Haes-Steril (Solution) Instructions for Use

Instructions
Dosage forms

ATC Code

B05AA07 (Hydroxyethyl starch)

Active Substance

Pentastarch

Pentastarch (USAN)

Clinical-Pharmacological Group

Plasma substitute

Pharmacotherapeutic Group

Plasma substitute

Pharmacological Action

A plasma substitute, hydroxyethyl starch (HES). HES is a high-molecular-weight compound consisting of polymerized glucose residues, obtained by hydroxyethylation of amylopectin, a natural polysaccharide contained in the starch of waxy maize and potatoes. Amylopectin is rapidly hydrolyzed in the blood; its presence in the bloodstream is about 20 minutes. To increase stability and duration of action, amylopectin is subjected to hydroxyethylation. The depth of this process is characterized by the degree of substitution.

The intensity and duration of the volume-substituting action of HES preparations are determined by the molecular weight and degree of substitution of the HES substance. The higher the degree of substitution, the longer HES remains in the circulating blood. With a C₂/C₆ ratio greater than 8, HES is metabolized in the body significantly more slowly than with a ratio of less than 8.

Pentastarch has a molecular weight of about 200,000 daltons and a degree of substitution of about 0.5; the C₂/C₆ ratio, which determines the substitution features, is 6.

It improves the rheological properties of blood by reducing hematocrit values, reduces plasma viscosity, reduces erythrocyte aggregation, and promotes the restoration of impaired microcirculation.

It is deposited in the cells of the reticuloendothelial system (RES), which has no clinical significance.

Pharmacokinetics

After IV infusion, pentastarch undergoes intensive metabolism, breaking down (under the action of serum amylase) into low-molecular-weight fragments. Metabolites with a molecular weight of less than 50,000 daltons are rapidly excreted by the kidneys. About 70% of the dose is excreted in the urine within 24 hours and about 80% within a week.

Indications

As a plasma substitute for hypovolemia and shock associated with surgical interventions, injuries, infectious diseases, and burns; microcirculation disorders; therapeutic hemodilution.

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
I98.8	Other specified disorders of circulatory system in diseases classified elsewhere
R57.0	Cardiogenic shock
R57.1	Hypovolemic shock
R57.2	Septic shock
R57.8	Other types of shock
T78.2	Anaphylactic shock, unspecified
T79.4	Traumatic shock

ICD-11 code	Indication
1G41	Sepsis with septic shock
4A84.30	Exercise-induced anaphylaxis
4A84.31	Cold-induced anaphylaxis
4A84.3Z	Anaphylaxis caused by unspecified physical factors
4A84.4	Anaphylaxis caused by inhalation of allergens
4A84.5	Anaphylaxis caused by contact with allergens
4A84.6	Secondary anaphylaxis in mast cell disease
4A84.Z	Anaphylaxis, unspecified
BE2Y	Other specified diseases of the circulatory system
MG40.0	Cardiogenic shock
MG40.1	Hypovolemic shock
MG40.Z	Shock, unspecified
NF0A.4	Traumatic shock, not elsewhere classified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Solution

It is set individually, depending on the severity of hemodynamic disorders and the clinical situation. The daily dose and infusion rate are calculated based on the amount of blood loss, hemoglobin, and hematocrit levels. It is administered intravenously, by drip.

The minimum effective dose should be used. Treatment should be carried out with constant hemodynamic monitoring; upon achieving target hemodynamic parameters, the infusion should be stopped.

Adverse Reactions

From the blood coagulation system: very common – decrease in hematocrit and development of dilutional hypoproteinemia; common (frequency depends on the administered dose) – increased bleeding time and APTT, decrease in the content of coagulation factor VIII complex and von Willebrand factor.

From the immune system: very rare – anaphylactic reactions of varying severity.

From the skin and subcutaneous tissues: rare – persistent but reversible skin itching.

From the liver and biliary tract: frequency not established – liver damage.

From the urinary system: rare – pain in the kidney area; frequency not established – impaired renal function.

From laboratory parameters: common – increased activity of plasma alpha-amylase, not associated with impaired pancreatic function; possible – changes in the concentration of glucose, protein, fatty acids, cholesterol, sorbitol dehydrogenase in plasma, ESR values, biuret test, specific gravity of urine.

Contraindications

Hypersensitivity to HES; burns, sepsis, intracranial hypertension, arterial hypertension, ongoing intracranial or intracerebral bleeding, chronic heart failure, renal failure or renal replacement therapy, severe hepatic failure, pulmonary edema, condition after organ transplantation, overhydration, hypervolemia, dehydration, severe coagulopathy, severe hyperchloremia or severe hypernatremia, hypokalemia, hemodialysis; children and adolescents under 18 years of age; first trimester of pregnancy.

Do not use in open-heart surgery under cardiopulmonary bypass.

Contraindicated for use in intensive care patients (usually in the intensive care unit).

With caution compensated chronic heart failure, chronic liver diseases, blood coagulation disorders, von Willebrand disease, hemorrhagic diathesis, hypofibrinogenemia, patients who have undergone surgery and/or have trauma, elderly age, second and third trimesters of pregnancy; breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy, use is possible only for vital indications, in cases where the potential benefit to the mother outweighs the potential risk to the fetus. When using pentastarch during pregnancy, the risk of anaphylactic reactions and the possible risk of fetal brain damage must be considered. If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure. Should be used with caution in chronic liver diseases.

Use in Renal Impairment

Contraindicated in renal failure or during renal replacement therapy.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients (over 65 years of age). To prevent complications from the cardiovascular system and kidneys caused by hypervolemia, elderly patients require careful dose selection and monitoring during treatment.

