IgA and IgG Subclass Deficiencies Medication

Updated: Aug 14, 2014
  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
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Medication

Medication Summary

The use of antibiotics to treat infections caused by S pneumoniae, H influenzae, and Moraxella catarrhalis must be aggressive. Prophylactic antibiotics can be beneficial in selected cases

Intravenous immunoglobulin (IVIg) is not a conventional therapy and has not been approved by the US Food and Drug Administration (FDA) for selective IgA deficiency, IgG subclass deficiency, or specific antibody deficiency. For empiric use of IVIg in these patients, clinicians must consider the expense and current shortage of IVIg supplies in the United States. In addition, exercise caution in patients with absent IgA serum levels because of the possibility of anaphylaxis with all IVIg preparations, except for Gammagard.

The overall consensus among clinical immunologists is that a dosage of IVIg of 400-600 mg/kg/mo or a dosage that maintains trough serum IgG levels of more than 500 mg/dL is desirable. Patients with X-linked agammaglobulinemia and meningoencephalitis require dosages of 1 g/kg and perhaps intrathecal therapy. Measurement of preinfusion (trough) serum IgG levels every 3 months until a steady state is achieved and then every 6 months if the patient is stable may be helpful in adjusting the dosage to achieve adequate serum levels. For persons who have a high catabolism of infused IgG, frequent infusions (eg, every 2-3 wk) of small doses may maintain the serum level in the reference range. The rate of elimination of IgG may be increased during active infection; measuring serum IgG levels and increasing dosages or shortening intervals may be required.

For replacement therapy in patients with primary immune deficiency, all brands of IVIg are probably equivalent, although viral-inactivation processes differ (eg, solvent detergent washing vs pasteurization, liquid vs lyophilized methods). The choice may depend on the hospital or home-care formulary and on local availability and cost. The dosage, manufacturer, and lot number should be recorded for each infusion to review then for adverse events or other consequences. Recording all adverse effects that occur during the infusion is crucial. Monitoring liver and renal function periodically, approximately 3-4 times yearly, is also recommended.

The FDA recommends that, for patients at risk for renal failure (eg, those with preexisting renal insufficiency diabetes, volume depletion, sepsis, paraproteinemia, age >65 y, and use nephrotoxic drugs), recommended dosages should not be exceeded, and infusion rates and concentrations should be the minimum practical levels.

Initial treatment should be administered under the close supervision of experienced personnel. The risk of adverse reactions in the initial treatments is high, especially in patients with infections and in those who form immune complexes. In patients with active infection, infusion rates may need to be slowed and the dose halved (ie, 200-300 mg/kg), with the remaining dose given the next day to achieve a full dose. Treatment should not be discontinued. After normal serum IgG levels are achieved, adverse reactions are uncommon unless patients have active infections.

With the new generation of IVIg products, adverse effects are reduced. Adverse effects include tachycardia, chest tightness, back pain, arthralgia, myalgia, hypertension or hypotension, headache, pruritus, rash, and low-grade fever. Relatively serious reactions are dyspnea, nausea, vomiting, circulatory collapse, and loss of consciousness. Patients with profound immunodeficiency or patients with active infections tend to have severe reactions.

Anticomplementary activity of IgG aggregates in the IVIg, and the formation of immune complexes are thought to be related to adverse reactions. The formation of oligomeric or polymeric IgG complexes that interact with Fc receptors and that trigger the release of inflammatory mediators is another cause. Most adverse reactions are rate related. Slowing the infusion rate or discontinuing therapy until symptoms subside may diminish the reaction. Pretreatment with ibuprofen at 5-10 mg/kg every 6-8 hours, acetaminophen at 15 mg/kg/dose, diphenhydramine at 1 mg/kg/dose, and/or hydrocortisone at 6 mg/kg/dose (maximum, 100 mg) 1 hour before the infusion may prevent adverse reactions. In some patients with a history of severe adverse effects, analgesics and antihistamines may be repeated.

