immune globulin IV (IGIV) (Rx)

>10%

Privigen

• Headache (45%)
• Fatigue (16.3%)
• Nausea (13.8%)
• Chills (11.3%)
• Vomiting (11.3%)

Flebogamma

• Headache (21.7%)
• Pyrexia (19.6%)
• Pain (15.2%)
• Injection site reaction (13%)

Asceniv

• Headache (24%)

1-10%

Privigen

• Back pain (10%)
• Pain (8.8%)
• Elevated body temperature (8.8%)
• Diarrhea (7.5%)
• Cough (6.3%)
• Stomach discomfort (6.3%)
• Blood total bilirubin increased (5.3%)
• Hematocrit decreased (5.3%)
• Blood lactate dehydrogenase increased (5.3%)

Flebogamma

• Diarrhea (8.7%)
• Rigors (8.7%)
• Infusion site inflammation (6.6%)
• Urticaria (6.5%)

Gammagard S/D or Gammagard

• Headache (5.1-5.2%)
• Chills (2.7%)
• Elevated temperature (1.8%)
• Fatigue (1-1.8%)
• Pyrexia (1.5%)
• Nausea (1.5%)
• Emesis (1.3%)
• Hypertension (1%)
• Flushing (1%)

Asceniv

• Sinusitis (10%)
• Nausea (9%)
• Acute sinusitis (7%)
• Fatigue (7%)
• Muscle spasms (7%)
• Bronchitis (5%)
• Diarrhea (5%)
• Nose bleed (5%)
• Muscle pain (5%)
• Oropharyngeal pain (5%)
• Pain in extremity (5%)
• Itching (5%)

<1%

Gammagard S/D or Gammagard

• Chills
• Rigor
• Pain in extremity
• Diarrhea
• Migraine
• Dizziness
• Vomiting
• Leg cramps
• Flu-like symptoms
• Exanthema
• Loss of appetite
• Anxiety
• Backache
• Urticaria

Frequency Not Defined

Carimune NF

• Arthralgia
• Myalgia
• Transient skin reactions (eg, rash, erythema, pruritus, urticaria, eczema, dermatitis)

Postmarketing Reports

Respiratory: Apnea, acute respiratory distress syndrome (ARDS), transfusion-related acute lung injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm

Cardiovascular: Cardiac arrest, thromboembolism, vascular collapse, hypotension

Neurological: Coma, loss of consciousness, seizures, tremor

Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis

Hematologic: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test

General/Body: Whole pyrexia, rigors

Musculoskeletal: Back pain

Gastrointestinal: Hepatic dysfunction, abdominal pain

Contraindications

Hypersensitivity to gamma globulin, thimerosal

Isolated IgA deficiency

Hyperprolinemia (Privigen)

Cautions

Risk of transmitting infectious agents (eg, viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) agent); all infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider

Severe hypersensitivity reactions may occur; in case of hypersensitivity, discontinue the Privigen infusion immediately and institute appropriate treatment (see Contraindications)

Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients (see Black Box Warnings)

Aseptic meningitis syndrome (AMS) may occur infrequently following treatment with immune globulin products; discontinuation of treatment has resulted in remission of AMS within several days without sequelae; AMS usually begins within several hours to 2 days following IGIV treatment

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur following treatment with IGIV products

Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration; IGIV recipients should be monitored for clinical signs and symptoms of hemolysis; if signs and/or symptoms of hemolysis are present after IGIV infusion, appropriate confirmatory laboratory testing should be done

Postpone live virus vaccines for at least 3 months

Maltose-containing brands may give false high for glucose in certain glucose-testing systems

Various passively transferred antibodies in immunoglobulin preparations may lead to misinterpretation of the results of serological testing

Transfusion-Related Acute Lung Injury (TRALI)

