Rekormon

Rekormon – drug with erythropoietic and hemopoietic action.

Form of release and structure

Dosage forms of release of Rekormon:     

• The lyophilized powder for preparation of solution for injections: white, homogeneous; solvent – transparent, colourless; the prepared solution – colourless, transparent or slightly opalescent (in bottles, on 5 bottles in plastic pallets complete with solvent (in ampoules, on 5 pieces), on 2 pallets in a cardboard pack);
• Lyophilisate for preparation of solution for hypodermic introduction: homogeneous powder or porous mass of almost white or white color; solvent – colourless, transparent; the prepared solution – colourless, transparent or slightly opalescent (in two-section cartridges for the syringe handles "Reko-Pen": in one section – lyophilisate, in another – solvent of 1 ml, on 1 or 3 cartridges in a cardboard pack);
• Solution for injections (intravenous and hypodermic administration): colourless, transparent or slightly opalescent (on 1000/2000 ME: in the syringe tubes on 0,3 ml, on the 3rd syringe tube in blister strip packagings complete with injection cannulas, on 2 packagings in a cardboard pack; on 10 000/20 000/30 000 ME: in the syringe tubes on 0,6 ml, on the 3rd syringe tube in blister strip packagings complete with injection cannulas, on 2 (on 10 000/20 000 ME) or on 1 or 4 (on 30 000 ME) packagings in a cardboard pack.

With lyophilisate is a part of 1 bottle:

• Active ingredient: эпоэтин a beta – 1000, 2000 or 5000 ME;
• Additional components: urea, L-leucine, L-threonine, L-phenylalanine, sodium chloride, hydrosodium phosphate, dihydrosodium phosphate, calcium chloride, polysorbate 20, L-glutaminic acid, L-izoleytsin, glycine.

Solvent: water for injections – 1 ml.

With lyophilisate is a part of 1 cartridge:

• Active ingredient: эпоэтин a beta – 10 000 or 20 000 ME;
• Additional components: urea, L-izoleytsin, L-leucine, L-threonine, sodium chloride, hydrosodium phosphate, dihydrosodium phosphate, calcium chloride, polysorbate 20, L-glutaminic acid, L-phenylalanine, glycine.

Solvent: benzyl alcohol, chloride a benzalkoniya, water for injections.

1 syringe tube of injection solution is a part:

• Active ingredient: эпоэтин a beta – 1000, 2000, 10 000, 20 000 or 30 000 ME;
• Additional components: urea, sodium chloride, a L-leucine, L-threonine, L-phenylalanine, hydrosodium phosphate, dihydrosodium phosphate, calcium chloride, polysorbate 20, glycine, L-izoleytsin, L-glutaminic acid, water for injections.

Indications to use

• Symptomatic anemia: renal genesis at the patients who are not receiving dialysis yet against the background of chronic diseases of kidneys at the patients who are on dialysis, at solid and hematologic not myeloid tumors at the adults receiving chemotherapy;
• Anemia at the premature newborns who were born to 34 weeks of pregnancy weighing 0,75-1,5 kg (prevention);
• Increase in volume of donor blood which is intended for the subsequent autotransfusion (taking into account the registered probability of development of the thromboembolic phenomena and only for patients with moderate anemia (at hemoglobin (Hb) of 100-130 g/l or 6,21-8,07 mmol/l), without lack of iron) in cases when it is impossible to receive enough stored blood and in the course of performing planned large elective surgery can be required the large volume of blood (≥5 units for men, ≥4 units for women).

Contraindications

Absolute:

• Stroke or myocardial infarction within the previous month;
• Uncontrollable arterial hypertension;
• The increased risk of development of a deep vein thrombosis (in the presence of the anamnestic data indicating a venous thromboembolism) or unstable stenocardia (in case of Rekormon's appointment for the purpose of increase in volume of donor blood);
• Age up to 3 years (for drug in cartridges);
• Existence of hypersensitivity to the benzoic acid (at use of solution of Rekormon in cartridges);
• Hypersensitivity to drug components.

Relative (Rekormon appoint with care in the presence of the following diseases / states):

• Chronic liver failure;
• Refractory anemia in the presence of blasttransformirovanny cells;
• Epilepsy;
• Thrombocytosis;
• Weight is up to 50 kg (at appointment for the purpose of increase in volume of donor blood);
• The period of pregnancy and lactation (because of insufficiency of clinical data).

