Tetraspan 6 (Solution) Instructions for Use

Marketing Authorization Holder

B.Braun Melsungen AG (Germany)

ATC Code

B05AA07 (Hydroxyethyl starch)

Dosage Form

Tetraspan 6

Solution for infusion: containers 250, 500 or 1000 ml, bottles 500 ml.

Dosage Form, Packaging, and Composition

1000 ml – plastic containers (10) – cardboard boxes.
250 ml – plastic containers (20) – cardboard boxes.
500 ml – plastic containers (20) – cardboard boxes.
500 ml – polyethylene bottles (10) – cardboard boxes.

Clinical-Pharmacological Group

Plasma substitute

Pharmacotherapeutic Group

Plasma substitute

Pharmacological Action

Tetraspan 6 is a colloidal plasma-substituting solution containing 6% hydroxyethyl starch (HES) in a balanced electrolyte solution. The average molecular weight of HES is 130,000 daltons, and the molar substitution degree is 0.42.

Tetraspan 6 is an iso-oncotic solution, the volume effect of which is 100%. The duration of the volume effect mainly depends on the molar substitution degree of HES and, to a lesser extent, on the average molecular weight of HES.

HES hydrolysis products are oncotically active molecules excreted by the kidneys.

Tetraspan 6 may reduce hematocrit and plasma viscosity. With isovolemic administration, the volume-replacing effect persists for at least 6 hours.

The cation composition in Tetraspan 6 is identical to the physiological concentration of electrolytes in plasma. The anions are represented by chlorides, acetates, and malates, the purpose of which is to minimize the risk of hyperchloremia and acidosis. The addition of acetates and malates instead of lactates is due to the reduced risk of lactic acidosis.

Pharmacokinetics

HES is a substance consisting of molecules with different molecular weights and degrees of molar substitution. Both of these values affect the elimination rate. Small molecules are eliminated during glomerular filtration, while large molecules undergo enzymatic hydrolysis by alpha-amylase and are subsequently excreted by the kidneys. The rate of hydrolysis is lower the higher the substitution degree.

Approximately 50% of the administered HES dose is excreted in the urine within 24 hours. After a single administration of 1000 ml of Tetraspan 6, the plasma clearance is 19 ml/min, and the area under the concentration-time curve is 58 mg×h/ml. The serum T_1/2 is 12 hours.

Indications

• Prevention and treatment of relative and absolute hypovolemia, shock developing as a result of bleeding or trauma, intraoperative blood loss, burns, sepsis;
• Acute normovolemic hemodilution, therapeutic hemodilution;
• Priming of the extracorporeal circulation apparatus.

ICD codes

Dosage Regimen

For intravenous administration.

The daily dose and infusion rate depend on the amount of blood loss and hemodynamic parameters.

Maximum daily dose for adults

Up to 50 ml/kg body weight of Tetraspan 6 (which corresponds to 3.0 g/kg body weight of HES). This corresponds to 3500 ml of Tetraspan 6 for a patient weighing 70 kg. When using Tetraspan 6 in children, dosages should be individualized according to hemodynamic status and comorbidities: in children aged 10-18 years, the maximum daily dose is 33 ml/kg body weight; in children 2-10 years old, the maximum daily dose is 25 ml/kg body weight.

Maximum infusion rate

The maximum infusion rate depends on the clinical situation. Patients in the acute phase of shock can receive up to 20 ml/kg body weight per hour (which corresponds to 0.33 ml/kg body weight per minute or 1.2 g/kg body weight of HES per hour).

In life-threatening conditions, rapid administration of 500 ml of solution (under pressure) is possible.

Duration of therapy

The duration of therapy depends on the duration and severity of hypovolemia, the hemodynamic effect resulting from the therapy, and the level of hemodilution.

Adverse Reactions

The most frequent side effects are directly related to the therapeutic effects of HES solutions and the dosage, i.e., hemodilution, which is the result of an increase in the intravascular space without the concomitant administration of blood components. Dilution of coagulation factors may also occur. Hypersensitivity reactions occur very rarely and are not dose-dependent.

Effect on the blood and lymphatic systems

Decrease in hematocrit and decrease in plasma protein content as a result of hemodilution.

Relatively high doses of HES lead to dilution of coagulation factors and thus to impaired hemostasis. Bleeding time and aPTT (Activated Partial Thromboplastin Time) may increase, and FVIII/vWF (von Willebrand factor) activity may decrease after high-dose administration of the drug.

Effect on biochemical parameters

Administration of HES solutions may cause a short-term increase in serum alpha-amylase levels, which should not be interpreted as impaired pancreatic function.

Anaphylactic reactions

Anaphylactic reactions of varying severity may occur during HES administration. Therefore, all patients receiving HES solutions should be under constant medical supervision for the occurrence of anaphylactic reactions. If anaphylactic reactions occur, administration should be stopped immediately and emergency therapy initiated.

Contraindications

• Hyperhydration, including pulmonary edema;
• Severe renal failure with oliguria or anuria;
• Intracranial hemorrhage;
• Severe hyperkalemia;
• Severe hypernatremia or severe hyperchloremia;
• Decompensated severe hepatic failure;
• Congestive heart failure;
• Children under 2 years of age;
• Hypersensitivity to one or more components of the drug.

Use with caution in coagulation disorders, especially in identified or suspected von Willebrand disease.

Use in Pregnancy and Lactation

Currently, there are no reliable clinical data on the use of Tetraspan 6 during pregnancy, so it can be used in pregnant women only in cases where the expected benefit of treatment with the drug outweighs the possible risk to the fetus (especially in the first trimester).

Since it is unknown whether HES in Tetraspan 6 is excreted in breast milk, the possibility of discontinuing breastfeeding should be considered when prescribing the drug to nursing women.

Use in Hepatic Impairment

Contraindicated in decompensated severe hepatic failure.

Use in Renal Impairment

Contraindicated in severe renal failure with oliguria or anuria.

Volume overload, which can occur due to overdose, should always be avoided, which is especially dangerous for patients with renal failure.

Pediatric Use

Contraindicated in children under 2 years of age.

Geriatric Use

Volume overload, which can occur due to overdose, should always be avoided, which is especially dangerous for elderly patients.

Special Precautions

For the earliest possible detection of anaphylactic reactions, the first 10-20 ml should be administered slowly and under constant medical supervision.

Volume overload, which can occur due to overdose, should always be avoided, which is especially dangerous for patients with concomitant cardiac pathology, renal failure, as well as for elderly patients.

Serum electrolyte levels, fluid balance, and renal function should be monitored.

In case of severe dehydration, the water-electrolyte balance should first be normalized. To correctly determine the patient’s blood group, a blood sample must be taken before the administration of Tetraspan 6. Due to the risk of allergic (anaphylactoid/anaphylactic) reactions, the patient should be under constant observation, and a low initial infusion rate of the drug should be ensured.

Overdose

Overdose of Tetraspan 6 may lead to hypervolemia. In this case, administration of the drug should be stopped immediately and, if necessary, diuretics should be administered.

Drug Interactions

To date, no interactions between Tetraspan 6 and other drugs or dietary supplements have been identified.

Storage Conditions

Store at a temperature not exceeding 25°C (77°F) in places inaccessible to children. Do not freeze!

Shelf Life

Shelf life – 2 years.

Dispensing Status

For use in hospitals.

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.