Octagam Mechanism of Action

Pharmacotherapeutic group: Immune sera and immunoglobulins: immunoglobulins, normal human, for intravascular administration. ATC Code: J06 BA02.
Pharmacology: Pharmacodynamics: 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 prepared from pooled plasma from not fewer than 1000 donations. 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.
Paediatric population: A prospective open-label phase III study was performed with Octagam 5% in 17 children/adolescent patients (median age 14.0 years, range 10.5 to 16.8) suffering from primary immunodeficiency disorders. Patients were treated for a period of 6 months. The clinical efficacy was satisfying, as the number of days with infections or fever, and the number of days out of school were low, and the type and severity of infections was comparable to those observed in the normal population. No severe infections leading to hospitalisation were observed. It is also noteworthy that the number of infectious episodes was lower, when IgG plasma levels were maintained around 6 g/l than when the IgG plasma levels were around 4 g/l.
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.
Human normal immunoglobulin has an average half-life ranging from 26 to 41 days, as measured in immunodeficient patients. 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.
Paediatric population: A prospective open-label phase III study was performed with Octagam 5% in 17 children/adolescent patients (median age 14.0 years, range 10.5 to 16.8) suffering from primary immunodeficiency disorders. Patients were treated for a period of 6 months.
During the treatment period, the average Cmax in steady state was 11.1 ± 1.9 g/l; the average trough level was 6.2 ± 1.8 g/l. The terminal half-life of total IgG was 36 ± 11 days with a median of 34 days. The volume of distribution for the total IgG was 3.7 ± 1.4 l and the total body clearance was 0.07 ± 0.02 l/day.
Toxicology: Preclinical safety data: Immunoglobulins are normal constituents of the human body. Studies of repeated dose toxicity, genotoxicity, and toxicity to reproduction in animals are impracticable due to induction of and interference by developing antibodies to heterologous proteins. Since clinical experience provides no evidence for carcinogenic or mutagenic potential of immunoglobulins, no experimental studies in heterologous species were performed.