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Immune Globulin

IV / Subcutaneous

Pronunciation: i-MUNE GLOB-ue-lin
Class: Immune globulin

Trade Names

Gammagard Liquid
- Injection, solution 100 mg/mL

Gammaked
- Injection, solution 100 mg/mL

Gamunex-C
- Injection, solution 100 mg/mL

Pharmacology

Replaces normal human immunoglobulin G (IgG) antibodies.

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Pharmacokinetics

Absorption

C max is approximately 19 mg/mL (IV).

Elimination

Half-life is approximately 35 days (IV).

Indications and Usage

Gamunex-C and Gammaked

Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP); treatment of idiopathic thrombocytopenic purpura (ITP); treatment of primary humoral immunodeficiency.

Gammagard Liquid

Treatment of primary humoral immunodeficiency.

Contraindications

History of anaphylactic or severe systemic reaction to administration of human immune globulin; IgA-deficient patients with antibodies against IgA and/or a history of hypersensitivity.

Dosage and Administration

Chronic Inflammatory Demyelinating Polyneuropathy ( Gamunex-C and Gammaked )
Adults Loading dose

IV 2 g/kg given in divided doses over 2 to 4 consecutive days.

Maintenance dose

IV 1 g/kg administered over 1 day or divided into 2 doses of 0.5 g/kg given on 2 consecutive days every 3 wk.

Idiopathic Thrombocytopenic Purpura ( Gamunex-C and Gammaked )
Adults and children

IV 2 g/kg given on 2 consecutive days; if after administration of the first dose an adequate increase in platelet count is observed at 24 h, the second dose may be withheld. An alterative regimen of 0.4 g/kg given on 5 consecutive days may also be used. The 2-day regimen is not recommended for patients with expanded fluid volumes or in whom fluid volume may be a concern.

Primary Humoral Immunodeficiency
Gamunex-C and Gammaked Adults and children

IV 300 to 600 mg/kg every 3 to 4 wk. The dosage may be adjusted over time to achieve the desired trough levels and clinical responses. In patients at risk for measles exposure who routinely receive a dosage less than 400 mg/kg every 3 to 4 wk, administer a dose of at least 400 mg/kg just prior to the expected exposure or as soon as possible after a known exposure.

Adults

Subcutaneous Establish the weekly dose by converting the monthly immune globulin IV dose into a weekly equivalent. In patients receiving immune globulin IV preparations other than Gamunex-C or Gammaked , multiply the previous immune globulin IV dose in grams by the dose adjustment factor of 1.37 and divide the result by the number of weeks between doses of immune globulin IV preparation (ie, 3 or 4). Over time, the dose may need to be adjusted to achieve the desired clinical response and serum IgG trough level. Measure the patient's serum trough level on immune globulin IV and as early as 5 wk after switching to subcutaneous administration; the target serum IgG trough level on weekly subcutaneous treatment is expected to be the last immune globulin IV trough level plus 340 mg/dL. Monitor the patient's IgG trough level every 2 to 3 mo on subcutaneous treatment. To adjust the dose based on these trough levels, calculate the difference in the last IgG trough level from the target IgG trough level, and then find this difference in the following table and the corresponding amount (in milliliters) by which to increase or decrease the weekly dose based on the patient's body weight.

Gamunex-C and Gammaked Weekly Subcutaneous Dosage Adjustment Difference from target IgG trough level (mg/dL) Body weight (kg) 10 15 20 30 40 50 60 70 80 90 100 110 120 Dosage adjustment (mL/wk) 50 1 1 2 3 3 4 5 6 7 8 8 9 10 100 2 3 3 5 7 8 10 12 13 15 17 18 20 150 3 4 5 8 10 13 15 18 20 23 25 28 30 200 3 5 7 10 13 17 20 23 27 30 33 37 40 250 4 6 8 13 17 21 25 29 33 38 42 46 50 300 5 8 10 15 20 25 30 35 40 45 50 55 60 350 6 9 12 18 23 29 35 41 47 53 58 64 70 400 7 10 13 20 27 33 40 47 53 60 67 73 80 450 8 11 15 23 30 38 45 53 60 68 75 83 90 500 8 13 17 25 33 42 50 58 67 75 83 92 100

Dose adjustment in milliliters is based on the slope of the serum IgG trough level response to subcutaneous administration of Gamunex-C or Gammaked dose increments (approximately 6 mg/dL per increment of 1 mg/kg/wk).

