Hydroxyethyl starch 130 (Solution) Instructions for Use

ATC Code

B05AA07 (Hydroxyethyl starch)

Active Substance

Hydroxyethyl starch 130/0.4 (USAN)

Clinical-Pharmacological Group

Plasma substitute

Pharmacotherapeutic Group

Plasma substitute

Pharmacological Action

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 waxy maize. Amylopectin is rapidly hydrolyzed in the blood, its presence in the bloodstream is about 20 minutes. To increase stability and prolong the 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-replacing effect 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.

Hydroxyethyl starch 130/0.4 is an iso-oncotic plasma-substituting solution, due to which its administration increases the volume of intravascular fluid in proportion to the volume of the drug administered. The molar substitution degree of hydroxyethyl groups of this HES is 0.4, the average molecular weight is 130,000 Da.

Infusion of 500 ml of the drug over 30 minutes leads to a plateau-like increase in blood volume by approximately 100% of the administered volume, maintained for 4-6 hours. When correcting hypovolemia with the drug, the therapeutic effect lasts at least 6 hours.

The stable volemic effect of the drug is 100% for 4 hours from the moment of its introduction into the vascular bed. The therapeutic effect lasts up to 6 hours.

Pharmacokinetics

The pharmacokinetics of HES is complex and depends on molecular weight, molar substitution degree, and the nature of C2/C6 substitution with hydroxyl groups.

After a single administration of 500 ml of the drug, its T_1/2 from blood plasma in the first elimination phase is 1.4 hours, and in the second phase it is 12.1 hours and returns to baseline after 24 hours.

With repeated administration of 500 ml of 6% HES 130/0.4 solution for 10 days, no significant accumulation of HES in blood plasma was detected. Hydroxyethyl starch is hydrolyzed by serum amylase and is also metabolized by the kidneys.

After 24 hours, about 50% of hydroxyethyl starch is excreted in the urine. T_1/2 is about 3-6 hours.

After administration of 500 ml of HES 130/0.4 solution, the plasma clearance is 31.4 ml/min.

Hydroxyethyl starch is not dialyzable.

Indications

Treatment of hypovolemia in acute blood loss, if the use of crystalloid solutions is insufficient.

ICD codes

Dosage Regimen

Administer Hydroxyethyl Starch 130/0.4 only in a hospital setting for the treatment of hypovolemia when crystalloid solutions are insufficient.

Determine the daily dose and infusion rate based on the individual’s blood volume deficit and clinical response. Use the lowest effective dose to achieve and maintain adequate hemodynamic status.

Base all treatment decisions on continuous hemodynamic monitoring. Do not administer if the patient’s hematocrit falls below 30%.

For most adults, the maximum daily dose is 50 ml per kg of body weight. For a patient weighing 70 kg, this equates to approximately 3500 ml per day.

Adjust the infusion rate according to the clinical situation. For acute hypovolemia, administer the initial dose rapidly. For maintenance therapy, use a slower, controlled rate.

Discontinue infusion immediately at the first signs of a hypersensitivity reaction, such as sudden facial redness, hypotension, or difficulty breathing.

Monitor renal function and blood coagulation parameters closely during and for at least 90 days after treatment. Avoid use in patients with pre-existing renal impairment or severe coagulation disorders.

Do not mix this solution with other medications in the same intravenous container or administration set.

Adverse Reactions

Blood and lymphatic system disorders: very common – decreased hematocrit, hypoproteinemia; common – blood coagulation disorders, increased bleeding time.

Immune system disorders: very rare – anaphylactic reactions of varying severity.

Allergic reactions: anaphylactoid reactions of varying severity, characteristic of all colloidal solutions, are possible. These reactions manifest as sudden redness of the face and neck, decreased blood pressure, shock, respiratory arrest, and cardiac arrest.

General disorders: common – pruritus, difficult to treat (with prolonged administration in medium and high doses). Itching may persist for a week after discontinuation of therapy and even for several months and be highly intense.

Laboratory and instrumental data: common – increased plasma amylase activity, not associated with impaired pancreatic function. Hyperamylasemia develops due to the formation of a hydroxyethyl starch-amylase complex, which is not excreted by the kidneys.

Contraindications

Hypervolemia; decompensated chronic heart failure, cardiogenic pulmonary edema; severe blood coagulation disorders; intracranial hemorrhage; dehydration requiring correction of water and electrolyte balance; severe renal failure with oliguria or anuria; patients on hemodialysis; sepsis; burns; severe liver diseases; conditions after organ transplantation; pronounced blood coagulation disorders (including severe hemorrhagic diathesis, hypocoagulation); hyperchloremia; hypernatremia; hypokalemia; severely ill patients, including those in intensive care units; during open heart surgery; children under 18 years of age; first trimester of pregnancy; increased individual sensitivity to HES (including to starch);

With caution

Compensated chronic heart failure, chronic renal failure, chronic liver diseases, hemorrhagic diathesis, hypofibrinogenemia.

Use in Pregnancy and Lactation

Currently, there are no reliable clinical data on use during pregnancy. Contraindicated in the first trimester of pregnancy.

Contraindicated during breastfeeding.

Use in Hepatic Impairment

Contraindication severe liver diseases.

Use in Renal Impairment

Contraindication severe renal failure with oliguria or anuria; patients on hemodialysis.

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

Special caution is recommended in patients with blood coagulation disorders, mild to moderate heart failure, renal failure, and chronic liver diseases.

HES administration should be discontinued at the first signs of kidney damage, coagulopathy.

It is recommended to monitor renal function for at least 90 days after the end of HES use.

In case of anaphylactoid/anaphylactic reactions, urgent resuscitation assistance should be provided in accordance with current guidelines. The mechanism of development of anaphylactoid reactions after administration of hydroxyethyl starch preparations has not been fully established.

In patients undergoing open heart surgery using cardiopulmonary bypass, the use of hydroxyethyl starch is not recommended due to the risk of massive bleeding.

When treating patients with hypovolemia, severe hemodilution should be avoided. In case of repeated use, blood coagulation parameters should be carefully monitored.

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.

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 dose of the drug used. Volume overload associated with drug overdose or high infusion rate should be avoided. The dose of the drug should be selected with caution, especially in patients with lung and cardiovascular diseases. Serum electrolyte levels, water balance, and renal function should be carefully monitored.

With rapid administration in large volumes, acute left ventricular failure and pulmonary edema, blood coagulation disorders may develop. If complaints of chest tightness, difficulty breathing, back pain, chills, cyanosis, circulatory and respiratory disorders occur, administration of the drug should be stopped and symptomatic therapy should be carried out.

Due to the possible risk of anaphylactoid reactions, caution should be exercised when administering the drug to patients who have previously received HES therapy.

With repeated administration, blood coagulation should be monitored.

In hypofibrinogenemia, HES 130/0.4 for blood volume replacement should be administered only in life-threatening conditions.

Caution is recommended in patients with hemorrhagic diathesis against the background of hypernatremia and dehydration.

If the hematocrit is less than 30%, simultaneous administration of red blood cell mass or whole blood is recommended.

During treatment, renal function should be monitored and adequate hydration maintained.

The use of HES may lead to a false-positive doping test result.

Drug Interactions

When used concomitantly with aminoglycosides, the risk of nephrotoxicity increases, so it is recommended to avoid simultaneous long-term use of hydroxyethyl starch and aminoglycosides.

Do not mix the drug containing HES with other drugs in one container and in one system.

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.