Immune Globulin IV, IVIG, IGIV
Indications/Dosage
Labeled
- agammaglobulinemia
- bacterial infection prophylaxis
- chronic inflammatory demyelinating polyneuropathy (CIDP)
- dermatomyositis
- hypogammaglobulinemia
- immune thrombocytopenic purpura (ITP)
- Kawasaki disease
- measles prophylaxis
- multifocal motor neuropathy
General dosing information:
- Immune globulin products are not pharmaceutically equivalent but are considered to have comparable efficacy. For patients receiving chronic immune globulin therapy, consider product changes carefully; begin with conservative infusion times and increase monitoring if products are substituted.[53366]
- In general, immune globulin should be dosed based on actual body weight in patients weighing up to 100 kg with a body mass index (BMI) less than 30 kg/m2. Some experts recommend using adjusted body weight for dosing immune globulin if the patient exceeds these parameters or is greater than 20% over their ideal body weight.[53364][53365]
Off-Label
- acute disseminated encephalomyelitis
- encephalitis
- Guillain-Barre syndrome
- hyperbilirubinemia
- multisystem inflammatory syndrome in children (MIS-C)
- myasthenia gravis
- myocarditis
- pemphigus
- pericarditis
- polymyositis
- post-transfusion purpura
- respiratory syncytial virus (RSV) infection
- sepsis
- Stevens-Johnson syndrome
- tetanus
- thrombocytopenia
- toxic epidermal necrolysis
- varicella (chickenpox) infection prophylaxis
For the treatment of primary immunodeficiency (e.g., agammaglobulinemia or hypogammaglobulinemia)
Intravenous dosage (Asceniv)
Adults
300 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration. The target trough is at least 600 mg/dL. The dose may be proportionally adjusted starting with the second infusion using the patient's trough concentration and initial dose.[64039]
Children and Adolescents 12 to 17 years
300 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration. The target trough is at least 600 mg/dL. The dose may be proportionally adjusted starting with the second infusion using the patient's trough concentration and initial dose.[64039]
Intravenous dosage (Bivigam)
Adults
300 to 800 mg/kg/dose IV every 3 to 4 weeks. If needed, adjust dose based on clinical response and desired trough concentration. The target trough is at least 600 mg/dL. The dose may be proportionally adjusted starting with the second infusion using the patient's trough concentration and initial dose.[42658]
Children and Adolescents 6 years and older
300 to 800 mg/kg/dose IV every 3 to 4 weeks. If needed, adjust dose based on clinical response and desired trough concentration. The target trough is at least 600 mg/dL. The dose may be proportionally adjusted starting with the second infusion using the patient's trough concentration and initial dose.[42658]
Intravenous dosage (Carimune NF)
Adults
400 to 800 mg/kg/dose IV every 3 to 4 weeks. The first infusion of Carimune NF in previously untreated agammaglobulinemic or hypogammaglobulinemic patients must be given as a 3% solution; if tolerated, subsequent infusions may be administered at a higher concentration.[42654]
Infants, Children, and Adolescents
400 to 800 mg/kg/dose IV every 3 to 4 weeks. The first infusion of Carimune NF in previously untreated agammaglobulinemic or hypogammaglobulinemic patients must be given as a 3% solution; if tolerated, subsequent infusions may be administered at a higher concentration.[42654]
Intravenous dosage (Flebogamma 10%)
Adults
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response.[41553]
Intravenous dosage (Flebogamma 5% or Gammagard Liquid or Gammagard S/D)
Adults
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response.[41552] [42655] [42955]
Children and Adolescents 2 years and older
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response.[41552] [42655] [42955]
Intravenous dosage (Gammaplex 5%)
Adults
300 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired serum trough concentrations.[42661]
Children and Adolescents 2 years and older
300 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired serum trough concentrations.[42661]
Intravenous dosage (Gammaplex 10%)
Adults
300 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired serum trough concentrations.[61745]
Children and Adolescents 3 years and older
300 to 800 mg/kg/dose IV every 3 to 4 weeks.[61745]
Intravenous dosage (Gamunex-C or Gammaked)
Adults
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust the dose by monitoring clinical response and IgG trough concentration.[51240] [54820]
Infants, Children, and Adolescents
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust the dose by monitoring clinical response and IgG trough concentration.[51240] [54820]
Intravenous dosage (Octagam 5%)
Adults
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration.[30276]
Children and Adolescents 6 years and older
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration.[30276]
Intravenous dosage (Panzyga)
Adults
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration.[63463]
Children and Adolescents 2 years of age and older
300 to 600 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration.[63463]
Intravenous dosage (Privigen)
Adults
200 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration.[42659]
Children and Adolescents 3 years of age and older
200 to 800 mg/kg/dose IV every 3 to 4 weeks. Adjust dose and frequency based on clinical response and desired IgG trough concentration.[42659]
Subcutaneous dosage (Gammagard Liquid 10%)
Adults
Subcutaneous doses are based on the previously established intravenous IVIG dose. Initially, convert the dose by multiplying the current IVIG dose in grams by 1.37, then divide by the number of weeks between IV doses (e.g., if IVIG is administered every 3 weeks, divide by 3). Start the initial subcutaneous dose approximately 1 week after the last IV infusion and administer weekly. Obtain an IgG trough concentration prior to converting from IV to subcutaneous treatment to guide dosage adjustments. Adjust dose and frequency based primarily on clinical response; desired IgG trough concentration should also be considered. Calculate the difference between the patient's target IgG trough concentration and the actual IgG trough concentration during subcutaneous administration. Use the table provided in the product-specific package insert to adjust the dose based on this difference and the patient's body weight.[42655]
Children and Adolescents 2 years and older
Subcutaneous doses are based on the previously established intravenous IVIG dose. Initially, convert the dose by multiplying the current IVIG dose in grams by 1.37, then divide by the number of weeks between IV doses (e.g., if IVIG is administered every 3 weeks, divide by 3). Start the initial subcutaneous dose approximately 1 week after the last IV infusion and administer weekly. Obtain an IgG trough concentration prior to converting from IV to subcutaneous treatment to guide dosage adjustments. Adjust dose and frequency based primarily on clinical response; desired IgG trough concentration should also be considered. Calculate the difference between the patient's target IgG trough concentration and the actual IgG trough concentration during subcutaneous administration. Use the table provided in the product-specific package insert to adjust the dose based on this difference and the patient's body weight.[42655]
Subcutaneous dosage (Gammaked or Gamunex-C)
Adults
Subcutaneous doses are based on the previously established intravenous IVIG dose. Initially, convert the dose by multiplying the current IVIG dose in grams by 1.37, then divide by the number of weeks between IV doses (e.g., if IVIG is administered every 3 weeks, divide by 3). To convert the calculated initial subcutaneous dose in grams to mL, multiply by 10. Start the initial subcutaneous dose 1 week after the last IV infusion and administer weekly. Obtain an IgG trough concentration prior to converting from IV to subcutaneous treatment to guide dosage adjustments. Adjust dose and frequency based primarily on clinical response; desired IgG trough concentration should also be considered. An IgG trough concentration may be measured as early as 5 weeks after switching from IV to subcutaneous administration. Calculate the difference between the patient's target IgG trough concentration and the actual IgG trough concentration during subcutaneous administration. The projected target trough level is the last IVIG trough level plus 340 mg/dL. Use the table provided in the product-specific package insert to adjust the dose based on this difference and the patient's body weight. To determine whether further dosage adjustments are necessary, monitor IgG trough concentration every 2 to 3 months.[51240] [54820]
Children and Adolescents 2 years and older
Subcutaneous doses are based on the previously established intravenous IVIG dose. Initially, convert the dose by multiplying the current IVIG dose in grams by 1.37, then divide by the number of weeks between IV doses (e.g., if IVIG is administered every 3 weeks, divide by 3). To convert the calculated initial subcutaneous dose in grams to mL, multiply by 10. Start the initial subcutaneous dose 1 week after the last IV infusion and administer weekly. Obtain an IgG trough concentration prior to converting from IV to subcutaneous treatment to guide dosage adjustments. Adjust dose and frequency based primarily on clinical response; desired IgG trough concentration should also be considered. An IgG trough concentration may be measured as early as 5 weeks after switching from IV to subcutaneous administration. Calculate the difference between the patient's target IgG trough concentration and the actual IgG trough concentration during subcutaneous administration. The projected target trough level is the last IVIG trough level plus 340 mg/dL. Use the table provided in the product-specific package insert to adjust the dose based on this difference and the patient's body weight. To determine whether further dosage adjustments are necessary, monitor IgG trough concentration every 2 to 3 months.[51240] [54820]
For the treatment of immune thrombocytopenic purpura (ITP)
NOTE: Carefully consider the relative risks and benefits before prescribing the higher dose regimen (e.g., 1 g/kg) in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.
Intravenous dosage (general neonatal dosing)
Neonates
1 g/kg/dose IV once daily for 2 consecutive days. Alternatively, 400 mg/kg/dose IV once daily for 5 consecutive days may be administered. Monitor closely until there is a sustained rise in the platelet count into the normal range. It is important to note that the platelet count in all neonates falls during the first 4 to 7 days of life.[53269] [53270] [53271]
Intravenous dosage (Carimune NF)
Adults
400 mg/kg/dose IV once daily given for 2 to 5 consecutive days. If the platelet count falls less than 30,000/microliter or the patient manifests clinically significant bleeding after induction therapy, 400 mg/kg/dose IV may be given as a single infusion. If an adequate response does not result, the dose can be increased to 800 mg/kg/dose to 1 g/kg/dose IV given as a single infusion.[42654]
Infants, Children, and Adolescents
800 mg/kg/dose to 1 g/kg/dose IV once daily for 2 consecutive days; if platelet count is adequate (30,000 to 50,000/microliter) 24 hours after the initial dose, therapy may be discontinued. Alternatively, 400 mg/kg/dose IV once daily for 2 to 5 consecutive days may be administered. If the platelet count falls below 30,000/microliter or there is clinically significant bleeding after induction therapy, give 400 mg/kg/dose IV as a single infusion. If adequate response does not result, the dose can be increased to 800 mg/kg/dose to 1 g/kg/dose IV administered as a single infusion. May administer intermittently as needed to maintain adequate platelet count.[42654] [46250] [53266] [53267] [53268] [53448] [53449]
Intravenous dosage (Flebogamma 10%)
Adults
1 g/kg/dose IV once daily for 2 consecutive days.[41553]
Children and Adolescents 2 years and older
1 g/kg/dose IV once daily for 2 consecutive days.[41553]
Intravenous dosage (Gammagard S/D)
Adults
1 g/kg IV as a single dose. If the patient's response is inadequate, 1 g/kg/dose IV may be administered on alternate days for up to 3 doses.[42955]
Intravenous dosage (Gammaked)
Adults
400 mg/kg/dose IV given on 5 consecutive days. Alternatively, 1 g/kg/dose IV once daily for 2 consecutive days. If after the administration of the first dose, an adequate increase in the platelet count is observed at 24 hours, the second dose may be withheld.[46250]
Infants, Children, and Adolescents
800 mg/kg/dose to 1 g/kg/dose IV once daily for 2 consecutive days; if platelet count is adequate (30,000 to 50,000/microliter) 24 hours after the initial dose, therapy may be discontinued. Alternatively, 400 mg/kg/dose IV once daily for 2 to 5 consecutive days may be administered. If the platelet count falls below 30,000/microliter or there is clinically significant bleeding after induction therapy, give 400 mg/kg/dose IV as a single infusion. If adequate response does not result, the dose can be increased to 800 mg/kg/dose to 1 g/kg/dose IV administered as a single infusion. May administer intermittently as needed to maintain adequate platelet count.[42654] [46250] [53266] [53267] [53268] [53448] [53449]
Intravenous dosage (Gamunex-C)
Adults
400 mg/kg/dose IV once daily for 5 consecutive days. Alternatively, 1 g/kg/dose IV once daily for 2 consecutive days may be administered; if platelet count is adequate 24 hours after the initial 1 g/kg dose, therapy may be discontinued.[51240]
Infants, Children, and Adolescents
400 mg/kg/dose IV once daily for 5 consecutive days. Alternatively, 1 g/kg/dose IV once daily for 2 consecutive days may be administered; if platelet count is adequate 24 hours after the initial 1 g/kg dose, therapy may be discontinued.[51240] [53266] [53267] [53268]
Intravenous dosage (Gammaplex 5%)
Adults
1 g/kg/day IV given on 2 consecutive days (total of 2 g/kg). Adequate data on the platelet response after 400 mg/kg/day for 5 consecutive days are not available for Gammaplex.[42661]
Intravenous dosage (Gammaplex 10%)
Adults
1 g/kg/day IV given on 2 consecutive days (total of 2 g/kg). Adequate data on the platelet response after 400 mg/kg/day for 5 consecutive days are not available for Gammaplex.[61745]
Intravenous dosage (Octagam 10%)
Adults
1 g/kg/dose IV once daily for 2 consecutive days.[57655]
Intravenous dosage (Privigen)
Adults
1 g/kg/day IV for 2 consecutive days (total of 2 g/kg).[42659]
Adolescents 15 years and older
1 g/kg/day IV for 2 consecutive days (total of 2 g/kg).[42659]
Intravenous dosage (Panzyga)
Adults
1 g/kg/day IV for 2 consecutive days (total of 2 g/kg).[63463]
For bacterial infection prophylaxis in immunocompromised patients
for the prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell Chronic Lymphocytic Leukemia (CLL)
Intravenous dosage (Gammagard S/D)
Adults, Adolescents, and Children
400 mg/kg/dose IV given every 3 to 4 weeks.[42955]
for the prevention of serious bacterial infections in hematopoietic cell transplantation (HCT) recipients with severe hypogammaglobulinemia (immunoglobulin G less than 400 mg/dL)†
Intravenous dosage
Infants and Children (first 100 days post-HCT)
400 mg/kg/dose IV once monthly. Monitor IgG trough concentration every 2 weeks during IVIG therapy, and adjust dose and frequency to maintain a IgG concentration greater than 400 mg/dL. In general, the half-life of IVIG among HCT patients is much shorter than that of healthy patients; larger doses may be required.[51812]
Infants and Children (beyond 100 days post-HCT)
500 mg/kg/dose IV every 3 to 4 weeks.[51812]
Adults and Adolescents (first 100 days post-HCT)
500 mg/kg/dose IV once weekly. Monitor IgG trough concentration every 2 weeks during IVIG therapy; adjust dose and frequency to maintain a IgG concentration greater than 400 mg/dL. In general, the half-life of IVIG among HCT patients is much shorter than that of healthy patients; larger doses may be required.[51812]
Adults and Adolescents (beyond 100 days post-HCT)
500 mg/kg/dose IV every 3 to 4 weeks.[51812]
for the prevention of serious bacterial infections in HIV-infected patients who have hypogammaglobulinemia (immunoglobulin G less than 400 mg/dL)†
Intravenous dosage
Infants and Children
400 mg/kg/dose IV every 2 to 4 weeks.[34361]
For measles prophylaxis
Intravenous dosage (Gammaked and Gammunex-C)
Adults
400 mg/kg IV as a single dose should be administered as soon as possible after exposure in patients with primary immunodeficiency. If a patient receives less than 400 mg/kg/dose IV every 3 to 4 weeks and is at risk for measles exposure (e.g., outbreak, travel to an endemic area), administer at least 400 mg/kg IV as single dose immediately prior to expected exposure.[46250] [51240] Administration of immune globulin can prevent or modify measles in patients who are nonimmune if it is administered within 6 days of exposure.[55005]
Infants, Children, and Adolescents
400 mg/kg IV as a single dose should be administered as soon as possible after exposure in patients with primary immunodeficiency. If a patient receives less than 400 mg/kg/dose IV every 3 to 4 weeks and is at risk for measles exposure (e.g., outbreak, travel to an endemic area), administer at least 400 mg/kg IV as single dose immediately prior to expected exposure.[46250] [51240] Administration of immune globulin can prevent or modify measles in patients who are nonimmune if it is administered within 6 days of exposure.[55005]
Intravenous dosage (Octagam 5%)
Adults
