Refortan HES 6% - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Refortan® HES 6% - 6% of the isotonic solution hydroxyethyl derivative partial hydrolysis of waxy maize starch - hydroxyethyl starch (HES) with an average molecular weight of 200,000 daltons and a degree of molar substitution of 0.45 - 0.55. Refortan® HES 6% - izoonkotichesky solution, due to the ability to bind and retain water has isovolemic action which is stable for at least 3-4 hours and an increase in blood volume (CBV) with almost equivalent to the entered volume of the preparation.The colloid osmotic pressure (COD) and central venous pressure (CVP) significantly increase depending on the volume introduced, with lowered values, they increase to normal. Physico-chemical parameters of the original substance of the drug provide high efficacy in hypovolaemia due to the normalization of central and peripheral hemodynamics, microcirculation, improved delivery and consumption of oxygen by organs and tissues, normalization of vascular wall permeability, reduction of local inflammatory response, activation of a full immune response, mobilization of blood elements and physiological deposition and their involvement in active metabolism against a background of moderate hemodilution.

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

Pharmacokinetics:The maximum concentration (Cmax) is 11.1 ± 2.7 mg / ml. Depending on the rate of administration, the half-life (T1 / 2) is about 5-6 hours. After administration, the drug is cleaved with serum a-amylase and excreted in the urine (24 hours - about 50%) and bile.A small amount accumulates in the reticuloendothelial system (without manifestation of toxic effects on the liver, lungs, spleen and lymph nodes), where it is cleaved by a-amylase. HES is poorly excreted in dialysis; there is no data on the efficiency of HES removal by hemofiltration. Thanks to a well-controlled vollemic effect, as well as favorable rheological properties (reduced blood viscosity and hematocrit, reduced platelet aggregation), Refortan® HES 6% is suitable for volume replacement both for short and medium term.

Indications:

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

Contraindications:

- hypersensitivity to starch or other components of the drug;

- sepsis;

- burns;

- hyperhydration;

- hypervolemia;

- hypokalemia;

- Hypernatremia;

- Hyperchloremia;

- chronic heart failure in the stage of decompensation;

- kidney failure;

- pulmonary edema;

- intracranial hemorrhages or acute disturbance of cerebral circulation according to hemorrhagic type;

- severe bleeding disorders;

- hemodialysis;

- dehydration;

- Patients in critical condition (usually patients residing in intensive care unit);

- Patients who underwent open heart surgery under conditions of artificial circulation;

- condition after organ transplantation;

hepatic failure of severe severity;

- intracranial hypertension;

- First trimester of pregnancy;

- age to 18 years.

Carefully:

Compensated chronic heart failure; hepatic insufficiency of mild and moderate severity; disorders of blood clotting, hemorrhagic diathesis; patients who underwent surgery and / or with trauma; old age (over 65 years); second and third trimester of pregnancy.

Pregnancy and lactation:

The safety of HES during pregnancy has not been studied. Although in animal studies it has been established that Refortan HES 6% does not have embryotoxic and teratogenic effects, the use of the drug in the 1st trimester of pregnancy is contraindicated. In the 2nd and 3rd trimesters of pregnancy, Refortan® HES 6% can be used only for vital indications, when the potential benefit exceeds the possible risk.When using this drug during pregnancy, you should consider the risk of anaphylactic reactions and the possible risk of damage to the fetal brain.

It is not known whether HES is excreted in breast milk, and therefore it is recommended to stop breastfeeding while using Refortan® HES 6%.

Dosing and Administration:

Refortan® HES 6% is given as an intravenous infusion. In the absence of other prescriptions, the drug is administered intravenously drip according to the need to replace the volume of the circulating plasma.

The daily dose and the rate of intravenous administration are calculated depending on blood loss, hemoglobin concentration and hematocrit. If possible, the lowest effective dose should be given.

Beginning of the administration of the drug Refortan® HES 6% should be limited to the initial stage of the recovery of bcc. The duration of administration should not exceed 24 hours.