Gammagard Adults and children 2 y and older

IV 300 to 600 mg/kg every 3 to 4 wk based on clinical response. Adjust dose according to IgG levels and clinical response, as the frequency and dose of immune globulin may vary from patient to patient.

Subcutaneous Initial dose is 1.37 times the previous immune globulin IV dose divided by number of weeks between IV doses. Start the initial subcutaneous dose approximately 1 wk after the last immune globulin IV infusion. Base maintenance dose on clinical response and target IgG trough level. To calculate the target trough IgG level for subcutaneous treatment, add 281 mg/dL to the IgG trough level obtained after the last IV treatment.

To guide dose adjustment, calculate the difference between the patient's target serum IgG trough level and the IgG trough level during subcutaneous treatment. Find this difference in the columns of the following table and the corresponding amount (in milliliters) by which to increase or decrease the weekly dose based on the patient's body weight. If the difference between measured and target trough levels is less than 100 mg/dL then no adjustment is necessary.

Gammagard Liquid Subcutaneous Dosage Adjustment   Difference between measured and target IgG trough levels Dosage adjustment (mL/wk) Body weight 100 mg/dL 200 mg/dL 300 mg/dL 400 mg/dL 10 kg 2 mL 4 mL 6 mL 8 mL 20 kg 4 mL 8 mL 11 mL 15 mL 30 kg 6 mL 11 mL 17 mL 23 mL 40 kg 8 mL 15 mL 23 mL 30 mL 50 kg 9 mL 19 mL 28 mL 38 mL 60 kg 11 mL 23 mL 34 mL 45 mL 70 kg 13 mL 26 mL 40 mL 53 mL 80 kg 15 mL 30 mL 45 mL 60 mL 90 kg 17 mL 34 mL 51 mL 68 mL 100 kg 19 mL 38 mL 57 mL 75 mL 110 kg 21 mL 42 mL 62 mL 83 mL 120 kg 23 mL 45 mL 68 mL 91 mL 130 kg 25 mL 49 mL 74 mL 98 mL 140 kg 26 mL 53 mL 79 mL 106 mL

Derived using a linear approximation to the nomogram method with a slope of 5.3 kg/dL.

General Advice

  • Prior to use, allow solution to reach room temperature. Do not shake.
  • If dilution is required, dilute with dextrose 5% in water; do not dilute with saline.
  • If an adverse reaction occurs during infusion, slow or stop the infusion. If symptoms subside promptly, the infusion may be resumed at a lower rate.
  • Sites for subcutaneous infusion administration include the abdomen, thighs, upper arms, or lower back, and should be at least 2 inches apart; the maximum number of infusion sites is 8. Rotate sites each week.
  • Infuse in a separate line without mixing with other IV fluids or medications.
  • Gamunex-C and Gammaked
  • For IV administration for the treatment of primary humoral immunodeficiency, ITP, and CIDP; may also be administered subcutaneously for the treatment of primary humoral immunodeficiency.
  • Use only 18-gauge needles to penetrate the stopper of the 10 mL vial; 16-gauge needles may be used for all other vial strengths.
  • Content of vials may be pooled under aseptic conditions into sterile infusion bags.
  • For IV administration, the initial infusion rate for at least the first 30 min should be 1 mg/kg/min for treatment of primary humoral immunodeficiency or ITP, and 2 mg/kg/min for treatment of CIDP. If the initial infusion rate is tolerated, increase to 8 mg/kg/min.
  • For subcutaneous administration, the infusion rate is 20 mL/h per site.
  • Gammagard
  • For IV administration, the initial infusion rate is 0.5 mL/kg/h (0.8 mg/kg/min) for 30 min. Increase every 30 min if tolerated up to 5 mL/kg/h (8 mg/kg/min).
  • For subcutaneous administration, the initial infusion rate for patients weighing 40 kg or more is 30 mL/site at 20 mL/h/site and for patients weighing less than 40 kg is 20 mL/site at 15 mL/h/site. The maintenance infusion rate for patients weighing 40 kg or more is 30 mL/site at 20 to 30 mL/h/site and for patients weighing less than 40 kg is 20 mL/site at 15 to 20 mL/h/site.