Acute renal failure is a rare but important complication of IVIg treatment. Reports suggest that IVIg products with sucrose as a stabilizer may be associated with a heightened risk for this renal complication. Acute tubular necrosis, vacuolar degeneration, and osmotic nephrosis suggest osmotic injury to the proximal renal tubules. The infusion rate for sucrose-containing IVIg should not exceed 3 mg sucrose/kg/min. Risk factors for this adverse reaction include preexisting renal insufficiency, diabetes mellitus, dehydration, age older than 65 years, sepsis, paraproteinemia, and concomitant use of nephrotoxic agents. For patients at increased risk, BUN and creatinine levels should be monitored before the start of treatment and before each infusion. If renal function deteriorates, the product should be discontinued.

IgE antibodies to IgA are reported to cause severe transfusion reactions in IgA-deficient patients. A few reports describe true anaphylaxis in patients with selective IgA deficiency and common variable immunodeficiency (CVID) who developed IgE antibodies to IgA after treatment with Ig. However, in clinical experience, this is rare. In addition, this is not a problem for patients with X-linked agammaglobulinemia (Bruton disease) or severe combined immunodeficiency (SCID). Caution should be exercised in patients with Ig deficiency (< 7 mg/dL) who need IVIg because of IgG subclass deficiencies. IVIg preparations with low concentrations of contaminating IgA are advised (see the Table below).

Table. Immune Globulin, Intravenous [56, 57, 58, 59] (Open Table in a new window)

Brand(Manufacturer)

Manufacturing Process

pH

Additives (IVIg products containing sucrose are most often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs])

Parenteral Form and Final Concentrations

IgA Content mcg/mL

Carimune NF

(CSL Behring)

Kistler-Nitschmann fractionation; pH 4, nanofiltration

6.4-6.8

6% solution: 10% sucrose, < 20 mg NaCl/g protein

Lyophilized powder 3%, 6%, 9%, 12%

Trace

Flebogamma

(Grifols USA)

Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization

5.1-6

Sucrose free, contains 5% D-sorbitol

Liquid 5%

< 50

Gammagard Liquid 10%

(Baxter Bioscience)

Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation

4.6-5.1

0.25M glycine

Ready-for-use Liquid 10%

37

Gamunex

(Talecris Biotherapeutics)

Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation

4-4.5

Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycine

Liquid 10%

46

Gammaplex

(Bio Products)

Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation

4.8-5.1

Contains sorbitol (40 mg/mL); do not administer if fructose intolerant

Ready-for-use solution 5%

< 10

Iveegam EN

(Baxter Bioscience)

Cohn-Oncley fraction II/III; ultrafiltration; pasteurization

6.4-7.2

5% solution: 5% glucose, 0.3% NaCl

Lyophilized powder 5%

< 10

Polygam S/D

Gammagard S/D

(Baxter Bioscience for the American Red Cross)

Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated

6.4-7.2

5% solution: 0.3% albumin, 2.25% glycine, 2% glucose

Lyophilized powder 5%, 10%

< 1.6 (5% solution)

Octagam

(Octapharma USA)

9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events

Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization

5.1-6

10% maltose

Liquid 5%

200

Panglobulin

(Swiss Red Cross for the American Red Cross)

Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration

6.6

Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl

Lyophilized powder 3%, 6%, 9%, 12%

720

Privigen Liquid 10%

(CSL Behring)

Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration

4.6-5

L-proline (approximately 250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose)

Ready-for use liquid 10%

< 25

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Immunoglobulin

Class Summary

Subcutaneous administration of immune globulin may be considered for some patients.

Immune globulin subcutaneous (Vivaglobin)

IgG antibodies that neutralize a wide variety of bacterial and viral agents. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade. Peak serum IgG levels are lower and trough IgG levels are higher than those achieved with IVIG. SC administration results in stable steady-state IgG levels when administered weekly. Available as a 160-mg/mL SC injectable.

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