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)

Dosing and uses of Gammagard S/D, Carimune NF (immune globulin IV (IGIV))

• Adult
• Pediatric

 

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