Volyuven

General characteristics. Structure:

Active ingredients: Weed 60 g (Au - a 2-hydroxyethyl) starch *, 9 g of sodium of chloride, electrolytes: Na + 154 mmol/l, Cl-of 154 mmol/l, theoretical osmolarity 308 ¼Äß¼/l, titrable acidity less than 1 mmol of NaOH/l, pH 4.0-5.5.

* with extent of molar substitution 0.4; with an average molecular weight of 130 000 Yes.

Excipients: sodium hydroxide for correction pH, Acidum hydrochloricum for correction pH, water for injections.

Pharmacological properties:

Pharmacodynamics. Plasma substituting drug. Volyuven is solution of hydroxyethylated starch (GEK) which is received from amylopectin of corn of wax ripeness and characterize on the molecular weight and extent of substitution. For Volyuven average molecular weight makes 130 000 Yes, and extent of substitution 0.4 that means that 4 hydroxyethyl groups are the share of 10 glucosic remains of amylopectin. GEK it is structurally related to a glycogen that explains its high tolerance and low risk of anaphylactic reactions. Volyuven differs in high stability of solution and does not give flocculation at fluctuations of temperature.

Volyuven is isooncotic plasma substituting solution thanks to what at its introduction the volume of intravascular liquid increases in proportion to the entered Volyuven's volume.

The lasting volemichesky effect of Volyuven makes 100% during 4 h from the moment of administration of drug in a vascular bed. The therapeutic effect proceeds to 6 h.

Pharmacokinetics. The pharmacokinetics of GEK has difficult character and depends on the molecular weight of GEK, extent of molar substitution of substance and the nature of molar substitution of C2/C6 by hydroxylic groups.

Later in/in introductions of GEK molecules weighing less than 60 000-70 000 Yes (a threshold of renal filtering) are quickly removed with urine, and larger molecules are split by blood plasma α-amylase then too are removed through kidneys. The extent of substitution of GEK is less, the quicker drug is hydrolyzed by α-amylase and to be brought out of an organism, the accumulation in fabrics (in particular, in cells of immune system) and a blood plasma is less. The nature of substitution of C2/C6 exerts impact on volemichesky effect of drug. This indicator at Volyuven makes 9:1, i.e. hydroxylic groups are located in more situation of stability of C2 in 9 times more, than in C6. If is in situation C2 ≥ 8 hydroxylic groups, then the volemichesky effect of GEK is stabler, than at GEK with this indicator less than 8.

The average molecular weight of Volyuven of in vivo the first minutes after infusion makes in a blood plasma 70 000-80 000 And remains above a threshold of renal filtering during the entire period of treatment.

After introduction of 500 ml of Volyuven his clearance in a blood plasma makes 31.4 ml/min. After single introduction of 500 ml of the drug T1/2 in a blood plasma in the first phase of removal makes 1.4 h, and in the second phase - 12.1 h.

At single introduction of 500 ml of Volyuven of a molecule of GEK are completely brought out of an organism in 24 h. At repeated introduction of 500 ml of solution of GEK 130/0.4 within 10 days of essential accumulation of substance in a blood plasma it is not revealed.

Pharmacokinetics in special clinical cases. At patients with stable disturbance of functions of kidneys (from a lung to heavy) and KK <50 ml/min. of Cmax of GEK in blood was slightly above, than at patients with KK> 50 ml/min. at the same entered drug dose (500 ml). Disturbance of functions of kidneys did not influence T1/2 in a final phase of removal and at a size Cmax of GEK in a blood plasma. At KK> 30 ml/min. with urine 59% of the entered drug dose were removed, and at KK of 15-30 ml/min. - 51%.

In comparison with GEK 200/0.5 Volyuven possess the improved pharmacokinetics (metabolism and removal is optimized), at preservation of its plasma substituting effect. At the same time drug has the maximum safety in comparison with the previous generations of GEK since exerts the minimum impact on system of a hemostasis even at repeated introduction of high doses, and also there is practically no its accumulation in fabrics.

Indications to use:

— treatment and prevention of a hypovolemia of any genesis and shock (owing to injuries, including a spine injury with injury of a spinal cord, blood loss, a burn, sepsis, multiorgan insufficiency, to the postoperative period, acute adrenal insufficiency, an anaphylaxis and other states which are followed by development of a collapse);

— acute normovolemichesky hemodilution;

— therapeutic hemodilution;

— filling of the device of extracorporal blood circulation.

Route of administration and doses:

The drug is administered in the way long in/in infusion. The first 10-20 ml of solution should be entered slowly, at careful observation of a condition of the patient, in connection with risk of emergence of anaphylactoid reactions.

The daily dose and speed of infusion depend on degree of blood loss, maintenance or recovery of a hemodynamics and on hemodilution degree (blood cultivation).

In the situations demanding bystry compensation of a hypovolemia and the emergency completion of OTsK it is possible to use 500 ml of solution in plastic containers under pressure. At the same time before Volyuven's introduction it is necessary to remove air from a container for the purpose of prevention of developing of an air embolism.

The maximum daily dose makes 50 ml/kg of mass of bodies/days that corresponds to 3750 ml/days at the body weight of the patient of 75 kg.

