HETASTARCH- hetastarch injection
Teva Parenteral Medicines, Inc
DESCRIPTION
6% Hetastarch in 0.9% Sodium Chloride Injection (Hetastarch Injection) is a sterile, nonpyrogenic solution for intravenous administration.
The composition of each 100 mL is as follows:
Hetastarch���������������������.
6 g
Sodium Chloride, USP���������������
0.9 g
Water for Injection, USP��������������
qs
pH adjusted with Sodium Hydroxide, NF if necessary
Concentration of Electrolytes (mEq/L): Sodium 154, Chloride 154
pH: approximately 5.5 with negligible buffering capacity
Calculated Osmolarity: approximately 309 m0sM
Hetastarch is an artificial colloid derived from a waxy starch composed almost entirely of amylopectin. Hydroxyethyl ether groups are introduced into the glucose units of the starch, and the resultant material is hydrolyzed to yield a product with a molecular weight suitable for use as a plasma volume expander and erythrocyte sedimenting agent. Hetastarch is characterized by its molar substitution and also by its molecular weight. The molar substitution is approximately 0.75 which means hetastarch has an average of approximately 75 hydroxyethyl groups for every 100 glucose units. The weight average molecular weight is approximately 600,000 with a range of 450,000 to 800,000 and with at least 80% of the polymers falling within the range of 20,000 to 2,500,000. Hydroxyethyl groups are attached by either linkage primarily at C-2 of the glucose unit and to a lesser extent at C-3 and C-6. The polymer resembles glycogen, and the polymerized D-glucose units are joined primarily by ?-1,4 linkages with occasional ?-1,6 branching linkages. The degree of branching is approximately 1:20 which means that there is an average of approximately one ?-1,6 branch for every 20 glucose monomer units.
The chemical name for hetastarch is hydroxyethyl starch.
The structural formula is as follows:
Structural Formula
Amylopectin derivative in which R2 and R3 are H or CH2 CH2 OH and R6 is H, CH2 CH2 OH, or a branching point in the starch polymer connected through an ?-1,6 link to additional D-glucopyranosyl units.
Hetastarch injection is a clear, pale yellow to amber solution. Exposure to prolonged adverse storage conditions may result in a change to a turbid deep brown or the formation of a crystalline precipitate. Do not use the solution if these conditions are evident.
The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. The container solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary.
The closure system has two ports; the one for the administration set has a tamper evident plastic protector.
CLINICAL PHARMACOLOGY
The plasma volume expansion produced by hetastarch injection approximates that of 5% Albumin (Human). Intravenous infusion of hetastarch injection results in expansion of plasma volume that decreases over the succeeding 24 to 36 hours. The degree of plasma volume expansion and improvement in hemodynamic state depend upon the patient's intravascular status.
Hetastarch molecules below 50,000 molecular weight are rapidly eliminated by renal excretion. A single dose of approximately 500 mL of hetastarch injection (approximately 30 g) results in elimination in the urine of approximately 33% of the dose within 24 hours. This is a variable process but generally results in an intravascular hetastarch concentration of less than 10% of the total dose injected by two weeks. A study of the biliary excretion of hetastarch in 10 healthy males accounted for less than 1% of the dose over a 14 day period. The hydroxyethyl group is not cleaved by the body but remains intact and attached to glucose units when excreted. Significant quantities of glucose are not produced as hydroxyethylation prevents complete metabolism of the smaller polymers.
The addition of hetastarch to whole blood increases the erythrocyte sedimentation rate. Therefore hetastarch injection is used to improve the efficiency of granulocyte collection by centrifugal means.
In randomized, controlled, comparative studies of hetastarch injection (n=92) and Albumin (n=85) in surgical patients, no patient in either treatment group had a bleeding complication and no significant difference was found in the amount of blood loss between the treatment groups.1-4
INDICATIONS AND USAGE
Hetastarch injection is indicated in the treatment of hypovolemia when plasma volume expansion is desired. It is not a substitute for blood or plasma.
The adjunctive use of hetastarch injection in leukapheresis has also been shown to be safe and efficacious in improving the harvesting and increasing the yield of granulocytes by centrifugal means.
