Immune globulin subcutaneous (IGSC) is a protein solution that contains at least 98% immunoglobulin G (IgG). It is indicated for the treatment of primary immunoglobulin deficiency in adults and pediatric patients 2 years and older and chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. Lifelong replacement therapy with human immune globulin provides passive immunity to decrease susceptibility to life-threatening infections in patients with predominant antibody deficiencies. Administration of IGSC is more frequent as compared with IVIG. The more frequent IGSC administration leads to more consistent serum IgG concentrations, with lower peaks, higher troughs, and relatively stable steady-state serum concentrations compared to the high peaks and low troughs seen with IVIG. The fluctuating serum IgG concentrations seen with once monthly administration of IVIG are likely associated with certain adverse events (i.e., headaches seen with high peaks, fatigue, joint symptoms, and general malaise seen with low troughs). The use of IGSC may decrease the incidence of such adverse events.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Do not freeze. Do not use solutions that were previously frozen.
-Do not shake the vial.
-Do not mix with other parenteral products.
-Immune globulin subcutaneous (IGSC) contains no preservative. Discard unused product immediately after use.
Subcutaneous Administration
Preparation
-Cutaquig:
--Solution is clear and colorless that may turn slightly opalescent and pale yellow during storage. Do not use if solution appears cloudy or contains particulates.
-Before preparing the dose, allow vials to reach room temperature.
-Withdraw desired dose from vial(s) with syringe of a size compatible with the infusion pump.
-Cuvitru:
--Solution may be clear and colorless, pale yellow, or light brown. Do not use if solution is cloudy, turbid, or contains particulates.
-Before preparing the dose, allow vials to reach room temperature.
-Withdraw desired dose from vial(s) with syringe of a size compatible with the infusion pump.
-Once dose is drawn in the syringe, complete the administration within 2 hours to prevent formation of particles caused by siliconized syringes.
-Hizentra:
--Solution is clear and pale yellow to light brown. Do not use solution if it is cloudy or contains particulates.
-Withdraw desired dose from vial(s) with syringe of a size compatible with the infusion pump. If using prefilled syringe(s), they are ready to use. The prefilled syringes can be placed directly in the infusion pump if the prefilled syringe size matches the pump requirements. If the prefilled syringe size does not match the infusion pump requirements, transfer the contents of the prefilled syringe to another syringe of a size compatible with the infusion pump.
-Xembify:
--Solution is clear to slightly opalescent and colorless to pale yellow. Do not use solution if cloudy, turbid, discolored, or contains particulates.
-Before preparing the dose, allow vials to reach room temperature.
-Withdraw desired dose from vial(s) with syringe of a size compatible with the infusion pump.
-Once dose is drawn in the syringe, complete the administration within 2 hours to prevent formation of particles caused by siliconized syringes.
Subcutaneous Infusion
-Injections are usually made into the abdomen, thighs, upper arms, and/or upper leg/hip area. Never infuse into areas where the skin is tender, bruised, red, or hard. Avoid infusing into scars, tattoos, or injured/inflamed skin areas. Rotate the injection site with each administration.
-Cleanse injection site(s) with an alcohol wipe or other appropriate antiseptic beginning at the center of each infusion site and moving outward in a circular motion. Allow infusion site(s) to dry. If using multiple simultaneous injection sites, they should be at least 2 inches or 4 inches (Cuvitru) apart. The number and location of injection sites depends on the volume of the total dose and specific product.
-Grasp the skin between thumb and forefinger around the injection site 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. Secure the needle with sterile tape. 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.
-Simultaneous subcutaneous infusion may be facilitated by use of a multi-needle administration set or more than 1 infusion device.
-The maximum infusion volume and rate are dependent on specific product:
-Cutaquig:
--May infuse in up to 6 sites simultaneously.
-The maximum infusion volume and rate are dependent on age:
--Adults and Adolescents 17 years: For the first 2 infusions, do not exceed 25 mL per site and 20 mL/hour per site. For subsequent infusions, if tolerated, may gradually increase infusion volume by approximately 10 mL per site and infusion rate by 10 mL/hour per site every 2 to 4 weeks to a maximum infusion volume of 40 mL per site and a maximum infusion rate of 52 mL/hour per site.
-Children and Adolescents 7 to 16 years: For the first 2 infusions, do not exceed 15 mL per site and 15 mL/hour per site. For subsequent infusions, if tolerated, may gradually increase infusion volume by approximately 5 to 10 mL per site and infusion rate by 5 to 10 mL/hour per site every 2 to 4 weeks to a maximum infusion volume of 29 mL per site and a maximum infusion rate of 25 mL/hour per site.
-Children 2 to 6 years: For the first 2 infusions, do not exceed 10 mL per site and 15 mL/hour per site. For subsequent infusions, if tolerated, may gradually increase infusion volume by approximately 5 to 10 mL per site and infusion rate by 5 to 10 mL/hour per site every 2 to 4 weeks to a maximum infusion volume of 15.5 mL per site and a maximum infusion rate of 25 mL/hour per site.
-Cuvitru:
--May infuse in up to 4 sites simultaneously.
