Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 5% (Flebogamma, Gammaplex)
- 10% (Flebogamma, Asceniv, Bivigam, Gammagard, Gammaplex, Gamunex-C, Gammaked, Octagam, Panzyga, Privigen)
injectable solution, freeze-dried preparation (Gammagard S/D)
- 2.5g
- 5g
- 10g
injection, lyophilized powder for reconstitution (Carimune NF)
- 3g
- 6g
- 12g
Primary Immunodeficiency Syndrome
Indicated as replacement therapy for primary humoral immunodeficiency (PI); this includes, but is not limited to, the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies (SCID)
See Administration
Flebogamma, Gammagard S/D, Gamunex-C, Gammagard Liquid, Gammaked, Octagam, Panzyga
Privigen
Gammaplex, Bivigam, Asceniv
Gammagard Liquid, Gammaked, Gamunex-C (SC administration) Gammagard Liquid (SC administration)
- Initial SC dose: 1.37 × previous intravenous dose divided by # of weeks between intravenous doses
- Initial SC infusion rate: Do not exceed 30 mL per infusion site and do not exceed rate of 20 mL/hr/site
- Maintenance SC dose: Based on clinical response and target IgG trough level
- Maintenance SC infusion rate: Do not exceed 30 mL per infusion site and do not exceed rate of 20-30 mL/hr/site
Immune Thrombocytopenic Purpura
Indicated for treatment of immune thrombocytopenic purpura (ITP) to raise platelet counts to control or prevent bleeding
Gammagard S/D
Gammaplex, Octagam, Privigen, Flebogamma 10%
- 1 g/kg/day IV for 2 days
Gammaked, Gamunex-C
- 1 g/kg IV x 2 days or 400 mg/kg IV x 5 days
Carimune NF
- Acute: 400 mg/kg/day IV for 2-5 days
- Chronic: 400 mg/kg IV PRN to control significant bleeding or maintain platelet count >30,000/cu.meter
Panzyga
- 1 g/kg IV BID for 2 consecutive days
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Indicated for CIDP to improve neuromuscular disability and impairment
Gamunex-C
- Load: 2 g/kg IV in divided doses for 2-4 days
- Maintenance: 1000 mg/kg/day IV for 1 day q3Week or 500 mg/kg/day for 2 days q3Week
Privigen
- Loading dose: 2 g/kg (20 mL/kg) in divided doses over 2-5 consecutive days
- Maintenance dose: 1 g/kg (10 mL/kg) administered in 1-2 infusions on consecutive days, q3Week
Bone Marrow Transplant
500 mg/kg IV beginning on days 7 & 2 pretransplantation, THEN qWk through 90 days post-transplantation
Multifocal Motor Neuropathy
Gammagard Liquid
- Indicated as a maintenance therapy to improve muscle strength and disability in adults with multifocal motor neuropathy
- 0.5-2.4 g/kg/month IV based on clinical response
- Initial infusion rate: 0.5 mL/kg/hr IV (0.8 mg/kg/min)
- Maintenance infusion rate: Advance if tolerated to 5.4 mL/kg/hr IV (9 mg/kg/min)
Dermatomyositis (Off-label)
1 g/kg IV x2 consecutive days, THEN 400 mg/kg qMonth, generally for 6-mth course
Guillain-Barre; Lambert-Eaton Myasthenic; Stiffman Syndrome (Off-label)
Neonatal Hemochromatosis (Off-label)
1 g/kg IV qWk to pregnant woman 18th week until end of gestation
Orphan Designations
Octagam: Stiff person syndrome
Octagam: Dermatomyositis
Gamunex-C: Myasthenia gravis
Sponsors
- Octapharma USA, Inc; 121 River Street; Hoboken, NJ 07030
- Grifols Therapeutics, Inc; 79 TW Alexander Drive; Research Triangle Park, NC
Other Indications & Uses
Primary immunodeficiencies
Bone marrow transplant indicated for Gamunex (Canada); was indicated for one US product (Gamimune N) which has been discontinued; other brands used off-label
Off-label: secondary immunodeficiencies, dermatomyositis, Guillain-Barre synd, myasthenia gravis, multifocal motor neuropathy, relapsing-remitting multiple sclerosis, Lambert-Eaton myasthenic syndrome, stiffman syndrome, pemphigus vulgaris, SLE, HDN, multiple myeloma, TSS, streptococcal necrotizing fasciitis, Churg-Strauss syndrome, refractory autoimmune hemolytic anemia, opsoclonus-myoclonus, Hyper IgE syndrome, FAIT, Parvovirus B19 infection w/ anemia, delayed pressure urticaria, epidermolysis bullosa, neonatal hemochromatosis, birdshot retinochoroidopathy, acute disseminated encephalomyelitis, Rasmussen's syndrome, enteroviral meningoencephalitis
Dosage Forms & Strengths
injectable solution
- 5% (Flebogamma, Gammaplex)
- 10% (Flebogamma, Asceniv, Gammagard, Gammaplex, Gamunex-C, Gammaked, Octagam, Panzyga, Privigen)
injectable solution, freeze-dried preparation (Gammagard S/D)
- 2.5g
- 5g
- 10g
injection, lyophilized powder for reconstitution (Carimune NF)
- 3g
- 6g
