How Privigen Works
The mechanism of action of intravenous immunoglobulin (IVIg) is complex and is not
completely understood. It involves modulation of the expression and function of
Fc receptors, interference with the activation of the complement and cytokine networks,
regulation of cell growth, and other significant processes. These intricate effects
underscore how important immunoglobulins are in the immune homeostasis of healthy
individuals.7,8
Two widely studied and accepted
mechanisms of IVIg action are supplementation of essential antibodies and immunomodulatory effects. In supplementation, IVIg therapy
is used to provide protective antibodies to patients with immunodeficiencies
by delivering immune antibodies against common pathogens. With immunomodulatory
effects, a number of events take place7:
- Blockade and modulation of Fc receptors
- Modulation of complement activation and anti-inflammatory effects
- Anti-idiotypic neutralization of pathogenic auto- or alloantibodies
- Selective down-regulation of antibody production
- Accelerated catabolism of pathogenic autoantibodies
- Regulation of apoptosis
Each of these mechanisms may be involved in the beneficial effects of IVIg for different
immune-mediated diseases.7,8
The variety of IVIg interactions reflects the complexity of immune regulation and
the diversity of effector functions of Ig antibodies.7,8
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Mechanism of Action in Primary Immunodeficiency Disease
In patients with primary immunodeficiency disease (PIDD), Privigen provides the
missing protective antibodies (replacement therapy). Privigen is manufactured from
the pooled plasma of thousands of blood donors and, therefore, includes a broad
variety of antibody specificities against common pathogens to which the donor population
has been exposed. Moreover, the antibodies in Privigen are structurally and functionally
intact, and their effector functions are fully operative.1,8 The mechanism
of action in PIDD has not been fully elucidated.
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Mechanisms of Action in ITP
The mechanism of action of immunoglobulin G (IgG) in immune thrombocytopenic purpura
(ITP) is complex and not fully understood. However, the success of treating ITP
with IgG appears to be due to competitive inhibition of Fc receptors on phagocytic
cells, creating reticuloendothelial system (RES) blockade. Continuing research does indicate that other mechanisms may also contribute
to inhibiting the thrombocytopenia, such as mediation of FcγRIIb, which appears
to play a critical role in IVIg function. Another
proposed mechanism involves the regulatory properties of anti-idiotypic antibodies,
which possibly regulate the immune system. Other
mechanisms that may also play a role include the long-term effects of IVIg on the
immune system.9
Although IVIg has been used to treat ITP, the mechanism of action is still unclear.
Ongoing research will be needed to better understand how IVIg affects ITP.9
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Important Safety Information
Immune Globulin Intravenous (Human), 10% Liquid, Privigen® is indicated as replacement therapy for patients with primary immunodeficiency (PI) associated with defects in humoral immunity, including but not limited to common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. Privigen is also indicated to raise platelet counts in patients with chronic immune thrombocytopenic purpura (ITP).
WARNING: Use of Immune Globulin Intravenous (IVIg) products, particularly those containing sucrose, have been associated with renal dysfunction, acute renal failure, osmotic nephropathy, and death. Privigen does not contain sucrose. Administer Privigen at minimum rate practicable in patients at risk of renal dysfunction or acute renal failure. At-risk patients include those with preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, or paraproteinemia; over 65 years of age; or receiving known nephrotoxic drugs. See full prescribing information for complete boxed warning.
Privigen is contraindicated in patients with history of anaphylactic or severe systemic reaction to human immune globulin, in patients with hyperprolinemia, and in IgA-deficient patients with antibodies to IgA and history of hypersensitivity.
Monitor patient vital signs throughout infusion of Privigen. In cases of severe hypersensitivity or anaphylactic reactions, discontinue administration and institute appropriate medical treatment. In patients at risk for developing renal failure, monitor urine output and renal function, including blood urea nitrogen and serum creatinine. Also monitor patients with risk factors for thrombotic events; consider baseline assessment of blood viscosity for those at risk of hyperviscosity.
Patients could experience increased serum viscosity, hyperproteinemia or hyponatremia; infrequently, aseptic meningitis syndrome (AMS) may occur (most often with high doses and/or rapid IVIg infusion). There have been reports of IVIg-related hemolysis, hemolytic anemia, and pulmonary adverse events, including transfusion-related acute lung injury (TRALI). Avoid high-dose regimen where fluid volume is of concern.
Privigen is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.
In clinical studies of patients being treated with Privigen for PI, the most serious adverse reaction was hypersensitivity (one subject). Adverse reactions observed in >5% of subjects with PI were headache, pain, nausea, fatigue, chills, vomiting, joint swelling/effusion, pyrexia, and urticaria.
In clinical studies of patients being treated with Privigen for chronic ITP, the most serious adverse reactions were AMS (one subject) and hemolysis (eight subjects). Adverse reactions seen in >5% of subjects with chronic ITP were headache, pyrexia/hyperthermia, positive DAT, anemia, vomiting, nausea, increases in conjugated and unconjugated bilirubin, hyperbilirubinemia, and increased blood lactate dehydrogenase.
Treatment with Privigen might interfere with a patient's response to live virus vaccines and could lead to misinterpretation of serologic testing.
For more information about Privigen, please see full prescribing information.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.