-The maximum infusion volume and rate are dependent on weight:
--Weight 40 kg or more: Do not exceed 60 mL per site. For the first 2 infusions, do not exceed 10 to 20 mL/hour per site. For subsequent infusions, if tolerated, may increase to maximum of 60 mL/hour per site. For patients utilizing 4 infusion sites, the maximum infusion rate for all sites combined is 240 mL/hour.
-Weight less than 40 kg: For the first 2 infusions, do not exceed 20 mL per site and 10 to 20 mL/hour per site. For subsequent infusions, if tolerated, may increase to maximum of 60 mL per site and 60 mL/hour per site. For patients utilizing 4 infusion sites, the maximum infusion rate for all sites combined is 240 mL/hour.
-Hizentra:
--May infuse in up to 8 sites simultaneously.
-The maximum infusion volume and rate are dependent on indication:
--Primary immunodeficiency: For the first infusion, do not exceed 15 mL per site and 15 mL/hour per site. For subsequent infusions, if tolerated, may increase to a maximum of 25 mL per site and 25 mL/hour per site.
-Chronic inflammatory demyelinating polyneuropathy (CIDP): For the first infusion, do not exceed 20 mL per site and 20 mL/hour per site. For subsequent infusions, if tolerated, may increase to a maximum of 50 mL per site and 50 mL/hour per site.
-Xembify:
--May infuse in up to 6 sites simultaneously.
-Do not exceed 25 mL per site and 25 mL/hour per site.
Severe hypersensitivity or infusion-related reactions, such as anaphylactic shock, anaphylactoid reactions, or angioedema, may occur with immune globulin subcutaneus (IGSC); immediately discontinue the infusion and administer appropriate treatment for severe hypersensitivity reactions. Infusion reactions have included swollen face or tongue, pharyngeal edema, fever (7.9% to 11.6%), chills, flushing, dizziness, hypertension (3.5%), hypotension, sinus tachycardia, malaise, wheezing, rigors, and myalgia. Additional adverse reactions reported in clinical trials of IGSC include cough (6% to 10.5%), fatigue (5.9% to 12.5%), asthenia, urticaria (4.1% to 5.3%), dermatitis (5.3% to 11.6%), rash (4.1% to 7.8%), headache (6.9% to 29.2%) or migraine (6.1%), nasal congestion (7.9%), ear pain or otalgia (5.3%), arthralgia (1.7% to 7%), back pain (1.7% to 9.3%), extremity pain (1.8% to 8.2%), fall (1.7% to 5.3%), myalgia, and myositis. Stevens-Johnson syndrome, epidermolysis, erythema multiforme, eczema (atopic dermatitis), alopecia, and skin discoloration have also been reported with immune globulin products in postmarketing surveillance.
A local injection site reaction has been commonly reported (20% to 100%) in patients receiving immune globulin subcutaneous (IGSC). Most reactions have been classified as mild or moderate and decreased over time; however, some patients have discontinued treatment due to severe infusion site reactions. The most common local adverse reactions have been infusion site erythema (10% to 50%), pain (13% to 20%), swelling/induration (6% to 68%), bruising (16%), nodule (16%), pruritus (5% to 15%), scab (6%), and infusion site warmth. Infusion site skin ulcer and skin necrosis have also been reported during postmarketing surveillance. Gentle local massage or application of warmth has been used to accelerate the recovery of local reactions.
As with other products derived from or purified with human blood components, the possibility of transmitting a viral infection or variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent exists in patients receiving immune globulin subcutaneous (IGSC). The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing processes. During a clinical trial of patients with chronic inflammatory demyelinating polyneuropathy, 3.4% to 7% of immune globulin-treated patients experienced naso-pharyngitis, compared to 1.8% of placebo-treated patients. Upper respiratory tract infection occurred in 3.4% to 5.3% of immune globulin-treated patients, compared to 3.5% of placebo-treated patients. Report all infections thought to have been transmitted by IGSC to the manufacturer.
Leukopenia and neutropenia were reported in 7.9% of pediatric patients receiving immune globulin subcutaneous (IGSC) in clinical trials (n = 38). Leukopenia, pancytopenia, increased hemoglobin, and decreased haptoglobin have also been reported during postmarketing surveillance with immune globulin products. Hemolysis and hemolytic anemia have been associated with IVIG administration and may also occur with IGSC. Delayed hemolytic anemia secondary to immune globulin can develop due to enhanced red blood cell sequestration, and acute hemolysis consistent with intravascular hemolysis has been reported. Blood group antibodies present in IGSC may act as hemolysins and induce immunoglobulin adherence to red blood cells; positive direct antiglobulin (Coombs') test results have been reported with immune globulin usage. Monitor patients for clinical signs and symptoms of hemolysis, particularly patients with risk factors. Consider appropriate laboratory testing in higher risk patients, including measurement of hemoglobin or hematocrit prior to infusion and within approximately 36 to 96 hours post infusion. If signs and/or symptoms of hemolysis are present after IGSC infusion, perform appropriate confirmatory laboratory testing.
