Infukoll HES^® (Solution) Instructions for Use

Marketing Authorization Holder

Serumwerk Bernburg, AG (Germany)

Contact Information

Serumwerk Bernburg AG (Germany)

ATC Code

B05AA07 (Hydroxyethyl starch)

Active Substance

Pentastarch

Pentastarch (USAN)

Dosage Forms

	Infukoll HES®	Solution for infusion 6%: 100 ml, 250 ml or 500 ml bottles
		Solution for infusion 10%: 100 ml, 250 ml or 500 ml bottles

Dosage Form, Packaging, and Composition

Solution for infusion 6% as a colorless or yellowish, transparent or slightly opalescent liquid.

Excipients: Isotonic solution (Na⁺ 154 mmol/l, Cl^– 154 mmol/l), water for injections.

100 ml – bottles (1).
100 ml – bottles (10).
250 ml – bottles (1).
250 ml – bottles (10).
250 ml – polymeric bags “Propyflex” (Propyflex^®) (1).
250 ml – polymeric bags “Propyflex” (Propyflex^®) (10).
500 ml – bottles (1).
500 ml – bottles (10).
500 ml – polymeric bags “Propyflex” (Propyflex^®) (1).
500 ml – polymeric bags “Propyflex” (Propyflex^®) (10).

Solution for infusion 10% as a colorless or yellowish, transparent or slightly opalescent liquid.

Excipients: Isotonic solution (Na⁺ 154 mmol/l, Cl^– 154 mmol/l), water for injections.

100 ml – bottles (1).
100 ml – bottles (10).
250 ml – bottles (1).
250 ml – bottles (10).
250 ml – polymeric bags “Propyflex” (Propyflex^®) (1).
250 ml – polymeric bags “Propyflex” (Propyflex^®) (10).
500 ml – bottles (1).
500 ml – bottles (10).
500 ml – polymeric bags “Propyflex” (Propyflex^®) (1).
500 ml – polymeric bags “Propyflex” (Propyflex^®) (10).

Clinical-Pharmacological Group

Plasma substitute

Pharmacotherapeutic Group

Plasma substitute

Pharmacological Action

The infusion solution Infukoll HES^® is a 6% and 10% solution, respectively, of a synthetic colloid, hydroxyethyl starch, derived from potato starch, in an isotonic solution with an average molecular weight of 200,000 daltons and a degree of substitution of 0.45-0.55. Due to its ability to bind and retain water (including from the interstitial space into the intravascular space), the drug has a volume effect within 85-100% and 130-140% of the administered volume for the 6% and 10% solutions, respectively, which is stably maintained for 4-6 hours.

The physicochemical parameters of the original substance of the drug Infukoll HES^® ensure high therapeutic efficacy in hypovolemia and shock, as well as when used for therapeutic hemodilution by normalizing central and peripheral hemodynamics, microcirculation, improving oxygen delivery and consumption by organs and tissues, restoring porous capillary walls (normalizing vascular wall permeability), reducing the local inflammatory response, activating a full immune response, mobilizing blood cells from physiological deposition and involving them in active metabolism against the background of moderate hemodilution.

In addition, the drug improves the rheological properties of blood by reducing hematocrit levels, and also reduces plasma viscosity, reduces platelet aggregation and prevents erythrocyte aggregation.

The drug does not exhibit local irritant or immunotoxic effects. Depositing in the cells of the reticuloendothelial system, the drug does not have a toxic effect on the liver, lungs, spleen, and lymph nodes.

The similarity of the structure of the drug Infukoll HES^® with the structure of glycogen explains the high level of drug tolerance and the almost complete absence of adverse reactions.

Under the action of serum amylase, the drug Infukoll HES^® is broken down into low molecular weight fragments (less than 70,000 daltons), which are excreted by the kidneys.

Pharmacokinetics

At 12 hours after drug administration, T_1/2 is 4.94 hours. The clearance rate is 7.33 ml/min. C_max in serum is 11.1±2.7 mg/ml; on day 3 after administration, trace amounts of the drug are detected in the serum. Within the first 12 hours after the start of drug administration, 24.48±3.93 mg/ml of Infukoll HES is present in the urine (49% of the administered amount).