Given possible anaphylactic reactions, the first 10 to 20 ml of the drug Refortan® HES 6% should be administered slowly, with careful monitoring of the patient's condition. You should also consider the risk of overloading the circulatory system with too rapid administration or too high a dose of the drug.Therapy should be carried out against a background of constant control of hemodynamics - in order to interrupt the infusion as soon as the corresponding target level of hemodynamic parameters is reached.

In young patients without a risk of cardiovascular or pulmonary complications, the limit of using a colloidal volumetric drug is a hematocrit less than 30%.

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

The maximum daily dose is 30 ml / kg / day (1.8 g HES / kg / day).

For patients weighing 75 kg, this corresponds to 2250 ml of the drug Refortan® HES 6%. Due to the availability of limited data on the use of HES in children, its use in this category of patients is not recommended.

Side effects:

Possible side effects are listed below in the descending frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 10000, <1/1000), very rarely (<1/10000), the frequency is not established (according to available data, the estimate is not possible).

Disorders from the blood and lymphatic system

Often: a decrease in hematocrit and plasma protein concentration due to hemodilution.

Often (depending on the dose administered): relatively high doses of HES lead to a decrease in the concentration of clotting factors. As a consequence, a transient increase in clotting time and bleeding time is possible.

Disturbances from the liver and bile ducts

Frequency not set: liver damage.

Disturbances from the skin and subcutaneous fat

Infrequently: prolonged daily administration of HES in the range of medium to high doses can cause itching, which is difficult to cure. It can appear and in a few weeks after the end of therapy and persist for a long time.

Disorders from the kidneys and urinary tract

Rarely: In rare cases, there was reported pain in the kidney area. In such cases, it is necessary to stop the infusion of the drug, ensure sufficient fluid intake and exercise frequent monitoring of serum creatinine levels.

Frequency not set: impaired renal function.

Immune system disorders

Rarely: there were reports of individual cases of anaphylactoid reactions to HES (frequency, in terms of the number of infusion units - about 0.085%).In most cases, such reactions appear as vomiting, a slight increase in temperature, chills, pruritus and urticaria. There was an increase in the submaxillary and parotid salivary glands, an influenza-like syndrome, including headache, muscle pain and edema of the lower limbs.

Heavy intolerance reactions accompanied by shock and symptoms, life-threatening (sometimes up to stop the cardiac activity and respiration) are extremely rare (frequency - based on the amount of infusion units - about 0.006%).

If there is an intolerance reaction, it is necessary to immediately stop the infusion of the drug and at the same time begin the usual emergency measures (see section "Special instructions").

Impact on laboratory performance

Often: when using HES, an increase in serum amylase activity is possible, which is not related to the clinical manifestation of pancreatitis. Hyperamilazemia is caused by the formation of a complex of "HES-amylase", which is slowly excreted by the kidneys.

When using HES, the following laboratory parameters may be altered: the concentration of glucose, protein, fatty acids, cholesterol, sorbitol dehydrogenase in blood plasma, ESR, biuret assay, specific gravity of urine.

Overdose:

Symptoms: hypervolemic syndrome.

Treatment: immediate discontinuation of the drug infusion; diuretics may be prescribed.

Interaction:

When mixed with other medicinal products in one container or in one system, there may be phenomena of pharmaceutical incompatibility. Before each introduction should be carefully (at least visually) to monitor the compatibility of drugs. Nevertheless, this does not allow to exclude cases of chemical and pharmacological interaction, which is not determined visually. HES with simultaneous use with aminoglycoside antibiotics can potentiate their nephrotoxicity.

Special instructions:

Refortan® HES 6% does not affect the definition of the blood group. It should be borne in mind that too rapid intravenous administration of the drug, as well as its use in high doses, can lead to violations of hemodynamics. In the process of treatment, it is necessary to monitor the sufficient intake of fluid into the body (at least 2-3 liters of fluid per day), monitor the electrolyte composition of blood serum and fluid balance, as well as kidney function. To prevent the occurrence of hyperhydration,which can lead to decompensation of heart failure in patients with heart disease in history, it is necessary to monitor cardiac activity and BCC.