Storage/Stability

Store for up to 36 mo from the date of manufacture at 36° to 46°F; vials may be stored for up to 6 mo ( Gamunex-C and Gammaked ) or 12 mo ( Gammagard ) at temperatures not to exceed 77°F at any time during the 36 mo ( Gamunex-C and Gammaked ) or first 24 mo ( Gammagard ) of shelf life, after which they must be used immediately or discarded. Do not freeze. Vials are for single use only; discard unused portion.

Gamunex-C and Gammaked injection solution from multiple vials that have been pooled in an infusion bag should be infused within 8 h of pooling.

Drug Interactions

Hydantoins (eg, phenytoin)

The risk of hydantoin-induced hypersensitivity myocarditis may be increased. Use with caution. Monitor hematologic findings and cardiac function if these agents are coadministered.

Live vaccines (eg, measles, mumps, rubella, varicella)

Passive transfer of antibodies may transiently interfere with the immune response to live virus vaccines. Health care providers should be informed of recent therapy with immune globulin if a patient is to receive vaccinations so appropriate measures can be taken.

Laboratory Test Interactions

Various passively transferred antibodies in immunoglobulin preparations can confound the results of serological testing. Passive transmission of antibodies to erythrocyte antigens (eg, A, B, D) may cause a positive direct or indirect antiglobulin (Coombs) test.

Adverse Reactions

Cardiovascular

Hypertension (9%); heart rate increased, increased systolic blood pressure (6%); tachycardia (5%); cerebral vascular accident, chest pain, deep vein thrombosis, hypotension, MI, phlebitis, transient ischemic attack (postmarketing).

CNS

Headache (58%); fatigue (16%); asthenia, dizziness (10%); migraine (7%); anxiety, aseptic meningitis, burning sensation, insomnia, tremor (postmarketing).

Dermatologic

Rash (10%); pruritus (8%); urticaria (7%); allergic dermatitis, hyperhidrosis (postmarketing).

EENT

Rhinitis (51%); pharyngitis (41%); epistaxis (23%); ear pain (18%); oropharyngeal pain (13%); pharyngeal pain (7%).

GI

Diarrhea (28%); nausea, vomiting (21%); upper abdominal pain (11%); abdominal pain, dyspepsia (6%).

Hematologic

Ecchymosis, purpura (40%); hemorrhage (29%); petechiae (21%); thrombocytopenia (15%); anemia (6%); hemolysis, hemolytic anemia, leukopenia, positive direct Coombs test (postmarketing).

Hypersensitivity

Anaphylactic reaction, anaphylactic shock, hypersensitivity (postmarketing).

Lab Tests

Elevated ALT (18%); elevated alkaline phosphatase (13%); elevated AST (9%); decreased alkaline phosphatase (3%).

Local

Injection-site reactions (75%).

Musculoskeletal

Rigors (13%); back pain, pain in extremity (8%); arthralgia (7%); neck pain (6%).

Respiratory

Cough increased (54%); asthma (29%); dyspnea, oxygen saturation decreased, pulmonary edema, pulmonary embolism, transfusion-related acute lung injury (postmarketing).

Miscellaneous

Fever (30%); chills (23%); flu syndrome (6%); acute renal dysfunction/failure, edema (postmarketing).

Precautions

Warnings

Renal dysfunction and failure

Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin IV products in predisposed patients. Patients predisposed to renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age older than 65 y, volume depletion, sepsis, or paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving immune globulin IV products containing sucrose. Gamunex-C , Gammagard , and Gammaked do not contain sucrose.

For patients at risk of renal dysfunction or failure, administer at the minimum concentration available and the minimum infusion rate practicable.


