ng should be considered along with the mother’s clinical need for ASCENIV and any potential adverse effects on thebreast-fed infant from ASCENIV or from the underlying maternal condition.
8.4 Pediatric Use
ASCENIV was eva luated in 11 pediatric subjects (6 children less than 12 years and 5 adolescents age 12 – 16 years) withprimary humoral immunodeficiency (PI). The pharmacokinetic (PK), safety, and effectiveness profile of ASCENIV inadolescent subjects appeared to be comparable to that demonstrated in adult subjects. There are insufficient PK, safety,and effectiveness data from pediatric subjects younger than 12 years. Safety and effectiveness has not been studied inpediatric patients with PI who are under the age of 3 years (see Clinical Studies [14]).
8.5 Geriatric Use
Clinical studies of ASCENIV did not include sufficient numbers of subjects aged 65 and over to determine whether they responddifferently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderlyand younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of thedosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or otherdrug therapy.
10 OVERDOSAGE
With intravenous administration, overdose may lead to fluid overload and hyperviscosity. Patients at risk of complications of fluidoverload and hyperviscosity include elderly patients and those with cardiac or renal impairment.
11 DESCRIPTION
ASCENIV is a purified, sterile, ready-to-use preparation of concentrated human immunoglobulin G (IgG) antibodies. The product isa clear to opalescent liquid, which is colorless to pale yellow. The distribution of IgG subclasses is similar to that of normal plasma.
The active ingredient is human immunoglobulin purified from source human plasma and processed using a modified classicalCohn Method 6 / Oncley Method 9 fractionation procedure. ASCENIV contains 100 ± 10 mg/mL protein, of which not less than96% is human immunoglobulin obtained from source human plasma. It is formulated in water for injection containing 0.100-0.140M sodium chloride, 0.20-0.29 M glycine, 0.15–0.25% polysorbate 80, with pH 4.0–4.6. ASCENIV contains ≤ 200 µg/mL of IgA.
Each plasma donation used for the manufacture of ASCENIV is collected from FDA-licensed facilities. Plasma donations must testnegative for hepatitis B virus (HBV) surface antigen (HBsAg), antibodies to human immunodeficiency virus (HIV) strains 1 and 2(anti-HIV-1/2), and antibodies to the hepatitis C virus (anti-HCV) as determined by enzyme immunoassay (EIA). In addition, eachplasma unit must test negative and/or non-reactive for HIV RNA, HCV RNA, HBV DNA, Hepatitis A Virus (HAV) RNA, andParvovirus B19 (B19 virus) DNA as determined by Nucleic Acid Amplification Testing (NAT) of plasma minipools.
NATs for HIV,HAV, HBV, HCV and B19 virus DNA are alsoperformed on a sample of the manufacturing pool. The limit for B19 virus DNA in amanufacturing pool is set not to exceed 104 IU/mL and all other NAT results must be negative.
The manufacturing process of ASCENIV employs three steps to remove/inactivate adventitious viruses to minimize the risk of virustransmission.
The steps are"Precipitation and removal of fraction III" during cold ethanol fractionation, classical "solvent/detergent |
