg/mL.151

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

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

Hizentra 20%: ≤50 mcg/mL of IgA.294

Octagam 5%: ≤200 mcg/mL of IgA.263

Privigen 10% Liquid: ≤25 mcg/mL of IgA.292

Latex Sensitivity

Some packaging components (e.g., diluent vial stopper) of Gammagard S/D contain natural rubber latex.151 279

Some individuals may be hypersensitive to natural latex proteins.283 284 285 Take appropriate precautions if this preparation is considered for individuals with a history of latex sensitivity.283 284 285

Corn Allergy

Octagam 5% contains maltose, a disaccharide sugar derived from corn.263 Contraindicated in those with acute hypersensitivity reaction to corn;263 patients with known corn allergies should avoid Octagam 5% .263

General Precautions

Thrombotic Effects

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 IGIV.125 151 252 253 254 255 256 257 258 259 263 265 266 282 292 308 These thrombotic effects could also occur in patients receiving immune globulin subcutaneous.294

IGIV-induced alterations of blood rheology (e.g., platelet activation, increased blood viscosity) and infusion-related hypertensive effects appear to contribute to the development of thrombotic complications.252 253 256 260

Patients with a history of atherosclerosis, multiple cardiovascular risk factors, hypertension, impaired cardiac output, cerebrovascular disease, coronary artery disease, coagulation or hypercoagulable disorders (e.g., factor V Leiden), prolonged periods of immobilization, advanced age, obesity, diabetes mellitus, acquired or inherited thrombotic disorder, previous thrombotic or thromboembolic event, or known or suspected hyperviscosity, and/or those receiving estrogen-containing products may be at increased risk.125 151 263 265 266 292 294 308

Weigh potential risks and benefits of immune globulin against those of alternative therapies in all patients in whom immune globulin is being considered.125 151 263 265 266 292 308

Prior to immune globulin therapy, carefully evaluate patients with thrombotic risk factors (e.g., those with advanced age, hypertension, cerebrovascular disease, CAD, diabetes mellitus, high serum levels of a monoclonal protein, a history of prolonged immobilization [e.g., bed-bound], and/or a history of thrombotic episodes).125 252 253 255 256 257 259 260 263 308

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).125 151 263 265 266 282 292 294 308

Use IGIV infusion solutions with protein concentrations of ≤5% in patients with thrombotic risk factors.252 253 255 256 257 259 260

Follow manufacturer’s recommendations regarding initial and maximum rates for IGIV or immune globulin subcutaneous infusion and monitor patients with thrombotic risk factors closely for signs of acute thrombosis.151 252 253 258 292 294 308

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.125 151 263 265 266 282 292 294 308

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) and, if necessary, perform confirmatory laboratory testing.125 151 263 265 266 282 292 294 308 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.292 294 308

Hemolytic anemia also can develop subsequent to immune globulin therapy due to enhanced RBC sequestration and/or intravascular RBC destruction.125 151 263 265 266 282 292 294 308

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (noncardiogenic pulmonary edema) reported in patients receiving IGIV125 151 263 265 266 282 292 308 and could also occur in patients receiving immune globulin subcutaneous.294 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.125 151 263 265 266 282 292 294 308

Monitor patients receiving immune globulin for adverse pulmonary reactions.125 151 263 265 266 282 292 294 308

If transfusion-related acute lung injury is suspected, perform appropriate tests for the presence of antineutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the product and patient serum.125 151 263 265 266 282 292 294 308 Manage using oxygen therapy with adequate ventilatory support.125 151 263 265 266 282 292 294 308

Aseptic Meningitis Syndrome

Aseptic meningitis syndrome reported infrequently in patients receiving immune globulin, especially at high doses (e.g., >1 g/kg) and/or by rapid IV infusion;125 151 211 263 265 266 282 292 308 could also occur in patients receiving immune globulin subcutaneous.294 Symptoms (e.g., severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, vomiting) may occur within several hours to 2 days following IGIV administration.125 151 211 212 263 265 266 282 292 308

In patients exhibiting such symptoms, perform a thorough neurologic examination, including CSF studies, to rule out other causes of meningitis.125 151 263 265 266 282 294 308 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,125 151 211 212 263 265 266 282 294 308 but negative culture results.265 266 292

Syndrome has resolved without sequelae within several days following discontinuance of the immune globulin.125 151 211 212 263 265 266 282 294 308

Hyperproteinemia, Increased Viscosity, and Hyponatremia

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV.263 265 292 308 The hyponatremia is likely to be pseudohyponatremia, as demonstrated by decreased calculated serum osmolality or elevated osmolar gap.263 265 292 308

If hyponatremia occurs, it is critical to distinguish true hyponatremia from pseudohyponatremia.263 265 292 308 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.263 265 292 308 (See Thrombotic Effects under Cautions.)