Route of administration and dosage

The anemia connected with chronic diseases of kidneys
Way of introduction of Rekormon: subcutaneously or intravenously within 2 minutes. Solution is entered by the patient who is on a hemodialysis via the arteriovenous shunt at the end of dialysis session. Hypodermic administration of drug is recommended to the patients who is not receiving a hemodialysis (to avoid a puncture of peripheral veins).

The purpose of therapy is the hemoglobin indicator ranging from 100 to 120 (as much as possible) of g/l. At increase for 4 weeks of Hb more than by 20 g/l (1,3 mmol/l) Rekormon's dose is lowered. At arterial hypertension, cardiovascular and cerebrovascular diseases the week growth of hemoglobin and its target indicators define individually, on the basis of a clinical picture. Patients need careful observation for the purpose of selection of the minimum dose providing the maximum effect.

Therapy is carried out in 2 steps including correction and a maintenance therapy.

Correction (the maximum week dose – 720 ME/kg a week irrespective of a way of introduction):

• Hypodermic introduction: 3 times a week in an initial dose of 20 ME/kg. At insufficient effect (less than 2,5 g/l a week) increase in a dose each 28 days on 20 ME/kg 3 times a week is possible. The total week dose of drug can be divided into daily introductions also;
• Intravenous administration: 3 times a week in an initial dose of 40 ME/kg. At insufficient effect in a month increase in a dose up to 80 ME/kg 3 times a week is possible. Further the dose is increased in case of need by 20 ME/kg by 3 times a week, with a monthly interval.

The maintenance therapy is carried out for the purpose of maintenance of a target indicator of Hb (100-120 g/l), for this purpose at first Rekormon's dose needs to be reduced twice from the previous dose. Further correction is carried out individually, at an interval of 14 or 28 days. The week dose at hypodermic introduction can be entered for 1 reception or to divide into 3 or 7 introductions to week. After stabilization of a state at drug use transition to Rekormon's introduction of 1 times to 2 weeks is possible once a week (increase in a dose can be required).

As a rule, therapy long. In case of need it can be interrupted at any time.

Symptomatic anemia at solid and hematologic not myeloid tumors against the background of receiving chemotherapy
Way of introduction of Rekormon: subcutaneously.

Initial week dose – 30 000 ME (450 ME/kg a week). Frequency rate of use – once or 3 or 7 introductions to week.

Drug appoint ≤110 g/l (6,83 mmol/l) at Hb. Maximum indicator of Hb of-130 g/l (8,07 mmol/l).

At increase in 4 weeks of Hb at 10 g/l (0,62 mmol/l) dose adjustment is not carried out. At lower speed of increase in an indicator the dose is doubled.

If in 8 weeks increase in hemoglobin on 10 g/l is not reached, therapy is cancelled as the further effect of treatment is improbable.

Therapy is continued for 4 weeks after the termination of chemotherapy.

The maximum week dose – 60 000 ME.

After achievement of a desirable indicator of hemoglobin Rekormon's dose is reduced by 25-50%.

For the purpose of prevention of increase in Hb more than 130 g/l can be required a further dose decline.

At increase of hemoglobin it is more, than on 20 g/l (1,3 mmol/l) a month, the dose decline for 25-50% is shown.

Anemia at premature newborns (prevention)
Rekormon it is possible to apply only in the syringe tubes.

Solution is entered 3 times a week subcutaneously in a dose of 250 ME/kg. It is recommended to begin therapy as soon as possible, it is desirable – about 3 days of life. Course duration – 6 weeks.

The drug dose for children and teenagers is defined by age (than less age, especially high doses of drug are required). Because of impossibility to predict the individual response to therapy, it is recommended to begin introduction with the standard mode of dosing. At the anemia associated with chronic diseases of kidneys children should not appoint Rekormon up to 2 years.

Preparation for capture of donor blood
Way of introduction of Rekormon: intravenously (within 2 minutes) or subcutaneously.

Frequency rate of use – 2 times a week, course duration – 4 weeks. At the hematocrit indicator (≥ 33%) allowing to carry out blood sampling, Rekormon is recommended to enter at the end of the procedure.

The hematocrit throughout all course of therapy should not exceed 48%.

Rekormon's dose is defined by the doctor-transfuziologom and the surgeon individually on the basis of the required volume of blood and an erythrocyte reserve.

The volume of blood is expressed in units (1 unit = 180 ml of erythrocytes) and is defined by estimated blood loss, the available techniques of preservation of blood and the general condition of the patient; the purpose is the volume allowing to avoid hemotransfusion from other donor.