400 mg/kg IV as a single dose should be administered as soon as possible after exposure in patients with primary immunodeficiency. If a patient receives less than 400 mg/kg/dose IV every 3 to 4 weeks and is at risk for measles exposure (e.g., outbreak, travel to an endemic area), administer at least 400 mg/kg IV as single dose immediately prior to expected exposure.[30276] Administration of immune globulin can prevent or modify measles in patients who are nonimmune if it is administered within 6 days of exposure.[55005]
Children and Adolescents 6 to 17 years
400 mg/kg IV as a single dose should be administered as soon as possible after exposure in patients with primary immunodeficiency. If a patient receives less than 400 mg/kg/dose IV every 3 to 4 weeks and is at risk for measles exposure (e.g., outbreak, travel to an endemic area), administer at least 400 mg/kg IV as single dose immediately prior to expected exposure.[30276] Administration of immune globulin can prevent or modify measles in patients who are nonimmune if it is administered within 6 days of exposure.[55005]
Intravenous dosage (Panzyga)
Adults
400 mg/kg IV as a single dose administered as soon as possible after exposure in patients with primary humoral immunodeficiency. Administration of an extra dose of immune globulin can prevent or modify measles in patients if it is administered within 6 days of exposure. If a patient is at risk of future measles exposures and receives less than 530 mg/kg/dose every 3 to 4 weeks, increase the dose to at least 530 mg/kg/dose (to provide a serum concentration of 240 mIU/mL of measles antibodies for at least 22 days after infusion).[63463]
Children and Adolescents 2 to 17 years
400 mg/kg IV as a single dose administered as soon as possible after exposure in patients with primary humoral immunodeficiency. Administration of an extra dose of immune globulin can prevent or modify measles in patients if it is administered within 6 days of exposure. If a patient is at risk of future measles exposures and receives less than 530 mg/kg/dose every 3 to 4 weeks, increase the dose to at least 530 mg/kg/dose (to provide a serum concentration of 240 mIU/mL of measles antibodies for at least 22 days after infusion).[63463]
Intravenous dosage (all products† except Gammaked, Gammunex-C, Octagam, and Panzyga)
Adults
400 mg/kg IV as a single dose should be administered as soon as possible after exposure in patients with immunodeficiency and pregnant women without evidence of immunity. Administration of immune globulin can prevent or modify measles in patients who are nonimmune if it is administered within 6 days of exposure. Exposed persons should subsequently receive MMR vaccine, administered no earlier than 8 months after IVIG, providing the vaccine is not contraindicated.[55005]
Infants, Children, and Adolescents
400 mg/kg IV as a single dose should be administered as soon as possible after exposure in patients younger than 12 months (who have not received 1 dose of measles-containing vaccine) and those of any age with immunodeficiency. Administration of immune globulin can prevent or modify measles in patients who are nonimmune if it is administered within 6 days of exposure. Exposed persons should subsequently receive MMR vaccine, administered no earlier than 8 months after IVIG, providing the patient is 12 months and older and the vaccine is not contraindicated.[55005]
For the treatment of Kawasaki disease
Intravenous dosage (Gammagard S/D)
Infants, Children, and Adolescents
1,000 mg/kg IV as a single dose or 400 mg/kg/dose IV daily for 4 consecutive days beginning within 7 days of fever onset. Administer concurrently with moderate- to high-dose aspirin.[42955]
Intravenous dosage (all products† except Gammagard S/D)
Infants, Children, and Adolescents
2,000 mg/kg IV as a single dose within 10 days of illness onset but as soon as possible after diagnosis. Administer concurrently with moderate- to high-dose aspirin. Treat patients presenting after day 10 of illness if they have unexplained persistent fever or coronary artery abnormalities with ongoing systemic inflammation (e.g., elevated ESR and CRP). Consider a second dose (2,000 mg/kg) in patients with persistent or recrudescent fever at least 36 hours after completion of the initial IVIG infusion.[61950]
For the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment
Intravenous infusion dosage (Gamunex-C or Gammaked)
Adults
2 g/kg IV loading dose in divided doses over 2 to 4 consecutive days. May then be administered as a maintenance dose of 1 g/kg/dose administered as a single infusion or as 2 infusions of 500 mg/kg/dose given on 2 consecutive days every 3 weeks. Some patients may not require continued maintenance therapy beyond 6 months to maintain therapeutic response.[51240] [54820]
Intravenous infusion dosage (Panzyga)
Adults
2 g/kg IV loading dose divided into 2 daily doses of 1 g/kg given on 2 consecutive days. May then be administered as a maintenance dose of 1 to 2 g/kg/dose IV divided in 2 daily doses administered over 2 consecutive days every 3 weeks.[63463]
Intravenous infusion dosage (Privigen)
Adults
2 g/kg IV loading dose in divided doses over 2 to 5 consecutive days then 1 g/kg/dose IV administered in 1 to 2 infusions on consecutive days every 3 weeks. Maintenance therapy beyond 6 months has not been studied.[42659]
Intravenous dosage (products other than Gamunex-C, Gammaked, Panzyga, or Privigen)†
Children and Adolescents
2 g/kg IV as a total dose divided over 2 to 5 consecutive days. Some experts suggest the minimum effective dose should be used for maintenance therapy (generally every 3 to 6 weeks) based on clinical effectiveness.[53272] [53339] [53340] [53341]
For the treatment of HIV-associated thrombocytopenia†
Intravenous dosage
Adults
1 g/kg IV daily for 2 days when there is active bleeding or platelet counts are less than 10 x 109/L was recommended by a panel of 14 clinical and practice guideline experts.[42611] This recommendation was based on data from 4 published randomized controlled trials.[42663] [42665] [42666] [42667] These trials were of mixed quality with only 2 requiring patients to have thrombocytopenia (less than 50 x 109/L) at baseline.[42663] [42667] Additionally, the dosing regimens evaluated in these trials were not standardized, and the trials included a small number of patients (range, 12 to 30 patients). Despite these limitations, the panel deemed the results to be favorable toward IVIG use.
Neonates, Infants, Children, and Adolescents
Safety and efficacy have not been established.
For the treatment of dermatomyositis and polymyositis†
Intravenous dosage (Octagam 10%)
Adults
2 g/kg IV divided in equal doses over 2 to 5 consecutive days every 4 weeks.[57655] [68308] [68309] [68311] [68322]
Children and Adolescents
2 g/kg (Max: 70 g) IV divided in equal doses over 1 to 5 consecutive days every 2 weeks for initial therapy and then every 4 to 6 weeks.[53272] [53273] [53276] [68313] [68314] [68137] [68318]
Intravenous dosage (excluding Octagam 10%)†
Adults
2 g/kg IV divided in equal doses over 2 to 5 consecutive days every 4 weeks.[68308] [68309] [68311] [68322]
Children and Adolescents
2 g/kg (Max: 70 g) IV divided in equal doses over 1 to 5 consecutive days every 2 weeks for initial therapy and then every 4 to 6 weeks.[53272] [53273] [53276] [68313] [68314] [68137] [68318]
For the treatment of Guillain-Barre syndrome†
Intravenous dosage
Adults
IVIG has been recommended as an acceptable, first-line agent for Guillain-Barre Syndrome.[24601] In one study, 150 patients with acute Guillain-Barre syndrome, who were unable to walk independently, were randomized to receive either plasma exchange or IVIG 400 mg/kg IV once daily for 5 successive days. More patients randomized to receive IVIG improved their motor function than in the plasma exchange group, and the patients receiving IVIG responded at a faster rate.[24599]
Children and Adolescents
1 g/kg/dose IV daily for 2 consecutive days.[53272] Alternatively, 400 mg/kg/dose IV daily for 5 consecutive days produced similar recovery rates and a lower incidence of early relapse when compared to the 2-day regimen in a randomized trial of 95 pediatric patients.[53346]
For the treatment of myasthenia gravis†
in adult patients
Intravenous dosage
Adults
1 g/kg IV once daily for 1 to 2 days.[63192] [63193] [63194] Guidelines suggest IVIG in patients with life-threatening symptoms, in patients with significant bulbar dysfunction in preparation for surgery, when a rapid response to treatment is needed, when other treatments are ineffective, and prior to beginning corticosteroids if deemed necessary to prevent or minimize exacerbations. May consider IVIG as maintenance therapy for patients with refractory disease or those in whom immunosuppressive agents are relatively contraindicated.[61823]
in pediatric patients
Intravenous dosage
Infants, Children, and Adolescents
2 g/kg IV as a total dose divided over 1 to 5 days. Improvement is typically seen within 1 week. Duration of clinical effect is 4 to 6 weeks. If additional therapy is required, adjust dose based on response; use minimum effective dose. In comparison to plasmapheresis, IVIG may provide equal efficacy and better tolerability in pediatric patients.[53272] [53287] [53289] [53290]
Neonates
2 g/kg IV as a total dose divided over 1 to 5 days.[53272] 400 mg/kg/dose IV once daily for 5 days was used successfully in a 35 week preterm neonate with transient neonatal myasthenia gravis already receiving neostigmine. The neonate was weaned from the ventilator after the third dose of IVIG.[53286] In comparison to plasmapheresis, IVIG may provide equal efficacy and better tolerability in pediatric patients.[53287]
For the treatment of neonatal hyperbilirubinemia† due to hemolytic disease of the newborn (e.g., isoimmune hemolytic disease, Rh incompatibility)
Intravenous dosage
Premature Neonates 32 weeks and older and Neonates
0.5 to 1 g/kg/dose IV over 2 hours; may repeat dose in 12 hours if necessary. Therapy is most effective when initiated promptly after diagnosis.[34425] [53293] [53294] [68260] [68261]
For the treatment of post-transfusion purpura†
Intravenous dosage
Adults
A review written by the University Hospital Consortium lists IVIG as an acceptable, first-line agent in the treatment of post-transfusion purpura.[24601] The effects of IVIG were studied in 11 patients with post-transfusion purpura. In the same report, the results of the treatment of an additional 8 patients described in the literature were also summarized. One patient failed therapy due to under dosing and 1 other patient died of CHF. Out of the 17 remaining patients, 16 were determined to have good or excellent results. Five different IVIG preparations were used in the study with no obvious differences in efficacy. The total dose of IVIG per course ranged from 52 to 180 g.[24602] (NOTE: For many clinical conditions, a total dose of 2 g/kg IV divided evenly over 2 to 5 days represents the typical dose.)
For the treatment of refractory pemphigus vulgaris†
Intravenous dosage
Adults
Multiple regimens have been studied. In a small study, 11 patients were treated with 2 induction cycles of rituximab (375 mg/m2 IV weekly) for 3 weeks and intravenous immune globulin, IVIG 2 g/kg IV in the fourth week followed by once monthly infusions of rituximab (375 mg/m2) and IVIG 2 g/kg for 4 consecutive months. If the patient was clinically free of disease following this regimen, 7 additional infusions of IVIG were given. All patients experienced improvement between the third and sixth infusions of rituximab with complete clearance between the seventh and ninth infusions. Nine of the 11 patients had a sustained remission lasting for 22 to 37 months of observation (duration of follow-up after the discontinuation of rituximab therapy was 15 to 37 months). These patients were able to discontinue all conventional immunosuppressive therapy and remained free of pemphigus lesions during the remission period.[32859] In a placebo-controlled study, receipt of a single-course of IVIG by a drip infusion led to symptom improvement among patients whose symptoms did not respond to at least 20 mg/day of prednisolone equivalent. Specifically, 85 days after IVIG 400 mg/kg/day for 5 consecutive days, no additional treatment was needed for 85% of patients. In contrast, 71% of patients who got 200 mg/kg/day for 5 consecutive days and 27% of placebo recipients did not need additional treatment. Additional treatment was given when symptoms were unchanged for 2 weeks or when symptoms were aggravated.[41196] In another study, repeated IVIG receipt led to a sustained remission in all 21 patients with severe cutaneous and mucosal disease who had not responded to the prolonged use of oral prednisone and multiple immunosuppressive agents. Patients received IVIG 2 g/kg every 4 weeks until all lesions healed. The interval between doses was gradually increased to 6, 8, 10, 12, 14, and 16 weeks. IVIG was stopped once the patient remained disease-free with a 16-week interval between doses; the mean total number of IVIG cycles given per patient was 18 (range, 14 to 34), and the mean therapy duration was 27.1 months (range, 23 to 34 months). The remission continued in all 21 patients after IVIG cessation; the mean time interval between the last IVIG treatment and the last office visit was 20.4 months. Once IVIG treatment began, the doses of oral prednisone and immunosuppressive agents were reduced until both were discontinued.[41197]
For the maintenance treatment of multifocal motor neuropathy to improve muscle strength and disability
Intravenous dosage (Gammagard Liquid 10%)
Adults
0.5 to 2.4 g/kg/month IV based on clinical response; initial infusion rate is 0.8 mg/kg/minute (Max: 9 mg/kg/minute).[42655]
For the adjuvant treatment of neonatal sepsis†
Intravenous dosage
Neonates
Efficacy data are limited and variable; dosage regimens vary. 500 to 1,000 mg/kg/dose IV once daily for 1 to 6 days beginning as soon as sepsis is diagnosed is a commonly used dosage range.[53352] [53354] A meta-analyses of 3 prospective, randomized studies reported septic neonates receiving IVIG (n = 55) had a decreased death rate; analyses concluded IVIG administration in addition to conventional therapy increased the survival of early-onset of neonatal sepsis nearly 6-fold.[53352] However, the results from the large International Neonatal Immunotherapy Study (n = 3,493) concluded that IVIG 500 mg/kg/dose IV every 48 hours for 2 doses did not affect the outcomes of suspected or proven neonatal sepsis.[53353] Pediatric guidelines recommend against the routine use of IVIG in patients with septic shock; however, select patients (e.g., those with toxic shock syndrome, necrotizing fasciitis, primary humoral immunodeficiencies, or low immunoglobulin concentrations) may benefit from such treatment.[64985]
For the treatment of acute myocarditis†
Intravenous dosage
Infants, Children, and Adolescents
2 g/kg IV as a single dose. Efficacy data is limited and variable. Data from a cohort study of 46 pediatric patients suggested those treated with IVIG (n = 21) had improved left ventricular function recovery and survival at 1 year.[53298] Systemic reviews and multi-institutional analyses have failed to prove efficacy or survival benefit.[53300] [53301] [53302] [53303] [66775]
Neonates
2 g/kg IV as a single dose. Efficacy data is limited and variable. Data from a cohort study of 46 pediatric patients suggested those treated with IVIG (n = 21) had improved left ventricular function recovery and survival at 1 year.[53298] Systemic reviews and multi-institutional analyses have failed to prove efficacy or survival benefit.[53300] [53301] [53302] [53303] [66775]
For postexposure varicella (chickenpox) infection prophylaxis† in at-risk populations
NOTE: Use only if varicella-zoster immune globulin is unavailable.[66745]
Intravenous dosage
Adults
400 mg/kg/dose IV as a single dose administered as soon as possible (preferably within 96 hours), but up to 10 days after exposure in those without evidence of immunity.[34362] [51900] [66745] [68723]
Infants, Children, and Adolescents
400 mg/kg/dose IV as a single dose administered as soon as possible (preferably within 96 hours), but up to 10 days after exposure in those without evidence of immunity.[34361] [66745]
For the treatment of immune-mediated encephalitis†, including acute disseminated encephalomyelitis† (ADEM)
Intravenous dosage
Adults
1 g/kg/dose IV once daily for 2 days or 400 mg/kg/dose IV once daily for 5 days.[53272] [64893] [67800] [67918] [67919] [67920] [67921]
Infants, Children, and Adolescents
1 g/kg/dose IV once daily for 2 days or 400 mg/kg/dose IV once daily for 5 days.[53272] [67801] [67917]
For the treatment of Stevens-Johnson syndrome† (SJS) and/or toxic epidermal necrolysis† (TEN)
Intravenous dosage
Adults
2 to 3 g/kg IV divided over 1 to 4 days. Total doses ranging from 0.8 to 7.4 g/kg have been reported.[68070] [68088] [68089] [68090]
Infants, Children, and Adolescents
2 g/kg IV divided over 1 to 4 days. Total doses ranging from 1.5 to 5.8 g/kg have been reported.[53359] [53360] [53361] [53362] [53363] [68093]
For the treatment of tetanus†
Intravenous dosage
Adults
200 to 400 mg/kg IV once if tetanus immune globulin is not available.[64478]
Infants, Children, and Adolescents
200 to 400 mg/kg IV once if tetanus immune globulin is not available.[64478] [66745]
For the management of multisystem inflammatory syndrome in children (MIS-C) post SARS-CoV-2 exposure†
Intravenous dosage
Infants, Children, and Adolescents
2 g/kg (based on ideal body weight; Max: 100 g/dose) IV as a single dose in combination with low-to-moderate methylprednisolone or equivalent glucocorticoid. The dose may be divided in patients with cardiac dysfunction or fluid overload (1 g/kg IV every 24 hours for 2 doses).[65314] [65707] [65720] [66644] The National Institutes of Health (NIH) treatment guidelines recommend against the routine use of IVIG monotherapy for the treatment of MIS-C, unless glucocorticoid use is contraindicated.[65314]
For the treatment of recurrent pericarditis†