Volume Overload

Manufacturers of Gamunex-C 10% and Privigen 10% Liquid state that high-dose IGIV regimens (1 g/kg daily for 1–2 days) used for treatment of chronic ITP are not recommended in individuals with expanded fluid volumes or when fluid volume may be a concern.265 292

Individuals with Bleeding Disorders

Bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy.134 Manufacturer states that IGIM should not be used in individuals with severe thrombocytopenia or any coagulation disorder that would contraindicate IM injections.154

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety.134 In these cases, use a fine needle (23 gauge or smaller) and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.134 If patient is receiving antihemophilia therapy, administer the IM dose shortly after a scheduled dose of such therapy.134

Specific Populations

Pregnancy

Category C.125 151 154 263 265 266 282 292 294 308

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

Lactation

Not evaluated in nursing women.263 265 292 294 308

Not known whether immune globulin is distributed into milk following IM, IV, or sub-Q administration;266 281 use with caution in nursing women.266

Pediatric Use

GamaSTAN S/D: Manufacturer states safety and efficacy of IGIM not established in pediatric patients;154 however, passive immunization with IGIM is recommended by ACIP, AAP, and CDC in pediatric patients under certain circumstances.105 115 133 150 186 231 286 (See Hepatitis A Virus [HAV]) Infection [Preexposure Prophylaxis], Hepatitis A Virus [HAV] Infection [Postexposure Prophylaxis], and Measles, under Uses.)

Carimune: 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

Flebogamma 5% DIF: Safety and efficacy not established in pediatric patients.282

Gammagard Liquid 10%: Safety and efficacy not established in children <2 years of age.266 Safety and efficacy have been established for IV or sub-Q replacement therapy in pediatric patients 2–16 years of age with primary immunodeficiency.266 No differences in safety and efficacy profiles in pediatric patients compared with adults; pediatric-specific dosage not required to achieve desired serum IgG concentrations.266

Gammaplex 5% Liquid: Evaluated in a limited number of children and adolescents with primary immunodeficiency.308 Data insufficient to determine whether safety and efficacy are different compared with adults.308

Gamunex-C 10%: IV route evaluated in a limited number of children and adolescents with primary immunodeficiency or ITP; pharmacokinetics, efficacy, and safety were similar to that reported in adults (except vomiting and fever were reported more frequently in pediatric patients); no pediatric-specific IV dosage requirements were necessary to achieve desired serum IgG concentrations.265 Safety and efficacy for chronic inflammatory demyelinating polyneuropathy not established in pediatric patients.265 Safety and efficacy of sub-Q route not established in pediatric patients.265

Hizentra 20%: Safety and efficacy not established in pediatric patients <2 years of age.294 Safety and efficacy have been established for sub-Q 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; pediatric-specific dosage not required to achieve desired serum IgG concentrations.294

Octagam 5%: Evaluated in a limited number of children 6–16 years of age; no apparent differences in pharmacokinetics, efficacy, or safety compared with adults.263 No pediatric-specific dosage requirements were necessary to achieve desired serum IgG concentrations.263

Privigen 10% Liquid: 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; no apparent differences in safety and efficacy compared with adults.292 No pediatric-specific dosage requirements were necessary to achieve desired serum IgG concentrations.292 Safety and efficacy for treatment of chronic ITP not established in pediatric patients <15 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.125 151 263 265 266 282 292 294 308

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.263 265 266 292 308 Use with caution;125 265 292 308 do not exceed recommended dosage;125 265 266 292 administer at the minimum concentration available and minimum practicable infusion rate.125 151 263 265 266 282 292 308 (See Renal Effects under Cautions and see Geriatric Patients under Dosage and Administration.)