The possibility of donorship is defined preferential by blood volume at this patient and an initial hematocrit. These indicators define an endogenous erythrocyte reserve which can be calculated by a formula:

Endogenous erythrocyte reserve = the volume of blood [ml] x (a hematocrit – 33):100

For men: the volume of blood [ml] = 44 [ml/kg] x the weight [kg] + 1600 [ml] (with a weight ≥ 45 kg)

For women: volume of blood [ml] = 41 [ml/kg] x weight [kg] + 1200 [ml].

Maximum week dose:

• Hypodermic introduction: 1200 ME/kg;
• Intravenous administration: 1600 ME/kg.

The unit-dose syringe is ready to the use. The solution which is contained in it does not contain preservatives and is sterile. It is possible to apply only transparent light or slightly opalescent solution which does not contain visible inclusions. If after a single dose in the syringe tube there is a solution quantity, its repeated introduction is inadmissible.

The cartridge for the syringe handle "Reko-Pen" is two-section, in one section there is a lyophilisate for preparation of solution for hypodermic introduction, in another – solvent with preservatives. For solution preparation the cartridge according to the instruction is entered into the syringe handle.

Side effects

During Rekormon's use development of the following disturbances is possible (> 10% – very often;> 1% and <10% – is frequent;> 0,1% and <1% – infrequently;> 0,01% and <0,1% – are rare; <0,01% – are very rare):

• Cardiovascular system: often – arterial hypertension (development or strengthening already available), in particular in case of bystry increase in a hematocrit; infrequently – hypertensive crisis with the encephalopathy phenomena (in the form of headaches and confusion of consciousness, sensitive and motive disturbances – disturbances of gait, the speech, up to toniko-clonic spasms), tromboembolic episodes at oncological patients and at the patients preparing for autotransfusion (accurate relationship of cause and effect is not established);
• Central nervous system: often – headaches, including suddenly developing migrenepodobny headaches;
• Hemopoietic system: dozozavisimy increase in number of thrombocytes (norms does not go beyond, passes independently at treatment continuation), in particular after intravenous administration of solution; seldom – thrombosis of shunts (the risk of development increases at an inadequate geparinization), in particular in the presence of a tendency to lowering of arterial pressure or at complications of an arteriovenous fistula (including a stenosis, aneurism); very seldom – a thrombocytosis;
• Allergic reactions: seldom – an itch, skin rash, a small tortoiseshell; very seldom – anaphylactoid reactions;
• Laboratory indicators: decrease in concentration of ferritin in serum against the background of increase in Hb, reduction of serumal indicators of exchange of iron; patients with uraemia have a passing hyperpotassemia (accurate relationship of cause and effect is not established), a hyperphosphatemia; at premature newborns: very often – decrease in concentration of ferritin in serum, insignificant increase in number of thrombocytes, up to 12-14 in the afternoon lives;
• Others: reactions in a solution injection site, grippopodobny symptoms (in particular in an initiation of treatment; as a rule, carry poorly or moderately expressed character and pass independently in several hours or days), including fever, a fever, an ostealgia or extremities, headaches, a febricula.

As a result of carrying out post-marketing observation development of a partial krasnokletochny aplasia (PKKA) connected with formation of the antibodies neutralizing anti-erythropoetin was in some cases recorded.

Special instructions

At inadequate use of Rekormon by healthy people (for example as dope) can sharply increase a hemoglobin indicator that is followed by complications from cardiovascular system, life-threatening.

The first dose of drug needs to be entered under control of the doctor as development of anaphylactoid reactions was in some cases noted.

During treatment it is regularly necessary to control indicators of thrombocytes, a hematocrit and Hb.

Before Rekormon's appointment it is necessary to exclude a lack of folic acid and B12 vitamin as it can exert impact on therapy, reducing its efficiency.

It is necessary to exclude deficit of iron before purpose of drug, and also to exercise control throughout all use of Rekormon. In cases of need additional therapy can be appointed iron preparations.

At severe forms of a fenilketonuriya it is necessary to consider availability of phenylalanine as an additional component: in each cartridge – to 0,5 mg, in everyone the syringe tube – to 0,3 or 0,6 mg (in dosages of 1000/2000 ME or 10 000/20 000/30 000 ME).