Intravenous dosage
Adults
400 to 500 mg/kg/dose IV once daily for 5 days or 1 g/kg/dose IV once daily for 2 days, then repeat dose every 4 weeks for several months.[60439] [67418] [67419]
Children and Adolescents
400 to 500 mg/kg/dose IV once daily for 5 days or 1 g/kg/dose IV once daily for 2 days, then repeat dose every 4 weeks for several months.[60439] [67418] [67419]
For the treatment of respiratory syncytial virus (RSV) infection† in high-risk immunocompromised patients (i.e., hematologic malignancies, HSCT recipients, solid organ transplant patients)
NOTE: Guidelines recommend treatment with aerosolized or systemic ribavirin and IVIG for patients with RSV upper respiratory tract infection disease (URTID) undergoing allogeneic HSCT or recipients of allogeneic HSCT with lower respiratory tract infection disease (LRTID) or risk factors for progression to RSV LRTID and death.[68208] [68226] For solid organ transplant patients, the addition of IVIG and corticosteroids to ribavirin can be considered for lung transplant recipients with URTID or LRTID.[68241]
Intravenous dosage
Adults
500 mg/kg/dose IV in combination with aerosolized or systemic ribavirin. Dosing frequency has ranged from one-time to every 48 hours for 5 to 7 doses in clinical studies.[68203] [68202] [68211] [68212] [68223] [68224] [68225] [68240]
Infants, Children, and Adolescents
400 to 500 mg/kg/dose IV in combination with aerosolized or systemic ribavirin. Dosing frequency has ranged from one-time to every 48 hours for 5 to 7 doses in clinical studies.[68203] [68219] [68220] [68221] [68222]
Therapeutic Drug Monitoring
Maximum Dosage Limits
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
To minimize the risk for further acute renal function deterioration or renal failure, use the minimum recommended IVIG dose administered at the minimum concentration available and the minimum practicable intravenous rate. Recommended infusion rates may vary by product. Avoid sucrose-containing IVIG products if possible. If renal deterioration occurs despite adequate volume status, it is recommended to discontinue the IVIG.[53382]
† Off-label indicationReferences
How Supplied
Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 0.5g Powder for Injection (00944-2620) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune 1g Powder for Injection (44206-0505) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune NF 1g Powder for Injection (44206-0415) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Panglobulin NF 1g Powder for Injection (52769-0415) (American National Red Cross) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 1g Powder for Injection (44206-0120) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 1g Powder for Injection (00078-0120) (Novartis Pharmaceuticals Corporation) (off market)Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 2.5g Powder for Injection (00944-2620) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune 3g Powder for Injection (44206-0506) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune NF 3g Powder for Injection (44206-0416) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Panglobulin NF 3g Powder for Injection (52769-0416) (American National Red Cross) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 3g Powder for Injection (44206-0122) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 3g Powder for Injection (00078-0122) (Novartis Pharmaceuticals Corporation) (off market)Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 5g Powder for Injection (00944-2620) (Baxalta Inc, a Shire Company) (off market)
Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 5g Powder for Injection (00944-2655) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 5g Powder for Injection (00944-2656) (Baxalta Inc, a Shire Company) nullImmune Globulin Lyophilisate for solution for injection
Gammar-P IV 5g Powder for Injection (00053-7486) (CSL Behring) (off market)
Immune Globulin Lyophilisate for solution for injection
Gammar-P IV 5g Powder for Injection (00053-7486) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Iveegam 5g Powder for Injection (54129-0233) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Iveegam EN 5g Powder for Injection (64193-0250) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Polygam S/D 5% Powder for Injection (00944-0471) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune 6g Powder for Injection (44206-0507) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune NF 6g Powder for Injection (44206-0417) (CSL Behring) null
Immune Globulin Lyophilisate for solution for injection
Panglobulin 6g Powder for Injection (52769-0268) (American National Red Cross) (off market)
Immune Globulin Lyophilisate for solution for injection
Panglobulin NF 6g Powder for Injection (52769-0417) (American National Red Cross) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 6g Powder for Injection (44206-0124) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 6g Powder for Injection (00078-0124) (Novartis Pharmaceuticals Corporation) (off market)Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 10g Powder for Injection (00944-2620) (Baxalta Inc, a Shire Company) (off market)
Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 10g Powder for Injection (00944-2655) (Baxalta Inc, a Shire Company) (off market)Immune Globulin Lyophilisate for solution for injection
Gammagard S/D 10g Powder for Injection (00944-2658) (Baxalta Inc, a Shire Company) nullImmune Globulin Lyophilisate for solution for injection
Gammar-P IV 10g Powder for Injection (00053-7486) (CSL Behring) (off market)
Immune Globulin Lyophilisate for solution for injection
Carimune 12g Powder for Injection (44206-0508) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Carimune NF 12g Powder for Injection (44206-0418) (CSL Behring) nullImmune Globulin Lyophilisate for solution for injection
Panglobulin 12g Powder for Injection (52769-0269) (American National Red Cross) (off market)Immune Globulin Lyophilisate for solution for injection
Panglobulin NF 12g Powder for Injection (52769-0418) (American National Red Cross) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 12g Powder for Injection (44206-0226) (CSL Behring) (off market)Immune Globulin Lyophilisate for solution for injection
Sandoglobulin 12g Powder for Injection (00078-0244) (Novartis Pharmaceuticals Corporation) (off market)Immune Globulin Solution for injection
Flebogamma 5% 0.5g Solution for Injection (61953-0003) (Grifols USA, LLC) (off market)Immune Globulin Solution for injection
Flebogamma 5% 10g Solution for Injection (61953-0003) (Grifols USA, LLC) (off market)Immune Globulin Solution for injection
Flebogamma 5% 2.5g Solution for Injection (61953-0003) (Grifols USA, LLC) (off market)Immune Globulin Solution for injection
Flebogamma 5% 5g Solution for Injection (61953-0003) (Grifols USA, LLC) (off market)Immune Globulin Solution for injection
Flebogamma DIF 5% 0.5g Solution for Injection (61953-0004) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Flebogamma DIF 5% 10g Solution for Injection (61953-0004) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Flebogamma DIF 5% 2.5g Solution for Injection (61953-0004) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Flebogamma DIF 5% 20g Solution for Injection (61953-0004) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Flebogamma DIF 5% 5g Solution for Injection (61953-0004) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamimune N 5% Solution for Injection (00026-0646) (Bayer Pharmaceuticals Corporation) (off market)Immune Globulin Solution for injection
Gammaplex 2.5g/50ml Solution for Injection (64208-8234) (Bio Products Laboratory) (off market)Immune Globulin Solution for injection
Gammaplex 5% 10g Solution for Injection (64208-8234) (Bio Products Laboratory) nullImmune Globulin Solution for injection
Gammaplex 5% 20g Solution for Injection (64208-8234) (Bio Products Laboratory) nullImmune Globulin Solution for injection
Gammaplex 5% 5g Solution for Injection (64208-8234) (Bio Products Laboratory) nullImmune Globulin Solution for injection
Octagam 5% 10g Solution for Injection (68982-0840) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 5% 1g Solution for Injection (68982-0840) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 5% 2.5g Solution for Injection (68982-0840) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 5% 25g Solution for Injection (68982-0840) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 5% 5g Solution for Injection (68982-0840) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 5% Solution for Injection (67467-0843) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
Octagam 5% Solution for Injection (67467-0843) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
Venoglobulin S 5% Solution for Injection (49669-1614) (Alpha Therapeutic Corp) (off market)Immune Globulin Solution for injection
Venoglobulin S 5% Solution for Injection (49669-1613) (Alpha Therapeutic Corp) (off market)Immune Globulin Solution for injection
Venoglobulin S 5% Solution for Injection (49669-1612) (Alpha Therapeutic Corp) (off market)Immune Globulin Solution for injection
Vigam 5% Solution for Injection (64208-1948) (Bio Products Laboratory) (off market)Immune Globulin Solution for injection
ASCENIV Liquid 5g 10% Solution for Injection (69800-0250) (ADMA Biologics) null
Immune Globulin Solution for injection
BIVIGAM 10% 10g Liquid (69800-6503) (ADMA Biologics) nullImmune Globulin Solution for injection
BIVIGAM 10% 10g Liquid (59730-6503) (Biotest Pharmaceuticals Corporation) (off market)Immune Globulin Solution for injection
BIVIGAM 10% 5g Liquid (69800-6502) (ADMA Biologics) null
Immune Globulin Solution for injection
BIVIGAM 10% 5g Liquid (59730-6502) (Biotest Pharmaceuticals Corporation) nullImmune Globulin Solution for injection
Flebogamma DIF 10% 10g Solution for Injection (61953-0005) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Flebogamma DIF 10% 20g Solution for Injection (61953-0005) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Flebogamma DIF 10% 5g Solution for Injection (61953-0005) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamimune N 10% Solution for Injection (00026-0649) (Bayer Pharmaceuticals Corporation) (off market)Immune Globulin Solution for injection
Gamimune N 10% Solution for Injection (00026-0648) (Bayer Pharmaceuticals Corporation) (off market)Immune Globulin Solution for injection
Gammagard Liquid 10g 10% Solution for Injection (00944-2700) (Baxalta Inc, a Shire Company) nullImmune Globulin Solution for injection
Gammagard Liquid 1g 10% Solution for Injection (00944-2700) (Baxalta Inc, a Shire Company) nullImmune Globulin Solution for injection
Gammagard Liquid 2.5g 10% Solution for Injection (00944-2700) (Baxalta Inc, a Shire Company) nullImmune Globulin Solution for injection
Gammagard Liquid 20g 10% Solution for Injection (00944-2700) (Baxalta Inc, a Shire Company) nullImmune Globulin Solution for injection
Gammagard Liquid 30g 10% Solution for Injection (00944-2700) (Baxalta Inc, a Shire Company) nullImmune Globulin Solution for injection
Gammagard Liquid 5g 10% Solution for Injection (00944-2700) (Baxalta Inc, a Shire Company) nullImmune Globulin Solution for injection
Gammaked 10% 10g Solution for Injection (76125-0900) (Kedrion Biopharma Inc) nullImmune Globulin Solution for injection
Gammaked 10% 1g Solution for Injection (76125-0900) (Kedrion Biopharma Inc) nullImmune Globulin Solution for injection
Gammaked 10% 2.5g Solution for Injection (76125-0900) (Kedrion Biopharma Inc) (off market)Immune Globulin Solution for injection
Gammaked 10% 20g Solution for Injection (76125-0900) (Kedrion Biopharma Inc) null
Immune Globulin Solution for injection
Gammaked 10% 5g Solution for Injection (76125-0900) (Kedrion Biopharma Inc) nullImmune Globulin Solution for injection
Gammaplex 10% 10g Solution for Injection (64208-8235) (Bio Products Laboratory) nullImmune Globulin Solution for injection
Gammaplex 10% 20g Solution for Injection (64208-8235) (Bio Products Laboratory) nullImmune Globulin Solution for injection
Gammaplex 10% 5g Solution for Injection (64208-8235) (Bio Products Laboratory) nullImmune Globulin Solution for injection
Gamunex 10% Solution for Injection (00026-0645) (Bayer Pharmaceuticals Corporation) (off market)Immune Globulin Solution for injection
Gamunex 10% Solution for Injection (13533-0645) (Grifols USA, LLC) (off market)Immune Globulin Solution for injection
Gamunex-C 10% 10g Solution for Injection (13533-0800) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamunex-C 10% 1gm Solution for Injection (13533-0800) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamunex-C 10% 2.5g Solution for Injection (13533-0800) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamunex-C 10% 20g Solution for Injection (13533-0800) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamunex-C 10% 40g Solution for Injection (13533-0800) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Gamunex-C 10% 5g Solution for Injection (13533-0800) (Grifols USA, LLC) nullImmune Globulin Solution for injection
Octagam 10% 10g Solution for Injection (68982-0850) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 10% 20g Solution for Injection (68982-0850) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 10% 2g Solution for Injection (68982-0850) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 10% 30g Solution for Injection (68982-0850) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
Octagam 10% 5g Solution for Injection (68982-0850) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga 10% 10g Solution for Injection (68982-0820) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
panzyga 10% 1g Solution for Injection (68982-0820) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
panzyga 10% 2.5g Solution for Injection (68982-0820) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
panzyga 10% 20g Solution for Injection (68982-0820) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
panzyga 10% 30g Solution for Injection (68982-0820) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
panzyga 10% 5g Solution for Injection (68982-0820) (Octapharma USA Inc.) (off market)Immune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 10g Solution for Injection (68982-0822) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 10g Solution for Injection (00069-1312) (Pfizer Injectables) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 1g Solution for Injection (68982-0822) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 1g Solution for Injection (00069-1011) (Pfizer Injectables) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 2.5g Solution for Injection (68982-0822) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 2.5g Solution for Injection (00069-1109) (Pfizer Injectables) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 20g Solution for Injection (68982-0822) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 20g Solution for Injection (00069-1415) (Pfizer Injectables) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 30g Solution for Injection (68982-0822) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 30g Solution for Injection (00069-1558) (Pfizer Injectables) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 5g Solution for Injection (68982-0822) (Octapharma USA Inc.) nullImmune Globulin Solution for injection
panzyga Immune Globulin Intravenous (Human) - ifas 10% 5g Solution for Injection (00069-1224) (Pfizer Injectables) nullImmune Globulin Solution for injection
Privigen 10% 10g Solution for Injection (44206-0437) (CSL Behring) nullImmune Globulin Solution for injection
Privigen 10% 20g Solution for Injection (44206-0438) (CSL Behring) nullImmune Globulin Solution for injection
Privigen 10% 40g Solution for Injection (44206-0439) (CSL Behring) nullImmune Globulin Solution for injection
Privigen 10% 5g Solution for Injection (44206-0436) (CSL Behring) nullImmune Globulin Solution for injection
Venoglobulin S 10% Solution for Injection (49669-1623) (Alpha Therapeutic Corp) (off market)Immune Globulin Solution for injection
Venoglobulin S 10% Solution for Injection (49669-1622) (Alpha Therapeutic Corp) (off market)Immune Globulin Solution for injection
Venoglobulin S 20% Solution for Injection (49669-1624) (Alpha Therapeutic Corp) (off market)Description/Classification
Description
Immune globulin IV (IVIG) is an intravenous solution composed primarily of human immunoglobulin G (IgG), with trace amounts of IgA and IgM. IVIG is derived from the pooled human plasma of thousands of donors, ensuring a diversified collection of antibodies with variable antigen-binding regions. All samples undergo human immunodeficiency virus (HIV), hepatitis B, and hepatitis C testing. Although the amount of each IgG subclass is similar to that of human plasma in all IVIG formulations, titers among specific antigens, preparation methods, viral inactivation steps, stabilizing agents, osmolality, and IgA content differ among products. Thus, IVIG products have comparable efficacy but are not pharmaceutically equivalent. IVIG is used for a variety of conditions; its primary indication is as replacement therapy for patients with antibody deficiencies. IVIG is used to provide immediate passive immunity after suspected exposure to an organism for which no active immunization exists or if there is inadequate time to develop active immunization, and as replacement therapy for patients with antibody deficiencies. IVIG also has been used successfully to treat immune thrombocytopenic purpura (ITP), Kawasaki syndrome (mucocutaneous lymph node syndrome), dermatomyositis, and chronic inflammatory demyelinating polyneuropathies (CIDP). It has been used for a variety of other clinical conditions. Intravenous immune globulins have been available since the late 1980s, and many products are commercially available.
