Aranesp

Active material: darbèpoètin alpha
When ATH: B03XA02
CCF: The stimulator of erythropoiesis
ICD-10 codes (testimony): D63
When CSF: 19.01.02.01
Manufacturer: AMGEN EUROPE B.V. (Netherlands)

DOSAGE FORM, COMPOSITION AND PACKAGING

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.4 ml – glass syringes with needles (1) – packs cardboard.
0.4 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.375 ml – glass syringes with needles (1) – packs cardboard.
0.375 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.5 ml – glass syringes with needles (1) – packs cardboard.
0.5 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.3 ml – glass syringes with needles (1) – packs cardboard.
0.3 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.4 ml – glass syringes with needles (1) – packs cardboard.
0.4 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.5 ml – glass syringes with needles (1) – packs cardboard.
0.5 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.3 ml – glass syringes with needles (1) – packs cardboard.
0.3 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.4 ml – glass syringes with needles (1) – packs cardboard.
0.4 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.5 ml – glass syringes with needles (1) – packs cardboard.
0.5 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.3 ml – glass syringes with needles (1) – packs cardboard.
0.3 ml – glass syringes with needles (1) – packings Valium planimetric (4) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

0.6 ml – glass syringes with needles (1) – packs cardboard.
0.6 ml – glass syringes with needles (1) – packings Valium planimetric (1) – packs cardboard.

Solution for injection clear, colorless.

Excipients: sodium dïgïdrofosfata monohydrate, sodium hydrogen phosphate, sodium chloride, polysorbate 80, water d / and.

1 ml – glass syringes with needles (1) – packs cardboard.
1 ml – glass syringes with needles (1) – packings Valium planimetric (1) – packs cardboard.

Pharmacological action

Stimulator of hematopoiesis, antianemic nutraceutic. Darbèpoètin Alpha is produced using gene technology in Chinese hamster ovary cells (CHO-K1). Stimulates erythropoiesis by the same mechanism, as the endogenous erythropoietin. Darbèpoètin Alpha contains five N-linked carbohydrate chains, While endogenous hormone and recombinant human erythropoietins (rčÈpo) have just three circuits. Additional remains of sugars, with a molecular point of view, do not differ from those, presented in the endogenous hormone. Due to the high content of carbohydrates darbèpoètin Alpha has a longer T_1/2, compared to rčÈpo, and hence, and greater activity in vivo. Despite these changes the molecular structure of darbèpoètin Alpha retains a very narrow specificity to the èritropoètinovomu receptor.

Survival and progression of tumors were examined in total at 2833 patients within 5 large controlled studies. From them 4 were double blind and placebo controlled, and 1 – Open. IN 2 the studies included patients, which has been done chemotherapy. IN 2 research the target hemoglobin level equal or higher installed 130 g / l, and three other – in the range of 120 to 140 g / l. In an open study obtained differences in overall survival between the Group, receiving rčÈpo treatment and control. IN 4 placebo-controlled trials risk indicators were in favor of control and were within the range of 1.25 to 2.47. In these 4 Research has identified an unexplained statistically reliable increase in mortality compared to control patients with typical kinds of cancer and anemia, treatment which was held rčÈpo. Comparison of frequency of thrombosis and other complications in groups, treated rčÈpo and control, does not give a satisfactory explanation of the causes of this increase.

Also systematic analysis was conducted 57 research, comprising a total of more 9000 patients with cancer. Meta-analysis of overall survival risk amounted to 1.08 in favor of control (DI 95%: 0.99-1.18; 8167 patients in 42 research).

Patients, treated rčÈpo, noted increased relative risk of thromboembolic events (RR = 1.67. DI 95%: 1.35-2.06; 6.769 patients in 35 research). Thus, There are sufficient data, indicating the potential for significant harm in treating cancer patients rčÈpo. It is not clear, to what extent this applies to cases of recombinant human eritropoetinov to reach the target haemoglobin levels less than 130 g/l in patients with cancer, who are receiving chemotherapy, Since there were few data analyzed patients with such characteristics.

