Topics

These highlights do not include all the information needed to use 6% Hetastarch in 0.9% Sodium Chloride Injection safely and effectively. See full prescribing information for 6% Hetastarch in 0.9% Sodium Chloride Injection.6% Hetastarch in 0.9% Sodium Chl | Hetastarch in Sodium Chloride [Hospira, Inc.] | BioPortfolio

13:08 EST 27th January 2019 | BioPortfolio
Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

6% Hetastarch in 0.9% Sodium Chloride 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 6% Hetastarch in 0.9% Sodium Chloride 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.

Dosage for Acute Use in Plasma Volume Expansion

6% Hetastarch in 0.9% Sodium Chloride Injection is administered by intravenous infusion only. Total dosage and rate of infusion depend upon the amount of blood or plasma lost and the resultant hemoconcentration.

The amount usually administered is 500 to 1000 mL. Doses of more than 1500 mL per day for the typical 70 kg patient (approximately 20 mL per kg of body weight) are usually not required. Higher doses have been reported in postoperative and trauma patients where severe blood loss has occurred [see Warnings and Precautions (5) ].

250 to 700 mL of 6% Hetastarch in 0.9% Sodium Chloride Injection with citrate anticoagulant is administered by aseptic addition to the input line of the centrifugation apparatus at a ratio of 1:8 to 1:13 to venous whole blood. The 6% Hetastarch in 0.9% Sodium Chloride Injection and citrate should be thoroughly mixed to assure effective anticoagulation of blood as it flows through the leukapheresis machine.

CAUTION: Before administering to the patient, review these directions:

Visual Inspection

To Open

Preparation for Administration

When stored at room temperature, 6% Hetastarch in 0.9% Sodium Chloride Injection admixtures of 500-560 mL with citrate concentrations up to 2.5% were compatible for 24 hours. The safety and compatibility of additives other than citrate have not been established.

Single-use container:

6% Hetastarch in 0.9% Sodium Chloride Injection has not been adequately evaluated to establish its safety in uses over extended periods other than leukapheresis. 6% Hetastarch in 0.9% Sodium Chloride Injection has been associated with coagulation abnormalities in conjunction with an acquired, reversible von Willebrand's-like syndrome and/or Factor VIII deficiency when used over a period of days. Replacement therapy should be considered if a severe Factor VIII deficiency is identified. If a coagulopathy develops, it may take several days to resolve. Certain conditions may affect the safe use of 6% Hetastarch in 0.9% Sodium Chloride Injection on a chronic basis. For example, in patients with subarachnoid hemorrhage where 6% Hetastarch in 0.9% Sodium Chloride Injection is used repeatedly over a period of days for the prevention of cerebral vasospasm, significant clinical bleeding may occur. Intracranial bleeding resulting in death has been reported.

Slight declines in platelet counts and hemoglobin levels have been observed in donors undergoing repeated leukapheresis procedures using 6% Hetastarch in 0.9% Sodium Chloride Injection due to the volume expanding effects of hetastarch and to the collection of platelets and erythrocytes. Hemoglobin levels usually return to normal within 24 hours. Hemodilution by 6% Hetastarch in 0.9% Sodium Chloride Injection may also result in 24 hour declines of total protein, albumin, calcium, and fibrinogen levels. Regular and frequent clinical evaluation and complete blood counts (CBC) are necessary for proper monitoring of 6% Hetastarch in 0.9% Sodium Chloride Injection use during leukapheresis. If the frequency of leukapheresis is to exceed the guidelines for whole blood donation, you may wish to consider the following additional tests: total leukocyte and platelet counts, leukocyte differential count, hemoglobin and hematocrit, prothrombin time (PT), and partial thromboplastin time (PTT).

Life threatening anaphylactic/anaphylactoid reactions including death have been rarely reported with 6% Hetastarch in 0.9% Sodium Chloride Injection. Patients may develop hypersensitivity reaction to corn starch from which this product is made. If a hypersensitivity reaction occurs, administration of the drug should be discontinued immediately and the appropriate treatment and supportive measures should be undertaken until symptoms have resolved.

6% Hetastarch in 0.9% Sodium Chloride Injection has not been adequately evaluated to establish its safety in situations other than treatment of hypovolemia in elective surgery.

Large volumes of 6% Hetastarch in 0.9% Sodium Chloride Injection may transiently alter the coagulation mechanism due to hemodilution and a direct inhibitory action on Factor VIII. Administration of volumes of 6% Hetastarch in 0.9% Sodium Chloride Injection that are greater than 25% of the blood volume in less than 24 hours may cause significant hemodilution reflected by lower hematocrit and plasma protein values. Administration of packed red cells, platelets, or fresh frozen plasma should be considered if clinically indicated.