At children 2 years which transferred operative measures are aged younger (excepting cardiological), portability at use Volyuvena in the course of operations was comparable to portability of 5% of albumine.

For completion of OTsK at adults the maximum dose makes 50 ml/kg/days; children and teenagers at the age of 10-18 years have 33 ml/kg/days; children at the age of 2-10 years have 25 ml/kg/days; newborns and children under 2 years have 25 ml/kg/days.

Volyuven it is possible to enter repeatedly within several days, depending on a clinical situation. Duration of treatment depends on duration and weight of a hypovolemia, on hemodynamic efficiency of drug and on hemodilution.

Features of use:

Use at pregnancy and feeding by a breast. Clinical data on drug use Volyuven at pregnancy and in the period of a lactation are absent.

Use of drug at pregnancy is possible only if the potential advantage for mother exceeds possible risk for a fruit.

In pilot studies on animals the direct or mediated adverse effect on the course of pregnancy, development of an embryo/fruit, childbirth and post-natal development is not revealed. Signs of teratogenecity were not observed.

Use at abnormal liver functions. Extra care is required at a heavy liver failure.

Use at renal failures. Drug is contraindicated to use at a renal failure of heavy degree with an oliguria or an anury and at the patients who are on a hemodialysis.

Use for children. Udetya 2 years which transferred operative measures are aged younger (excepting cardiological), portability at use Volyuvena in the course of operations was comparable to portability of 5% of albumine.

Special instructions. As well as at use of other solutions, when performing plasma substituting therapy it is necessary to avoid an overload liquid. The risk of an overhydratation especially increases for patients with heart failure or heavy renal failures. In this case indications for injection should be specified.

Preference should be given in cases of heavy dehydration to saline solutions. Extra care is required at a heavy liver failure or disorders of fibrillation, including in hard cases of an angiohemophilia. It is important to observe providing with enough liquid, regular control of function of kidneys and balance of liquid.

It is necessary to control blood serum electrolytes. At treatment of patients whose blood group is not defined it must be kept in mind that Volyuven's introduction in high doses can influence an agglutination test and yield false positive results at blood typing.

Introduction of GEK can lead to increase in level of serumal amylase. This effect has to be considered not as disturbance from function of a pancreas and as result of formation of a complex of GEK with amylase with the subsequent delay of its removal through kidneys. Now cases of such interaction are unknown. Drug does not influence increase in level of glucose in blood serum after hydrolysis by α-amylase and can be applied at patients with a diabetes mellitus.

Use in pediatrics. The dose for children should be selected individually according to the need for colloids and taking into account weight of a basic disease, indicators of a hemodynamics, a water balance.

Side effects:

Dermatological reactions: at long introduction in high doses - a skin itch.

From laboratory indicators: increase in concentration of serumal amylase is possible. At use of drug in high doses owing to effect of a dilyution cultivation of components of blood, decrease in a hematocrit, and also factors of coagulation and proteins of plasma is possible. In this regard during infusion activity of blood-coagulation factors of VIII (Villebrand) can be reduced. The bleeding time and other indicators of coagulability of blood can increase. However these changes are considerably reduced in comparison with those at infusion of GEK of the previous generations, and are recovered to initial level in 6 h after the drug infusion termination.

Others: allergic reactions of varying severity.

Interaction with other medicines:

It is necessary to avoid Volyuven's mixing with other drugs. If it is required in exceptional cases, then it is necessary to check compatibility of medicines (opacification, precipitation), to follow rules of an asepsis when mixing and to provide good hashing.

Contraindications:

— overhydratation;

— hypervolemia;

— congestive heart failure;

— heavy disturbances of a blood coagulation;

— intracranial bleeding;

— a condition of dehydration when correction of water and electrolytic balance is required;

— a renal failure of heavy degree with an oliguria or an anury;

— use for the patients who are on a hemodialysis;

— hyperchloremia;

— hypernatremia;

— hypersensitivity to drug.

Overdose:

Symptoms: blood circulatory system overload (for example, fluid lungs).

Treatment: the termination of administration of drug, if necessary it is necessary to appoint diuretic.

Storage conditions:

Drug should be stored in the unavailable to children, dry, protected from light place at a temperature not above 25 °C; not to freeze. A drug period of validity in the containers "frifleks" - 3 years, in bottles - 5 years. It is necessary to use only transparent solutions in the unimpaired packagings. After opening of a bottle or a container solution should be used immediately. Unused solution has to be destroyed.

Issue conditions:

According to the recipe

Packaging:

250 ml - containers the polyolefin "фрифлекс" (15) - boxes cardboard.
250 ml - containers the polyolefin "фрифлекс" (20) - boxes cardboard.
250 ml - containers the polyolefin "фрифлекс" (30) - boxes cardboard.
500 ml - containers the polyolefin "фрифлекс" (15) - boxes cardboard.
500 ml - containers the polyolefin "фрифлекс" (20) - boxes cardboard.
500 ml - containers the polyolefin "фрифлекс" (30) - boxes cardboard.
500 ml - bottles plastic with a loop holder for a dropper (10) - a box cardboard.
500 ml - bottles plastic with a loop holder for a dropper (20) - a box cardboard.