Abdominal pain (3.9% to 6.1%), diarrhea (6% to 18.8%), nausea (8.2% to 12.2%), and vomiting (5.4% to 10.5%) have been reported in clinical trials of patients receiving immune globulin subcutaneus (IGSC). Elevated hepatic enzymes (increased AST and ALT) were reported in 5.3% to 7.9% of pediatric patients receiving IGSC in clinical trials. Hepatic dysfunction and elevated hepatic enzymes have also been reported in postmarketing surveillance with immune globulin products.
Aseptic meningitis syndrome, characterized by severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting, has occurred with immune globulin subcutaneous (IGSC) and usually begins within several hours to 2 days after immune globulin treatment. It may occur more frequently in female patients or in association with high doses (more than 2 g/kg) and/or rapid infusion of immune globulin product. Patients exhibiting such signs and symptoms should receive a thorough neurological examination, including cerebrospinal fluid studies, to rule out other causes of meningitis. Cerebrospinal fluid studies frequently show pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein concentrations up to several hundred mg/dL. Discontinuation of immune globulin treatment has resulted in remission of the syndrome within several days without sequelae. Other neurological or psychiatric adverse reactions identified during postmarketing surveillance with IGSC or immune globulin products include paresthesias, tremor, agitation, coma, loss of consciousness, and seizures.
Thromboembolism, including thrombosis and pulmonary embolism, may occur with immune globulin subcutaneous (IGSC). Adverse reactions associated with thrombosis and reported with immune globulin products include palpitations, chest pain (unspecified), cardiovascular collapse, and cardiac arrest. Thrombosis can occur in patients without any known risk factors; however, patients most at risk include age over 65 years, multiple cardiovascular risk factors, prolonged immobilization, estrogen use, hypercoagulable conditions, history of venous or arterial thrombosis, indwelling central vascular catheters, and/or hyperviscosity. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity including those with cryoglobulins, fasting chylomicronemia/markedly high triglycerides, or monoclonal gammopathies. For patients at risk of thrombosis, administer IGSC at the minimum dose and infusion rate practicable. Ensure adequate hydration in all patients before administration, and monitor for signs and symptoms of thrombosis. Instruct patients to immediately report pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, or numbness or weakness on 1 side of the body.
Transfusion-related acute lung injury (TRALI) may occur in patients administered human immune globulin products. TRALI is characterized by noncardiogenic pulmonary edema, severe acute respiratory distress syndrome (ARDS), hypoxemia (hypoxia), normal left ventricular function, and fever. Typically, it occurs within 1 to 6 hours after transfusion. Dyspnea, apnea, cyanosis, laryngospasm, and bronchospasm have also been noted postmarketing with immune globulins. Monitor patients for pulmonary adverse reactions during immune globulin subcutaneous (IGSC) treatment. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient's serum. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support. Asthma (10.5%) and oropharyngeal pain (5.3% to 6.3%) have also been reported in clinical trials of patients receiving IGSC.
Renal dysfunction, renal failure (unspecified), acute renal tubular necrosis, proximal tubular nephropathy, osmotic nephrosis (nephropathy), and death may occur with use of human immune globulin products, especially those containing sucrose. Of note, none of the immune globulin subcutaneous (IGSC) products contain sucrose as a stabilizer. Administer IGSC products at the minimum rate of infusion practicable for patients judged to be at risk of developing renal dysfunction because of preexisting renal insufficiency or predisposition to acute renal failure. Patients predisposed to acute renal failure include those with diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal function assessment including urine output, serum creatinine, and blood urea nitrogen concentrations before IGSC administration and periodically thereafter is recommended. Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk of developing acute renal failure. Also, correct hypovolemia before IGSC is infused. Discontinuation of IGSC may be warranted if renal function deteriorates. Instruct patients to immediately report oliguria, sudden weight gain, fluid retention/edema, and/or shortness of breath.
Immune globulin subcutaneous (IGSC) is for administration by subcutaneous injection only. Do not administer IGSC via intravenous administration or intramuscular administration. Use IGSC cautiously in patients with a history of human immunoglobulin hypersensitivity. IGSC is contraindicated in individuals with a history of anaphylactic or severe systemic reaction to administration of human immune globulin or to any of the components such as polysorbate 80, and thus, are contraindicated for use by patients with polysorbate 80 hypersensitivity. Hizentra is contraindicated for use by patients with hyperprolinemia because it contains the stabilizer L-proline. Severe hypersensitivity reactions may occur with IGSC, even in patients who have tolerated previous treatment with human immune globulin. If a hypersensitivity reaction occurs, discontinue IGSC infusion immediately and institute appropriate treatment.
Immune globulin subcutaneous (IGSC) is contraindicated for use in patients with IgA deficiency who have antibodies against IgA and a history of hypersensitivity to human immunoglobulin treatment. Patients with IgA deficiency and known anti-IgA antibodies have a higher risk of developing potentially severe hypersensitivity and/or anaphylactic reactions (including anaphylaxis and shock) with administration of IGSC.
