Рефортан® GEK of 6%, Refortan® of GEK of 10%

General characteristics. Structure:

Рефортан® GEK of 6%

active ingredient: hydroxyethylstarch (GEK 200/0,5) - 60,0 g.

Colloid osmotic pressure: ~ 38 Mbar = 28 mm of mercury.

Рефортан® GEK of 10%

active ingredient: hydroxyethylstarch (GEK 200/0,5) - 100,0 g.

Colloid osmotic pressure: ~ 85 Mbar = 65 mm of mercury.

Рефортан® GEK of 6/10%

excipients: sodium chloride, water for injections.

Theoretical osmolarity: ~ 300 ¼Äß¼«½ý/l

Value рН: from 4,0 to 7,0

Pharmacological properties:

Pharmacodynamics. Рефортан® GEK is 6/10% isotonic solution of hydroxyethyl derivative partial hydrolysis of wax-like corn starch - hydroxyethylstarch (GEK) with an average molecular weight of 200 000 дальтон and extent of molar substitution 0,45-0,55. Due to ability to connect and hold water drug possesses volemichesky action which is steady, at least, during 6 h, and increase in the volume of the circulating blood (VCB) at the same time ~ 100% (Refortan® of GEK of 6%) / ~ 130% (Refortan® of GEK of 10%) of volume of the administered drug.

Physical and chemical parameters of original substance of drug provide high performance at a hypovolemia and shock, and also when using for therapeutic cultivation of blood (hemodilution) due to normalization of the central and peripheral hemodynamics, microcirculation, improvement of delivery and consumption of oxygen by bodies and fabrics, normalization of permeability of a vascular wall, decrease in local inflammatory reaction, activation of a full-fledged immune response, mobilization of uniform elements of blood and physiological deposition and their involvement in active metabolism against the background of moderate hemodilution.

Besides, drug improves rheological properties of blood due to decrease in an indicator of a hematocrit, and also reduces viscosity of plasma, reduces aggregation of thrombocytes and interferes with aggregation of erythrocytes.

Pharmacokinetics. The maximum concentration (With max) - 11,1±2,7 mg/ml. Depending on rate of administering and the purpose of infusion (achievement normo-or hypervolemias) time of semi-removal (T1/2) makes about 5-6 h. After introduction drug is removed by kidneys (for 24 h - about 70%) and with bile. A small amount collects in reticuloendothelial system (without manifestation of toxic action on a liver, lungs, a spleen and lymph nodes) where it is split by amylase.

Indications to use:

• prevention and treatment of a hypovolemia and shock at operations, acute blood losses, injuries, infectious diseases and burns;
• therapeutic hemodilution.

Route of administration and doses:

Рефортан® GEK is appointed in the form of intravenous infusions.

In the absence of other instructions the drug is administered intravenously kapelno according to requirement of substitution of volume of the circulating plasma.

Considering possible anaphylactic reactions, the first 10-20 ml of the drug Refortan® of GEK should be entered slowly, at careful observation of a condition of the patient. It is necessary to consider risk of an overload of the blood circulatory system at too bystry administration or too high dose of drug.

The daily dose and speed of intravenous administration are calculated depending on blood loss, concentration of hemoglobin and an indicator of a hematocrit. At young patients without risk of emergence of cardiovascular or pulmonary complications a limit of use of colloid objemzameshchayushchy drug the hematocrit less than 30% is considered.

Рефортан® GEK of 6%
Age                      Average daily         Maximum daily
                                      dose (ml/kg)                        dose (ml/kg)
Adults and children
12 years                                                            33 33 are more senior
Children of 6-12 years                                                      15-20 33
Children of 3-6 years                                                        15-20 33
Newborns and
 children up to 3 years                                                      10-15 33

Рефортан® GEK of 10%

Age                        Average daily     Maximum daily
                                      dose (ml/kg)                 dose (ml/kg)
Adults and children
12 years                                                         20 20 are more senior
Children of 6-12 years                                                   10-15 20
Children of 3-6 years                                                     10-15 20
Newborns
and children up to 3 years                                                   8-10 20

The maximum daily dose makes Refortan® of GEK of 10%: 20 ml/kg/days (2 g of GEK/kg/days); Рефортан® GEK of 6%: 33 ml/kg/days (2 g of GEK/kg/days).

The maximum speed of infusions depends on initial indicators of a hemodynamics and makes about 20 ml/kg an hour.

Carrying out hemodilution can be carried out in the conditions of an isovolemia (with bloodletting) or hypervolemias (without bloodletting).

Daily dose and speed of intravenous administration:
• a low dose - once 250 ml/days during 0,5-2 h,
• an average dose - once 500 ml/days during 4-6 h,
• a high dose - twice on 500 ml/days during 8-24 h.

Duration of a course of treatment depends on area of the indication and OTsK.

Features of use:

At the beginning of therapy by the drug Refortan® of GEK control of level of creatinine of blood serum is necessary. At extreme values of indicators of creatinine (1,2-2,0 mg/dl or, respectively, 106-177 µmol/l, i.e. a renal failure) it is necessary to estimate at compensation stages carefully indications to performing the corresponding therapy and to exercise frequent control of intracellular and extracellular balance of liquid, and also of secretory function of kidneys.

At a lack of fibrinogen drug can be used only at assistance in case of emergency when life of the patient is in danger in the absence of donor blood.