• Noncardiogenic pulmonary edema may occur following treatment with IGIV products TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever
• Symptoms typically appear within 1-6 hr following treatment; monitor patients for pulmonary adverse reactions
• If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the product and the patient's serum
• TRALI may be managed using oxygen therapy with adequate ventilatory support

Pregnancy

No human data are available to indicate the presence or absence of drug-associated risk

Animal reproduction studies have not been conducted

Unknown if immune globulin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity

Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation

Lactation

No human data are available to indicate the presence or absence drug-associated risk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Pooled human immune globulins from donors used as replacement therapy for primary and secondary immunodeficiencies; may interfere with Fc receptors on the cells of the reticuloendothelial system for autoimmune disorders including cytopenias and ITP; may offer passive immunity by increasing antibody titer and antigen-antibody reaction potential

Absorption

Peak plasma concentration

• 2,227-2,427 mg/dL (Asceniv)
• 1,929-2,069 mg/dL (Flebogamma)
• 2,340 mg/dL (Privigen)
• 2,050 mg/dL (Gammagard)
• 2,122-2,184 mg/dL (Bivigam)

Peak plasma time

• 2.78-2.93 hr (Asceniv)
• 27.8-37.3 days (Privigen)
• 3.47-4.05 hr (Bivigam)

AUC

• 32,128-35,905 mg·day/dL (Asceniv)
• 31,159-32,894 mg·day/dL (Flebogamma)
• 78,748-98,521 mg·day/dL (Privigen)
• 29,139 mg·day/dL (Gammagard)
• 27,841-35,509 mg·day/dL (Bivigam)

Distribution

Vd (steady-state): 76.79-89.57 mL/kg (Asceniv); 44-87 mL/kg (Flebogamma); 0.584-0.640 dL/kg (Bivigam)

Elimination

Half-life

• 23.47-39.7 days (Asceniv)
• 34.1 days (Gammagard S/D)
• 21 days (Carimune NF)
• 30-32 days (Flebogamma)
• 27.8-37.3 days (Privigen)
• 35 days (Gammagard)
• 19.6-33.5 days (Bivigam)

Clearance

• 1.47-1.68 mL/day/kg (Asceniv)
• 109-139 mL/day (Flebogamma)
• 1.3 mL/kg/day (Privigen)
• 0.0197-0.0141 dL/kg/day (Bivigam)

IV Preparation

Dilution is dependent upon mfr & brand; do not shake, avoid foaming; discard unused portion

Gammagard S/D, Polygam S/D: reconstitute with SWI; when diluted aseptically in a sterile laminar air flow hood, may store diluted solution under refrigeration for up to 24 hr; if reconstituted outside of laminar flow hood, use within 2 hr. Gammagard requires a filter, supplied by mfr.

Gamunex incompatible w/ saline, dilute in D5W if necessary

Asceniv, Flebogamma: Do not mix with other IGIV products or other IV medications; do not dilute, do not microwave

IV Administration

For initial treatment, a lower concentration and/or a slower rate of infusion should be used

Administer in separate infusion line from other medications; if using primary line, flush with saline prior administration

Decrease dose, rate &/or concentration of infusion in pts who may be at risk of renal failure

Decreasing rate or stopping the infusion may help relieve some adverse effects (flushing, changes in pulse rate, changes in blood pressure)

Epinephrine should be available during administration

IV Infusion Rates

Asceniv

• Initial rate: 0.5 mg/kg/min for the first 15 min
• May increase (if tolerated) q5min to up to 8 mg/kg/min (0.08 mL/kg/min)

Carimune NF

• Infuse at <2 mg/kg/min
• Start at 10–20 drops (0.5–1 mL) per min
• After 15–30 min, rate of infusion may be further incr to 30–50 drops (1.5–2.5 mL) per min
• If patient tolerates first 3% soln infusion, subsequent infusions may be administered at higher rate or concentration

Flebogamma 5%

• Initiate at 0.5 mg/kg/min
• If well-tolerated during first 30 min, increase rate gradually to not to exceed 5 mg/kg/min
• Patients at risk for developing renal dysfunction: infuse at not to exceed 3 mg/kg/min