When using 6% Hetastarch in 0.9% Sodium Chloride Injection for plasma volume expansion, caution should be taken to avoid excessive hemodilution and circulatory overload especially in those patients at risk for developing congestive heart failure and pulmonary edema. 6% Hetastarch in 0.9% Sodium Chloride Injection is primarily excreted via the kidneys so caution should be exercised in patients who have impaired renal function. Although the risk of circulatory overload is largely dependent on the clinical circumstances, use of doses higher than 20 mL/kg/24h will increase the risk significantly. Increased risk of coagulation abnormalities and bleeding is also associated with higher doses. Monitor patients' vital signs and hemoglobin, hematocrit, platelet count, prothrombin time and partial thromboplastin time.

Bilirubin Levels

Indirect bilirubin levels of 8.3 mg/L (normal 0.0-7.0 mg/L) have been reported in 2 out of 20 normal subjects who received multiple infusions of 6% Hetastarch in 0.9% Sodium Chloride Injection. Total bilirubin was within normal limits at all times; indirect bilirubin returned to normal by 96 hours following the final infusion. The significance, if any, of these elevations is not known; however, caution should be observed before administering 6% Hetastarch in 0.9% Sodium Chloride Injection to patients with a history of liver disease.

Serum Amylase Levels

Elevated serum amylase levels may be observed temporarily following administration of 6% Hetastarch in 0.9% Sodium Chloride Injection although no association with pancreatitis has been demonstrated. Serum amylase levels cannot be used to assess or to evaluate for pancreatitis for 3-5 days after administration of 6% Hetastarch in 0.9% Sodium Chloride Injection. Elevated serum amylase levels persist for longer periods of time in patients with renal impairment. Hetastarch has not been shown to increase serum lipase.

Hemodialysis

6% Hetastarch in 0.9% Sodium Chloride Injection is not eliminated by hemodialysis. The utility of other extracorporeal elimination techniques has not been evaluated.

The serious adverse events reported in clinical trials are increased mortality and renal replacement therapy renal in critically ill patients.

Most common adverse reactions are hypersensitivity, coagulopathy, hemodilution, circulatory overload and metabolic acidosis.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Three randomized controlled trials (RCTs) followed critically ill adult patients treated with different HES products for 90 days.

One trial (N=804) in severe sepsis patients using HES product (not approved in the U.S.) reported increased mortality (relative risk, 1.17; 95% CI, 1.01 to 1.36; p=0.03) and RRT (relative risk, 1.35; 95% CI, 1.01 to 1.80; p=0.04) in the HES treatment arm.

Another trial (N=196) using different HES in severe sepsis patients reported no difference in mortality (relative risk, 1.20; 95% CI, 0.83 to 1.74; p=0.33) and a trend for RRT (relative risk, 1.83; 95% CI, 0.93 to 3.59; p=0.06) in HES patients.

A third trial (N=7000) using different HES in a heterogeneous patient population consisting of critically ill adult patients admitted to the ICU reported no difference in mortality (relative risk, 1.06; 95% CI, 0.96 to 1.18; p=0.26) but increased use of RRT (relative risk, 1.21; 95% CI, 1.00 to 1.45; p=0.04) in HES patients.

Because adverse reactions are reported voluntarily post-approval from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

The following adverse reactions have been identified and reported during the post-approval use of HES products:

Mortality

Renal

need for renal replacement therapy

Hypersensitivity reactions

including death, life-threatening anaphylactic/anaphylactoid reactions, cardiac arrest, ventricular fibrillation, severe hypotension, non-cardiac pulmonary edema, laryngeal edema, bronchospasm, angioedema, wheezing, restlessness, tachypnea, stridor, fever, chest pain, bradycardia, tachycardia, shortness of breath, chills, urticaria, pruritus, facial and periorbital edema, coughing, sneezing, flushing, erythema multiforme, and rash [see Warnings and Precautions (5.3) ].

Cardiovascular reactions

including circulatory overload, congestive heart failure, and pulmonary edema [see Warnings and Precautions (5.4) ].

Hematologic reactions

including intracranial bleeding, bleeding and/or anemia due to hemodilution [see Warnings and Precautions (5.4) ] and/or Factor VIII deficiency, acquired von Willebrand's-like syndrome, and coagulopathy including rare cases of disseminated intravascular coagulopathy and hemolysis.

Metabolic reactions

including metabolic acidosis.

Other reactions

including vomiting, peripheral edema of the lower extremities, submaxillary and parotid glandular enlargement, mild influenza-like symptoms, headaches, and muscle pains. Hydroxyethyl starch-associated pruritus has been reported in some patients with deposits of hydroxyethyl starch in peripheral nerves.

6% Hetastarch in 0.9% Sodium Chloride Injection should be used with caution in patients who have been anticoagulated with other drugs that negatively influence the coagulation system.