The immune globulins present in immune globulin subcutaneous (IGSC) products may interfere with the immune response to vaccination, specifically with live virus vaccines including measles, mumps, rubella, and varicella. The recommended interval of time before administration of an antibody-containing product after receipt of a live antigen is 2 weeks. Administration of measles- or varicella-containing vaccines, if indicated, is recommended to be delayed 8 or more months from the time of IVIG administration; due to similar pharmacokinetic properties between IV and subcutaneous immune globulin after administration, the equivalent interval is recommended with IGSC therapy. If simultaneous administration of an antibody-containing product and measles-containing vaccine or varicella vaccine is unavoidable, administer at different sites and revaccinate or test for seroconversion after the recommended interval. The duration of interference of antibody-containing products with the immune response to the measles component of measles-containing vaccine, and possibly varicella vaccine, is dose-related. Yellow fever, oral Ty21a typhoid vaccine, and live-attenuated influenza vaccine are exceptions to these recommendations. These live-attenuated vaccines can be administered at any time before, after, or simultaneously with an antibody-containing product without substantially decreasing the antibody response.
As with other products derived from or purified with human blood components, the possibility of transmitting hepatitis, Creutzfeldt-Jakob disease (CJD), and other bacterial or viral infection exists in patients receiving immune globulin subcutaneous (IGSC). The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing processes. To date, no cases of viral transmission have been identified for IGSC products. Report all infections thought to have been transmitted by IGSC to the manufacturer.
Thromboembolism is known to be associated with immune globulin therapy, regardless of the route of administration. For patients at risk of thrombosis, administer IGSC at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, hypertriglyceridemia, or monoclonal gammopathies. Thrombosis can occur in patients without any known risk factors; however, patients most at risk include older adults, those with multiple cardiovascular risk factors (known cardiac disease), prolonged immobilization, 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.
Renal dysfunction, acute renal failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephropathy, and death may occur with the use of human immune globulin products such as immune globulin SC, SCIG, IGSC. To reduce the risk of acute renal failure, caution should be undertaken in patients at increased risk (e.g., patients with any degree of renal impairment or renal disease, diabetes mellitus, patients older than 65 years, dehydration or hypovolemia, sepsis, paraproteinemia, or concomitant nephrotoxic drug therapy); periodic monitoring of renal function tests and urinary output are particularly important. In patients at risk of developing renal dysfunction, consider lower, more frequent dosing. If renal function deteriorates, consider product discontinuation. Adequately hydrate the patient before the initiation of the infusion of SCIG; assess the blood urea nitrogen (BUN) concentration and serum creatinine concentration before SCIG receipt and at appropriate intervals thereafter. Administer SCIG at the minimum practicable rate of infusion for patients judged to be at risk of developing renal dysfunction.
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. Additionally, false positive readings in assays that depend on detection of beta-D-glucans for diagnosis of fungal infections may occur; this may persist during the weeks after immune globulin infusion. While taking Cutaquig, falsely elevated glucose readings may occur with some types of blood glucose testing systems (for example, those based on the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase methods). These symptoms may falsely interpret the maltose in Cutaquig as glucose. When administering Cutaquig, measure blood glucose with a glucose-specific method.
During clinical trials of patients with primary immunodeficiency or chronic inflammatory demyelinating polyneuropathy, no differences in safety or efficacy were observed between subjects 18 to 65 years and those older than 65 years. However, geriatric patients may be at an increased risk for developing renal failure or thrombotic events and should be monitored closely. Do not exceed the recommended dose, and infuse at the minimum rate practicable.
Immune globulin SC, SCIG, IGSC has not been studied in pregnancy. It is not known whether immune globulin SC, SCIG, IGSC can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. According to the Advisory Committee on Immunization Practices (ACIP), fetal adverse events have not occurred after administration of immune globulin preparations to pregnant women. Use immune globulin SC, SCIG, IGSC during pregnancy only if clearly indicated.
Use of immune globulin SC, SCIG, IGSC has not been evaluated in women who are breast-feeding, and excretion of IGSC in breast milk is unknown. Case reports of 2 nursing mothers receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk.
Monitor patients for clinical signs and symptoms of hemolysis, particularly patients with risk factors. Consider appropriate laboratory testing in higher risk patients, including measurement of hemoglobin or hematocrit prior to infusion and within approximately 36 to 96 hours post infusion. If signs and/or symptoms of hemolysis are present after immune globulin subcutaneous (IGSC) infusion, perform appropriate confirmatory laboratory testing. IGSC 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). Delayed hemolytic anemia secondary to immune globulin can develop due to enhanced red blood cell sequestration, and acute hemolysis consistent with intravascular hemolysis has been reported. Risk factors related to the development of hemolysis include high doses (2 g/kg or more) as a single infusion or divided over several days and non-O blood type. An underlying inflammatory state may also contribute to the risk of hemolysis, however the role is uncertain.