Indications

• Prevention and treatment of hypovolemia and shock during surgeries, acute blood loss, trauma, infectious diseases, and burns;
• Microcirculation disorders;
• Therapeutic blood dilution (hemodilution), including in the therapy of fetoplacental insufficiency and preeclampsia in pregnant women, antiphospholipid syndrome in women, in in vitro fertilization programs, polycythemia in newborns, in the treatment of obliterative lesions of the vessels of the lower extremities, chronic obstructive pulmonary diseases, ischemic strokes (acute and subacute stages, acute ischemic stroke with reduced cardiac output and microangiopathies, in the presence of signs of dehydration and hypovolemia, in the presence of signs of hemoconcentration /hematocrit number more than 35%/).

ICD codes

Dosage Regimen

Infukoll HES^® is administered as an intravenous infusion.

The doses of Infukoll HES^® (6% solution) are presented in the table.

In the absence of other prescriptions, Infukoll HES^® is administered intravenously by drip in accordance with the need to replace the circulating fluid volume and the required level of hemodilution.

Newborns and children under 3 years of age are recommended to be prescribed the average daily dose of the drug. Due to the peculiarities of the water-electrolyte status in children, careful monitoring of hydration levels and electrolyte content is recommended.

Considering possible anaphylactic reactions, the first 10-20 ml of Infukoll HES^® should be administered slowly, with careful monitoring of the patient’s condition.

The daily dose and rate of intravenous administration are calculated depending on blood loss, hemoglobin concentration, and hematocrit. In young patients without the risk of cardiovascular and pulmonary damage, the limit for the use of a colloidal volume replacement drug is considered to be a hematocrit of 30% or less.

The maximum infusion rate depends on the initial hemodynamic parameters and is approximately 20 ml/kg body weight/hour.

The maximum daily dose is up to 33 ml and 20 ml of the drug (for the 6% and 10% solutions, respectively) per 1 kg of body weight/day (2 g of hydroxyethyl starch/1 kg/day).

Standard protocol for therapeutic hemodilution in ischemic stroke

1. “Loading dose” depending on the hematocrit level

A) with a hematocrit number less than 40% (hypervolemic therapeutic hemodilution): 500 ml of 6% Infukoll HES^® solution and 500 ml of electrolyte solution over 1 hour;

B) with a hematocrit number greater than 40% (isovolemic therapeutic hemodilution): withdrawal of 500 ml of blood with simultaneous administration of 500 ml of 6% Infukoll HES^® solution and 500 ml of electrolyte solution over 1 hour.

2. Therapeutic hemodilution on days 1-4

A) with a hematocrit number less than 40% (hypervolemic therapeutic hemodilution): 1000 ml of 6% Infukoll HES^® solution and 1000 ml of electrolyte solution over 24 hours;

B) with a hematocrit number greater than 40% (isovolemic therapeutic hemodilution): withdrawal of 500 ml of blood with simultaneous administration of 500 ml of 6% Infukoll HES^® solution and 500 ml of electrolyte solution over 24 hours.

3. Therapeutic hemodilution on days 5-10

Hypervolemic therapeutic hemodilution: 500 ml of 6% Infukoll HES^® solution and 500 ml of electrolyte solution over 12 hours.

4. Use of cardiac glycosides according to the standard protocol in accordance with clinical indications.

5. Inhibition of platelet aggregation

A) Days 1-4: single injection of acetylsalicylic acid 500 mg/day (if intracranial bleeding is excluded);

B) Days 5-10: single injection of acetylsalicylic acid 500 mg/day and ascorbic acid (vitamin C) orally 400 mg/day.

6. Use of hemorheologically active drugs (agents that improve cerebral circulation) and agents that improve cerebral metabolism

• Nootropics according to clinical indications;
• Pentoxifylline in average doses (intravenously 200-300 mg 2 times/day).

Therapeutic hemodilution should be started as early as possible (at the first contact with the patient).

Acute significant increase in intracranial pressure is a contraindication to further therapeutic hemodilution.