Classifications
- Antineoplastic and Immunomodulating Agents
- Immunomodulating Agents
- Immunoglobulins
- Immunoglobulins, Normal Human
- Immunoglobulins
- Immunomodulating Agents
References
Administration Information
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
- Titers against specific antigens vary between manufacturers. Due to this variance, some clinicians feel strongly that IV immune globulin products are not equivalent.
- Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Asceniv:
- Asceniv is a clear or slightly opalescent, colorless to pale yellow solution; do not use if the solution is cloudy or turbid or contains particulate matter. Do not use any solution that has been frozen, heated, or shaken.
- Allow refrigerated product to come to room temperature before use and maintain at room temperature during administration.
- Do not mix with other IVIG products or other intravenous medications or fluids.
- No reconstitution is necessary.
- Do not dilute.
- If large doses are to be administered, several vials may be pooled using aseptic technique into sterile infusion bags.
- The recommended initial IV infusion rate is 0.5 mg/kg/minute for 15 minutes; if tolerated, increase gradually every 15 minutes to a maximum rate of 8 mg/kg/minute.
- For patients at risk of developing renal dysfunction or thromboembolic events, use the minimum practicable infusion rate. Consider discontinuation if renal function deteriorates.
- Storage: Vials are for single use only; use promptly and discard any unused portion immediately.[64039]
Bivigam 10%:
- Allow product to come to room temperature before use; do not use any solution that has been frozen, heated, or shaken.
- Do not mix Bivigam with other IVIG products or other intravenous medications or fluids. If large doses of Bivigam are to be administered, several vials may be pooled using aseptic technique into sterile infusion bags. Discard any unused product; each vial is single-use only.
- Initial IV infusion rate is 0.5 mg/kg/minute for 10 minutes. If no adverse reactions occur, the rate may be gradually increased every 20 minutes by 0.8 mg/kg/minute to a maximum of 6 mg/kg/minute.
- Monitor vital signs throughout the infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient.
- For patients judged to be at risk for renal dysfunction or thrombotic events, administer at the minimum infusion rate practicable, and consider discontinuation if renal function deteriorates.[42658]
Carimune NF:
- Reconstitute with sterile water for injection, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection according to the manufacturer's directions. To aid in dissolution, gently swirl the vial; avoid shaking and foaming. Dissolution may take up to 20 minutes. Bring to room temperature prior to administration. The solution should be clear. Do not use if particulate matter is present. Solutions are stable for 24 hours under refrigeration if reconstituted in a sterile laminar flow hood. Otherwise, use promptly and discard unused portions. Do not freeze.
- The mL/kg/minute rate depends on the solution concentration. Use a 3% immunoglobulin solution for the first infusion to previously untreated patients with either agammaglobulinemia or hypogammaglobulinemia; higher concentrations may be used for subsequent infusions if the initial infusion is well tolerated. A 6% solution is recommended for patients with ITP. Begin the initial IV infusion at 0.5 mg/kg/minute and, if tolerated, increase to 1 mg/kg/minute after 30 minutes. The amount infused may be increased stepwise to a maximum of 2 mg/kg/minute for patients at risk of renal dysfunction or thromboembolic events and a maximum of 3 mg/kg/minute for everyone else. For patients at risk of acute renal failure, use the minimum practicable concentration and infusion rate. If side effects occur, stop or slow the infusion until symptoms subside. Filtering is not necessary, but if used, a pore size of 15 microns or larger will be less likely to slow infusion, especially with higher solution concentrations; 0.2 micron antibacterial filters may be used.
- Administer by a separate infusion line. Do not mix with other medications or fluids.[42654]
Flebogamma 5% or 10%:
- No reconstitution necessary. Throw away unused product, as it does not contain preservatives. Do not use if cloudy, turbid, contains particles, or was previously frozen.
- Do not dilute with IV fluids. Compatibility with drugs or solutions has not been established; do not mix with other IVIG products.
- For 5% products, an in-line filter with a pore size of 15 to 20 microns is recommended. A 0.2 micron filter may be used, but the infusion rate may be slowed.[41552]
- Infuse through a dedicated line. Flebogamma 5% and 10% DIF can be administered sequentially into a primary intravenous line containing 0.9% Sodium Chloride Injection or flushed with 0.9% Sodium Chloride Injection without causing precipitation or turbidity.[48515]
- For 5% products, initially infuse at 0.01 mL/kg/minute for 30 minutes. If no adverse reactions occur, the rate may be gradually increased to a maximum of 0.1 mL/kg/minute. Dose titration to a maximum rate of less than 0.06 mL/kg/minute is recommended for patients at least 65 years of age or who are judged to be at risk of renal dysfunction. Infuse at the minimum infusion rate practicable for patients judged to be at risk for developing renal dysfunction or thromboembolic events.[41552]
- For 10% product, initially infuse at 0.01 mL/kg/minute (1 mg/kg/minute). If no adverse reactions occur, the rate may be gradually increased to a maximum of 0.08 mL/kg/minute (8 mg/kg/minute). In patients over 65 years of age, at risk of renal dysfunction, or at risk of thrombotic events, infuse at the minimum infusion rate practicable; consider product discontinuation if renal function deteriorates.[41553]
- Record lot numbers of the drug vials administered.
- Monitor vital signs throughout the infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient.
Gamimune-N:
- No reconstitution necessary. If dilution is desired, use 5% Dextrose Injection; Gamimune-N is incompatible with sodium chloride solutions.
- Initial IV infusion rate should be 0.01 to 0.02 mL/kg/minute for 30 minutes. If no adverse reactions occur, the rate may be gradually increased to a maximum of 0.08 mL/kg/minute.
Gammagard Liquid 10%:
- Do not use if solution has discoloration, cloudiness, or particulate matter; appearance can vary from colorless to light yellow. Do not shake.
- No reconstitution necessary. If dilution is desired, use 5% Dextrose Injection; do NOT use normal saline. Compatibility with other drugs or solutions has not been established; do not mix with other IVIG products.
- Prior to use, allow solution to reach ambient room temperature. Do not heat the product; the vials may take up to 60 minutes to reach room temperature. Promptly use contents of each single-use vial; no preservatives are present. Discard any partially used vials.
- Use of an in-line filter is optional. Infuse through a dedicated line.
- Monitor vital signs throughout the infusion. Adverse reactions such as headaches, flushing, and changes in pulse rate and blood pressure may be related to the infusion rate; slow or stop the infusion if they occur. If symptoms subside promptly, infusion may be resumed at a lower rate that does not cause symptom recurrence.
- For primary immunodeficiency, initiate infusion at 0.5 mL/kg/hour for 30 minutes. If no adverse reactions occur, rate may be gradually increased every 30 minutes to a maximum of 5 mL/kg/hour. For multifocal motor neuropathy, initiate infusion at 0.5 mL/kg/hour and titrate, if tolerated, to a maximum of 5.4 mL/kg/hour as the maintenance infusion rate. Dose titration to a maximum rate of less than 2 mL/kg/hour is recommended for patients more than 65 years or who are at risk of renal dysfunction or thrombotic complications. Consider discontinuation if renal function deteriorates.[42655]
Gammar-P IV:
- NOTE: Manufacturer's directions for reconstitution must be read thoroughly before attempting to reconstitute this product.
- Both the diluent and the lyophilized powder should be at room temperature before reconstitution. Total dissolution may take up to 20 minutes. The solution should be clear. Reconstituted injections contain approximately 50 mg of IgG per mL. The product contains no preservatives and infusion must be initiated within 3 hours of reconstitution. If not used within this time frame, do not administer and dispose of the solution.
- Administer by a separate infusion line. Do not mix with other medications or fluids; do not mix with other IVIG products.
- Use of an in-line filter is optional. A pore size of at least 15 microns may not slow the infusion rate.
- Begin the infusion rate at 0.01 mL/kg/minute and increase to 0.02 mL/kg/minute after 15 to 30 minutes. Because of the risk of acute renal failure, FDA recommends maximum 3 mg sucrose/kg/minute (3 mg immune globulin/kg/minute) infusion rate.
Gammagard S/D:
- NOTE: Manufacturer's directions for reconstitution must be read thoroughly before attempting to reconstitute this product.
- Both the diluent and the lyophilized powder should be at room temperature before reconstitution. The solution should be clear to slightly opalescent and colorless to pale yellow. Do not use if there are particles or if there is color to the solution.
- Use within 2 hours of reconstitution if prepared outside of a sterile laminar air flow hood. The reconstituted product may be stored at 2 to 8 degrees C for up to 24 hours if prepared in a sterile laminar air flow hood.
- Using the supplied administration set, administer by a separate infusion line. Use the antecubital vein, if possible, especially for the 10% solution. Do not mix with other medications or fluids; do not mix with other IVIG products.
- Initial infusion rate for the 5% solution should begin at 0.008 mL/kg/minute. If the patient does not experience any discomfort, rate may be gradually increased to a maximum of approximately 0.066 mL/kg/minute. If the highest rate is tolerated, the 10% solution may be used with an initial rate of 0.008 mL/kg/minute and a maximum rate of 0.133 mL/kg/minute.[42955]
Gammaplex 5% or 10%:
- The solution should be clear to slightly opalescent and colorless. Do not use if there are particles (cloudy) or if there is color to the solution. Do not shake or use if it has been frozen.
- Gammaplex should be at room temperature (up to 77 degrees F) at the time of administration. After piercing the cap, promptly administer; there are no preservatives, and it is for single use only. Dispose of partially used or unused product. If large doses are to be administered, several vials may be pooled using aseptic technique. Begin infusion within 2 hours after pooling.
- Infuse using an infusion set preferably fitted with an in-line 15 to 20 micron filter. Infuse using a separate infusion line. Do not mix with other IV medications (including normal saline) or other IVIG products. An infusion pump may be used to control the rate of administration.
- For patients judged to be at risk for renal dysfunction or thrombotic events, administer at the minimum infusion rate practicable, and discontinue if renal function deteriorates.
- For 5% product, initially infuse at 0.01 mL/kg/minute (0.5 mg/kg/minute) for 15 minutes. If well tolerated, the rate may be gradually increased to a maximum of 0.08 mL/kg/minute (4 mg/kg/minute).
- For 10% product, initially infuse at 0.005 mL/kg/minute (0.5 mg/kg/minute) for 15 minutes. If well tolerated, the rate may be gradually increased to a maximum of 0.08 mL/kg/minute (8 mg/kg/minute).
- Monitor vital signs throughout the infusion. If side effects occur, slow or stop the infusion. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient. The observation time of patients after administration may vary. If the patient has not received an IgG product, is switched from an alternative IVIG product, or has had a long interval since the previous infusion, prolong the observation time for adverse reactions after Gammaplex infusion.[42661] [61745]
Gamunex-C or Gammaked:
- Gamunex-C or Gammaked should be at room temperature (up to 77 degrees F) at the time of administration. Do not use if turbid, discolored, or previously frozen. Also, do not use if the solution contains particulates. The solution should be clear and colorless to a pale yellow. Do not shake. No reconstitution is necessary. If dilution is required, dilute with 5% Dextrose Injection; do not dilute with normal saline.
- Only 18 gauge needles should be used to penetrate the stopper for dispensing the product from the 10 mL vials; 16 gauge needles should only be used with the 25 mL vial sizes and larger. Needles or dispensing pins should only be inserted within the stopper area delineated by the raised ring. After piercing the cap, promptly administer; there are no preservatives, and it is for single use only. Dispose of partially used or unused product. Contents of the vials may be pooled under aseptic conditions into sterile infusion bags and infused within 8 hours after pooling.
- Infuse using a separate infusion line. Do not mix with other IV medications, fluids, or other IVIG products. The infusion line may be flushed with 5% Dextrose Injection or 0.9% Sodium Chloride Injection. Recommended initial infusion rate is 0.01 mL/kg/minute (1 mg/kg/minute) for ITP or primary immunodeficiency, and 2 mg/kg/minute for CIDP. If well-tolerated, the rate may be gradually increased to a maximum of 0.08 mL/kg/minute (8 mg/kg/minute). If side effects occur, rate may be reduced, or infusion interrupted until symptoms subside; resume at a rate that is comfortable for the patient. For patients judged to be at risk for renal dysfunction or thrombotic events, administer at the minimum infusion rate practicable, and discontinue if renal function deteriorates.[51240] [54820]
Iveegam EN:
- Reconstitute with Sterile Water for Injection according to the manufacturer's directions. To aid in dissolution, agitate and rotate the vial; avoid vigorous shaking. Reconstituted injections contain approximately 50 mg of IgG per mL. The solution should be clear. Do not use if there are particles or if there is color to the solution.
- Infuse at a rate of 1 to 2 mL/minute through a separate infusion line. Do not mix with other IVIG products.
Octagam 5% or 10%:
- No reconstitution necessary. Do not use if cloudy, turbid, contains particles, or was previously frozen.
- Bottles may be pooled under aseptic conditions into sterile infusion bags and administered within 8 hours after pooling.
- Throw away any unused product, as it does not contain preservatives. Each vial is single-use only.
- If an in-line filter is used, the pore size should be 0.2 to 200 microns. Infuse through a dedicated line. Compatibility with other drugs or solutions has not been established; do not mix with other IVIG products.[30276] [57655]
- For the 5% product, the initial infusion rate should be 0.01 mL/kg/minute for 30 minutes. If no adverse reactions occur, rate may be increased to 0.02 mL/kg/minute for the next 30 minutes. If tolerated, infusion may be further increased to 0.04 mL/kg/minute for the next 30 minutes. Do not exceed a maximum of 0.07 mL/kg/minute. For geriatric patients and patients at risk for renal dysfunction or thrombosis, infuse at the minimum infusion rate practicable.[30276]
- For the 10% product, the initial infusion rate should be 0.01 mL/kg/minute for 30 minutes. If no adverse reactions occur, rate may be increased to 0.02 mL/kg/minute for the next 30 minutes. If tolerated, infusion may be further increased to 0.04 mL/kg/minute for the next 30 minutes. If tolerated, the infusion may be further increased to 0.08 mL/kg/minute for the next 30 minutes. Do not exceed a maximum of 0.12 mL/kg/minute. For geriatric patients and patients at risk for renal dysfunction or thrombosis, infuse at the minimum infusion rate practicable, not to exceed 0.03 mL/kg/minute.[57655]
- Monitor vital signs throughout the infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate. Discontinue if renal function deteriorates.[30276] [57655]
Panglobulin NF:
- Reconstitute with Sterile Water for Injection, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection according to the manufacturer's directions. To aid in dissolution, gently swirl the vial; avoid shaking and foaming. Dissolution may take up to 20 minutes. Reconstituted injections should be at room temperature prior to administration. Solutions are stable for 24 hours under refrigeration if reconstituted in a sterile laminar flow hood; otherwise, use promptly and discard unused portions.