Immune globulin subcutaneous: Only limited number of patients ≥65 years of age were included in clinical studies of Gammagard Liquid 10% or Hizentra 20%;266 294 no overall differences in safety or efficacy were observed compared with younger patients.266 294

Renal Impairment

Patients receiving IGIV who have any degree of preexisting renal insufficiency are at increased risk for acute renal failure; ensure that such patients are not volume depleted and are well hydrated263 308 and administer IGIV at the minimum concentration available and minimum practicable rate of infusion.125 151 249 263 265 266 282 292 308 (See Renal Effects under Cautions and see Renal Impairment under Dosage and Administration.)

Common Adverse Effects

IGIM: Injection site reactions (pain,154 263 tenderness,154 muscle stiffnessa ).

IGIV: Infusion site reactions (pain, irritation);265 266 280 282 292 chest, hip, joint, back, or extremity pain;151 263 265 266 282 308 leg cramps;151 arthralgia125 263 265 282 or myalgia;125 308 GI effects (diarrhea,265 266 282 nausea,151 263 265 266 282 292 308 vomiting);151 263 265 266 282 308 chills;151 263 266 282 292 308 fever/hyperthermia;151 263 265 266 282 292 308 asthenia;265 malaise;282 fatigue;151 266 282 292 308 insomnia;308 dizziness;263 265 266 lightheadedness;151 headache;151 263 265 266 282 292 308 migraine headache;266 immediate anaphylactoid and hypersensitivity reactions;125 allergic and cutaneous reactions263 282 such as rash,125 266 erythema,125 pruritus,125 265 266 urticaria,125 151 265 266 eczema,125 or dermatitis;125 flushing;151 hypertension or fluctuations in BP;263 308 palpitations;282 tachycardia;266 282 increased liver function test results;263 265 282 asthma;265 282 wheezing;151 282 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

Immune globulin subcutaneous: Administration site reactions (erythema, pain, swelling, pruritus, heat),265 266 294 headache,265 266 294 migraine headache,294 fever,265 266 GI effects (nausea, vomiting, diarrhea, upper abdominal pain),266 294 increased heart rate,266 increased systolic blood pressure,266 fatigue,265 266 294 pain (back pain, extremity pain),294 arthralgia,265 cough,294 rash,294 pruritus.294

Interactions for Immune Globulin

Live Vaccines

Antibodies present in immune globulin preparations may interfere with the immune response to some live virus vaccines, including measles, mumps, and rubella virus vaccine live (MMR) and varicella virus vaccine live;105 125 134 185 263 265 292 294 308 no evidence of interference with the immune response to influenza virus vaccine live intranasal, yellow fever virus vaccine live, typhoid vaccine live oral, rotavirus vaccine live oral, zoster vaccine live, or poliovirus vaccine live oral (OPV; no longer commercially available in US).101 105 134 185 (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 a clinically important effect on the immune response to the vaccines or toxoids.105 134

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Hepatitis A virus vaccine inactivated

Anti-HAV antibody passively acquired from immune globulin may decrease active immune response stimulated by the vaccine, but seroconversion rates are not affected105 186 195 197 208

May administer simultaneously at separate sites using different syringes105 186 194 195 208 289

Influenza virus vaccine live intranasal

No evidence that immune globulin preparations interfere with immune response to the vaccine101 105 134 185

Vaccine may be given simultaneously with or at any interval before or after immune globulin101 105 134 185

Measles, mumps, rubella, and varicella virus vaccines

Antibodies in immune globulin can interfere with the immune response to measles and rubella antigens contained in MMR or MMRV;105 125 131 134 154 185 263 266 294 308 effect on the immune response to mumps or varicella antigens is unknown105 134

Duration of interference depends on amount of antigen-specific antibody in the immune globulin preparation134 185

MMR, MMRV, or varicella vaccine should not be administered simultaneously with or for specified intervals before or after administration of immune globulin105 125 134 185 263 265

ACIP and AAP recommend deferring administration of MMR, MMRV, or varicella vaccine for 3 months following IGIM for preexposure or postexposure HAV prophylaxis;105 134 154 185 186 for 5 months following IGIM for measles prophylaxis in immunocompetent individuals;105 134 185 for 6 months following IGIM for measles prophylaxis in immunodeficient individuals;105 134 185 for 8 months following IGIV for replacement therapy of immunodeficiencies105 134 185 or for postexposure varicella prophylaxis;269 for 8–10 months following IGIV for treatment of ITP;105 134 185 and for 11 months following IGIV for Kawasaki disease105 134 185