Minor intracranial bleeding is not a contraindication to further therapeutic hemodilution.

Administration of the 6% Infukoll HES^® solution should be continuous, including at night.

The volume of the administered 6% Infukoll HES^® solution should be correlated with the contractility of the myocardium (heart rate control).

It is possible to use the corresponding volume of the 10% Infukoll HES^® solution with corrective administration of an electrolyte solution (it is necessary to avoid sodium overload in this case).

During isovolemic hemodilution, the occurrence of hypovolemia is unacceptable: blood withdrawal should occur simultaneously with the administration of the 6% Infukoll HES^® solution, the rate of blood withdrawal should never exceed the rate of administration of the Infukoll HES^® solution.

It is advisable to achieve an initial reduction in the hematocrit number by 12-15%.

In case of a threat of cerebral edema, the following are indicated: elevated body position (30°); head position facilitating venous outflow; rapid administration of hyperosmotic drugs (glycerol, sorbitol).

Administration of cortisone and diuretics is not indicated.

Adverse Reactions

Allergic reactions rarely – persistent but reversible skin itching; extremely rarely – anaphylactoid reactions.

Contraindications

• Hyperhydration;
• Hypervolemia;
• Decompensated heart failure;
• Renal failure with decompensated oliguria or anuria;
• Cardiogenic pulmonary edema;
• Intracranial bleeding;
• Severe blood coagulation disorders;
• Hypersensitivity to starch and other components of the drug.

Contraindications to the use of therapeutic hemodilution in acute cerebrovascular accidents

• Severe hemorrhagic diathesis;
• Myocardial infarction within the last 6 weeks;
• Angina pectoris functional class IV, all variants of unstable angina;
• Circulatory insufficiency stage IIB-III;
• Chronic renal failure (creatinine level more than 2 mg/dl);
• Significant increase in intracranial pressure;
• History of seizures;
• Profuse bleeding;
• Baseline hematocrit number <35%;
• Arterial hypertension poorly controlled by antihypertensive therapy (systolic BP >180 mm Hg and diastolic – >120 mm Hg)

Use in Pregnancy and Lactation

Infukoll HES^® should be used with caution in the first trimester of pregnancy.

In case of fetoplacental insufficiency and preeclampsia in pregnant women with elevated blood pressure, treatment should be carried out against the background of antihypertensive therapy.

It has been established that the drug does not have embryotoxic or teratogenic effects.

Use in Renal Impairment

Contraindicated in renal failure with decompensated oliguria or anuria, chronic renal failure (creatinine level more than 2 mg/dl).

Pediatric Use

Used according to indications and in doses taking into account the patient’s age.

Special Precautions

The drug should be prescribed with caution in hemorrhagic diatheses, in intracranial hypertension, in conditions of dehydration (requires preliminary corrective therapy) and severe water-electrolyte balance disorders.

It should be taken into account that too rapid intravenous administration of the drug, as well as the use in high doses, can lead to hemodynamic disturbances.

During treatment, it is necessary to monitor serum ionogram and fluid balance, and renal function.

If intolerance reactions occur, the administration of the drug should be stopped immediately and the necessary emergency measures should be taken.

It should be taken into account that the use of the drug may increase serum amylase activity, which is not associated with clinical manifestations of pancreatitis. The drug Infukoll HES^® can be used in the conservative and surgical treatment of patients with destructive pancreatitis.

Administration of the drug to patients with diabetes mellitus is not accompanied by an increase in blood glucose levels, so the drug Infukoll HES^® can be used in the conservative and surgical treatment of this category of patients.

It has been established that the drug does not have a mutagenic effect.

Overdose

To date, no cases of overdose with Infukoll HES^® have been reported.

Drug Interactions

Pharmaceutical interaction

When mixed with other medicinal products in one container and in one system, incompatibility phenomena may be observed.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Infukoll HES^® should be used only if the solution is clear and the packaging is undamaged.

Shelf Life

Shelf life – 5 years for the drug in glass bottles; 3 years for the drug in polymeric bags.

Dispensing Status

Infukoll HES^® is dispensed by prescription.

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.