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 for the treatment of 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 rapidly raise platelet counts to prevent bleeding in patients with chronic immune thrombocytopenic purpura (ITP).
WARNING: Renal dysfunction, acute renal failure, osmotic nephrosis, and death may be associated with the administration of Immune Globulin Intravenous (Human) (IVIg) products in predisposed patients. Administer IVIg products at the minimum infusion rate possible. Renal dysfunction and acute renal failure occur more commonly in patients receiving IVIg products containing sucrose. Privigen does not contain sucrose. See full prescribing information for complete boxed warning.
Privigen is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin, in patients with hyperprolinemia, and in IgA-deficient patients with antibodies to IgA and a history of hypersensitivity.
In patients at risk for developing renal failure, monitor urine output and renal function, including blood urea nitrogen and serum creatinine. Thrombotic events have been reported with Privigen and other IVIg treatments. Monitor patients with risk factors for thrombotic events, including a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.
Aseptic meningitis syndrome (AMS) may occur infrequently with Privigen and other IVIg treatments; AMS may occur more frequently with high doses and/or rapid infusion of IVIg. Hemolysis, hemolytic anemia, and pulmonary adverse events have also been reported. There have been reports of noncardiogenic pulmonary edema in patients administered IVIg. If transfusion-related acute lung injury is suspected, test product and patient for antineutrophil antibodies.
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, the most common adverse reactions with Privigen were headache, pain, nausea, pyrexia/hyperthermia, fatigue, and chills. Anemia was an additional common adverse reaction in patients being treated with Privigen for chronic ITP. The most serious adverse reactions in chronic ITP patients were aseptic meningitis syndrome in one subject and hemolysis in eight subjects.
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.