Pharmacokinetics

In connection with a high carbohydrate concentration of circulating in the blood darbèpoètina Alpha exceed the minimum concentration required for stimulation of erythropoiesis for a longer time, compared to equivalent doses rčÈpo, to reduce the frequency of introduction of darbèpoètina Alpha with saving the equivalent level of biological response.

Patients with chronic renal insufficiency

Distribution

V_d roughly equivalent to the volume of plasma (50 ml / kg).

When s/to the introduction of the drug its bioavailability was 37%.

In the course of clinical trials minimum drug accumulation was observed when any method of introduction.

Deduction

T_1/2 was 21 no (standard deviation (With) 7.5) at / in the introduction. Clearance darbèpoètina alpha- 1.9 ml / h / kg (With 0.56).

When the monthly p/to the introduction darbèpoètina Alpha in the dose of 0.6 to 2.1 µg/kg it T_1/2 was 73 no (With 24). A longer T_1/2 Alpha darbèpoètina when s/to the introduction, compared with, due to the absorption kinetics. In preclinical studies have demonstrated, that kidney klirens darbèpoètina Alpha is minimal (to 2% total clearance) and has no effect on T_1/2 preparation of serum.

Route of Administration does not affect the dose darbèpoètina alpha, necessary to maintain the achieved hemoglobin.

Pharmacokinetics in special clinical situations

Pharmacokinetics darbèpoètina Alpha studied in children (3-16 years) with chronic renal failure, staying or not staying on dialysis, with this sampling was carried out from the moment a single p/or to the in/in the injection of up to one week (168 no) after administration. Sampling periods were the same length, as in adults with chronic renal insufficiency. The comparative analysis showed, that the pharmacokinetics of Alpha darbèpoètina in adults and children with chronic renal insufficiency is similar. After the on/in the introduction of the drug noted approximately 25%-distinction between adults and children on the importance of the AUC_0-∞; Nonetheless, the distinction for the children was less than 2 times the range of the AUC_0-∞. After p/to the introduction of the drug value AUC_0-∞ children and adults was similar. After the on/in the, and after s/to the introduction of the drug, T_1/2 the drug in adults and children with chronic renal insufficiency was similar.

Patients with cancer, receiving chemotherapy

Absorption

When p / injection dose 2.25 µg/kg adult cancer patients average C_max darbèpoètina alpha, component 10.6 ng / ml (With 5.9), achieved on average over 91 no (With 19.7). These options are consistent with linear pharmacokinetics in a wide range of doses (from 0.5 to 8 µg/kg weekly introduction and from the 3 to 9 µg/kg when administered 1 once every 2 of the week).

Distribution and excretion

Pharmacokinetic parameters have not changed in repeated introduction within 12 Sun. (weekly introduction or introduction 1 once every 2 of the week). Noted the expected modest increase (< 2-multiple) serum concentrations of the drug when it reaches the equilibrium condition, but there were no signs of its accumulation in reappointing. Pharmacokinetic studies have been performed involving patients during chemotherapy-induced anemia, that in combination with chemotherapy p/to receive injections of Alpha darbèpoètina the dose 6.75 mg / kg 1 once every 3 of the week. In this study, the average value of T_1/2 was 74 no (With 27).

Testimony

— treatment of symptomatic anaemia in adults and children with chronic renal insufficiency;

— treatment of symptomatic anemia in adult patients with nemieloidnymi malignant neoplasms, receiving chemotherapy.

Dosage regimen

Treatment with Aranesp should hold doctors, having the experience of its application, according to the testimony of.

Aranesp is supplied ready for use in pre-filled syringes.

Treatment of symptomatic anaemia in adults and children with chronic renal insufficiency.

Symptoms of anemia and effects may vary depending on the age of the patients, their sex and severity of the disease; in each case, an analysis of individual patient data from clinical physician.

Aranesp you can enter n/a or/in. P/to the introduction is preferable for patients, not receiving hemodialysis, to avoid puncture of peripheral veins.