Gammagard S/D

• Infuse 5% soln at 0.5 mL/kg/hr
• If well tolerated (at each step) & no hx of ADRs to IGIV & no significant risk factors for renal dysfunction or thrombotic complications may gradually incr to not to exceed 4 mL/kg/hr, THEN 10% soln starting at 0.5 mL/kg/hr, and finally may increase gradually to not to exceed 8 mL/kg/hr
• Patients at risk of renal damage or thrombotic complications: NMT <3.3 mg/kg/min (<2 mL/kg/hr of a 10% solution or <4mL/kg/hr of a 5% solution)
• Recommend antecubital veins esp for 10% soln
• Rapid rate of admin may cause flushing & changes in pulse rate & BP

Gammaplex

• 0.5 mg/kg/min (0.01 mL/kg/min) IV for 15 minutes, THEN
• May increase (if tolerated) to 4 mg/kg/min (0.08 mL/kg/min)
• Use inline 15-20 micron filter during infusion

Gammaked

• Primary immunodeficiency: 1 mg/kg/min IV initially; maintenance up to 8 mg/kg/min IV if tolerated
• Primary immunodeficiency (SC maintenance): 20 mL/hr/site
• ITP: 1 mg/kg/min IV initially; maintenance up to 8 mg/kg/min IV if tolerated
• CIDP: 2 mg/kg/min IV initially; maintenance up to 8 mg/kg/min IV if tolerated

Gamunex-C

• Primary immunodeficiency, ITP: initial 1 mg/kg/min; maint: 8 mg/kg/min if tolerated
• CIDP: initial 2 mg/kg/min; maint: 8 mg/kg/min if tolerated

Privigen

• Start at 0.5 mg/kg/min
• If well tolerated, gradually increase up 8 mg/kg/min
• Patients at risk of renal damage or thrombotic complications: administer at minimum infusion rate that is practicable

Panzyga

• First 30 min: 1 mg/kg/min (0.01 mL/kg/min)
• New patients; maximum rate (as tolerated): 8 mg/kg/min (0.08 mL/kg min)
• Experienced patients treated for primary immunodeficiency; maximum rate: 12-14 mg/kg/min (0.12-0.14 mL/kg/min)
• Patients with pre-existing or at risk for developing renal insufficiency: Do not exceed infusion rate of 3.3 mg/kg/min (0.033 mL/kg/min)

Storage

Bivigam, Asceniv: Refrigerate at 2-8°C (36-46°F); do not freeze

Carimune NF: Prior to reconstitution, store ≤30°C (86°F), do not freeze; following reconstitution, refrigerate at 2-8°C (36-46°F)

Flebogamma DIF: Store at 2-25°C (36-77°F); keep in original carton to protect from light; do not freeze or use if solution has been frozen

Gammagard Liquid: Prior to use, may store at 2-8°C (36-46°F) for up to 36 months or at ≤25°C (≤77°F) for up to 24 months; do not freeze

Gammagard S/D: Store at ≤25°C (≤77°F) for up to 24 months; refrigerate diluted solution at 2-8°C (36-46°F) for up to 24 hr if originally prepared in a sterile laminar air flow environment

Gammaked or Gamunex-C: Store at 2-8°C (36-46°F); may be stored at ≤25°C (≤77°F) for up to 6 months

Gammaplex: Store at 2-25°C (36-77°F); keep in original carton to protect from light; do not freeze or use if solution has been frozen

Octagam 10% or Panzyga: Store at 2-8°C (36-46°F) for 24 months from the date of manufacture; within these first 12 months, may store up to 9 months at ≤25°C (≤77°F); after storage at ≤25°C (≤77°F) use or discard product

Privigen: Store at ≤25°C (≤77°F); do not freeze or use if solution has been frozen; protect from light