If MMR, MMRV, or varicella vaccine is administered simultaneously (at a separate site) or at a shorter-than-recommended interval, ACIP and AAP recommend administration of an additional vaccine dose at the recommended interval after the immune globulin dose, unless serologic testing is feasible and indicates an adequate antibody response to the vaccine134 185

Poliovirus vaccine live oral (OPV; no longer commercially available in US)

No evidence that immune globulin preparations interfere with immune response to the vaccine101 105 185 186

Vaccine may be given simultaneously with or at any interval before or after immune globulin101 105 185

Rotavirus vaccine

Potential for decreased antibody response to rotavirus vaccine in infants who recently received immune globulin;296 309 safety and efficacy data not available regarding use of rotavirus vaccine in infants who have received immune globulin within the last 42 days295 296

ACIP and AAP state rotavirus vaccine may be administered simultaneously with or at any time before or after antibody-containing blood products105 134 296 309

Tests, blood glucose (based on glucose dehydrogenase pyrroloquinolinequinone [GDH-PQQ] or glucose-dye oxidoreductase)

Maltose-containing IGIV preparations (e.g., Octagam): Potential for falsely elevated blood glucose test results263 267

May result in inappropriate insulin administration and life-threatening hypoglycemia263 267

Risk that true cases of hypoglycemia could go untreated if hypoglycemic state is masked by falsely elevated blood glucose determinations263 267

Use test methods not affected by maltose (e.g., methods that use glucose dehydrogenase nicotine adenine dinucleotide [GDH-NAD], glucose oxidase, or glucose hexokinase) in patients receiving maltose-containing IGIV preparations263 267

Tests, immunohematology (Coombs’ test)

Passively transferred blood group antibodies (e.g., anti-A, anti-B, anti-D) may result in positive direct antiglobulin (Coombs’) test results; possible interference with hematologic studies or transfusion cross-matching procedures125 151 263 265 266 292 294 308

Tests, serologic

Patients receiving immune globulin may have passively acquired antibodies that could cause false-positive serologic test results and misinterpretation of these test results265 266 292

Typhoid vaccine live oral

No evidence that immune globulin preparations interfere with immune response to the vaccine101 105 134 185

Vaccine may be given simultaneously with or at any interval before or after immune globulin101 105 134 185

Yellow fever virus vaccine live

No evidence that immune globulin preparations interfere with immune response to the vaccine101 105 134 185

Vaccine may be given simultaneously with or at any interval before or after immune globulin101 105 134 185

Zoster vaccine live

Vaccine may be given simultaneously with or at any interval before or after immune globulin134

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

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

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: 12–45 days.263 266 280 282 292 308

Stability

Storage

Parenteral

Injection for IM Use

GamaSTAN S/D: 2–8°C.154 Do not freeze.154

Injection for IV Infusion

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

Gammagard Liquid 10%: 2–8°C for ≤36 months.266 Within the first 24 months from the date of manufacture, may be removed from refrigeration and stored for up to 12 months at 25°C.266 Do not store at room temperature if >24 months have elapsed since date of manufacture.266 Do not freeze.266 Vials are for single use only.266

Gammaplex 5% Liquid: 2–25°C for ≤24 months.308 Protect from light by storing in original carton.308 Do not freeze; discard if frozen.308 Promptly use bottles that have been entered; discard partially used bottles.308 If contents of bottles are pooled under aseptic conditions, begin IV infusion within 2 hours of pooling.308

Gamunex-C 10%: 2–8°C for 36 months;265 may be stored for up to 6 months at ≤25°C 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 If contents of full vials are pooled under aseptic conditions, use within 8 hours of pooling.265

Octagam 5%: 2–25°C for 24 months after the date of manufacture.263 Do not freeze.263 Promptly use single-use bottles that have been entered.263 Discard partially used bottles.263

Privigen 10% Liquid: Room temperature ≤25ºC for up to 36 months after the 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 of ≤30°C.125 Use promptly if reconstituted outside of sterile laminar airflow conditions; use within 24 hours if reconstituted in a sterile laminar flow hood using aseptic technique and stored under refrigeration.125 Discard partially used vials.125 Do not freeze solution.125

Gammagard S/D: ≤25°C; do not freeze.151 Discard partially used vials.151 Use within 2 hours after reconstitution if reconstituted outside of sterile laminar airflow conditions; use within 24 hours if reconstituted in a sterile laminar flow hood using aseptic technique and stored at 2–8°C.151