If there is a lack of fibrinogen, the drug can be used only in case of emergency care, when the life of the patient is at risk in the absence of components of the donor blood. In connection with the risk of allergic (anaphylactoid) reactions, careful monitoring of the patient's condition and the establishment of a low rate of drug administration are necessary. Symptoms of anaphylaxis may appear within a few minutes. Symptoms that cause anxiety are severe itching and redness of the skin (a sudden rush of blood to the face, neck). Sometimes the patient suffers suffocation, there is a feeling of "coma in the throat". Characteristic for the next stage are nausea and cramps in the abdomen, as well as tachycardia and arterial hypotension, which can lead to loss of consciousness, up to the stopping of breathing and the cessation of cardiac activity. In case of intolerance reactions, the drug should be stopped immediately and the necessary emergency measures taken.

Use of the drug Refortan® HES 6% is contraindicated in patients with renal insufficiency and / or receiving renal replacement therapy.

At the beginning of therapy with the Refortan® HES 6%, serum creatinine levels should be monitored.

When the first signs of renal impairment appear, the administration of Refortan® HES 6% should be discontinued. An increase in the need for renal replacement therapy was reported up to 90 days after the introduction of HES. It is recommended to monitor the state of kidney function for at least 90 days after the use of HES preparations.

The literature describes the relationship between the dose and frequency of itching in otoneurological diseases, such as severe hearing loss, tinnitus, and sound trauma. In these diseases, to limit the incidence of itching, it is recommended that the dosage of the Refortan® HES preparation be limited to 6% to 250 ml per day.

The use of the drug Refortan® HES 6% in patients with hepatic insufficiency of severe severity is contraindicated.

Caution should be used when using Refortan® HES 6% in patients with moderate and mild hepatic insufficiency and in patients with coagulation disorders.In the treatment of patients with hypovolemia, severe hemodilution should be avoided. In the case of repeated use of the drug should carefully monitor the parameters of blood coagulability. At the first signs of coagulopathy, the use of the drug Refortan® HES 6% should be discontinued.

Adequate long-term data on the use of the drug Refortan® HES 6% in patients who have undergone surgery or traumatized are absent. The expected benefit of treatment should be carefully correlated with uncertain long-term safety. Other available therapeutic measures should be considered.

In patients who undergo open heart surgery using the artificial circulation system, the use of HES preparations is not recommended because of the risk of massive bleeding.

To prevent complications of the cardiovascular system and kidneys caused by hypervolemia, elderly patients who are more likely to have cardiac and / or renal failure need careful dose selection and control during treatment.

Due to the availability of limited data on the use of HES in children, its use in this category of patients is not recommended.

Effect on the ability to drive transp. cf. and fur:The effect of the drug Refortan® HES 6% on the ability to drive vehicles and other mechanisms has not been studied.

Form release / dosage:

Solution for infusions 6%.

Packaging:

For 250 or 500 ml of the drug in vials:

1) of a colorless transparent glass of type II (Hebrew F), which are closed with a bromobutyl rubber stopper of type I (Hebrew F.) for piercing and a plastic lid under aluminum with a plastic holder fixed on a vial.

10 bottles in a cardboard box with instructions for use (for hospitals).

2) low-density polyethylene (Hebrew F), with a cap sealed onto the bottle, with an integrated rubber gasket and two opening rings and with a holder at the bottom of the bottle.

10 bottles along with the instructions for use are placed in a cardboard box (for hospitals).

Storage conditions:

At a temperature of no higher than 25 ° C in glass bottles. At a temperature of no higher than 30 ° C in polyethylene bottles. Do not freeze! Keep the medicine out of the reach of children!

Shelf life:

5 years in the original packaging.

Use only clear or slightly opalescent (no more than light yellow) solutions in undamaged vials. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014505 / 01

Date of registration:24.12.2008 / 04.10.2013

The owner of the registration certificate:BERLIN-PHARMA, CJSC BERLIN-PHARMA, CJSC Russia

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Representation: & nbspBERLIN-PHARMA, CJSCBERLIN-PHARMA, CJSC

Information update date: & nbsp23.01.2016

Illustrated instructions

Instructions

Refortan® HES 6% (Refortan® GAK 6%)