For the treatment of primary immunoglobulin deficiency (e.g., common variable immunodeficiency, agammaglobulinemia, hypogammaglobulinemia, Wiskott-Aldrich syndrome):
-for the treatment of primary immunoglobulin deficiency in patients switching from intravenous immune globulin:
Subcutaneous dosage (Cutaquig and Cuvitru):
Adults: Initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks beginning 1 week after previous IVIG infusion. Initially, convert the previous IVIG dose into a weekly equivalent by dividing the previous dose in grams by the number of weeks between doses; then multiply this dose by 1.3. Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used. For frequent dosing, divide the weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For biweekly dosing, multiply the weekly dose by 2. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Children and Adolescents 2 to 17 years: Initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks beginning 1 week after previous IVIG infusion. Initially, convert the previous IVIG dose into a weekly equivalent by dividing the previous dose in grams by the number of weeks between doses; then multiply this dose by 1.3. Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used. For frequent dosing, divide the weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For biweekly dosing, multiply the weekly dose by 2. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Subcutaneous dosage (Hizentra):
Adults: Initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks after receiving a regularly scheduled IVIG infusion for at least 3 months. Initially, convert the IVIG dose into a weekly equivalent by multiplying the previous IVIG dose in grams by 1.37, then dividing into weekly doses based on the previous IVIG weekly treatment interval (i.e., if IVIG is administered every 3 weeks, divide by 3). Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used. For frequent dosing, divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For frequent dosing or weekly dosing, give the first dose 1 week after the last IVIG infusion. For biweekly dosing (once every 2 weeks), multiply the calculated weekly dose by 2 and start treatment 1 to 2 weeks after the last IVIG infusion. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Children and Adolescents 2 to 17 years: Initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks after receiving a regularly scheduled IVIG infusion for at least 3 months. Initially, convert the IVIG dose into a weekly equivalent by multiplying the previous IVIG dose in grams by 1.37, then dividing into weekly doses based on the previous IVIG weekly treatment interval (i.e., if IVIG is administered every 3 weeks, divide by 3). Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used. For frequent dosing, divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For frequent dosing or weekly dosing, give the first dose 1 week after the last IVIG infusion. For biweekly dosing (once every 2 weeks), multiply the calculated weekly dose by 2 and start treatment 1 to 2 weeks after the last IVIG infusion. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Subcutaneous dosage (Xembify):
Adults: Initiate subcutaneous infusion at regular intervals from once daily to once weekly beginning 1 week after the last IVIG infusion. Initially, convert the IVIG dose into a weekly equivalent by multiplying the previous IVIG dose in grams by 1.37, then dividing into weekly doses based on the previous IVIG weekly treatment interval (i.e., if IVIG is administered every 3 weeks, divide by 3). Provided the total weekly dose is maintained, any dosing interval from daily up to weekly can be used. For frequent dosing, divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). Measure IgG trough concentration as early as 5 weeks after initiating treatment and every 2 to 3 months as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Children and Adolescents 2 to 17 years: Initiate subcutaneous infusion at regular intervals from once daily to once weekly beginning 1 week after the last IVIG infusion. Initially, convert the IVIG dose into a weekly equivalent by multiplying the previous IVIG dose in grams by 1.37, then dividing into weekly doses based on the previous IVIG weekly treatment interval (i.e., if IVIG is administered every 3 weeks, divide by 3). Provided the total weekly dose is maintained, any dosing interval from daily up to weekly can be used. For frequent dosing, divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). Measure IgG trough concentration as early as 5 weeks after initiating treatment and every 2 to 3 months as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
-for the treatment of primary immunoglobulin deficiency in patients switching from immune globulin infusion 10% with recombinant human hyaluronidase (Hyqvia):
Subcutaneous dosage (Cuvitru):
Adults: Initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks beginning 1 week after previous immune globulin infusion. Initially, convert the previous immune globulin dose into a weekly equivalent by dividing the previous dose in grams by the number of weeks between doses; then multiply this dose by 1.3. Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used. For frequent dosing, divide the weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For biweekly dosing, multiply the weekly dose by 2. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Children and Adolescents 2 to 17 years: Initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks beginning 1 week after previous immune globulin infusion. Initially, convert the previous immune globulin dose into a weekly equivalent by dividing the previous dose in grams by the number of weeks between doses; then multiply this dose by 1.3. Provided the total weekly dose is maintained, any dosing interval from daily up to biweekly can be used. For frequent dosing, divide the weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For biweekly dosing, multiply the weekly dose by 2. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
-for the treatment of primary immunoglobulin deficiency in patients switching from other subcutaneous immune globulin products:
Subcutaneous dosage (Cutaquig, Cuvitru, and Hizentra):
Adults: Maintain the previous weekly IGSC dose and initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks beginning 1 week after the last IGSC infusion. For frequent dosing, divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For biweekly dosing, multiply the weekly dose by 2. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Children and Adolescents 2 to 17 years: Maintain the previous weekly IGSC dose and initiate subcutaneous infusion at regular intervals from once daily to once every 2 weeks beginning 1 week after the last IGSC infusion. For frequent dosing, divide the previous weekly dose by the desired number of times per week (e.g., for 3 times per week dosing, divide the weekly dose by 3). For biweekly dosing, multiply the weekly dose by 2. Measure IgG trough concentration 2 to 3 months after switching products and as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly or biweekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Subcutaneous dosage (Xembify):
Adults: Maintain the previous weekly IGSC dose and initiate subcutaneous infusion at regular intervals from once daily to once weekly beginning 1 week after the last IGSC infusion. Measure IgG trough concentration as early as 5 weeks after switching products and every 2 to 3 months as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
Children and Adolescents 2 to 17 years: Maintain the previous weekly IGSC dose and initiate subcutaneous infusion at regular intervals from once daily to once weekly beginning 1 week after the last IGSC infusion. Measure IgG trough concentration as early as 5 weeks after switching products and every 2 to 3 months as needed to guide subsequent dose and dosing interval adjustments. Calculate the difference in the patient's trough concentration from the target IgG trough concentration. Use dosage adjustment guidelines provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the weekly dose based on the patient's body weight. Clinical response should be the primary consideration in dose adjustment.
