Voluven - instructions for use, dose, side effects, contraindications

Active substances
Poly (O-2-hydroxyethyl) starch (with a degree of molar substitution of 0.4 average molecular weight 130,000 Da)	60.0 grams
Sodium chloride	9.0 grams
Excipients
Sodium hydroxide (for pH correction)	q.s.
Hydrochloric acid (for pH correction)	q.s.
Water for injections	up to 1000 ml
Electrolytes:
Na +	154.0 mmol / l
Cl^-	154.0 mmol / l
Theoretical osmolality	308 m.sm./L
Titrated acidity	less than 1 mmol NaOH/ l
pH	4,0-5,5

Description:

Transparent or slightly opalescent, colorless or slightly yellow solution.

Pharmacotherapeutic group:Plasmasuberant

ATX: & nbsp

B.05.A.A.07 Hydroxyethyl starch

Pharmacodynamics:

Voluven is an artificial colloid for replenishing the volume of circulating blood, the effects of which, such as increased intravascular volume and hemodilution, depend on molar substitution with hydroxyethyl groups (0.4), average molecular weight (130,000 Da), concentration (6%), doses and rate of infusion. Hydroxyethyl starch (HES) contained in the preparation Volyuven, is obtained from corn starch waxy ripeness, the nature of the substitution (the ratio of C₂/FROM₆) which is approximately 9: 1.

Infusion of 500 ml of the preparation Voluven 6% for 30 minutes leads to a plateau-like increase in the volume of circulating blood by approximately 100% of the introduced volume, and persists for 4-6 hours.

The therapeutic effect of the drug Volyuven 6% when replenishing the circulating blood volume deficiency is 100% and remains at least 6 hours.

Use in pregnant women who undergo a caesarean section: there are limited clinical data on the use of a single dose of Voluven 6% in pregnant women during a caesarean section using spinal anesthesia. Evaluation of efficacy has shown a significant advantage of Volyuven 6% in the prevention of arterial hypotension and the incidence of severe hypotension compared with the control group using a crystalloid solution (36.6% and 55.3% respectively).

Pharmacokinetics:

The pharmacokinetics of hydroxyethyl starch has a complex character and depends on the molecular weight, the degree of molar substitution, and the nature of the substitution (C₂/FROM₆). With intravenous injection of a molecule with a mass of less than 60 000-70 000 Da (threshold of renal filtration), it is easy to excrete with urine,and larger molecules are cleaved by the α-amylase of the blood plasma, after which they are also excreted through the kidneys.

Average in vivo the molecular weight of HES 130 / 0.4 in blood plasma is 70 000-80 000 Da immediately after infusion and remains above the threshold of renal filtration throughout the period of therapeutic action.

The volume of distribution is about 5.9 liters. 30 minutes after the start of infusion, the HES 130 / 0.4 (6%) content in the blood plasma is 75% of the maximum concentration. After 6 hours, its content in the blood plasma is reduced to 14%. After a single injection of 500 ml of a solution of hydroxyethyl starch, its content in the blood plasma practically returns to the initial level after 24 hours.

The clearance from the blood plasma was 31.4 ml / min after the administration of 500 ml of Voluven 6%, with the value AUC (the area under the concentration-time curve) was 14.3 mg / ml-h, which indicates a non-linear pharmacokinetics. The values of the half-life from plasma were t_1/2α= 1.4 hours and t_1/2β = 12.1 hours after a single injection of 500 ml of the drug.

When using a dose of 500 ml in patients with stable renal failure of varying severity AUC was found to be moderately elevated 1.7-fold (95% confidence interval 1.44 and 2.07) in patients with creatinine clearance <50 mL / min compared to patients with creatinine clearance> 50 mL / min.The terminal half-life and the maximum concentration of hydroxyethyl starch did not change. In patients with creatinine clearance ≥30 ml / min, 59% of the drug was found in the urine compared to 51% in patients with creatinine clearance from 15 to 30 ml / min.

Significant accumulation in blood plasma was not observed even after daily administration to volunteers of 500 ml of a 10% solution of hydroxyethyl starch 130 / 0.4 for 10 days.

