immune globulin IV (IGIV) (Gammagard S/D, Carimune NF, Carimune, Bivigam, Flebogamma, Gammagard, Gammaplex, Gamunex-C, IV Immune Globulin, IVIG, Octagam, Privigen, Flebogamma 10% DIF, Flebogamma 5% DIF, Gammaked)
Classes: Immune Globulins
Dosing and uses of Gammagard S/D, Carimune NF (immune globulin IV (IGIV))
Adult dosage forms and strengths
injectable solution
- 10% (100mg/mL)
- 5% (50mg/mL)
Primary Immunodeficiency Syndrome
Carimune NF
- 400-800 mg/kg IV q3-4wk or may increase frequency based on patient response
Gammagard S/D, Gamunex-C, Gammagard Liquid
- 300-600 mg/kg IV q4wk; adjust based on dosage and interval as well as serum IgG concentrations
Gammagard Liquid (SC administration)
- Initial SC dose: Previous IV dose/wk x 1.53/IV dosing interval (in weeks)
- 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
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
Bivigam (ready-to-use 10% liquid)
- 300-800 mg/kg IV q3-4wk
- Initial infusion rate is 0.5 mg/kg/min for the first 10 min; may increase q20min (if tolerated) by 0.8 mg/kg/min up to 6 mg/kg/min
Octagam
- 300-600 mg/kg IV q3-4wk
- Initial infusion rate: 0.5 mg/kg/min IV
Privigen
- 200-800 mg/kg IV q3-4 wk; adjust based on dosage and interval as well as serum IgG concentrations
Immune Thrombocytopenic Purpura
Gammagard S/d
- 1000 mg/kg IV; adjust doses based on platelet count and patient response; may administer up to 3 separate doses qOD PRN
Privigen
- 1000 mg/kg/day IV for 2 days
Gammaked
- 2 g/kg IV divided into 2 doses of 1 g/kg given on 2 successive days, OR
- 2 g/kg IV divided into 5 doses of 0.4 g/kg given on 5 consecutive days
Gamunex
- 1000 mg/kg/day IV for 1-2 days or 400 mg/kg/day for 5 days
Gamunex-C
- 1 g/kg IV x 2 days or 400 mg/kg IV x 5 days
- Initial infusion rate is 1 mg/kg/min; may increase to 8 mg/kg/min if tolerated
Carimune
- 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
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Initial dose: 2 g/kg IV given in divided doses over 2-4 successive days
Maintenance dose: 1 g/kg IV given on 1 day or in 2 divided doses (0.5 g/kg/dose) on 2 consecutive days q3weeks
Kawasaki Disease
Initiate IVIG within 10 days of diagnosis; use in combination with aspirin 80-100 mg/kg/day divided q6hr for 14 days; administer aspirin at 3-5 mg/kg IV qDay for >6-8wk
Gammagard S/d
- 1000 mg/kg IV once administered over 10 hr OR
- 400 mg/kg/day IV for 4 days; administer within 7 days of onset of fever
Bone Marrow Transplant
500 mg/kg IV beginning on days 7 & 2 pretransplantation, THEN qWk through 90 days post-transplantation
Chronic Inflammatory Demyelinating Polyneuropathy
Gamunex
- Load: 2 g/kg IV divided q6012hr for 2-4 days
- Maintenance: 1000 mg/kg/day IV for 1 day q3wk or 500 mg/kg/day for 2 days q3wk
Gamunex-C
- Load: 2 g/kg IV
- Maintenance: 1 g/kg IV as a single dose or 500 mg/kg IV x 2 days q3weeks
- Initial infusion rate is 2 mg/kg/min; may increase to 8 mg/kg/min if tolerated
B-cell Chronic Lymphocytic Leukemia
Gammagard S/d
- 400 mg/kg/dose IV q3-4wk
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)
400 mg/kg IV qDay x5 days or 1 g/kg qDay x 2 days
Neonatal Hemochromatosis (Off-label)
1 g/kg IV qWk to pregnant woman 18th week until end of gestation
Stiff Person Syndrome (Orphan)
Orphan indication sponsor
- Octapharma USA, Inc; 121 River Street; Hoboken, NJ 07030
Administration
Monitor: vascular status continuously, have epinephrine ready; see individual products for specific information on doses & infusion details
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
Pediatric dosage forms and strengths
injectable solution
- 10% (100mg/mL)
- 5% (50mg/mL)
Pediatric HIV, Prevention of Infection
400 mg/kg IV q2-4hr
Primary Immunodeficiency Syndrome
Flebogamma, Gammagard S/D, Gammagard Liquid
- 300-600 mg/kg IV q3-4wk
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
Octagam
- 300-600 mg/kg IV q3-4wk
- Initial infusion rate: 0.5 mg/kg/min IV
Privigen
- 200-800 mg/kg IV q3-4wk
Immune Thrombocytopenic Purpura
As in adults
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Initial dose: 2 g/kg IV given in divided doses over 2-4 successive days
Maintenance dose: 1 g/kg IV given on 1 day or in 2 divided doses (0.5 g/kg/dose) on 2 consecutive days q3weeks
Kawasaki Disease
As in adults
B-Cell Chronic Lymphocytic Leukemia
As in adults
Dermatomyositis (off-label)
As in adults
Guillain-Barre Syndrome (off-label)
As in adults
Gammagard S/D, Carimune NF (immune globulin IV (IGIV)) adverse (side) effects
1-10%
Chills (8.9%)
Headache (5.4%)
Generalized pain (3.6%)
Hypotension
Anaphylaxis related to infusion rate
Aseptic meningitis syndrome (rare)
Warnings
Black box warnings
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 the 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 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
Cautions
Postpone live virus vaccines for at least 3 months
Associated with various renal dysfunctions, incl ARF (especially those containing sucrose as stabilizer, eg, Gammar-P IV, Panglobulin); monitor renal function
Maltose-containing brands may give false high for glucose in certain glucose-testing systems
Closely monitor for signs and symptoms of hemolysis
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk
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 of Gammagard S/D, Carimune NF (immune globulin IV (IGIV))
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
Pharmacokinetics
Half-Life: 14-40 days (varies greatly by patients)
Onset: Immediate
Duration: 1-3 months (variable)
Peak Plasma Time: 2.9 days (Gammagard, Hizentra); 2.5 days (Vivaglobin); 48 hr (IM serum)
Vd: 0.09-0.13 L/kg
Administration
IV Preparation
Dilution is dependent upon mfr & brand; do not shake, avoid foaming; discard unused portion
Iveegam EN: reconstitute with SWI; use immediately after reconstitution
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.
Sandoglobulin: reconstitute with NS, D5W or SWI; when diluted aseptically in a sterile laminar flow hood, may store diluted solution under refrigeration for up to 24 hr
Gamunex incompatible w/ saline, dilute in D5W if necessary
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
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