It is necessary to consider that too bystry intravenous administration of drug, and also use in high doses can lead it to disturbances of a hemodynamics.

In the course of treatment it is necessary to monitor sufficient intake of liquid in an organism, to control electronic composition of blood serum and balance of liquid, and also function of kidneys.

At emergence of reactions of intolerance it is necessary to stop immediately administration of drug and to hold necessary urgent events. For prevention of developing of an overhydratation owing to what there can come the decompensation of heart failure at patients with heart diseases in the anamnesis, it is necessary to exercise control of cordial activity and OTsK.

It is necessary to consider that at use of the drug Refortan® of GEK increase in activity of amylase of blood serum is possible that it is not connected with clinical display of pancreatitis. The hyperamilasemia is caused by formation of the GEK amylase complex which is slowly removed by kidneys.

Side effects:

Owing to effect of hemodilution of infusion of the drug Refortan® of GEK lead, depending on a dose, to decrease in a hematocrit and concentration of proteins of a blood plasma. Also thereof there is no effect perhaps passing increase in a blood clotting time and bleeding time, however at the same time impact on function of thrombocytes and clinically significant bleeding does not come.

Long daily administration of the drug Refortan® of GEK in the range of average and high doses can often cause an itch which difficult gives in to stopping. It can appear also in several weeks after the end of therapy and to remain long time.

In literature the interrelation between a dose and frequency of developing of an itch at otonevrologichesky diseases, such as sharp decrease in hearing, a sonitus is described. At these diseases for reduction of frequency of developing of an itch recommend restriction of a dose to the maximum daily – Refortan® of GEK of 6% 500 ml (that corresponds 30 g of GEK/days) / Refortan® of GEK of 10% 250 ml (that corresponds to 25 g of GEK/days).

During performing infusion by the drug Refortan® of GEK, as well as in case of other colloid plasma substitutes, reactions of intolerance of all severity are possible. Anaphylactoid reactions can directly be shown as skin reactions or in the form of sudden rush of blood to a face and a neck (sudden reddening); and arterial hypotension and shock, up to a cardiac standstill and breath.

At conditions of dehydration with the subsequent (regular) oliguria and reduction of glomerular filtering, and also with a canalicular reabsorption infusion by the drug Refortan® of GEK can lead to an anury as in primary canalicular urine sated with GEK there can be an osmotic gradient. Therefore before administration of the drug Refortan® of GEK it is necessary (for stimulation of a diuresis) to carry out a regidratation by administration of osmotically free water in the form of infusion of solutions of glucose or hypotonic saline solutions.

It was in rare instances reported about pains in kidneys. In these cases it is necessary to stop drug infusion, to provide sufficient receipt in an organism of liquid and to exercise frequent control of level of creatinine of blood serum.

Interaction with other medicines:

When mixing with other medicines in one container or in one system the phenomena of pharmaceutical incompatibility can be observed. Gidroksietilkrakhmal at simultaneous use with aminoglikozidny antibiotics can exponentiate their nephrotoxicity.

Contraindications:

• hypersensitivity to starch or other components of drug;
• overhydratation;
• hypervolemia;
• hypopotassemia;
• hypernatremia;
• hyperchloremia;
• heart failure in a decompensation stage;
• a renal failure with an oliguria or an anury (creatinine> of 2 mg/dl or, respectively, 177 microns/l).
• cardiogenic fluid lungs;
• intracranial bleedings;
• the expressed disturbances of coagulability of blood;
• hemodialysis;
• dehydration.

With care:
• the compensated chronic heart, liver and renal failure;
• hemorrhagic diathesis;
• intracranial hypertensia.
Use at pregnancy and a lactation

Though it is established that Refortan® of GEK has no embriotoksichesky and teratogenic effect, use of drug in the 1st trimester of pregnancy is undesirable. In the 2nd and 3rd trimesters of pregnancy of Refortan® of GEK it is possible to apply only according to vital indications.

It is unknown whether Refortan® of GEK with breast milk therefore women should show care at purpose of this drug in the period of a lactation is allocated.

Overdose:

Hypervolemic syndrome.

Treatment: immediate termination of infusion of drug; purpose of diuretics is possible.

Storage conditions:

At a temperature not above 25 °C in glass bottles.

At a temperature not above 30 °C in polyethylene bottles.

Not to freeze. To store medicine in the place, unavailable to children!

Period of validity of 5 years in original packaging.

To use only transparent or slaboopalestsiruyushchy (no more than light yellow color) solutions in the unimpaired bottles.

Not to apply after expiry date.

Issue conditions:

According to the recipe

Packaging:

Solution for infusions of 6/10%.

On 250 or 500 ml of drug in bottles:

Рефортан® GEK of 6%

1) from colourless transparent glass like II (Evr. T.), closed a brombutilovy rubber stopper like I (Evr. T.) for piercing and a plastic cover under an aluminum running in with the plastic holder strengthened on a bottle.

2) from polyethylene of low density (Evr. T.), with the cap which is welded on upon a bottle, with the integrated rubber laying and two rings for opening and the holder at the bottom of a bottle.
On 10 bottles together with the application instruction place in a cardboard box (for hospitals).

Рефортан® GEK of 10%

from colourless transparent glass like II (Evr. T.), closed a brombutilovy rubber stopper like I (Evr. T.) for piercing and a plastic cover under an aluminum running in with the plastic holder strengthened on a bottle.

On 10 bottles together with the application instruction place in a cardboard box (for hospitals).