- The initial infusion rate should begin at 0.5 to 1 mL/minute and increased to 1.5 to 2.5 mL/minute after 15 to 30 minutes. Each rate increase should be done at 15 to 30 minute intervals. Because of the risk of acute renal failure, the FDA recommends a maximum infusion rate of 3 mg sucrose/kg/minute (2 mg immune globulin/kg/minute). Filtering is not necessary; however, if used, filter pore size should be 15 micromolar or larger to avoid slowing of the infusion; 0.2 micromolar antibacterial filters may be used.
- NOTE: A 3% immunoglobulin solution must be used for the first infusion to previously untreated patients with either agammaglobulinemia or hypogammaglobulinemia.
Panzyga:
- No reconstitution necessary. Do not use if cloudy, turbid, contains particles, or was previously frozen.
- Bottles may be pooled under aseptic conditions into sterile infusion bags and administered within 8 hours after pooling.
- Throw away any unused product, as it does not contain preservatives. Each vial is single-use only.
- If an in-line filter is used, the pore size should be 0.2 to 200 microns. Infuse through a dedicated line. Compatibility with other drugs or solutions has not been established; do not mix with other IVIG products.
- Recommended initial IV infusion rate for primary immunodeficiency is 1 mg/kg/minute (0.01 mL/kg/minute) for 30 minutes. If infusion is well tolerated, gradually increase every 15 to 30 minutes, as tolerated, to the maximum infusion rate of 14 mg/kg/minute (0.14 mL/kg/minute). Recommended initial IV infusion rate for chronic ITP is 1 mg/kg/minute (0.01 mL/kg/minute) for 30 minutes. If infusion is well tolerated, gradually increase every 15 to 30 minutes, as tolerated, to the maximum infusion rate of 8 mg/kg/minute (0.08 mL/kg/minute). Recommended initial IV infusion rate for CIDP is 1 mg/kg/minute (0.01 mL/kg/minute) for 30 minutes. If infusion is well tolerated, gradually increase every 15 to 30 minutes, as tolerated, to the maximum infusion rate of 12 mg/kg/minute (0.12 mL/mg/minute).
- Monitor vital signs during the infusion. If side effects occur, slow or stop the infusion until the symptoms subside. Restart the infusion at a lower rate that is comfortable for the patient.
- Titration to a maximum rate of less than 3.3 mg/kg/minute (0.033 mL/kg/minute) is recommended for patients who are at risk of renal dysfunction or thrombotic complications. Consider discontinuation if renal function deteriorates.
- After administration, line may be flushed with 5% Dextrose Injection or 0.9% Sodium Chloride Injection.[63463]
Polygam S/D:
- Total dissolution may take up to 20 minutes.
- Reconstitute with supplied diluent according to the manufacturer's directions. To aid in dissolution, agitate and rotate the vial; avoid vigorous shaking. The solution should be clear to slightly opalescent and colorless to pale yellow. Do not use if there are particles or if there is color to the solution.
- Use within 2 hours of reconstitution if prepared outside of a sterile laminar air flow hood. The reconstituted product may be stored at 2 to 8 degrees C for up to 24 hours if prepared in a sterile laminar air flow hood.
- Using the supplied administration set, administer in a separate infusion line. Use the antecubital vein, if possible, especially for the 10% solution. Do not mix with other medications or fluids; do not mix with other IVIG products.
- Initial IV infusion rate should begin at 0.008 mL/kg/minute. If the patient does not experience any discomfort, the rate may be gradually increased up to a maximum of approximately 0.066 mL/kg/minute for the 5% solution and 0.13 mL/kg/minute for the 10% solution. Maximum recommended rate for the 10% solution for a patient at risk for renal dysfunction is 0.03 mL/kg/minute.
Privigen:
- The solution should be clear to slightly opalescent and colorless to pale yellow. Do not use if there are particles (cloudy) or if there is color to the solution. Do not shake or use if it has been frozen.
- Do not mix with other IVIG products or other IV medications. If necessary, Privigen can be diluted with 5% Dextrose Injection. If large doses are to be administered, several vials may be pooled using aseptic technique. Promptly use contents of each single-use vial; no preservatives are present.
- Administer via a separate infusion line, which may be flushed with 5% Dextrose Injection or 0.9% Sodium Chloride Injection. An infusion pump may be used to control the administration rate. Recommended initial IV infusion rate for primary immunodeficiency and CIDP is 0.5 mg/kg/minute. If infusion is well tolerated, gradually increase to 8 mg/kg/minute (0.08 mL/kg/minute). Recommended initial IV infusion rate for chronic ITP is 0.5 mg/kg/minute (0.005 mL/kg/minute). If well tolerated, gradually increase to 4 mg/kg/minute (0.04 mL/kg/minute). Infuse at the minimum infusion rate practicable for patients at risk of renal dysfunction, thrombotic events, or volume overload. Monitor vital signs during the infusion. If side effects occur, slow or stop the infusion until the symptoms subside. Restart the infusion at a lower rate that is comfortable for the patient.[42659]
Subcutaneous Administration
Gammagard Liquid 10%:
- Gammagard Liquid may be given by subcutaneous infusion using a subcutaneous infusion pump.
- Cleanse the injection site with an alcohol wipe or other appropriate antiseptic.
- Injections are usually made into the abdomen, thighs, upper arms, and/or lower back. Rotate the injection site with each weekly administration. New sites should be at least 1 inch from a previous site. Never infuse into areas where the skin is tender, bruised, red, or hard. Avoid infusing into scars or stretch marks.
- If using multiple simultaneous injection sites, use Y-site connection tubing and secure to the administration tubing. Injection sites should be at least two inches apart. Do not use more than 8 sites simultaneously. For the first Gammagard Liquid 10% infusion, do not exceed a volume of 20 mL per injection site for patients weighing less than 40 kg or 30 mL per injection site for patients weighing 40 kg or more.
- Grasp the skin between two fingers and insert the needle into the subcutaneous tissue making sure not to inject into a blood vessel. Attach a sterile syringe to the end of the infusion tubing, and pull the plunger back gently. If you see blood in the tubing, take the needle out of the injection site, and throw away the tubing and needle. Try a different site with new infusion tubing and a new needle. Follow the manufacturer's instructions for filling the pump reservoir, preparing the pump, and for filling the administration tubing and Y-site connection tubing, if needed. Prime the administration tubing to ensure that no air is left in the tubing or needle.
- Follow the pump manufacturer's instructions to infuse the dose. For the first Gammagard Liquid 10% infusion, the maximum recommended infusion rate is 15 mL/hour per site for patients weighing less than 40 kg and 20 mL/hour per site for patients weighing 40 kg or more. The infusion rate may be increased to a maximum of 20 mL/hour per site for patients weighing less than 40 kg and 30 mL/hour per site for patients weighing 40 kg or more. Do NOT exceed a total of 160 mL/hour for all sites combined at any time for patients weighing less than 40 kg and 240 mL/hour for all sites combined at any time for patients weighing 40 kg or more.[42655]
Gammaked:
- Gammaked may be administered subcutaneously for the treatment of primary immunodeficiency. Gammaked should be at room temperature (up to 77 degrees F) at the time of administration. Do not use if turbid, discolored, or previously frozen. Also, do not use if solution contains particulates. The solution should be clear and colorless to a pale yellow. Do not shake.
- Using aseptic technique, inject an amount of air equivalent to the amount of product to be withdrawn. Multiple vials may be required to achieve the desired dose. After piercing the cap, promptly administer; there are no preservatives, and it is for single use only. Dispose of partially used or unused product.
- If using multiple simultaneous injection sites, use Y-site connection tubing and secure to the administration tubing. Injection sites should be at least two inches apart. Do not use more than 8 sites simultaneously.
- Grasp the skin between two fingers and insert the needle into the subcutaneous tissue making sure not to inject into a blood vessel. Attach a sterile syringe to the end of the infusion tubing, and pull the plunger back gently. If you see blood in the tubing, take the needle out of the injection site, and throw away the tubing and needle. Try a different site with new infusion tubing and a new needle. Follow the manufacturer's instructions for filling the pump reservoir, preparing the pump, and for filling the administration tubing and Y-site connection tubing, if needed. Prime the administration tubing to ensure that no air is left in the tubing or needle.
- Follow the pump manufacturer's instructions to infuse the dose. Infuse at a rate of 20 mL/hour per site.[54820]
Gamunex-C:
- Gamunex-C may be administered by subcutaneous infusion for the treatment of primary immunodeficiency.
- Gamunex-C is a clear, colorless to pale yellow solution; do not use if turbid. Do not use any solution that has been frozen or shaken.
- Allow refrigerated product to come to room temperature before use.
- No reconstitution necessary.
- Using aseptic technique, inject an amount of air equivalent to the amount of product to be withdrawn. Multiple vials may be required to achieve the desired dose.
- Follow the pump manufacturer's instructions to fill the pump reservoir and preparing the pump and tubing. Prime the administration tubing to ensure no air is left in tubing or needles.
- If using multiple simultaneous injection sites, use Y-site connection tubing and secure to the administration tubing. Injection sites should be at least 2 inches apart. In adult patients, do not use more than 8 sites simultaneously; most patients use 4 sites. In pediatric patients, do not use more than 6 sites simultaneously.
- Grasp the skin between 2 fingers and insert the needle into the subcutaneous tissue making sure not to inject into a blood vessel. Attach a sterile syringe to the end of the infusion tubing, and pull the plunger back gently. If you see blood in the tubing, take the needle out of the injection site, and throw away the tubing and needle. Try a different site with new infusion tubing and a new needle.
- For adult patients: Infuse at a rate of 20 mL/hour per infusion site.
- For pediatric patients weighing 25 kg or more: Initially, 15 mL/hour per infusion site; may increase up to 20 mL/hour/site.
- For pediatric patients weighing less than 25 kg: Infuse at a rate of 10 mL/hour per infusion site.[51240]
Clinical Pharmaceutics Information
From Trissel's 2‚Ñ¢ Clinical Pharmaceutics DatabaseImmune globulin (intravenous)
pH Range
Range: pH 4 to 7.2 See Product pH under Other Information.Sodium Content
Carimune NF- Sodium content depends on the diluent used. Gamimune N- Trace amounts of sodium only. Gammagard S/D- Contains sodium chloride 0.85%. Gammar P IV- Contains sodium chloride 0.5%. Gamunex- Contains only trace amounts of sodium. Iveegam EN- Contains sodium 3 mg/mL. Panglobulin- Sodium content depends on the diluent used. Polygam S/D- Contains sodium chloride 0.85%. Privigen- Trace amounts of sodium. Venoglobulin S- 5% is less than 0.0013 mEq/mL; 10% is less than 0.001 mEq/mL.Osmolality/Osmolarity
Carimune NF- Depends on the diluent and concentration. See Below. Cuvitru 20% - 280 to 292 mOsm/kg. Flebogamma 5%- 240 to 380 mOsm/L. Gamimune N- 10% is 274 mOsm/kg. Gammagard S/D- 5% is 636 mOsm/L; 10% is 1250 mOsm/L. Gammar P IV- 5% is 309 mOsm/L; 10% is 600 mOsm/L. Gamunex- 10% is 258 mOsm/kg. Iveegam EN- Over 240 mOsm/L. Octagam- 5% is 310 to 380 mOsm/kg. Panglobulin- Depends on the diluent and concentration. See Below. Polygam S/D- 5% is 636 mOsm/L; 10% is 1250 mOsm/L. Privigen- 10% is 320 mOsm/kg. Venoglobulin S- 5% is 300 mOsm/L; 10% is 330 mOsm/L. The osmolality of Carimune NF and Panglobulin depends on the diluent used in reconstitution and the resulting concentration. When reconstituted with the following diluents to a protein concentration ranging from 30 to 120 mg/mL (3 to 12%) the osmolalities are: Dextrose 5%- 444 (at 3%) to 1020 mOsm/kg (at 12%). Sodium chloride 0.9%- 498 (at 3%) to 1074 mOsm/kg (at 12%). Sterile water for injection- 192 (at 3%) to 768 mOsm/kg (at 12%).Stability
Immune globulin injections in intact containers stored as directed by the manufacturer is stable until the labeled expiration date. Parti et al. reported that reconstituted Gammagard S/D and Polygam immune globulins at concentrations of 5 and 10% were stable in the original glass vials and in polyvinyl chloride (PVC) plastic bags for 48 hours under refrigeration and for 12 hours at room temperature. The products remained visibly clear and protein content and antibody activity measurements all indicated the products remained stable and active throughout the study periods. Bing et al. reported that Gammagard SD repackaged in ethylene vinyl acetate (EVA) bags and polypropylene (IntraVia) bags was stable for 3 days at room temperature and 14 days under refrigeration. Wu and Lee reported that immune globulin 10% (Gammagard Liquid, Baxter) in intact containers within the labeled expiration date was stable when subjected to 12 months of room temperature storage at 25 degree C and 60% relative humidity after (1) refrigerated storage at 5 degree C for 15 months, and (2) 40 degree C and 75% relative humidity for 2 weeks followed by refrigerated storage at 5 degree C for 28 weeks. Infusion Solutions: The manufacturers of the various immune globulin products indicate the following compatibility characteristics with diluents and infusion solutions: Carimune NF- Reconstitute with dextrose 5%, sodium chloride 0.9%, and sterile water for injection. Flebogamma- Dilution with infusion solutions is not recommended. Gamimune N- Dextrose 5% should be used for dilution. Incompatible in sodium chloride 0.9%. Gammagard S/D- Use only the accompanying sterile water for injection for reconstitution. Use no other solutions. Gammar P- Use only sterile water for injection for reconstitution. Gammar P may be administered before or after dextrose 5% and also sodium chloride 0.9%. Gamunex- Dextrose 5% should be used for dilution. Incompatible in sodium chloride 0.9%. Iveegam EN- Reconstitute with the accompanying sterile water for injection. May be diluted with dextrose 5% or sodium chloride 0.9%. Panglobulin- Reconstitute with dextrose 5%, sodium chloride 0.9%, or sterile water for injection. Privigen- May be diluted with dextrose 5%. Venoglobulin S- Do not mix infusion solutions with Venoglobulin S. It may be administered before or after or flushed with dextrose 5% or sodium chloride 0.9%.Freezing
Immune globulin liquid products should be protected from freezing. If inadvertently frozen, they should be discarded.Filtration
Manufacturers' recommendations: Carimune NF- No filter required. Flebogamma- Filters with a porosity of 15 to 20 microns may be used, but 0.2-micron filters may slow the infusion rate. Gamimune N- No filter required. Gammagard S/D- Use of a filter is required. Gammar P IV- No filter required. Gamunex- No filter required. Iveegam EN- Use of a 15-micron filter is required. Panglobulin- No filter required. Polygam S/D- Use of a filter is required. Privigen- No filter required. Venoglobulin S- No filter required. Study 1: Huang et al. evaluated the impact of extractable and leachable materials from three kinds of sterilizing filters (polyvinylidene fluoride, polyethersulfone, and mixed cellulose ester) on the stability of a model monoclonal antibody formulation of IgG2. The extractable and leachable materials from the filters were found to be generally destabilizing.Sorption Leaching
Parti et al., and Bing et al. reported that immune globulin in glass containers, polyvinyl chloride (PVC) bags, ethylene vinyl acetate (EVA) bags, and polypropylene (IntraVia) bags exhibited no loss of activity due to sorption. Parti et al. also evaluated the leaching of diethylhexyl phthalate (DEHP) plasticizer from PVC bags by immune globulin stored in PVC containers for 48 hours under refrigeration and 12 hours at room temperature. Only small amounts of DEHP were leached ranging from undetectable qualities up to a maximum of 86 nanograms/mL.Other Information