Hemoglobin level in patients prone to individual variations, incl. Sometimes, above or below the desired target values. Rejecting hemoglobin levels beyond targets conduct dose modifications, the target value should be considered an interval from 100 g/l to 120 g / l. You should avoid strong increase hemoglobin above 120 g / l, for instructions on modifying the dose hemoglobin values above 120 g/l are presented below.. You should also avoid raising hemoglobin more than 20 g/l for 4 of the week. In this case also a correction dose.

Treatment with Aranesp includes two stage – phase correction and the supporting phase.

Use in children less 1 the year was not investigated.

Adults with chronic renal insufficiency

Phase correction

Initial dose at p/or to the in/in the introduction is 0.45 µg/kg body weight in a single weekly introduction. Alternatively, for patients, not receiving dialysis, allowed s/to the introduction of the drug in a dose 0.75 µg/kg body weight every 2 of the week. If increasing the concentration of hemoglobin is insufficient (less 10 g/l for 4 of the week), dose increase to approximately 25%. Increasing the dosage should not be carried out more often, than 1 once every 4 of the week.

If the hemoglobin exceeds 20 g/l for 4 of the week, drug dose should be reduced by approximately 25%. When, When hemoglobin level exceeds 120 g / l, You should consider reducing the dose of the drug. When hemoglobin continues to grow, dose should be reduced by approximately 25%. If after reducing dose, hemoglobin continues to rise, you need to temporarily discontinue use of the drug to start reducing the level of hemoglobin, You can then resume therapy, Moreover, the drug dose should be reduced by approximately 25% from the previous dose.

Haemoglobin should be measured weekly or every two weeks until it is stabilized. In the subsequent periods between measurements of hemoglobin can be increased.

Supporting phase

During maintenance phase can be continued once weekly a drug Aranesp or go to the introduction of fortnightly. The transfer of patients, dialysis, with weekly injections for the introduction once again in 2 of the week, the initial dose should be twice the dose, vvodivšuûsâ 1 once a week. Patient, not receiving dialysis, After reaching the required concentration of hemoglobin on the background of the appointment of the drug once a 2 of the week, its subcutaneous introduction can be 1 Once a month, using the original dose twice previous dose, vvodivšuûsâ times in 2 of the week.

Titration of dose to maintain the desired hemoglobin concentration should produce as often, as required.

If to maintain the desired hemoglobin needed dose optimization Aranespa, It is recommended to increase approximately 25%.

When, If there has been an increased hemoglobin more than 20 g/l for 4 of the week, drug dose should be reduced by approximately 25%, Depending on the speed of the increase. If the hemoglobin exceeds 120 g / l, You should consider reducing the dose of the drug. When hemoglobin continues to grow, dose should be reduced by approximately 25%. If after reducing dose, hemoglobin continues to rise, you need to temporarily discontinue use of the drug to start reducing the level of hemoglobin, You can then resume therapy, Moreover, the drug dose should be reduced by approximately 25% from the previous dose.

Should conduct a careful observation of patients to ensure adequate correction of anemia with applying the minimum approved, doses of Aranespa.

After any changes in dose or regimen, hemoglobin should be monitored every 1 or 2 of the week. Changing doses during maintenance phases must run no more 1 times a 2 of the week.

If you change the route of administration of the drug should use the same dosage and monitor the concentration of hemoglobin times in 1-2 weeks in order to maintain the required level of hemoglobin.

Patients, receive weekly 1, 2 or 3 rčÈpo injections, can be translated into a single mode of weekly introduction Aranespa or introduction 1 once every 2 of the week. Original weekly dose Aranespa (mcg/week) define, by dividing the total weekly dose rčÈpo (IU/week) on 200. Initial dose Aranespa (g/in 2 of the week) Introduction mode 1 once every 2 week define by dividing the total cumulative dose rčÈpo, imposed over the two-week period, on 200. In view of the known individual variability, for individual patients may require dose titration to optimal therapeutic effect.

When replacing rčÈpo on drug Aranesp measuring haemoglobin levels should be performed at least 1 times per week or 2 of the week, and route of administration of the drug should remain unchanged.