For the maintenance treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment:
NOTE: Maintenance therapy for CIDP has been studied for 6 months and for a further 12 months in a follow-up study. Therapy beyond these periods should be individualized based upon patient response and continued need for treatment.
Subcutaneous dosage (Hizentra):
Adults: 0.2 g/kg/dose subcutaneously once weekly given in 1 or 2 sessions over 1 or 2 consecutive days beginning 1 week after the last IVIG infusion. If CIDP symptoms worsen, consider increasing the dose to 0.4 g/kg/dose subcutaneously once weekly given in 2 sessions per week over 1 or 2 consecutive days. If CIDP symptoms worsen on the increased dose, consider reinitiating treatment with an IVIG product while discontinuing subcutaneous therapy.
For measles prophylaxis in patients with immunoglobulin deficiency who have been exposed to measles or are at risk of measles exposure:
Subcutaneous dosage (Cutaquig):
Adults: 400 mg/kg/dose subcutaneously as soon as possible and within 6 days of exposure. This dose should provide a serum concentration more than 240 milli-International Units/mL of measles antibodies for at least 2 weeks. If a patient is at risk of future measles exposure and receives a dose less than 245 mg/kg subcutaneously per week, increase the weekly dose to at least 245 mg/kg.
Children and Adolescents 2 to 17 years: 400 mg/kg/dose subcutaneously as soon as possible and within 6 days of exposure. This dose should provide a serum concentration more than 240 milli-International Units/mL of measles antibodies for at least 2 weeks. If a patient is at risk of future measles exposure and receives a dose less than 245 mg/kg subcutaneously per week, increase the weekly dose to at least 245 mg/kg.
Subcutanaous dosage (Cuvitru):
Adults: 400 mg/kg/dose subcutaneously as soon as possible and within 6 days of exposure. This dose should provide a serum concentration more than 240 milli-International Units/mL of measles antibodies for at least 2 weeks. If a patient is at risk of future measles exposure and receives a dose less than 230 mg/kg subcutaneously per week, increase the weekly dose to at least 230 mg/kg.
Children and Adolescents 2 to 17 years: 400 mg/kg/dose subcutaneously as soon as possible and within 6 days of exposure. This dose should provide a serum concentration more than 240 milli-International Units/mL of measles antibodies for at least 2 weeks. If a patient is at risk of future measles exposure and receives a dose less than 230 mg/kg subcutaneously per week, increase the weekly dose to at least 230 mg/kg.
Subcutaneous dosage (Hizentra):
Adults: At least 200 mg/kg/dose subcutaneously once weekly for 2 consecutive weeks OR, for patients receiving biweekly dosing, 400 mg/kg subcutaneously once. If a patient has been exposed to measles, administer this minimum dose as soon as possible after measles exposure.
Children and Adolescents 2 to 17 years: At least 200 mg/kg/dose subcutaneously once weekly for 2 consecutive weeks OR, for patients receiving biweekly dosing, 400 mg/kg subcutaneously once. If a patient has been exposed to measles, administer this minimum dose as soon as possible after measles exposure.
Maximum Dosage Limits:
-Adults
Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin.
-Geriatric
Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin.
-Adolescents
Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin.
-Children
2 to 12 years: Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin.
younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
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
Specific guidelines for dosage adjustments in renal impairment are not available. In patients at risk of developing renal dysfunction, consider lower, more frequent dosing.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Acetaminophen; Aspirin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Acetaminophen; Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Acyclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like acyclovir. Administer IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential risk for developing acute renal failure.
Adefovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like adefovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amikacin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Aminoglycosides: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Amlodipine; Celecoxib: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amphotericin B lipid complex (ABLC): (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amphotericin B liposomal (LAmB): (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amphotericin B: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Caffeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Dipyridamole: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Omeprazole: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Aspirin, ASA; Oxycodone: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Bacitracin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like bacitracin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Bismuth Subsalicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Bupivacaine; Meloxicam: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Capreomycin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like capreomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Celecoxib: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Celecoxib; Tramadol: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Choline Salicylate; Magnesium Salicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Cidofovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cidofovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Cisplatin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and immune globulin products (IVIG) are necessary. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Cisplatin can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins. IVIG has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death.
Colistimethate, Colistin, Polymyxin E: (Moderate) Use caution with concomitant Immune Globulin (IG) products and colistimethate sodium. IG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Colistin: (Moderate) Use caution with concomitant Immune Globulin (IG) products and colistimethate sodium. IG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Cyclosporine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cyclosporine. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Diclofenac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Diclofenac; Misoprostol: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Diflunisal: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Diphenhydramine; Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Diphenhydramine; Naproxen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Efgartigimod Alfa: (Moderate) Monitor for reduced efficacy of immune globulin during coadministration with efgartigimod. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as immune globulin, may reduce immune globulin exposure and efficacy. Consider efgartigimod discontinuation and the use of alternative therapies if long-term therapy with immune globulin is needed.