Other Drugs: All of the manufacturers of immune globulin recommend not admixing other drugs with any of the immune globulin products. Other Immune Globulins: Mixing differing brands of immune globulin may result in aggregate formation. Product pH: Various immune globulin products have pH ranges as noted below. Carimune NF, Panglobulin - pH 6.4 to 6.8; Cuvitru - pH 4.6 to 5.1; Flebogamma - pH 5 to 6; Gamimune N and Gamunex - pH 4 to 4.5; Gammagard S/D, Gammar-P IV, Iveegam EN, Polygam S/D - pH 6.4 to 7.2; Octagam - pH 5.1 to 6; Privigen - pH 4.6 to 5; and Venoglobulin S - pH 5.2 to 5.8.References
Adverse Reactions
Mild
- abdominal pain
- agitation
- alopecia
- anorexia
- anxiety
- arthralgia
- asthenia
- back pain
- chills
- cough
- dental pain
- diaphoresis
- diarrhea
- dizziness
- drowsiness
- dyspepsia
- ecchymosis
- epistaxis
- fatigue
- fever
- flushing
- gastroesophageal reflux
- headache
- hyperhidrosis
- hypoesthesia
- infection
- influenza
- injection site reaction
- insomnia
- lethargy
- maculopapular rash
- malaise
- musculoskeletal pain
- myalgia
- nasal congestion
- nausea
- ocular discharge
- ocular irritation
- ocular pain
- otalgia
- pallor
- paresthesias
- petechiae
- pharyngitis
- pruritus
- purpura
- rash
- rhinitis
- rhinorrhea
- sinusitis
- throat irritation
- tremor
- urticaria
- vomiting
- weakness
Moderate
- anemia
- angina
- bleeding
- bullous rash
- candidiasis
- chest pain (unspecified)
- confusion
- conjunctivitis
- cystitis
- depression
- dysarthria
- dyspnea
- dysuria
- edema
- elevated hepatic enzymes
- erythema
- hematuria
- hepatitis
- hot flashes
- hyperbilirubinemia
- hypertension
- hypoglycemia
- hyponatremia
- hypotension
- hypoxia
- infusion-related reactions
- jaundice
- leukopenia
- lymphadenopathy
- migraine
- palpitations
- paresis
- phlebitis
- photophobia
- sinus tachycardia
- synovitis
- thrombocytopenia
- wheezing
Severe
- acute respiratory distress syndrome (ARDS)
- anaphylactic shock
- anaphylactoid reactions
- angioedema
- anuria
- apnea
- aseptic meningitis
- azotemia
- bradycardia
- bronchospasm
- cardiac arrest
- coma
- cyanosis
- disseminated intravascular coagulation (DIC)
- eczema vaccinatum
- enterocolitis
- erythema multiforme
- hemolytic anemia
- myocardial infarction
- oliguria
- osmotic nephrosis
- pancytopenia
- pulmonary edema
- pulmonary embolism
- renal failure (unspecified)
- renal tubular necrosis
- retinal thrombosis
- seizures
- Stevens-Johnson syndrome
- stroke
- thromboembolism
- thrombosis
- visual impairment
0
- hemolysis
Transfusion-related acute lung injury (TRALI) is a life-threatening and potentially fatal complication of blood product administration; it has been reported rarely after IVIG administration. TRALI is characterized by severe respiratory distress, hypoxemia (hypoxia), fever, normal left ventricular function, and severe non-cardiogenic pulmonary edema. Symptoms typically begin 1 to 2 hours after administration and manifest fully within 1 to 6 hours. The clinical presentation may be subtle or significant. Radiographs show bilateral pulmonary infiltrates without evidence of cardiac compromise or fluid overload. Respiratory support may be necessary. Diuretics are not effective in TRALI as the cause involves microvascular injury, rather than fluid overload. The etiology of TRALI may be attributable to the presence of anti-HLA antibodies and/or anti-granulocyte antibodies in the plasma of multiparous females or donors who have received previous transfusions who serve as donors for the plasma-derived product. Recipients of IVIG should be monitored for pulmonary adverse events. If TRALI is suspected, both the product and the patient need to be tested for the presence of anti-neutrophil and anti-HLA antibodies.[26918] [30276] [39573] [41552] [41553] [46250] [42654] [42655] [42659] [42661] [42955] [51240] [53383] [53384] [53385] [57655]
Immune globulin is derived from human plasma. Based on effective donor screening and product manufacturing processes, IVIG carries an extremely remote risk of transmission of viral infection or disease. A theoretical risk for transmission of Creutzfeldt-Jakob disease also is considered to be extremely remote. Before prescribing IVIG, discuss the risks and benefits of its use with the patient. Infectious events reported during IVIG therapy include bronchitis (6% to 30%), upper respiratory tract infection (6% to 33%), fungal infection (6.5% to 9%), viral infection (6.3%), otitis media (7%), urinary tract infection (6.5% to 11%), vaginal candidiasis (9%), and flu-like syndrome (5% to 6%).[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [63463]
Respiratory adverse events including cough/increased cough (6% to 54%), dyspnea (5% to 11%; 8% of pediatric patients), epistaxis (11% to 23%), pharyngitis (10% to 41%), nasopharyngitis (22%), rhinitis (5% to 51%), asthma (15% to 29%), pharyngolaryngeal pain (6%), nasal congestion (6% to 52%), sinusitis (2% to 50%), sore throat, rhinorrhea (6.5% to 17%), sinus congestion, post-nasal drip, sinus pain, respiratory tract congestion (7%), upper respiratory tract infection (8% to 22%), bronchitis (5% to 20%), oropharyngeal pain, cyanosis, throat irritation (5.5% to 7%), acute otitis media (8% of pediatric patients), tonsillar disorder (8% of pediatric patients), painful respiration, hypoxemia, apnea, hyperventilation, throat tightness, acute respiratory distress syndrome (ARDS), and influenza-like illness (7.1%) have been reported with the use of immune globulin. Influenza (less than 1%) has also been reported with subcutaneous use in pediatric patients. Wheezing (3% to 14%), dyspnea, and bronchospasm (14% to 29%) may be associated with immune globulin infusion; slowing or stopping the infusion, as well as premedication with acetaminophen and antihistamines may help alleviate these reactions. Respiratory failure and transfusion-related acute lung injury have been reported with postmarketing use of IVIG.[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [57655] [63463] [64039]
Nausea (5% to 66.7%), vomiting (6% to 41.7%), and diarrhea (6% to 28%) are commonly reported adverse effects associated with immune globulin. Necrotizing enterocolitis (NEC) has been associated with high-dose immune globulin used for isoimmune hemolytic disease in preterm and term neonates. Other gastrointestinal adverse effects reported include abdominal pain or cramps (15% or less), dyspepsia (6% to 9%), stomach discomfort (6%), gastroenteritis (9% to 22%), gastroesophageal reflux (7%), and toothache (dental pain). Of note, vomiting was reported more frequently in pediatric patients vs. adult patients during clinical trials of immune globulin for primary immunodeficiency. Nausea, vomiting, abdominal pain/cramping, and loss of appetite (anorexia) may be associated with immune globulin infusion; slowing or stopping the infusion as well as premedication with acetaminophen and antihistamines may help alleviate these symptoms.[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [53417] [57655] [64039]
Renal dysfunction, including oliguria, anuria, acute renal failure (unspecified), osmotic nephrosis (osmotic nephropathy), acute renal tubular necrosis, proximal tubular nephropathy, and death have been reported in patients receiving IVIG. Increases in BUN (azotemia) and serum creatinine have been observed as soon as 1 to 2 days after infusion of IVIG. Progression to oliguria and anuria requiring dialysis has been observed; although, some patients have spontaneously recovered following cessation of treatment. Renal histopathologic examination suggested an osmotic injury to the proximal renal tubules (acute renal tubular necrosis, proximal tubular nephropathy, vacuolar degeneration, and osmotic nephrosis). Renal dysfunction is more common with the use of IVIG products containing sucrose as a stabilizer. Use IVIG with caution in patients at risk for developing renal dysfunction, including those with any pre-existing degree of renal insufficiency or renal disease, sepsis, paraproteinemia, diabetes mellitus, hypovolemia, dehydration, obesity, age more than 65 years, or concomitant use of nephrotoxic agents. Especially in such patients, use the minimum recommended dose of IVIG administered at the minimum concentration available and the minimum practicable rate. Ensure patients are not volume depleted prior to IVIG administration. Monitor renal function, including BUN, serum creatinine, and urine output at baseline and appropriate intervals thereafter. If renal function deteriorates, consider IVIG therapy discontinuation. Dysuria, cystitis, or urinary tract infection was reported in 5% of patients who received Gammaplex. There are postmarketing reports of renal pain with IVIG therapy.[30276] [39573] [41552] [41553] [46250] [42654] [42655] [42659] [42661] [42955] [51240] [57655]
Nervous system or psychiatric adverse events have been reported during the use of immune globulin. Headache (8% to 91.7%), dizziness (4.2% to 13%), and anxiety may be associated with the immune globulin infusion; slowing or stopping the infusion, as well as premedication with acetaminophen and antihistamines may help alleviate these symptoms. Other adverse events reported with immune globulin use include insomnia (6% to 9%), agitation, migraine (6.3% to 7%), restlessness, tremor, hypoesthesia, paresthesias, coma, loss of consciousness, confusion, nervousness, depression (6.3%), dysarthria (speech disorder), lethargy, and seizures.[30276] [41552] [41553] [46250] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [57655] [61745]
Aseptic meningitis syndrome (AMS) may rarely occur after IVIG therapy. Signs and symptoms appear within several hours to 2 days and include severe head pain, nuchal rigidity, drowsiness, pyrexia, photophobia, painful eye movements, and emesis. AMS may be more frequent after high-dose (more than 1,000 to 2,000 mg/kg/dose) or rapid-infusion IVIG treatment. Patients with a history of migraine may be at higher risk for this complication of IVIG. Patients presenting with signs and symptoms should undergo a thorough neurological evaluation, including cerebrospinal fluid (CSF) studies; the CSF is often positive for pleocytosis and elevated protein levels, with negative culture results. Discontinuation of IVIG treatment may result in remission of AMS within several days without sequelae.[23788] [30276] [41552] [41553] [46250] [42654] [42655] [42659] [42661] [42955] [57655]
Thromboembolism, cerebrovascular accident (stroke), transient ischemic attack, thrombophlebitis, deep vein thrombosis, vena cava thrombosis, arterial thrombosis, retinal thrombosis, and pulmonary embolism have all been associated with IVIG. Signs and symptoms include numbness or weakness (paresis) on 1 side of the body, pain, swelling, discoloration, and/or warmth of the arms or legs, and unexplained shortness of breath. Additional adverse events associated with thrombosis include chest pain (unspecified) (5% to 15%), pallor, decreased heart rate, vascular collapse, myocardial infarction, and cardiac arrest. These can occur in patients without any known risk factors; however, patients most at risk include age more than 65 years, multiple cardiovascular risk factors, impaired cardiac output, prolonged immobilization, diabetes mellitus, obesity, coagulation disorders, a history of vascular disease, atherosclerosis, previous thromboembolic event, and/or known or suspected hyperviscosity. Thrombosis was reported in an adult patient who received Gammaplex who also had a diagnosis of antiphospholipid syndrome. There is an increased risk of thromboembolic events in patients with dermatomyositis; do not exceed an IVIG infusion rate of 0.4 mL/kg/minute and monitor patients closely. Ensure that patients are not volume depleted prior to the initiation of IVIG. For patients judged to be at risk for developing thrombotic events, use the minimum recommended dose of IVIG administered at the minimum practicable rate. Monitor all patients receiving IVIG during and after each infusion and encourage patients to report any signs and symptoms of thrombosis.[30276] [41552] [41553] [42654] [42655] [42659] [42955] [46250] [42661] [51240] [57655]
Ecchymosis (8.7% to 40%), purpura (40%), bleeding/hemorrhage (29%), petechiae (21%), and thrombocytopenia (15%) have been reported during clinical trials of IVIG for the treatment of immune thrombocytopenic purpura (ITP). Other coagulation/lymphatic effects reported with IVIG use include anemia (6% to 11%), decreased hematocrit (5%), decreased hemoglobin, pancytopenia, leukopenia (7.1%), autoimmune pure red cell aplasia exacerbation, hemoglobinuria, hematuria, chromaturia, and lymphadenopathy (7%).[30276] [41552] [41553] [46250] [42654] [42655] [42659] [42661] [42955] [51240] [57655]
Antibodies present in IVIG may act as hemolysins and induce immunoglobulin adherence to red blood cells, causing a positive direct antiglobin test (DAT, Coombs' test), and rarely, hemolysis. Acute hemolysis consistent with intravascular hemolysis, severe hemolysis-related renal dysfunction/failure, and disseminated intravascular coagulation (DIC) have been reported with IVIG therapy. Hemolysis was reported in 7.1% of immune globulin-treated patients with chronic inflammatory demyelinating polyneuropathy (CIDP) during a clinical trial. In addition, delayed hemolytic anemia can develop after IVIG therapy due to enhanced red blood cell sequestration; cases have generally been reversible. Hemolytic events not associated with a positive DAT have also been observed in clinical trials. Risk factors related to the development of hemolysis include high doses (2,000 mg/kg or more) as a single infusion or divided over several days, and non-O blood type. An underlying inflammatory state reflected by elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) may also contribute to the risk of hemolysis, however the role is uncertain. Monitor patients receiving immune globulin for hemolysis and hemolytic anemia. In high risk patients, consider appropriate lab testing, including hemoglobin and hematocrit prior to therapy and for 36 to 96 hours after infusion. If signs and symptoms of hemolysis are present after the infusion, perform confirmatory lab testing. If a transfusion is indicated, perform adequate cross-matching to avoid exacerbating ongoing hemolysis.[30276] [41552] [41553] [42654] [42655] [42659] [42955] [46250] [51240] [57655]
Anaphylactoid reactions, including angioedema and anaphylactic shock, have been reported with IVIG use. Patients who are IgA deficient and have known antibodies to IgA may be at greater risk for developing severe hypersensitivity reactions. Epinephrine should be immediately available during IVIG infusions. If a hypersensitivity reaction occurs, immediately discontinue the infusion.[30276] [46250] [42654] [42655] [42659] [42661] [42955] [51240] [57655]
Erythema (6.3% to 9%) may occur at the site of intravenous or subcutaneous infusion. Some cutaneous reactions, such as urticaria or hives (5% to 6%), pruritus (6% to 8%), rash (unspecified) (6% to 10%), and dermatitis (9%) may be associated with IVIG infusion; slowing or stopping the infusion, as well as premedication with acetaminophen and antihistamines may help alleviate these symptoms. Stevens-Johnson syndrome, epidermolysis, bullous dermatitis/bullous rash, allergic dermatitis (6.3%), contact thermal burn or abrasion (7%), eczema vaccinatum (5% to 7%), maculopapular rash, alopecia, skin exfoliation, and erythema multiforme have been reported with the use of IVIG.[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [57655]
Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IVIG therapy. The hyponatremia is likely to be a pseudohyponatremia as demonstrated by a decreased calculated serum osmolality or elevated osmolar gap. Distinguishing between true hyponatremia and pseudohyponatremia is important since treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, further increased serum viscosity, and a disposition to thromboembolic events.[30276] [42654] [42655] [42659] [42955] [46250] [51240] [57655]
Musculoskeletal pain (5% to 25%), arthralgia (9.4% or less), back pain (4.3% to 16.7%), neck pain (6%), extremity pain, fibromyalgia, myalgia (5% to 6%), and muscle strain have been reported with immune globulin use. Accidental injury (13%) has also been reported. Musculoskeletal adverse events such as arthralgia, myalgia, back pain/backache, muscle cramps, and flu-like symptoms may be associated with IVIG infusion reaction; slowing or stopping the infusion, as well as premedication with acetaminophen and antihistamines may help alleviate these symptoms. Synovitis/tenosynovitis, joint swelling/effusion (6% to 11%), bursitis, chondromalacia patellae, epicondylitis, joint sprain, and trigger finger have been reported during clinical trials of IVIG. Muscle spasm, muscle weakness, and musculoskeletal stiffness have been reported with postmarketing use of IVIG.[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [57655]