- 12g
Primary Immunodeficiency Syndrome
Indicated as replacement therapy for primary humoral immunodeficiency (PI); this includes, but is not limited to, the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies (SCID)
See Administration
Gammagard S/D, Gammagard Liquid
Gammagard Liquid (SC administration)
- <2 years: Safety and efficacy not established
- 2-16 years (conversion from IV): Previous IV dose/wk X 1.53/IV dosing interval (in weeks)
- Infusion rate <40 kg: 15 mL/hr/site initially, may increase to 15-20 mL/hr/site (volume not to exceed 20 mL/site)
- Infusion rate 40 kg or greater: 20 mL/hr/site, may increase to 20-30 mL/hr/site (volume not to exceed 20 mL/site)
Gammaked
- 300-600 mg/kg IV q3-4wk
- SC weekly maintenance
- May switch to a weekly SC maintenance dose
- Initial SC dose = 1.37 x previous IVIG dose (grams) ÷ number of weeks between IVIG doses
- Adjust dose according to trough levels
Gammaplex
- 300-800 mg/kg IV q3-4wk
Carimune NF
- 200 mg/kg IV q4wk; may increase to 300 mg/kg q4wk
Privigen
- ≥3 years: 200-800 mg/kg IV q3-4wk
Asceniv
- <12 years: Safety and efficacy not established
- 12-17 years: 300-800 mg/kg IV q3-4wk
Immune Thrombocytopenic Purpura
Indicated for treatment of immune thrombocytopenic purpura (ITP) to raise platelet counts to control or prevent bleeding
Carimune NF
- Induction dose: 400 mg/kg/day IV for 2-5 days
- Acute ITP of childhood: May discontinue dose after Day 2 if platelets are 30-50,000/microL
- Maintenance of chronic ITP: 400 mg/kg IV PRN to control significant bleeding or maintain platelet count >30,000/microL
Gamunex-C
- 1 g/kg IV x 2 days or 400 mg/kg IV x 5 days
Privigen
- <15 years: Safety and efficacy not established
- ≥15 years: 1 g/kg/day IV for 2 days
Flebogamma
- <2 years: Safety and efficacy not established
- ≥2 years: 300-600 mg/kg IV q3-4wk
Kawasaki Disease
Indicated for acute disease in combination with aspirin to prevent or reduce occurrence of coronary artery abnormalities associated with Kawasaki disease
Ideally, initiate within 10 days of onset of fever with diagnosed or suspected Kawasaki disease (American Academy of Pediatrics, American Heart Association, American College of Chest Physicians guidelines)
2 g/kg IV as a single dose over 10-12 hr
Unless patients with Kawasaki disease present with comorbid influenza or viral illness, IVIG must be used with high-dose aspirin (80-100 mg/kg/day PO divided q6hr) or moderate-dose aspirin (30-50 mg/kg/day PO divided q6hr) for up to 14 days until fever resolved
Gammagard S/D
- 1 g/kg IV as a single dose OR
- 400 mg/kg/day IV for 4 consecutive days
- Begin treatment within 7 days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day PO in 4 divided doses)
B-Cell Chronic Lymphocytic Leukemia
As in adults
Dermatomyositis (off-label)
As in adults
Guillain-Barre Syndrome (off-label)
As in adults
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>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
Warnings
Black Box Warnings
Acute renal dysfunction and renal failure
- Associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death
- Administer IV at minimum concentration available and minimum rate of infusion in patients predisposed to acute renal failure; IVIG products containing sucrose as a stabilizer or at daily doses >400 mg/kg account for a disproportionate share of case reports involving renal failure
- Patients predisposed to acute renal failure
- Any degree of preexisting renal insufficiency
- Diabetes mellitus
- Age >65 years
- Volume depletion
- Sepsis
- Paraproteinemia
- Currently taking nephrotoxic drugs
Thrombosis
- Thrombosis may occur regardless of route of administration
- Risk factors include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors
- Thrombosis may also occur in the absence of known risk factors
- For patients at risk of thrombosis, administer at the minimum concentration available and at the minimum rate of infusion 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
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 & Lactation
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.
Pharmacology
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)
Administration
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
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Formulary
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