Efgartigimod Alfa; Hyaluronidase: (Moderate) Monitor for reduced efficacy of immune globulin during coadministration with efgartigimod. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as immune globulin, may reduce immune globulin exposure and efficacy. Consider efgartigimod discontinuation and the use of alternative therapies if long-term therapy with immune globulin is needed.
Etodolac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Fenoprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Flurbiprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Foscarnet: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like foscarnet. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ganciclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like ganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Gentamicin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Hydrocodone; Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen; Famotidine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen; Oxycodone: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen; Pseudoephedrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indomethacin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ketoprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ketorolac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Magnesium Salicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. There should be an interval of at least 5 months following administration of immune globulin, including varicella-zoster immune globulin, VZIG, before varicella vaccination. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations. (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of blood, plasma, and/or immunoglobulins because antibodies in these products can neutralize the vaccine.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of blood, plasma, and/or immunoglobulins because antibodies in these products can neutralize the vaccine.
Meclofenamate Sodium: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Mefenamic Acid: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Meloxicam: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Nabumetone: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Naproxen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Naproxen; Esomeprazole: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Naproxen; Pseudoephedrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Nonsteroidal antiinflammatory drugs: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Oxaprozin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Pamidronate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pamidronate. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Paromomycin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Pentamidine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pentamidine. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Piroxicam: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Plazomicin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Polymyxin B: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like polymyxin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Pozelimab: (Major) Avoid concomitant use of pozelimab and intravenous immune globulin (IVIG). If use is necessary, monitor for reduced clinical efficacy of pozelimab. Concomitant use may decrease serum pozelimab concentrations.
Ravulizumab: (Major) Administer a supplemental dose of ravulizumab and monitor for reduced efficacy of ravulizumab during concurrent use with immune globulin. Consult the manufacturer's recommendations for the supplemental dosage. Concomitant use of immune gloublin with ravulizumab may reduce ravulizumab exposure and efficacy.
Rotavirus Vaccine: (Major) Efficacy of live attenuated virus vaccines such as Rotavirus may be impaired by immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after immune globulin administration. Inform the immunizing physician of recent therapy with immune globulin so that appropriate measures can be taken.
Salsalate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Streptomycin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Streptozocin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like streptozocin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Sulindac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Sumatriptan; Naproxen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Tacrolimus: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like tacrolimus. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Tobramycin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Tolmetin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Valacyclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like valacyclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Valganciclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like valganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Vancomycin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Varicella-Zoster Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. There should be an interval of at least 5 months following administration of immune globulin, including varicella-zoster immune globulin, VZIG, before varicella vaccination. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations.
Zoledronic Acid: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like zoledronic acid. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Immune globulin subcutaneous (IGSC) supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. The exact mechanism by which immunoglobulins yield a therapeutic effect in immune deficiency states is not well understood. The pooled heterogenous IgG present in IGSC provides antibodies capable of altering toxins and microbes so that they are more readily and more efficiently engulfed by phagocytes. The passive immunity imparted by IGSC is capable of attenuating or preventing infectious diseases or deleterious reactions from toxins, mycoplasma, parasites, bacteria, and viruses. The amount of each IgG subclass in IGSC is similar to that of human plasma.
Immune globulin subcutaneous (IGSC) is administered by subcutaneous injection.
-Route-Specific Pharmacokinetics
Subcutaneous Route
The systemic availability of IGSC can be affected by several factors, including the site of administration and the rate of IgG catabolism. Catabolism of IgG is affected by the size and timing of a dose. After a large IVIG infusion, high plasma concentrations can saturate the Fc receptors and lead to increased IgG catabolism. IGSC is administered more frequently and results in lower serum IgG peaks and, hence, decreased IgG catabolism. The reduction in IgG catabolism leads to higher serum IgG trough concentrations, which may be beneficial for some patients.
-Cutaquig: In a sub-study (n = 37; ages 2 years and older) where patients were switched from IVIG to Cutaquig, the mean (SD) Cmax concentration for Cutaquig once weekly recipients with primary immunodeficiency was 13.47 (3.7) g/L as compared with 18.01 (4.5) g/L for IVIG recipients. The mean Cmin (11.66 g/L Cutaquig vs. 10.09 g/L IVIG), AUC (2,233 g x hour/L Cutaquig vs. 2,013 g x hour/L IVIG), and clearance (1.9 mL/kg/day Cutaquig vs. 1.5 mL/kg/day IVIG) were similar between the groups. The median Tmax was 49.62 hours for Cutaquig and 3.38 hours for IVIG. The mean (SD) actual IgG dose/kg body weight was 0.17 (0.066) g/kg/week for Cutaquig and 0.121 (0.049) g/kg/week for IVIG. Serum IgG and IgG subclass trough concentrations were nearly constant during the Cutaquig phase of the study, with higher mean concentrations after Cutaquig treatment compared with those after IVIG. At the end of the IVIG period, trough concentrations ranged from 5 to 15.1 g/L. Over the entire Cutaquig treatment period, individual trough concentrations of total IgG ranged between 4.4 to 24 g/L. Compared with weekly administration, dosing up to 7 times per week of Cutaquig is expected to result in comparable IgG exposures in adult and pediatric patients. Biweekly administration at double the weekly dose results in equivalent AUCs with a slightly higher IgG peak and slightly lower trough. Pharmacokinetic parameters for Cutaquig were comparable between age groups.