Otalgia (earache/pain 18%) has been reported in patients receiving IVIG. Ocular adverse events reported with IVIG include conjunctivitis (9% to 13%), ocular discharge (7%), ocular irritation (6.5% to 7%), ocular pain, and visual impairment/disturbance.[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [57655]
Elevated hepatic enzymes and hepatic dysfunction have been reported with the use of IVIG. Elevations in AST (13%), ALT (18%), alkaline phosphatase (3%), and lactate dehydrogenase (5%) have occurred. Elevations in AST and ALT are generally mild (less than 3 times the upper limit of normal), transient, and not associated with symptoms of liver disease. Hyperbilirubinemia (5.3%) and increases in unconjugated bilirubin (8.8% to 10.5%), conjugated bilirubin (8.8%), and total bilirubin (7%) were all noted during clinical trials. Jaundice and non-infectious hepatitis have been reported postmarketing.[30276] [42654] [42659] [42955] [46250] [51240] [57655]
An injection site reaction (5% to 15%), characterized by erythema (9%), pain (15%), irritation (15%), pruritus, edema, and swelling, has occurred with immune globulin. Phlebitis, including thrombophlebitis, has also been reported. Local reactions tend to be more common following hand vein infusions with higher concentrations of immune globulin solution (i.e., 10% vs. 5%); incidence may be reduced by administering immune globulin via the antecubital vein. Local reactions may also be common with subcutaneous infusion, particularly during the first week of infusion. Local reactions were reported in nearly 60% of subcutaneous infusions, and 75% of adult and adolescent patients during clinical trials for Gamunex-C; incidence rates were similar in pediatric trials (60% of infusions, 100% of patients). The incidence of local reactions may decrease with time in patients receiving chronic infusions. If local reactions occur, application of a warm compress to the infusion site may alleviate symptoms.[30276] [41552] [41553] [42654] [42655] [42659] [42661] [42955] [46250] [51240] [57655]
Infusion-related reactions may occur during immune globulin administration. Symptoms include flushing (6%), chest tightness, headache, chills (5% to 33.3%), rigors (7% to 37%), fever or increased body temperature (33.3% or less), diaphoresis, hyperhidrosis (6%), hot flush/hot flashes, dyspnea, wheezing (14%), bronchospasm, dizziness (6%), asthenia (5% to 15%), fatigue (16% or less), malaise (5%), gastrointestinal complaints (nausea, vomiting, upper abdominal pain and/or cramping, loss of appetite), hypotension (2.2% to 25%), diastolic hypotension (21% in pediatric patients), muscle symptoms (e.g., cramps, backache, arthralgia, myalgia), general flu-like symptoms, anxiety, palpitations, bradycardia (16%), sinus tachycardia (2.2% to 25%), dizziness, edema, and transient skin reactions. Hypertension occurred in 4.3% to 14.3% of patients during clinical trials. Four patients experienced reversible increases in systolic blood pressure to 180 mmHg or more during or within 1 to 4 hours after infusion. Of the 3 patients who had a history of hypertension, a patient with history of untreated hypertension also experienced a reversible increase in diastolic blood pressure from 84 mmHg to 135 mm Hg at 1 hour after the end of the infusion. All cases of hypertension resolved within 1 to 6 hours with observation or changes to oral antihypertensive therapy. Other general adverse events include accidental injury (13% to 16%), angina pectoris, chest discomfort (7% to 9%), extremity pain (10.7%), and falls (7%). Hyperhidrosis and hot flush/hot flashes have been noted in postmarketing reports. Compared to adult patients, fever was reported more frequently in pediatric patients during clinical trials of IVIG for idiopathic thrombocytopenic purpura (ITP) and primary immunodeficiency. Patients who have never received immune globulin, have been switched from a certain immune globulin product to another, or have had an interruption in immune globulin therapy more than 8 weeks may be at a higher risk for the development of an inflammatory reaction, especially with rapid infusion rates. Symptoms typically begin 30 to 60 minutes after initiation of the infusion and appear to be related to the infusion rate rather than the dose. Slowing or stopping the infusion usually allows these symptoms to resolve. Pretreatment with oral antihistamines and analgesics may help to alleviate these symptoms.[30276] [39573] [41552] [41553] [46250] [42654] [42655] [42659] [42661] [42955] [51240] [57655]
Life-threatening hypoglycemia can occur with the use of Octagam 5% and 10%. Some glucose monitoring systems interpret the maltose in Octagam as glucose. Inaccurate glucose readings can result in inappropriate administration of insulin. Furthermore, falsely elevated glucose readings could mask true cases of hypoglycemia. Monitor glucose in diabetic patients with a glucose-specific method only. Ensure blood glucose testing systems, including test strips, are appropriate to use with maltose-containing products.[30276] [57655]
References
Contraindications/Precautions
Absolute contraindications are italicized.
- corn hypersensitivity
- hereditary fructose intolerance
- hyperprolinemia
- IgA deficiency
- agammaglobulinemia
- albumin hypersensitivity
- aseptic meningitis
- breast-feeding
- cardiac disease
- coronary artery disease
- dehydration
- diabetes mellitus
- geriatric
- heart failure
- hemolysis
- hypertension
- hypertriglyceridemia
- hypervolemia
- hypogammaglobulinemia
- hyponatremia
- hypovolemia
- infants
- infusion-related reactions
- laboratory test interference
- migraine
- neonates
- obesity
- pregnancy
- renal disease
- renal failure
- renal impairment
- sepsis
- subcutaneous administration
- thromboembolism
- vaccination
- viral infection
Consider the patient's fluid status when considering the IVIG dose and product to be used. Administration of IVIG can significantly contribute to the daily fluid balance; high dose regimens (e.g., 1,000 mg/kg/day or more, for example) may put patients at increased risk for volume overload (hypervolemia).[42659] [46250] [51240] Monitor patients for signs and symptoms such as acute edema (peripheral or pulmonary) and dyspnea during infusions.
IVIG should be used cautiously in patients with a history of human immunoglobulin hypersensitivity. Carimune NF, Gammagard Liquid, Gammar-P I.V., Privigen, Bivigam, Gammaplex, Flebogamma 10%, Flebogamma 5%, Octagam 10%, Octagam 5%, and Gamunex-C are contraindicated in patients who with a history of anaphylactic or severe systemic reaction to immune globulin.[30276] [39573] [41553] [41552] [42654] [42655] [42658] [42659] [42661] [57655] IVIG products contain albumin and thus should be used with caution in patients with albumin hypersensitivity; some products contraindicate use. Octagam 5% is contraindicated for use by patients with an acute corn hypersensitivity, as the 5% liquid contains maltose (100 mg/mL).[30276] Octagam 10% also contains maltose (90 mg/mL); hypersensitivity reactions may occur in patients with corn allergy.[57655] Privigen is contraindicated for use by patients with hyperprolinemia because it contains the stabilizer L-proline.[42659] Gammaplex and Flebogamma 10% are contraindicated in patients with hereditary fructose intolerance as these products contain 50 mg of sorbitol per mL as an excipient; also, do not use in neonates and infants for whom sucrose or fructose tolerance has not been established.[42661]
IVIG is contraindicated in patients with IgA deficiency and antibodies against IgA along with a history of hypersensitivity reactions. IVIG should, in general, be avoided in patients with IgA deficiency. These patients often develop antibodies against IgA and are more likely to have anaphylactic or immune-mediated adverse reactions to pooled immune globulin products. Anaphylaxis can occur even if a product contains low amounts of IgA. Individuals with IgA deficiency should only receive IVIG with utmost caution in a setting where supportive care, including epinephrine, is immediately available.[30276] [41552] [42661] [42654] [42655] [42658] [42659] [42955] [46250] [51240] [57655]
Infusion-related reactions may occur with IVIG and are characterized by a rise in temperature, chills, nausea, and vomiting. Patients are at an increased risk for these reactions with the initial IVIG infusion, when switching brands of IVIG, or if there has been an interruption in therapy more than 8 weeks. The manufacturer of Carimune NF states these reactions have occurred in patients with agammaglobulinemia or hypogammaglobulinemia, suggesting these conditions may put patients at increased risk of IVIG infusion-related reactions. As the adverse reactions appear to be related to the rate of infusion, closely monitor infusion rates and the patient’s clinical state during IVIG infusion.[41552] [41553] [42654] [42659]
Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IVIG treatment. Signs and symptoms usually appear within several hours to 2 days and include severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting. AMS may occur more frequently after high-dose (e.g., more than 1,000 to 2,000 mg/kg/dose) and/or rapid-infusion IVIG treatment. In addition, patients with a history of migraine may be more susceptible to the development of aseptic meningitis syndrome due to IVIG.[23788] Patients presenting with signs and symptoms should undergo a thorough neurological evaluation, including CSF studies, to rule out other causes of meningitis. The diagnosis of aseptic meningitis is one of exclusion. Cerebrospinal fluid studies are frequently positive with pleocytosis up to several thousand cells per cubic mm, predominantly from the granulocytic series, and elevated protein concentrations up to several hundred mg/dL. Discontinuation of IVIG treatment has resulted in remission of aseptic meningitis syndrome within several days without sequelae.[30276] [41552] [42661] [42654] [42655] [42658] [42659] [42955] [46250] [51240] [57655]
IVIG is a derivative of human blood. As with other products derived from or purified with human blood components, the remote possibility of contamination with bacterial or viral infection, including hepatitis, or Creutzfeldt-Jakob disease (CJD) exists in patients receiving IVIG. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents; however, none of the processes are completely effective. Some viruses, such as parvovirus B19, are particularly difficult to remove or inactivate. Parvovirus B19 most seriously affects pregnant women and immune compromised individuals and symptoms include fever, drowsiness, chills, and rhinitis followed in about 2 weeks with rash and joint pain. There is also the possibility that unknown infectious agents are present in the pooled product. Health care professionals should discuss the risks and benefits of IVIG therapy prior to administration. Patients and caregivers should be encouraged to notify their health care provider if they develop infectious symptoms. All infections thought to have been transmitted by IVIG should be reported to the manufacturer.[30276] [39573] [41553] [41552] [42654] [42655] [42658] [42659] [42661] [57655]
Thromboembolism is known to be associated with IVIG therapy, regardless of the route of administration. Thrombosis can occur in patients without any known risk factors; however, patients most at risk include geriatric patients, those with multiple cardiovascular risk factors (e.g., known cardiac disease), impaired cardiac output (heart failure), prolonged immobilization, obesity, diabetes mellitus, use of estrogens, indwelling central venous catheters, acquired or inherited coagulation disorders, and patients with a history of a thrombotic event, vascular disease, atherosclerosis (coronary artery disease), and/or known or suspected hyperviscosity. Assessment of blood viscosity may be warranted for patients at risk for hyperviscosity such as those with cryoglobulins, fasting chylomicronemia, hypertriglyceridemia, or monoclonal gammopathies. Due to an increased risk of thromboembolic events, patients with dermatomyositis should be closely monitored and the infusion rate should not exceed 0.04 mL/kg/minute. Rapid infusion rates and high doses of IVIG may increase the risk in patients who are already at risk for thrombotic events. For patients at risk of developing thrombosis, use the minimum recommended dose of IVIG administered at the minimum practicable rate. Hyperproteinemia, increased serum viscosity, and hyponatremia may also occur in patients receiving IVIG therapy. Distinguish true hyponatremia from a pseudohyponatremia that is associated with or causally related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap. Treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thrombotic events. Ensure patients are not volume depleted prior to the initiation of IVIG and monitor for signs and symptoms of thrombosis during and after each infusion. Encourage patients to report any pain, swelling, discoloration, and/or warmth of the arms or legs, unexplained shortness of breath, chest pain/discomfort, unexplained tachycardia, and numbness or weakness on 1 side of the body. Elevation of systolic blood pressure to 180 mm Hg or more and/or diastolic blood pressure to more than 120 mm Hg has been observed during and shortly after infusion, especially in patients with a history or hypertension. Monitor blood pressure before, during, and after infusion.[30276] [41552] [42661] [42654] [42655] [42658] [42659] [42955] [46250] [51240] [54957] [57655]
IVIG products have been reported to be associated with renal impairment and dysfunction, acute renal failure, osmotic nephrosis, and death. Reports of renal dysfunction and acute renal failure have been associated with the use of many IVIG products, but IVIG products containing sucrose as a stabilizer accounted for a disproportionate share of the total number. Carimune NF and Gammar-P contain sucrose. Cautious use of IVIG is advised for patients with preexisting renal insufficiency and for patients judged to be at increased risk of developing renal insufficiency. Patients predisposed to acute renal failure include the elderly (more than 65 years of age); patients receiving known nephrotoxic drugs; patients with diabetes mellitus, dehydration, hypovolemia, sepsis, or paraproteinemia; and patients with any degree of preexisting renal impairment such as from renal disease. Especially in such patients, administer IVIG products at the minimum concentration available and at the minimum rate of infusion practicable. Ensure that patients are not volume depleted before the initiation of the IVIG infusion. Also, assess renal function including measurement of blood urea nitrogen (BUN) and serum creatinine before the initial IVIG infusion and again at appropriate intervals thereafter. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential increased risk for developing acute renal failure. If renal function deteriorates, consider IVIG discontinuation.[42654] [42658] [30276] [39573] [41553] [41552] [42655] [42659] [42661] [57655]
Certain cautions are to be used with patients receiving IVIG who must undergo vaccination. Inactivated vaccines can be administered any time before, after, or simultaneously with IVIG; if administered simultaneously, different administration sites should be used. In addition, the live vaccines Ty21a typhoid, yellow fever, live-attenuated influenza, zoster, and rotavirus vaccines may be administered at any time during IVIG therapy. Because of the passive transfer of antibodies, IVIG, like other antibody-containing blood products, can inhibit the immune response to measles, mumps, and rubella vaccines for 3 months or more. IVIG products also contain antibodies to varicella, however their effect on immune response to this virus is unknown. If simultaneous administration of measles-containing vaccine or varicella vaccine is unavoidable, administer the products at different sites, and revaccinate or test for seroconversion after the recommended interval. The duration of interference of IVIG with the immune response to the measles and possibly varicella vaccine is dose related; patients receiving standard-dose therapy must delay 8 months, while those receiving high-dose therapy must delay 10 to 11 months. The immunizing physician should be informed of recent IVIG therapy so appropriate measures can be taken. It is important to note that various antibodies acquired through passive transfer may confound the results of serological testing.[30276] [41552] [42661] [42654] [42655] [42658] [42659] [42955] [43236] [46250] [51240] [57655]