Hetastarch has been shown to have an embryocidal effect on New Zealand rabbits when given intravenously over the entire organogenesis period in a daily dose 1/2 times the maximum recommended therapeutic human dose (1500 mL) and on BD rats when given intraperitoneally, from the 16th to the 21st day of pregnancy, in a daily dose 2.3 times the maximum recommended therapeutic human dose. When hetastarch was administered to New Zealand rabbits, BD rats, and swiss mice with intravenous daily doses of 2 times, 1/3 times, and 1 times the maximum recommended therapeutic human dose respectively over several days during the period of gestation, no evidence of teratogenicity was evident.

There are no adequate and well-controlled studies in pregnant women. 6% Hetastarch in 0.9% Sodium Chloride Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether hetastarch is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when 6% Hetastarch in 0.9% Sodium Chloride Injection is administered to a nursing woman.

The safety and effectiveness of hetastarch in pediatric patients have not been established. Adequate, well-controlled clinical trials to establish the safety and effectiveness of 6% Hetastarch in 0.9% Sodium Chloride Injection in pediatric patients have not been conducted.

6% Hetastarch in 0.9% Sodium Chloride Injection is a sterile, nonpyrogenic solution for intravenous administration.

Each 100 mL contains:Hetastarch............................................................................ 6 gSodium Chloride, USP........................................................ 0.9 gWater for Injection, USP..................................................... qspH adjusted with Sodium Hydroxide, NF if necessaryConcentration of Electrolytes (mEq/L): Sodium (Na) 154, Chloride (Cl) 154 (not including ions for pH adjustment).pH: 5.5 (3.5 to 7.0)Total osmolar concentration is 308 mOsmol/liter (calc).

Hetastarch is a synthetic 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. 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 670,000 with a range of 550,000 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 ether 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 α-1,4 linkages with occasional α-1,6 branching linkages. The degree of branching is approximately 1:20 which means that there is one 1-6 branch for every 20 glucose monomer units.

The chemical name for hetastarch is hydroxyethyl starch.

The structural formula is as follows:

Amylopectin derivative in which R, R, and R are H or CHCHOH, or R is a branching point in the starch polymer connected through a 1-6 linkage to additional alpha-D-glucopyranosyl units.

Hetastarch is an artificial colloid pharmacologically classified as a plasma volume expander; 0.9% Sodium Chloride Injection is a fluid and electrolyte replenisher.

6% Hetastarch in 0.9% Sodium Chloride 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. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly.

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.

Exposure to temperatures above 25°C/77°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.

The plasma volume expansion produced by 6% Hetastarch in 0.9% Sodium Chloride Injection approximates that of 5% Albumin (Human). Intravenous infusion of 6% Hetastarch in 0.9% Sodium Chloride Injection results in expansion of plasma volume.

6% Hetastarch in 0.9% Sodium Chloride 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 6% Hetastarch in 0.9% Sodium Chloride 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 6% Hetastarch in 0.9% Sodium Chloride Injection 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, 6% Hetastarch in 0.9% Sodium Chloride Injection is used to improve the efficiency of granulocyte collection by centrifugal means.

Long-term studies of animals have not been performed to evaluate the carcinogenic potential of hetastarch.

Surgical Patients Comparative Studies

In randomized, controlled, comparative studies of 6% Hetastarch in 0.9% Sodium Chloride 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.

Pediatric Postoperative Volume Expander Study

In one small double-blind study, 47 infants, children, and adolescents (ages 1 year to 15.5 years) scheduled for repair of congenital heart disease with moderate hypothermia were randomized to receive either 6% Hetastarch in 0.9% Sodium Chloride Injection or Albumin as a postoperative volume expander during the first 24 hours after surgery. Thirty-eight children required colloid replacement therapy, of which 20 children received 6% Hetastarch in 0.9% Sodium Chloride Injection. No differences were found in the coagulation parameters or in the amount of replacement fluids required in the children receiving 20 mL/kg or less of either colloid replacement therapy. In children who received greater than 20 mL/kg of 6% Hetastarch in 0.9% Sodium Chloride Injection, an increase in prothrombin time was demonstrated (p=0.006). There were no neonates included in this study [see Use in Specific Populations (8.4) ].

Adult Critically Ill Studies

Three randomized controlled trials (RCTs) followed critically ill adult patients treated with different HES products for 90 days.

One trial (N=804) in severe sepsis patients using HES product (not approved in the U.S.) reported increased mortality (relative risk, 1.17; 95% CI, 1.01 to 1.36; p=0.03) and RRT (relative risk, 1.35; 95% CI, 1.01 to 1.80; p=0.04) in the HES treatment arm.

Another trial (N=196) using different HES in severe sepsis patients reported no difference in mortality (relative risk,1.20; 95% CI, 0.83 to 1.74; p=0.33) and a trend for RRT (relative risk, 1.83; 95% CI, 0.93 to 3.59; p=0.06) in HES patients.