In a pharmacokinetic study, eight patients with stable renal disease in the terminal stage requiring hemodialysis once received HES 130 / 0.4 (6%) at a dose of 250 ml (15 g), 3.6 g (24% of the dose) of HES was excreted during the 2-hour hemodialysis session. After 24 hours, the average concentration of hydroxyethyl starch in blood plasma was 0.7 mg / ml. After 96 hours, the mean HES concentration in the blood plasma was 0.25 mg / ml. Thus, the use of hydroxyethyl starch 130 / 0.4 (6%) in patients receiving hemodialysis is contraindicated.

Indications:

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

Contraindications:

- Hypersensitivity to active ingredients or to any of the excipients

- Sepsis

- Burns

- Renal failure or renal replacement therapy

- Continuing intracranial or intracerebral bleeding

- Resuscitation profile patients (usually residing in intensive care units)

- Hyperhydration

- Pulmonary edema

- Dehydration

- Severe hypernatremia or severe hyperchloremia

- Severe hepatic impairment

- Chronic heart failure

- Severe coagulopathy

- Patients who underwent organ transplantation

Carefully:

There is no information.

Pregnancy and lactation:

Pregnancy

Clinical data on the use of the drug Volyuven during pregnancy are limited.

Limited experience in using Volyuven 6% for caesarean section with spinal anesthesia did not reveal a negative effect on the mother and child.

Studies on animal use have not shown a direct or indirect adverse effect on the course of pregnancy, embryo / fetal development, childbirth and postnatal development. There were also no signs of teratogenicity.

Use of the drug Volyuven during pregnancy is only possible in those situations,when the potential benefit of using the drug in the mother exceeds the possible risk to the fetus.

Breast-feeding

The excretion of hydroxyethyl starch into breast milk has not been studied. The decision to continue or stop breastfeeding or to continue or stop using the drug Volyven should be taken in consideration of the benefits of breastfeeding for the baby and the benefits of using it for the mother.

Dosing and Administration:

For intravenous infusion.

The duration of application of hydroxyethyl starch should be limited to the initial phase of replenishment of the circulating blood volume and should not exceed 24 hours.

The first 10-20 ml of infusion should be administered slowly, with careful monitoring of the patient's condition in order to early detection of possible anaphylactic / anaphylactoid reactions.

The daily dose and the rate of infusion depend on the degree of hemorrhage, maintenance or recovery of hemodynamics, and on hemodilution (the effect of dilution).

The maximum daily dose of Voluven is 30 ml / kg body weight.

The lowest effective dose of the drug should be used. Treatment should be accompanied by continuous monitoring of hemodynamics, and when the necessary result is achieved, infusion should be discontinued.Do not exceed the recommended maximum daily dose.

Use in children

The experience of medical use in children is limited, and therefore the use of hydroxyethyl starch drugs in this age group is not recommended.

Side effects:

By frequency, unwanted effects are classified as follows:

Often	≥ 1/10
Often	≥ 1/100-< 1/10
Infrequently	≥ 1/1 000-< 1/100
Rarely	≥ 1/10 000-< 1/1 000
Rarely	< 1/10 000
Frequency not known	can not be calculated from the available data

Violations of the blood and lymphatic system

Rarely (high doses): when hydroxyethyl starch is introduced because of the dilution effect, clotting disorders that depend on the dose may be observed.

Immune system disorders

Rarely: medicines containing hydroxyethyl starch, can cause anaphylactic / anaphylactoid reactions (hypersensitivity, mild flu-like symptoms, bradycardia, tachycardia, bronchospasm, noncardiogenic pulmonary edema). In this case, it is necessary to stop the drug immediately and take the necessary urgent measures.

Disturbances from the skin

Often (dose-dependent): prolonged use of high doses of hydroxyethyl starch can cause itching, which is a known undesirable effect of such drugs.

Violations from laboratory indicators

Often (dose-dependent): with the introduction of hydroxyethyl starch, the serum concentration of amylase may increase, making it difficult to diagnose pancreatitis. The increase in amylase activity is associated with the formation of the amylase-hydroxyethyl starch complex, which is slowly eliminated and should not be considered as a diagnostic sign of pancreatitis.