IVIG products may contain blood group antibodies that act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin test (DAT, Coombs' test), and rarely, hemolysis. Delayed hemolytic anemia can develop after immune globulin therapy due to enhanced RBC sequestration. Acute hemolysis (consistent with intravascular hemolysis), severe hemolysis-related renal dysfunction, and disseminated intravascular coagulation (DIC) have occurred. Risk factors related to the development of hemolysis include high doses (2,000 mg/kg or more) as a single infusion or divided over several days and non-O blood type. An underlying inflammatory state reflected by elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) may also contribute to the risk of hemolysis, however the role is uncertain. Monitor patients receiving IVIG for hemolysis and hemolytic anemia. In higher risk patients, consider appropriate lab testing, including hemoglobin and hematocrit prior to therapy, 36 to 96 hours after infusion, and 7 to 10 days post infusion. If signs and symptoms of hemolysis are present after the infusion, perform confirmatory lab testing. If a transfusion is indicated, perform adequate cross-matching to avoid exacerbating ongoing hemolysis.[30276] [41552] [42661] [42654] [42655] [42658] [42659] [42955] [46250] [51240] [57655]
Studies with immune globulin IV (IVIG) during pregnancy have not been conducted in humans or animals, and the ability of IGIV to cause fetal harm or affect reproduction capacity is unknown.[51240] Immunoglobulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. In cases of maternal idiopathic thrombocytopenic purpura where Carimune was administered to the mother before delivery, the platelet response and clinical effect were similar in the mother and neonate.[42654] According to the Advisory Committee on Immunization Practices (ACIP), fetal adverse events have not occurred after administration of immune globulin preparations to pregnant women. Administer during pregnancy only if clearly needed.[43236]
Use of immune globulin IV (IVIG) has not been evaluated in women who are breast-feeding and excretion of IVIG into breast milk is unknown according to manufacturers.[51240] However, endogenous immune globulin is a normal component in breast milk.[60441] Case reports of 2 nursing mothers receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk.[48199] There is emerging consensus that IVIG may be the preferred treatment for postpartum mothers with multiple sclerosis who are breastfeeding, although 1 retrospective study failed to find a decrease in relapse rate among mothers who received IgG postpartum.[60441] In a retrospective study of patients with relapsing remitting multiple sclerosis, 73% of neonates were breast-fed for periods of 3 to 12 weeks with no adverse effects. Patients received IVIG through 12 weeks postpartum with regimens of 400 mg/kg/day for 5 days after delivery with additional booster doses at 6 and 12 week postpartum (n = 41) or 0.4 mg/kg/day for 5 days during weeks 6 to 8 of gestation with booster doses every 6 weeks until 12 weeks postpartum.[60442]
Subcutaneous administration of immune globulin should not be used in patients with immune thrombocytopenic purpura (ITP) because of the risk of hematoma.[51240]
Immune globulin administration may result in laboratory test interference. After infusion of immunoglobulins, the transitory rise of the various passively transferred antibodies in the blood may yield false positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, D) may cause a positive direct or indirect antiglobulin (Coombs') test.[30276] Measurement of blood glucose must be done with a glucose-specific method if a patient takes a parenteral product that contains maltose, such as Octagam IGIV. Blood glucose testing systems based on the glucose dehydrogenase pyrroloquinolinequinone quinone (GDH-PQQ) or on the glucose-dye-oxidoreductase methods falsely interpret the maltose contained in Octagam as glucose. Falsely elevated glucose readings during Octagam therapy have led to life-threatening hypoglycemia because of inappropriate administration of insulin. Falsely elevated glucose readings could also mask true cases of hypoglycemia. Read the product information of the blood glucose testing system including the information about the test strips to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system.[30276] [57655]
References
Mechanism of Action
Immunoglobulins are antibodies synthesized by B lymphocytes. IVIG is derived from the pooled human plasma of thousands of donors. Most preparations consist of intact immunoglobulin (Ig)G molecules with trace amounts of IgA, IgM, soluble CD4, CD8, human leukocyte antigen (HLA), and cytokines. The pooled, heterogenous IgG present in IVIG provides a plethora of antibodies capable of opsonization and neutralization of many toxins and microbes as well as complement activation. Although the amount of each IgG subclass in the parenteral products is similar to that of human plasma, the titers against specific antigens vary from manufacturer to manufacturer. The Fc fragment of the IgG molecule allows the molecule to interact with and signal through Fc- gamma receptors on B cells and other cells of the phagocytic system. The Fc fragment also interacts with the Fc-binding plasma proteins, which is essential for complement activation and microorganism clearance. The passive immunity imparted by IVIG is capable of attenuating or preventing infectious diseases or deleterious reactions from toxins, mycoplasma, parasites, bacteria, and viruses.[53218]
In immunomodulatory and anti-inflammatory disease states, it is believed the Fc fragment of IgG and the Fc-gamma receptors on target cells (e.g., macrophages, B cells, natural killer cells, plasma cells, eosinophils, neutrophils, platelets) interact to up-regulate or down-regulate inflammatory and immune responses. In autoimmune cytopenias and inflammatory neurologic disorders, blockade of Fc-gamma receptors on macrophages blocks the clearance of opsonized target cells and suppresses antibody-dependent cell-mediated cytotoxicity, respectively. Immunoglobulins may also modulate inflammatory response by preventing complement-mediated tissue damage and regulating the induction of anti-inflammatory cytokines and cytokine antagonists (e.g., interleukin 1-beta, interleukin-1 receptor antagonist, tumor necrosis factor alpha). Immunomodulatory response may be facilitated by the immunoregulatory effects of anti-idiotypic antibodies on B cells and autoantibodies, regulation of helper T cell production, and apoptosis of immune system gene expression.[53218]
In ITP treatment, IVIG produces an immediate rise in platelet count, usually lasting only a few weeks, although platelet stabilization for up to 1 year after administration has been reported.[23982]
Revision Date: 04/16/2013, 02:25:17 PMReferences
Pharmacokinetics
Most IVIG products are administered intravenously, and Gammagard Liquid or Gamunex-C may additionally be administered by subcutaneous infusion.[42655][54339][51240]
Within 24 hours, up to 30% of a dose may be removed by catabolism and distribution. Data concerning distribution are scant, but IVIG appears to distribute throughout intravascular (60%) and extravascular (40%) spaces, crosses the placenta (in increasing amounts after 30 weeks of gestation), and may be excreted into milk. The exact fate of IVIG is not well defined, but the serum half-life is that of immune globulin (IgG), approximately 21 to 29 days. Great interpatient variability exists for the half-life of IgG. Fever, infection, or high IgG concentrations appear to coincide with a shortened half-life whereas immunodeficiency appears to be associated with a longer half-life of IgG. For example, the apparent half-life of IgG after Octagam is approximately 40 days (range, 23 to 84 days) in immunosuppressed patients. As there are significant differences in the half-life of IgG among patients with primary immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response. The minimum serum concentration of IgG necessary for protection varies among patients and has not been established by controlled clinical studies.
Route-Specific Pharmacokinetics
Intravenous Route
Peak serum concentrations occur immediately after IV injection and are dose-related. Following infusion, IVIG products show a biphasic decay curve. The initial phase is characterized by an immediate post-infusion peak in serum IgG and is followed by rapid decay due to equilibration between the plasma and extravascular fluid compartments. The second phase is characterized by a slower and constant rate of decay.
After receipt of Octagam 300 to 450 mg/kg every 3 weeks or 400 to 600 mg/kg every 4 weeks, the mean total IgG serum concentration decreased approximately 47% to 55% over 28 days. The mean trough total IgG concentration after 6 or 7 infusions of Octagam was 766 to 871 mg/dL. The concentrations were similar to the patient's baseline trough total concentrations (883 to 986 mg/dL) on other IVIG products.
Subcutaneous Route
Some immune globulin products (e.g., Gammagard Liquid, Gamunex-C) have been administered as subcutaneous infusions. The subcutaneous dose required to provide an exposure non-inferior to the exposure from intravenous (IV) administration was 137% of the IV dose.[42655][54339][51240] Specifically, the mean adjusted SC dose was 137.3% (125.7 to 150.8%) of the IV dose for patients at least 12 years of age and 141% (100.5% to 160%) for patients younger than 12 years old. After subcutaneous administration, the peak IgG concentration occurred 2.9 (1.2 to 3.2) days later, and the mean peak concentration was 1,393 +/- 289 mg/dL. The mean trough concentration was 1,202 +/- 282 mg/dL. As compared with IV administration, the mean peak concentration was lower after subcutaneous administration, and the mean trough concentration was higher.[42655]
Special Populations
Pediatrics
Neonates
Volume of distribution in neonates has been reported with variance, ranging from 0.04 to 0.25 L/kg. The IVIG half-life is comparable to normal adult parameters with a reported range of 18 to 29 days.[53227][53228][53229] In a study of 15 neonates (gestational age 32 to 41 weeks; birth weight more than 1,500 grams), IVIG infusions of 500 mg/kg resulted in a mean peak IgG concentration of 2,171 mg/dL, 15 minutes after infusion; this dosage resulted in a significant increase in IgG concentrations greater than 8 days after the infusion. IVIG infusions of 1,000 mg/kg resulted in mean peak IgG concentrations of 2,734 mg/dL and resulted in significant increases in IgG concentrations more than 11 days after the infusion. A biphasic decay curve resulted in an initial rapid decay within 24 hours after infusion followed by a slower decay over the next 6 weeks. Plasma clearance was 3 mL/kg/day. Gestational age, birth weight, dose, and pretreatment serum IgG concentrations had minimal effect on pharmacokinetic parameters.[53228]
Children and Adolescents
The pharmacokinetics of intravenous and subcutaneous immune globulin are similar in children, adolescents, and adults.[51240] Both intravenous and subcutaneous infusions of immune globulin appear to be effective in children and with similar trough IgG concentrations achieved as in adults.[54339] No pediatric specific dose requirements are necessary to achieve the desired serum IgG levels. Dosage, as in adults, must be individualized and adjusted over time to achieve the desired trough levels and clinical responses.
Other
Immunodeficiency
Immunodeficiency appears to be associated with a longer half-life of IgG. For example, the apparent half-life of IgG after Octagam is approximately 40 days (range, 23 to 84 days) in immunosuppressed patients.[30276] As there are significant differences in the half-life of IgG among patients with primary immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient.
References
Pregnancy/Breast-feeding
pregnancy
Studies with immune globulin IV (IVIG) during pregnancy have not been conducted in humans or animals, and the ability of IGIV to cause fetal harm or affect reproduction capacity is unknown.[51240] Immunoglobulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. In cases of maternal idiopathic thrombocytopenic purpura where Carimune was administered to the mother before delivery, the platelet response and clinical effect were similar in the mother and neonate.[42654] According to the Advisory Committee on Immunization Practices (ACIP), fetal adverse events have not occurred after administration of immune globulin preparations to pregnant women. Administer during pregnancy only if clearly needed.[43236]
breast-feeding
Use of immune globulin IV (IVIG) has not been evaluated in women who are breast-feeding and excretion of IVIG into breast milk is unknown according to manufacturers.[51240] However, endogenous immune globulin is a normal component in breast milk.[60441] Case reports of 2 nursing mothers receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk.[48199] There is emerging consensus that IVIG may be the preferred treatment for postpartum mothers with multiple sclerosis who are breastfeeding, although 1 retrospective study failed to find a decrease in relapse rate among mothers who received IgG postpartum.[60441] In a retrospective study of patients with relapsing remitting multiple sclerosis, 73% of neonates were breast-fed for periods of 3 to 12 weeks with no adverse effects. Patients received IVIG through 12 weeks postpartum with regimens of 400 mg/kg/day for 5 days after delivery with additional booster doses at 6 and 12 week postpartum (n = 41) or 0.4 mg/kg/day for 5 days during weeks 6 to 8 of gestation with booster doses every 6 weeks until 12 weeks postpartum.[60442]
References
Interactions
Level 2 (Major)
- Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
- Measles/Mumps/Rubella Vaccines, MMR
- Ravulizumab
- Rotavirus Vaccine
- Rubella Virus Vaccine Live
- Varicella-Zoster Virus Vaccine, Live
Level 3 (Moderate)
- Acetaminophen; Aspirin
- Acetaminophen; Aspirin, ASA; Caffeine
- Acetaminophen; Aspirin; Diphenhydramine
- Acetaminophen; Ibuprofen
- Acyclovir
- Adefovir
- Amikacin
- Aminoglycosides
- Amlodipine; Celecoxib
- Amphotericin B
- Amphotericin B lipid complex (ABLC)
- Amphotericin B liposomal (LAmB)
- Aspirin, ASA
- Aspirin, ASA; Butalbital; Caffeine
- Aspirin, ASA; Caffeine
- Aspirin, ASA; Caffeine; Orphenadrine
- Aspirin, ASA; Carisoprodol
- Aspirin, ASA; Carisoprodol; Codeine
- Aspirin, ASA; Citric Acid; Sodium Bicarbonate
- Aspirin, ASA; Dipyridamole
- Aspirin, ASA; Omeprazole
- Aspirin, ASA; Oxycodone
- Aspirin, ASA; Pravastatin
- Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
- Bacitracin
- Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
- Bismuth Subsalicylate
- Bismuth Subsalicylate; Metronidazole; Tetracycline
- Bupivacaine; Meloxicam
- Butalbital; Aspirin; Caffeine; Codeine
- Capreomycin
- Celecoxib
- Celecoxib; Tramadol
- Chlorpheniramine; Ibuprofen; Pseudoephedrine
- Choline Salicylate; Magnesium Salicylate
- Cidofovir
- Cisplatin
- Colistimethate, Colistin, Polymyxin E
- Colistin
- Cyclosporine
- Diclofenac
- Diclofenac; Misoprostol
- Diflunisal
- Diphenhydramine; Ibuprofen
- Diphenhydramine; Naproxen
- Efgartigimod Alfa
- Etodolac
- Fenoprofen
- Flurbiprofen
- Foscarnet
- Ganciclovir
- Gentamicin
- Hydrocodone; Ibuprofen
- Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
- Ibuprofen
- Ibuprofen; Famotidine
- Ibuprofen; Oxycodone
- Ibuprofen; Pseudoephedrine
- Indomethacin
- Ketoprofen
- Ketorolac
- Lansoprazole; Naproxen
- Magnesium Salicylate
- Meclofenamate Sodium
- Mefenamic Acid
- Meloxicam
- Nabumetone
- Naproxen
- Naproxen; Esomeprazole
- Naproxen; Pseudoephedrine
- Nonsteroidal antiinflammatory drugs
- Oxaprozin
- Pamidronate
- Paromomycin
- Pentamidine
- Piroxicam
- Plazomicin
- Polymyxin B
- Salsalate
- Streptomycin
- Streptozocin
- Sulindac
- Sumatriptan; Naproxen
- Tacrolimus
- Tobramycin
- Tolmetin
- Valacyclovir
- Valdecoxib
- Valganciclovir
- Vancomycin
- Zoledronic Acid
References
Monitoring Parameters
- serum creatinine/BUN
- serum IgG concentrations
US Drug Names
- ASCENIV
- BIVIGAM
- Carimune
- Carimune NF
- Flebogamma
- Flebogamma DIF
- Gamimune N
- Gammagard
- Gammagard S/D
- Gammaked
- Gammaplex
- Gammar-P IV
- Gamunex
- Gamunex-C
- Iveegam
- Iveegam EN
- Octagam
- Panglobulin
- Panglobulin NF
- panzyga
- Polygam S/D
- Privigen
- Sandoglobulin
- Venoglobulin-S
- Vigam
