Hypogammaglobulinemia Medication

Updated: Dec 26, 2018
  • Author: Elizabeth A Secord, MD; Chief Editor: Michael A Kaliner, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The standard treatment for hypogammaglobulinemia is IgG replacement, which may be given intravenously or subcutaneously. [19, 13, 20] IgG preparations are approved by the US Food and Drug Administration (FDA) for treatment of primary immunodeficiency disease (primary humoral immunodeficiency) and a few additional indications, but considerable amounts of intravenous immunoglobulins (IVIG) are used "off label" for other conditions. [19, 20]

As reviewed by the American Academy of Allergy, Asthma, and Immunology, the benefit of IgG treatment for these primary immune deficiencies is based on category IIb evidence. [19] IVIG is approved for only two secondary immune deficiencies: B-cell chronic lymphocytic leukemia (B-CLL) and pediatric HIV. The use of IVIG for primary immune defects with normogammaglobulinemia and impaired specific antibody production is based on category III evidence only. [19]

A safe, effective administration of IgRT requires detailed attention to the selection of patient, patient preferences, product, administration facilities, and health insurance. It is best delivered by an expert in the field who is knowledgeable of diagnosis, treatment, and complexities. The AAAAI and primary immunodeficiency subcommittee has formulated eight guiding principles for successful IgRT therapy.

Dosing

IVIG

An acceptable starting dose is 400–600mg/kg every 3–4 weeks. [19, 20] After the fifth infusion, a steady state will be achieved. Annual trough levels measurement is enough. Dose or dosing interval needs to be adjusted to achieve optimal goals. Studies support individualizing the IgRT dose, dosing interval, and trough levels rather than a standardized dose in all patients to attain infection-free outcomes. It is best left to the discretion of the treating physician.

SCIG

Usual starting dose is 100–200 mg/kg of body weight each week. The dosing interval is flexible and can be given daily, weekly, biweekly, or monthly. The monthly dosing is only possible with addition of recombinant human hyaluronidase. Infusion rates generally range from 10 to 35 ml/hour/site with an infusion pump with volume of 15–40 ml per site. A 20% SCIG formulation allows lower volume and rate used per manufacturer’s guidelines. Typical sites are lower abdomen, outer thigh, upper arm, and buttock. A steady state can be monitored after 3 months.

Comparison of IVIG and SCIG (Open Table in a new window)

IVIG

SCIG

Advantages

 

Dosing — large dose

Intermittent and infrequent intervals

High levels of IgG

No venous access

Self infusion

Small volume

Steady state levels of IgG — less "wear-off’ effects

Compatible with working lifestyle

Home treatment — convenient

Less expensive

Rare IgA reactions

Disadvantages

 

Needs venous access

Trained personnel and healthcare facilities for administration

Large fluctuations — "wear-off" effects

More adverse effects

May not suit a busy working lifestyle

More frequent dosing and injections

Smaller volume/dose and multiple infusion sites

Needs education

Nonadherence issues likely

Some practitioners target trough levels 300 mg/dL higher than pretreatment levels, and trough levels >800 mg/dL may improve pulmonary outcomes. Some centers advocate a loading dose of 1 g/kg if the patient is agammaglobulinemic. [19, 13, 20]

Gammaglobulin may also be given intramuscularly or subcutaneously. [20] The latter format is useful when allergic reactions limit the dose or rate, but it is becoming increasingly popular even when these problems are not present. SCIG can be given at home by parents or by patients themselves, usually requiring several hours of infusion. Intramuscular gammaglobulin injections were the standard of care before IVIG became readily available and are still useful in certain patients because of the simplicity of administration and fewer reactions. However, local injection site pain can be significant, and the doses that can be given this way are limited.

Up to 44% of patients report adverse reactions to IVIG. These most commonly respond to decreasing the rate of the Ig infusion. Usually, the IVIG-associated reactions are infusion-related and include back pain, abdominal aching, nausea, rhinitis, asthma, chills, low-grade fever, myalgias, and headaches. Renal failure is a less common but serious adverse reaction that was predominately caused by sucrose-containing lyophilized IgG preparations that are no longer available in the United States. Infusion rate reduction, systemic steroids, histamine blockers, and antipyretics or nonsteroidal anti-inflammatory drugs (NSAIDs) can help treat or prevent the reactions.

Although the incidence of reactions is highest during the first infusion, they may occur in repeat infusions of the same product. Although anti-IgA antibodies can be associated with increased reactions, most patients (regardless of anti-IgA antibody status) tolerate IVIG that is not depleted of IgA (low-IgA products should be selected for treatment in patients who cannot tolerate IVIG that is not depleted of IgA). Thrombosis, myocardial infarction, hemolytic anemia, hyperviscosity syndrome, and aseptic meningitis are uncommon but reported adverse events.

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Vaccines

Class Summary

Polyvalent pneumococcal vaccine (PPV-23) protects against 23 serotypes of S pneumoniae; approximately 70% of invasive diseases caused by S pneumoniae result from these serotypes.

Pneumococcal 13-valent conjugate vaccine (PCV-13) protects against the 13 serotypes of S pneumoniae that cause the most severe pneumococcal infections in children.

Pneumococcal vaccine polyvalent (Pneumovax 23)

Inactive bacterial vaccine that induces active immunization to the serotypes contained in the vaccine.

Pneumococcal vaccine 13-valent (Prevnar 13)

Promotes active immunity against S. pneumoniae capsular serotypes 1,3,4,5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, which are all conjugated to CRM197 protein.

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Blood Product Derivatives

Class Summary

There are many FDA approved IgG preparations available in market with distinct features. The products used in the United States are derived from the plasma of screened donors in the United States The product undergoes several specific treatments to inactivate or remove blood borne pathogens that could be present. The preparations contain highly purified (generally >95 percent) polyvalent IgG. However, there are slight differences in the manufacturing procedures used by different producers, and different stabilizers (eg, sucrose, glucose, maltose or amino acids) used in the excipients making them unique and warrant precaution during substitution of immunoglobulin during treatment. Products also differ in storage requirements and shelf life. It is important for physician to familiarize and select appropriate product for his/her patient. Some of the products are listed below.2

FDA approved Immunoglobulin products available in US 2

A. Intravenous use (IV)

-Liquid-Bivigam 10%, Flebogamma DIF (5%, 10%), Gammaplex 5%, Octagam liquid (5%, 10%), Privigen 10%

-Lyophilized-Gammagard S/D 5%, Carimune NF 5%         

B. Intravenous and Subcutaneous use (SC)

-Liquid-Gammagard 10%, Gammaked 10%, Gamunex 10%

C. Subcutaneous use (SC)

                -Liquid-Cuvitru 20%, Hizentra 20%

                -Liquid with hyaluronidase-Hyqvia 10%

Immune globulin IV (IGIV; Bivigam, Flebogamma DIF, Gammaplex, Octagam, Privigen, Gammagard S/D, Carimune NF)

Immune globulins may work via several mechanisms, including the blockage of macrophage receptors, the inhibition of antibody production, the inhibition of complement binding, and the neutralization of pathologic antibodies.

Immune globulin SC (Gammaked, Gamunex, Cuvitru, Hizentra, Hyqvia)

Immune globulins neutralize circulating myelin antibodies through anti-idiotypic antibodies; downregulates proinflammatory cytokines, including interferon gamma; block Fc receptors on macrophages; suppress inducer T and B cells while augmenting suppressor T cells; block the complement cascade; promote remyelination; and may increase immunoglobulin G (IgG) in cerebrospinal fluid (10% of cases).

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