Special Precautions

To prevent complications from the cardiovascular system and kidneys caused by hypervolemia, elderly patients, who are more likely to have heart and/or renal failure, require careful dose selection and monitoring during treatment.

Particular caution should be exercised when using HES solutions in patients with blood coagulation disorders, with impaired liver function. The appropriateness of using HES for the treatment of hypovolemia should be carefully assessed and hemodynamic parameters should be monitored to control the achievement of the desired effect and determine the HES dose. Volume overload associated with drug overdose or high infusion rate should be avoided. The dose must be selected with caution, especially in patients with lung and cardiovascular diseases.

The administration of high doses of pentastarch to patients with hypovolemia should be avoided due to possible pronounced hemodilution. In case of repeated use of pentastarch, blood coagulation parameters must be carefully monitored.

If hypersensitivity reactions develop, the administration of pentastarch should be stopped immediately and the necessary emergency measures should be taken. Patients should be under continuous medical supervision; additional therapeutic measures should be taken depending on the patient’s condition.

When using pentastarch, blood volume, electrolyte concentration, leukocytes, platelets, hemoglobin, and blood coagulation parameters should be monitored. At the first signs of coagulopathy, the use of the drug should be discontinued.

In open-heart surgery associated with cardiopulmonary bypass, there is an increased risk of bleeding, so the use of HES is contraindicated.

Before starting and during the use of HES, renal function should be checked, constant monitoring of serum creatinine, water-electrolyte balance, and urine retention indicators should be carried out. At the first signs of kidney damage during treatment, the use of pentastarch should be discontinued. Renal function monitoring should be carried out for 90 days after the use of pentastarch (risk of kidney damage in the long term).

Impaired renal function during therapy with HES solution may worsen the initial hepatic failure (with portal hypertension) and may lead to mechanical obstruction of the bile ducts.

During treatment, sufficient fluid intake should be ensured (at least 2-3 liters of fluid per day).

When treating patients whose blood group is unknown, it should be borne in mind that the administration of large volumes of HES may complicate the interpretation of agglutination reaction results.

Pentastarch may give a positive result in doping control.

Drug Interactions

With simultaneous use with aminoglycosides, the risk of nephrotoxicity increases, so it is recommended to avoid simultaneous long-term use of pentastarch and aminoglycosides.

With simultaneous use with anticoagulants, an increase in bleeding time is possible.

Pentastarch is incompatible with solutions of other medicinal products.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Haes-Steril [Fresenius Kabi Deutschland, GmbH (Germany)]
Infusion solution 6% (HES 200/0.5): glass bottle 250 ml or 500 ml 10 pcs. with drip holders or without them, plastic bottle 250 ml or 500 ml 10 or 20 pcs. with drip holder loop, polyolefin "Freeflex" containers 250 ml or 500 ml 10, 15, 20 or 30 pcs.

Marketing Authorization Holder

Fresenius Kabi Deutschland, GmbH (Germany)

Dosage Form

Haes-Steril

Infusion solution 6% (HES 200/0.5): glass bottle 250 ml or 500 ml 10 pcs. with drip holders or without them, plastic bottle 250 ml or 500 ml 10 or 20 pcs. with drip holder loop, polyolefin "Freeflex" containers 250 ml or 500 ml 10, 15, 20 or 30 pcs.

Dosage Form, Packaging, and Composition

Infusion solution 6% colorless or slightly yellowish, transparent or slightly opalescent.

	1 L
Hydroxyethyl starch 200/0.5	60 g
Including: Na⁺ 154 mmol/L Cl^– 154 mmol/L PH 3.5-6.0 Titratable acidity less than 1 mmol NaOH/L Theoretical osmolarity 308 mOsm/L

Excipients : sodium chloride – 9 g, water for injections – up to 1 L, sodium hydroxide – q.s. for pH adjustment.

250 ml – glass bottles (10) – cardboard boxes.
250 ml – glass bottles with drip holders (10) – cardboard boxes.
250 ml – plastic bottles with drip holder loop (10) – cardboard boxes.
250 ml – plastic bottles with drip holder loop (20) – cardboard boxes.
250 ml – polyolefin “Freeflex” containers (1) – plastic bags (10) – cardboard boxes.
250 ml – polyolefin “Freeflex” containers (1) – plastic bags (15) – cardboard boxes.
250 ml – polyolefin “Freeflex” containers (1) – plastic bags (20) – cardboard boxes.
250 ml – polyolefin “Freeflex” containers (1) – plastic bags (30) – cardboard boxes.
500 ml – glass bottles (10) – cardboard boxes.
500 ml – glass bottles with drip holders (10) – cardboard boxes.
500 ml – plastic bottles with drip holder loop (10) – cardboard boxes.
500 ml – plastic bottles with drip holder loop (20) – cardboard boxes.
500 ml – polyolefin “Freeflex” containers (1) – plastic bags (10) – cardboard boxes.
500 ml – polyolefin “Freeflex” containers (1) – plastic bags (15) – cardboard boxes.
500 ml – polyolefin “Freeflex” containers (1) – plastic bags (20) – cardboard boxes.
500 ml – polyolefin “Freeflex” containers (1) – plastic bags (30) – cardboard boxes.

Haes-Steril [Fresenius Kabi Deutschland, GmbH (Germany)]
Infusion solution 10% (HES 200/0.5): glass fl. 250 ml or 500 ml 10 pcs. with drip holders or without them, plastic fl. 250 ml or 500 ml 10 or 20 pcs. with drip loop-holder, polyolefin "freeflex" containers 250 ml or 500 ml 10, 15, 20 or 30 pcs.