Injection for Sub-Q Infusion

Hizentra 20%: Room temperature (≤25°C) for up to 30 months as indicated by expiration date on outer carton and 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

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (Gammagard Liquid 10%)266

Compatible

Dextrose 5% in water

Incompatible

Sodium chloride 0.9%

Solution Compatibility (Gamunex-C 10%)265 HID

Compatible

Dextrose 5% in water

Incompatible

Sodium chloride 0.9%

Solution Compatibility (Octagam 5%)263

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Solution Compatibility (Privigen 10% Liquid)292

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Actions

  • Provides a broad spectrum of opsonic and neutralizing IgG antibodies against a wide variety of bacterial and viral agents.125 151 263 265 294 308

  • 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.a

  • Mechanism of action in the treatment of primary humoral immunodeficiency not fully elucidated.263 265 292 294 308

  • Mechanism by which IGIV increases platelet counts in the treatment of ITP not fully elucidated.125 130 139 140 142 265 292 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

  • GamaSTAN S/D: Contains 15–18% protein.154

  • 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 The distribution of IgG subclasses corresponds to that of normal serum.125

  • Flebogamma 5% DIF: Contains ≥97% IgG and trace amounts of IgA (typically <50 mcg/mL) and IgM.282 The distribution of IgG subclasses is approximately 66.6% IgG1, 28.5% IgG2, 2.7% IgG3, and 2.2% IgG4.282 Fc and Fab functions are maintained.282

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

  • Gammagard S/D: Following reconstitution, contains approximately 50 mg of protein per mL.151 Contains ≥90% IgG and trace amounts of IgA (<1 mcg/mL or <2.2 mcg/mL, depending on the formulation) and IgM.151 280 The distribution of IgG subclasses is similar to that of normal serum.151 Fc portion is maintained intact.280

  • Gammaplex 5% Liquid: 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

  • Gamunex-C 10%: Contains 9–11% protein;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 The 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 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 (10–30 mg/L), and trace amounts of sodium.294

  • 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 The 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

  • Privigen 10% Liquid: Contains 67.8% IgG1, 28.7% IgG2, 2.3% IgG3, and 1.2% IgG4.292 Fc and Fab functions of IgG molecule are retained.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

Advice to Patients

  • Importance of patients understanding potential risks (e.g., hypersensitivity reactions, renal effects, possible transmission of infectious agents) and benefits of therapy.125 151 263 265 266 294 308

  • 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

  • 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.125 151 249 263 265 266 292 294 308

  • 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

  • Importance of immediately informing clinician if shortness of breath, changes in mental status/confusion, chest pain, leg pain, swelling of the legs/feet, numbness in the face or extremities, weakness or paralysis, severe headache, visual disturbances, or other manifestations of thrombotic and embolic events occur.265 266 294 308

  • 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

  • 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

  • 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 Advise patients that such effects typically occur within 1–6 hours following infusion.263 265 266 294 308

  • Advise patients that immune globulin is prepared from pooled human plasma.263 265 266 292 294 308 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.125 151 154 227 263 265 266 294 308 Importance of reporting any infection believed to have been transmitted by the immune globulin preparation.125 151 263 265 266 282 292 308

  • Instruct patients to contact their clinician if they develop symptoms of HAV infection (e.g., poor appetite, tiredness, low-grade fever followed by nausea, vomiting, abdominal pain, dark urine, jaundice) or parvovirus B19 infection (e.g., fever, drowsiness, chills, runny nose followed by rash and joint pain 2 weeks later).151

  • 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

  • Advise patients receiving Octagam that this preparation contains 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 Importance of using glucose-specific test methods not affected by maltose.263 267

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.125

  • 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.125 151 263 265 266 280 282 292 294 308

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.125 151 263 265 266 292 308

  • Importance of informing patients of other important precautionary information.125 151 263 265 266 280 282 292 294 308 (See Cautions.)