A third trial (N=7000) using different HES in a heterogeneous patient population consisting of critically ill adult patients admitted to the ICU reported no difference in mortality (relative risk, 1.06; 95% CI, 0.96 to 1.18; p=0.26) but increased use of RRT (relative risk, 1.21; 95% CI, 1.00 to 1.45; p=0.04) in HES patients.

6% Hetastarch in 0.9% Sodium Chloride Injection is supplied sterile and nonpyrogenic in 500 mL single-use flexible plastic containers.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Rx only

Distributed by Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1287-3.0

Unit of Sale Concentration
NDC 0409-7248-03 30 g Hetastarch/500 mL
Case containing 12 Flexible Plastic Containers (6 g Hetastarch/100 mL)

Manufacturer

Hospira, Inc.

Active Ingredients

Source

Drugs and Medications [177 Associated Drugs and Medications listed on BioPortfolio]

6% hetastarch in 0.9% sodium chloride [hf acquisition co llc, dba healthfirst]

6% HETASTARCH IN 0.9% SODIUM CHLORIDE INJECTION 500mL BAG

Hespan [b. braun medical inc.]

These highlights do not include all the information needed to use HESPAN® (6% HETASTARCH IN 0.9% SODIUM CHLORIDE INJECTION) safely and effectively. See full prescribing information for HESPAN® (6% H...

Hextend [hospira, inc.]

HEXTEND                                                                                                 ...

Potassium chloride [novel laboratories, inc.]

These highlights do not include all the information needed to use POTASSIUM CHLORIDE safely and effectively. See full prescribing information for POTASSIUM CHLORIDE POTASSIUM CHLORIDE for oral solutio...

Potassium chloride for oral solution [virtus pharmaceuticals]

These highlights do not include all the information needed to use POTASSIUM CHLORIDE safely and effectively. See full prescribing information for POTASSIUM CHLORIDE. POTASSIUM CHLORIDE for oral soluti...

Clinical Trials [2141 Associated Clinical Trials listed on BioPortfolio]

Fluid Therapy During Brain Tumor Resection in Children

Fluid management of children during neurosurgery is not well established. Hypotonic solutions, commonly still used in pediatric patients, may enhance cerebral edema and worse operative con...

Clinical Evaluation of the Use of Sealed Capsule Irrigation With Sodium Chloride During Pediatric Cataract Surgery and IOL Implantation

This study involves using both a device that seals the capsular bag (where the lens is located) allowing safer irrigation of the capsular bag and sodium chloride to irrigate the capsular b...

Prevention of Contrast Nephropathy by Sodium Bicarbonate Versus Sodium Chloride and N-acetylcysteine

The objective of this study is to assess the efficacy of sodium bicarbonate compared with sodium chloride and oral N-acetylcysteine (NAC ) pretreatment for prevention of contrast nephropat...

Safety and Efficacy Study of the Use of Sodium Pyruvate Bronchodilation in Asthmatics

Sodium pyruvate in sodium chloride solution will be delivered by nebulization to the lungs. It is believed that this administration will produce bronchodilation in asthmatics as determined...

Sodium Chloride and Contrast Nephropathy

This phase II, open, non-inferiority, randomized and controlled clinical trial is aimed to ascertain the incidence of contrast nephropathy in outpatients undergoing CT scan with contrast. ...

PubMed Articles [2408 Associated PubMed Articles listed on BioPortfolio]

Separating the effects of 24-hour urinary chloride and sodium excretion on blood pressure and risk of hypertension: Results from PREVEND.

Research into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on bl...

Emergence of Chloride as an Overlooked Cardiorenal Connector in Heart Failure.

Several studies have recently challenged the sodium-centric view that has been dominating the field of heart failure (HF) and cardiorenal syndrome. The previously observed benefits of severe dietary r...

Long-term Physicochemical Stability of Concentrated Solutions of Sodium Valproate in Polypropylene Syringes for Administration in the Intensive Care Unit.

In some situations, drug solutions in higher concentrations are used in intensive care units. The objective of this study was to evaluate the physicochemical stability of concentrated solutions of val...

Diuretic Resistance in Cardio-Nephrology: Role of Pharmacokinetics, Hypochloremia, and Kidney Remodeling.

Diuretic resistance is among the most challenging problems that the cardio-nephrologist must address in daily clinical practice, with a considerable burden on hospital admissions and health care costs...

Formation and extent of peloid deposits in the Caspian Plain.

Main mud resources of brine lakes for balneological purpose form and accumulate in the zone of steppes and semi-deserts in the south and south-east of Russia (for example, in the Caspian Lowland). The...

Quick Search

Relevant Topics

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...


Drugs and Medication Quicklinks


Searches Linking to this Drug Record