Monitor

When initiating therapy, monitor patients for any adverse reactions during and after infusion. Assess renal function, including BUN and serum creatinine, before the initial infusion and at appropriate intervals thereafter. 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. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity. Monitor recipients for clinical signs and symptoms of hemolysis and pulmonary adverse reactions. Clinically assess patients with known renal dysfunction or renal failure, including patients with preexisting renal insufficiency, diabetes mellitus, age older than 65 y, volume depletion, sepsis, or paraproteinemia, or those receiving nephrotoxic agents, and monitor as appropriate during therapy. Conduct a thorough neurologic exam, including CSF studies, in patients exhibiting signs and symptoms suggestive of aseptic meningitis syndrome.


Pregnancy

Category C .

Lactation

Undetermined. WHO classifies immune globulin IV as compatible with breast-feeding.

Children

Safety and efficacy not established for subcutaneous administration or for the treatment of CIDP ( Gamunex-C and Gammaked ). Safety and efficacy not established in pediatric patients younger than 2 y ( Gammagard ).

Elderly

Use caution in elderly patients at increased risk for thromboembolic events or renal insufficiency. Do not exceed recommended doses and administer at the minimum infusion rate practicable.

Hypersensitivity

Hypersensitivity, including anaphylactic reactions, may occur. Contraindicated in IgA-deficient patients with antibodies against IgA and a history of hypersensitivity reaction.

Renal Function

Patients with preexisting renal insufficiency may be at increased risk of developing renal dysfunction; infuse immune globulin at the minimum acceptable rate.

Aseptic meningitis syndrome

May occur infrequently and usually begins within several hours to 2 days following therapy. Rule out other causes of meningitis if symptoms occur.

Blood-borne virus transmission

Immune globulin subcutaneous is made from human blood and may carry a risk of transmitting infectious agents (eg, Creutzfeldt-Jakob disease, viruses).

Hematoma

Do not administer subcutaneously to patients with ITP because of the risk of hematoma formation.

Hemolysis

Delayed hemolytic anemia can develop subsequent to immune globulin IV therapy, and acute hemolysis consistent with intravascular hemolysis has been reported.

Hyperproteinemia/Increased serum viscosity/Hyponatremia

May occur.

Thrombotic events

May occur. Risk is increased in patients with a history of atherosclerosis, multiple CV risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.

Transfusion-related acute lung injury

Noncardiogenic pulmonary edema may occur in patients following treatment with immune globulin IV products. Transfusion-related acute lung injury is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever; symptoms usually occur within 1 to 6 h of treatment. Manage using oxygen therapy and adequate ventilatory support.

Volume overload

The high-dose regimen (1 g/kg × 1 to 2 days) is not recommended for patients with expanded fluid volumes or in whom fluid volume may be a concern.

Overdosage

Symptoms

Fluid overload, hyperviscosity.

Patient Information

  • Provide home-treatment patients with instructions on subcutaneous infusion, including type of equipment and its maintenance, proper infusion techniques, selection of appropriate sites, maintenance of treatment diary, and measures to take if adverse reactions occur.
  • Inform patients of the early signs of hypersensitivity reactions (eg, anaphylaxis, generalized urticaria, hives, hypotension, tightness of the chest, wheezing) and advise them to notify their health care provider if they experience any of these symptoms.
  • Inform patients that the administration of immune globulin may interfere with the response to live virus vaccines and to inform their immunizing health care provider of recent therapy with immune globulin.
  • Advise patients to be aware of and immediately report to their health care provider any of the following symptoms: decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath; acute chest pain, leg pain, and swelling of the legs/feet; severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting; increased heart rate, fatigue, yellowing of the skin or eyes, and dark-colored urine; trouble breathing, chest pain, blue lips or extremities, and fever.
  • Inform patients that medication is made from human plasma and may contain infectious agents that can cause disease (eg, viruses). Explain that the risk has been reduced by donor screening, testing the donated plasma for certain viruses, and inactivating and/or removing certain viruses during manufacturing.

Copyright © 2009 Wolters Kluwer Health.

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