Preparations

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

Immune Globulin IM

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use

150–180 mg (of protein) per mL

GamaSTAN S/D (solvent/detergent treated)

Grifols

Immune Globulin IV

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

2.5 g (of protein)

Gammagard S/D (solvent/detergent treated)

Baxter

3 g (of protein)

Carimune NF (nanofiltered)

CSL Behring

5 g (of protein)

Gammagard S/D (solvent/detergent treated)

Baxter

6 g (of protein)

Carimune NF (nanofiltered)

CSL Behring

10 g (of protein)

Gammagard S/D (solvent/detergent treated)

Baxter

12 g (of protein)

Carimune NF (nanofiltered)

CSL Behring

Injection, for IV infusion

50 mg (of protein) per mL

Flebogamma 5% DIF (pasteurized)

Grifols

Gammaplex 5% Liquid (solvent/detergent treated)

Bio Products, FFF Enterprises

Octagam 5% (solvent/detergent treated)

Octapharma

100 mg (of protein) per mL

Privigen 10% Liquid

CSL Behring

Injection, for IV or subcutaneous infusion

100 mg (of protein) per mL

Gammagard Liquid 10%

Baxter

Gamunex-C 10% (caprylate/chromatography purified)

Grifols

Immune Globulin Subcutaneous

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous infusion

200 mg (of protein) per mL

Hizentra 20% Liquid

CSL Behring

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 2, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Centers for Disease Control and Prevention. Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2001; 50(RR-11):1-51.

101. Centers for Disease Control. Update on adult immunization: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991; 40(RR-12):1-15,47-50,58,67,68.

103. Furusho K, Kamiya T, Nakano H et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet. 1984; 2:1055-8. [IDIS 192212] [PubMed 6209513]

104. Newburger JW, Takahashi M, Burns JC et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986; 315:341-7. [IDIS 219258] [PubMed 2426590]

105. American Academy of Pediatrics. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

107. Centers for Disease Control and Prevention. Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 1997; 46(RR-18):7,14-7,27,33.

108. Arsura EL, Bick A, Brunner NG et al. High-dose intravenous immunoglobulin in the management of myasthenia gravis. Arch Intern Med. 1986; 146:1365-8. [IDIS 218035] [PubMed 3718134]

109. Nakano H, Saito A, Ueda K et al. Clinical characteristics of myocardial infarction following Kawasaki disease: report of 11 cases. J Pediatr. 1986; 108:198-203. [IDIS 212172] [PubMed 3944703]

110. Ippoliti G, Cosi V, Piccolo G et al. High-dose intravenous gammaglobulin for myasthenia gravis. Lancet. 1984; 2:809. [IDIS 191092] [PubMed 6148545]

111. Lederman HM, Roifman CM, Lavi S et al. Corticosteroids for prevention of adverse reactions to intravenous immune serum globulin infusions in hypogammaglobulinemic patients. Am J Med. 1986; 81:443-6. [IDIS 222252] [PubMed 3752145]

112. Snydman DR. Hepatitis in pregnancy. N Engl J Med. 1985; 313:1398-401. [IDIS 206813] [PubMed 3932857]

115. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services; 2010. Updates available from CDC website.

116. Anon. Safety of therapeutic immune globulin preparations with respect to transmission of human T-lymphotropic virus type III/lymphadenopathy-associated virus infection. MMWR Morb Mortal Wkly Rep. 1986; 35:231-3. [PubMed 3007971]

117. Wood CC, Williams AE, McNamara JG et al Antibody against the human immunodeficiency virus in commercial intravenous gammaglobulin preparations. Ann Intern Med. 1986; 105:536-8.

118. Piszkiewicz D, Mankarious S, Holst S et al. HIV antibodies in commercial immune globulins. Lancet. 1986; 1:1327. [PubMed 2872451]

119. Zuck TF, Preston MS, Tankersley DL et al. More on partitioning and inactivation of AIDS virus in immune globulin preparations. N Engl J Med. 1986; 314:1454-5. [PubMed 3010115]

120. White WB, Ryan RW, Staley DD et al. Passive transfer of antibodies to human T-cell lymphotropic virus type III in patients receiving high-dose intravenous immunoglobulin. JAMA. 1986; 255:2602-3. [IDIS 215191] [PubMed 3517395]

121. Wolfe WH, Miner JC, Armstrong FP et al. More on HTLV-III antibodies in immune globulin. JAMA. 1986; 256:2200.

122. Nelson RP Jr, Ledford DK, DeVoe PW et al. Hepatitis hyperimmune globulin and exposure to human immunodeficiency virus. Ann Intern Med. 1986; 105:465. [PubMed 3461738]

123. Hein R, McCue J, Mozen MM et al. Elimination of human immunodeficiency virus from immunoglobulin preparations. Lancet. 1986; 1:1217-8.