-Cuvitru: In a Cuvitru study (n = 60; ages 2 years and older), all patients were switched from IVIG to weekly subcutaneous Cuvitru, and the Cuvitru doses were 145% of the IVIG dose. All patients were treated with this dose for 12 weeks after which the dose was individualized for all subjects using trough IgG concentrations. At this dose adjustment, the mean ratio of the AUC for subcutaneous Cuvitru vs. IVIG was 109%. The peak IgG concentration occurred at a mean of 79 hours after subcutaneous Cuvitru administration. The median peak IgG concentrations were lower during subcutaneous treatment with Cuvitru (1,809 mg/dL) compared to IVIG administration (2,602 mg/dL for 3-week intervals and 2,521 mg/dL for 4-week intervals), consistent with the lower weekly dose compared with the IVIG dose administered every 3 to 4 weeks. The mean trough concentration for Cuvitru once weekly recipients (1,474 mg/dL) was higher compared with IVIG recipients (1,158 mg/dL for 3-week intervals and 1,019 mg/dL for 4-week intervals), a result of both higher monthly dose and more frequent dosing. In contrast to IVIG administered every 3 to 4 weeks, weekly subcutaneous administration results in relatively stable steady-state serum IgG concentrations. Pharmacokinetic parameters for Cuvitru did not differ significantly between age groups.
-Hizentra: The mean trough concentration for Hizentra once weekly recipients with primary immunodeficiency was 1,448 mg/dL (range, 952 to 2,623 mg/dL) as compared with 1,127 mg/dL (range, 702 to 1,810 mg/dL) for IVIG recipients. In these studies, all patients were switched from IVIG to Hizentra, and the Hizentra doses were individually adjusted to provide a systemic serum IgG exposure not inferior to that of the previous weekly equivalent IVIG dose. The average dose adjustment for Hizentra was 153% (range, 126% to 187%) of the previous weekly-equivalent IVIG dose. The mean weekly dose of Hizentra was 228 mg/kg (range, 141 to 381 mg/kg), and the mean weekly-equivalent dose of IVIG was 152 mg/kg (range, 86 to 254 mg/kg). In contrast to IVIG administered every 3 to 4 weeks, weekly subcutaneous administration results in relatively stable steady-state serum IgG concentrations. In patients with chronic inflammatory demyelinating polyneuropathy, the mean (SD) IgG trough concentrations after 24 weeks of treatment were 15.3 (2.57) g/L and 20.8 (3.23) g/L for treatment regimens of 0.2 g/kg and 0.4 g/kg, respectively. When switching from IVIG to weekly Hizentra dosing, the serum IgG trough concentration is projected to be approximately 16% higher than the last trough concentration during prior IVIG therapy. The serum trough concentration is projected to be approximately 10% higher than the last IVIG trough concentration when switching from IVIG to biweekly Hizentra dosing. When switching from weekly to biweekly Hizentra dosing, the trough is projected to be approximately 5% lower than the last weekly trough concentration. The serum trough concentration is projected to be approximately 3% to 4% higher than the last weekly trough concentration when switching from weekly Hizentra dosing to a regimen of 2 to 7 times per week. However, systemic exposure for IVIG, weekly Hizentra, biweekly Hizentra, or more frequent dosing with Hizentra is similar. For example, compared with weekly administration, biweekly administration at double the weekly dose results in comparable IgG exposure (equivalent AUCs with a slightly higher IgG peak and slightly lower trough) as predicted by PK modeling and simulation.
-Xembify: In a pharmacokinetic study (n = 49; ages 2 years and older), all patients were switched from IVIG to weekly subcutaneous Xembify, and the Xembify doses were 137% of the IVIG dose. All patients were treated with this dose for 13 to 14 weeks after which the dose was individualized for all subjects using trough IgG concentrations. At this dose adjustment, the mean ratio of the AUC for subcutaneous Xembify vs. IVIG was 104%. The average mean IgG trough concentration at steady state was higher for subcutaneous Xembify compared to IVIG (1,245 mg/dL vs. 957 mg/dL). The mean AUC (2,183 hour x mg/mL Xembify vs. 2,122 hour x mg/mL IVIG), Cmax (14 mg/mL Xembify vs. 22 mg/mL IVIG), and Tmax (76 hours Xembify vs. 5.8 hours IVIG) were reported for both groups. The apparent variability in Tmax in the subcutaneous phase can be attributed to the low fluctuation in IgG concentration and is unlikely to be of any clinical relevance. Pharmacokinetic parameters for Xembify did not differ significantly between age groups.
-Special Populations
Pediatrics
No pediatric-specific dose requirements are necessary for either weekly, biweekly, or more frequent dosing of IGSC. Pharmacokinetic studies of IGSC in pediatric patients (2 to 16 years) have shown pharmacokinetic parameters (AUC, Cmax, Cmin, Tmax, clearance) to be similar to values observed in adults.