Flebogamma DIF Mechanism of Action

Pharmacotherapeutic group: Immune Sera and Immunoglobulins: immunoglobulins, normal human, for intravascular administration. ATC code: J06BA02.
Pharmacology: Pharmacodynamics: Human normal immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents.
Human normal immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents.
Human normal immunoglobulin contains the IgG antibodies present in the normal population. It is usually prepared from pooled plasma from not fewer than 1000 donors. It has a distribution of immunoglobulin G subclasses closely proportional to that in native human plasma.
Adequate doses of this medicinal product may restore abnormally low immunoglobulin G levels to the normal range.
The mechanism of action in indications other than replacement therapy is not fully elucidated, but includes immunomodulatory effects. A significant increase in median platelet levels was achieved in a clinical trial in chronic ITP patients (64,000/μl) although it did not reach normal levels.
Two clinical trials were performed with Flebogamma 5% DIF if, one for replacement therapy in patients with primary immunodeficiency (both in adults and in children above 10 years) and another for immunomodulation in adults patients with immune thrombocytopenic purpura.
Pharmacokinetics: Human normal immunoglobulin is immediately and completely bioavailable in the recipient's circulation after intravenous administration. It is distributed relatively rapidly between plasma and extravascular fluid, after approximately 3 - 5 days equilibrium is reached between the intra- and extravascular compartments.
Flebogamma 5% DIF has a half-life of about 30 - 32 days. This half-life may vary from patient to patient, in particular in primary immunodeficiency.
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
Toxicology: Preclinical safety data: Single dose toxicity studies were carried out in rats and mice. The absence of mortality in the non-clinical studies performed with Flebogamma 5% DIF with dosages up to 2500 mg/kg, and the lack of any confirmed relevant adverse sign affecting respiratory, circulatory and central nervous system, of the treated animals supports the safety of Flebogamma 5% DIF.
Repeated dose toxicity testing and embryo-foetal toxicity studies are impracticable due to induction of, and interference with antibodies. Effects of the product on the immune system of the newborn have not been studied.