124. Buckley RH. Advances in the diagnosis and treatment of primary immunodeficiency diseases. Arch Intern Med. 1986; 146:377-84. [PubMed 3511876]

125. CSL Behring. Carimune NF nanofiltered, lyophilized (immune globulin intravenous [human]) prescribing information; Kankakee, IL. 2010 Oct.

126. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 1: Immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005; 54(RR-16):1-32.

127. Lee ML, Kingdon HS, Hooper J et al. Safety of an intravenous immunoglobulin preparation: lack of seroconversion for human immunodeficiency virus antibodies. Clin Ther. 1987; 9:300-3. [PubMed 3111704]

128. Nagashima M, Matsushima M, Matsuoka H et al. High-dose gammaglobulin therapy for Kawasaki disease. J Pediatr. 1987; 110:710-2. [IDIS 229078] [PubMed 2437278]

129. Murphy DJ, Huhta JC. Treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1987; 316:881. [PubMed 2434852]

130. Stiehm ER, Ashida E, Kim KS et al. Intravenous immunoglobulins as therapeutic agents. Ann Intern Med. 1987; 107:367-82. [IDIS 233645] [PubMed 3304051]

131. Centers for Disease Control and Prevention. Control and prevention of rubella: evaluation and management of suspected outbreaks, rubella in pregnant women, and surveillance for congenital rubella syndrome. MMWR Recomm Rep. 2001; 50(RR-12):1-23.

132. Centers for Disease Control Immunization Practices Advisory Committee (ACIP). Immunization of children infected with human T-lymphotropic virus type III/lymphadenopathy-associated virus. MMWR Morb Mortal Wkly Rep. 1986; 35:595-606. [PubMed 3018471]

133. Centers for Disease Control and Prevention. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998; 47(RR-8):1-57.

134. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-64.

135. Feigin RD, Barron KS. Treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1987; 316:881.

136. Winston DJ, Ho WG, Lin CH et al. Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Ann Intern Med. 1987; 106:12-8. [IDIS 224565] [PubMed 3024542]

137. Chirico G, Rondini G, Plebani A et al. Intravenous gammaglobulin therapy for prophylaxis of infection in high-risk neonates. J Pediatr. 1987; 110:437-42. [IDIS 227245] [PubMed 3102711]

138. Kurtsberg J, Friedman HS, Chaffee S et al. Efficacy of intravenous gamma globulin in autoimmune-mediated pediatric blood dyscrasias. Am J Med. 1987; 83(Suppl 4A):4-9. [IDIS 240219] [PubMed 3118707]

139. Lusher JM, Warrier I. Use of intravenous gamma globulin in children and adolescents with idiopathic thrombocytopenic purpura and other immune thrombocytopenias. Am J Med. 1987; 83(Suppl 4A):10-6. [IDIS 240220] [PubMed 3118703]

140. Hilgartner MW, Bussel J. Use of intravenous gamma globulin for the treatment of autoimmune neutropenia of childhood and autoimmune hemolytic anemia. Am J Med. 1987; 83(Suppl 4A):25-9. [IDIS 240222] [PubMed 3118705]

141. Sullivan KM. Immunoglobulin therapy in bone marrow transplantation. Am J Med. 1987; 83(Suppl 4A):34-45. [IDIS 240224] [PubMed 2823602]

142. Leickly FE, Buckley RH. Successful treatment of autoimmune hemolytic anemia in common variable immunodeficiency with high-dose intravenous gamma globulin. Am J Med. 1987; 82:159-62. [IDIS 225141] [PubMed 3799677]

143. Richmond GW, Ray I, Korenblitt A. Initial stabilization preceding enhanced hemolysis in autoimmune hemolytic anemia treated with intravenous gammaglobulin. J Pediatr. 1987; 110:917-9. [IDIS 230445] [PubMed 2438396]

144. NIH Consensus Development Conference. Intravenous immunoglobulin: prevention and treatment of disease. JAMA. 1990; 264:3189-93. [IDIS 275293] [PubMed 2255028]

145. Berkman SA, Lee ML, Gale RP. Clinical uses of intravenous immunoglobulins. Ann Intern Med. 1990; 112:278-92. [IDIS 263371] [PubMed 2404449]

146. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007; 56(RR-4):1-40.

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