Often (dose-dependent): when high doses are administered, dilution of blood can lead to the dilution of its components, such as clotting factors and other plasma proteins, and to a decrease in hematocrit.

Disturbances from the liver and bile ducts

The frequency is unknown (can not be calculated from the available data): Pan expression of the liver.

Disorders from the kidneys and urinary tract

The frequency is unknown (can not be calculated from the available data): Prenal infection.

Overdose:

As with any means of replenishing the volume of circulating blood, an overdose can lead to an overload of the cardiovascular system (for example, the development of pulmonary edema).In this case, you should immediately stop the drug and, if necessary, prescribe diuretics.

Interaction:

There is no data on the interaction, so mixing of the drug with other substances should be avoided. If in exceptional cases this is required, then compatibility (occurrence of turbidity or sediment) should be checked, strictly observed when mixing the aseptic rule and ensure good mixing.

Special instructions:

In connection with the possible risk of allergic (anaphylactic / anaphylactoid) reactions, it is necessary to carefully monitor the patient's condition and start the infusion of the drug at a low rate.

Adequate long-term data on the use of hydroxyethyl starch in patients who underwent surgery or trauma are not available. The expected benefit of treatment should be carefully correlated with uncertain long-term safety. Other available therapeutic measures should be considered.

Careful use of hydroxyethyl starch for the treatment of hypovolemia should be carefully evaluated and hemodynamic parameters monitored to monitor the achievement of the desired effect and determine the dose of the drug.

It is necessary to avoid overloading the volume associated with an overdose of the drug or with a high infusion rate. The dose of the drug should be selected with caution, especially in patients with diseases of the lungs and the cardiovascular system. The content of electrolytes in blood serum, water balance and kidney function should be carefully monitored.

The use of drugs based on HES is contraindicated in patients with renal insufficiency or receiving renal replacement therapy. At the first signs of impaired renal function, hydroxyethyl starch should be discontinued.

Studies have shown that up to 90 days after the use of HES, an increased need for renal replacement therapy is possible. It is recommended to monitor kidney function in hospitalized patients for a minimum of 90 days.

Care should be taken when using the drug in patients with impaired liver function or in patients with coagulopathy.

Patients with hypovolemia should avoid severe hemodilution associated with the use of high doses of HES solutions.

When re-introduction of HES, it is necessary to carefully monitor the parameters of blood coagulation.When the first signs of coagulopathy appear, the drug should be discontinued.

When conducting operations on the open heart in combination with extracorporeal circulation, the use of HES preparations is not recommended due to the risk of increased bleeding.

Only for single use.

Before use, remove the outer protective bag.

The solution should be used immediately after opening the package. Use only clear solution from intact packaging. Remains of unused solution should be destroyed.

Effect on the ability to drive transp. cf. and fur:

It was not reported on the effect of the drug on the ability to drive a vehicle and work with mechanisms.

Form release / dosage:

Solution for infusion, 6%.

Packaging:

For 250 ml or 500 ml in a polyolefin container (bag) "friffex". The container consists of two bags. The primary bag, with the solution of the drug contained in it, is made of a special polymer and is equipped with two ports. The outer protective bag is made of a polymer film. For 15, 20 or 30 containers together with the instruction for use are placed in a cardboard box (for hospitals).

For 500 ml in a plastic bottle, equipped with a loop-holder for a dropper, sealed with a combination of plastic proprietary lid "spike-shape". 10 or 20 bottles are placed together with instructions for use in a carton box (for hospitals).

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years in containers (bags) "friffex".

5 years in plastic bottles.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:For hospitals

Registration number:П N011337 / 01

Date of registration:30.01.2012

Expiration Date:Unlimited

The owner of the registration certificate:Fresenius Kabi Deutschland GmbHFresenius Kabi Deutschland GmbH Germany

Manufacturer: & nbsp

FRESENIUS KABI DEUTSCHLAND, GmbH Germany

Representation: & nbspFRESENIUS KABI DEYCHLAND GmbH FRESENIUS KABI DEYCHLAND GmbH Germany

Information update date: & nbsp26.03.2017

Illustrated instructions

Instructions

Voluven (Voluven)