In most cases the incomplete clinical answer is observed at deficit of iron and inflammations (as result of the progressing metastatic cancer or uraemia). Decrease in efficiency of therapy arises against the background of the following diseases / states: marrow fibrosis, hemolysis, chronic blood loss, the sharp increase in concentration of aluminum caused by a hemodialysis, deficit of folic acid or B12 vitamin. At an exception of all listed states at sudden decrease in maintenance of Hb, a reticulocytopenia and detection of antibodies to erythropoetin for an exception of PKKA it is necessary to conduct a marrow research. At development of PKKA Rekormon cancel and transfer the patient to therapy by other stimulators of an erythrogenesis.

In the presence of the antibodies neutralizing erythropoetin (confirmed or at suspicion) Rekormon it is not necessary to apply.

It is necessary to consider probability that the means stimulating an erythrogenesis can stimulate growth of a malignancy of any type.

At chronic diseases of kidneys or malignant tumors against the background of receiving chemotherapy development of episodes of increase in arterial pressure and deterioration in a course of already available arterial hypertension is possible, in particular at sharp increase in maintenance of Hb. If it is not possible to reduce arterial pressure medicamentally, it is necessary to cancel temporarily Rekormon. Arterial pressure needs to be controlled regularly (in particular at the beginning of drug use), including between dialysis sessions at patients with anemia of renal genesis. In some cases, even with a normal or low arterial pressure, at chronic diseases of kidneys hypertensive crisis with the encephalopathy phenomena can develop (immediate consultation is required from the therapist, in particular at emergence of sudden migrenepodobny acute headaches).

During therapy periodic control of serumal level of potassium (at development of a hyperpotassemia Rekormon temporarily cancel) is recommended.

At chronic diseases of kidneys during sessions of a hemodialysis it is required to increase a heparin dose (because of increase in a hemoglobin content). At an inadequate geparinization occlusion of dialysis system can develop. Carrying out early audit of the shunt and timely prevention of thromboses is recommended (for example, reception of acetylsalicylic acid).

During therapy moderate dozozavisimy increase in quantity of thrombocytes within norm can be observed (is returned to normal indicators independently).

Rekormon is shown only to those patients, it is the most important to them to avoid a homologous hemotransfusion, considering an advantage ratio with risk at a homologous transfusion.

Use of drug for premature newborns (for prevention of anemia) can lead to slight increase of number of thrombocytes (their regular control is recommended).

At a nephrosclerosis the issue of Rekormon's appointment should be resolved individually as the probability of more bystry deterioration in function of kidneys cannot be excluded.

In most cases increase in hemoglobin is followed by decrease in concentration of ferritin in serum. At anemia of renal genesis and at concentration of ferritin of serum less than 100 mkg/l or transferrin saturation less than 20% oral administration of iron preparations ^(Fe2+) in a daily dose of 200-300 mg is recommended.

Therapy by iron preparations patients with diseases of oncological and hematologic character should carry out by the same principles, at the same time at a multiple myeloma, nekhodzhkinsky lymphoma or a chronic lymphocytic leukosis with transferrin saturation less than 25% perhaps intravenous administration ^{of Fe3 +} in a dose of 100 mg a week. Iron preparations premature children (in a dose of 2 mg ^{of Fe2 +} in day) should appoint peroral therapy as soon as possible (the latest term – the fourteenth day of life). The dose of iron is defined by the level of serumal ferritin. If it with firmness remains at the level up to 100 mkg/ml, or in the presence of other signs of deficit of iron, the daily dose of iron preparations is increased up to 5-10 mg (therapy continue before stopping of signs of insufficiency of iron).

At moderate anemia before performing planned large surgeries Rekormon the beta and increases in risk of tromboembolic episodes appoint taking into account advantage of use of an epoetin.

It is necessary to consider that the cartridge with Rekormon's solution as preservative contains benzyl alcohol which can cause neurologic and other complications in newborns (sometimes – with a fatal outcome).

Medicinal interaction

Any interaction of Rekormon with other medicinal means / substances was not revealed so far.

To avoid incompatibility or decrease of the activity of Rekormon, to mix him with other drugs / injection solutions or it is impossible to use other solvent.

Terms and storage conditions

To store in protected from light, the place, unavailable to children, at a temperature of 2-8 °C, it is impossible to freeze drug.

Period of validity – 2 years.

The syringe handle "Reko-Pen" with the inserted cartridge can be stored for 1 month at a temperature of 2-8 °C. It is necessary to extract drug from the refrigerator only for carrying out an injection.