Children with chronic renal insufficiency

Phase correction

To children 11 and older initial dose at p/or to the in/in the introduction of the drug is 0.45 µg/kg body weight as a single injection 1 once a week. Patients, not receiving dialysis, You can apply the initial dose 0.75 µg/kg n/a 1 once every 2 of the week. If an increase in the level of hemoglobin is not enough (less 10 g/l for the 4-week period), It is necessary to increase the dose is approximately 25%. The dose should be no more 1 times a 4 of the week.

If the hemoglobin exceeds 20 g/l for 4 of the week, drug dose should be reduced by approximately 25% Depending on the degree of increase in hemoglobin. When, When hemoglobin level exceeds 120 g / l, You should consider reducing the dose of the drug. When hemoglobin continues to grow, dose should be reduced by approximately 25%. If after reducing dose, hemoglobin continues to rise, you need to temporarily discontinue use of the drug to start reducing the level of hemoglobin, You can then resume therapy, Moreover, the drug dose should be reduced by approximately 25% from the previous dose.

Haemoglobin should be measured weekly or 1 once every 2 weeks before its stabilization.

In the subsequent periods between measurements of hemoglobin can be increased.

Recommendations on correction of hemoglobin at children aged 1 Year to 10 years no.

Supporting phase

In children 11 and older in supporting phase therapy introduction Aranespa can continue in the mode 1 weekly or 1 once every 2 of the week. Patients, on dialysis, When translating them with the dosage Aranespa once a week in mode once in two weeks initially, should receive a dose of, equivalent to twice in a single week mode introduction. If the patient is not on dialysis, after, How to reach the target level of hemoglobin in the drug dosing mode 1 every two weeks, Aranesp can be assigned to s/c 1 once a month, When the initial dose should be twice the dose of the, that was applied 1 once every 2 of the week.

To children aged 1 Year to 18 years clinical data showed, patients, receiving rčÈpo 2 or 3 times a week, can be transferred to Aranesp, input 1 once a week, and patients receiving rčÈpo 1 Once a week can be translated to the introduction 1 once every 2 of the week. Initial dose for children Aranespa (mcg/week.), typed downloads or 1 once every 2 weeks can be determined by dividing the total weekly dose rčÈpo (IU/week.) on 240. Because of individual differences for individual patients need optimal therapeutic dose. When replacing rčÈpo on Aranesp, hemoglobin level should be monitored every 1-2 of the week, and if you want to apply the same method of drug administration.

Titration of dose to maintain the desired hemoglobin concentration should produce as often, as required.

If to maintain the desired hemoglobin needed dose optimization Aranespa, It is recommended to increase approximately 25%.

If the hemoglobin exceeds 20 g/l for 4 of the week, drug dose should be reduced by approximately 25% Depending on the degree of increase in hemoglobin. When, When hemoglobin level exceeds 120 g / l, You should consider reducing the dose of the drug. When hemoglobin continues to grow, dose should be reduced by approximately 25%. If after reducing dose, hemoglobin continues to rise, you need to temporarily discontinue use of the drug to start reducing the level of hemoglobin, You can then resume therapy, Moreover, the drug dose should be reduced by approximately 25% from the previous dose.

Patients should be carefully monitored, for confidence, that used the minimum recommended dose Aranespa provide adequate control of the symptoms of anemia.

After any changes in dose or regimen, hemoglobin should be monitored every 1 or 2 of the week. Changing doses during maintenance phases must run no more 1 times a 2 of the week.

If you change the route of administration of the drug should use the same dosage and monitor the concentration of hemoglobin times in 1-2 weeks in order to maintain the required level of hemoglobin.

Treatment of symptomatic anemia, chemotherapy-induced, in patients with cancer

In patients with anemia (eg, When hemoglobin concentrations equal or lower 100 g / l) Aranesp can be used n/a to increase hemoglobin, but not above 120 g / l. The symptoms and effects of anemia vary with the age of the patients, their sex and severity of the disease. In each case there is a need to look at individual clinical patient data.

Since the content of hemoglobin in the blood – individual rate, characterized by pronounced diversity, some patients as its contents may exceed the target level, and be less than its. In this case helps correction doses of the drug, taking into account that, the target hemoglobin level is from 100 g/l to 120 g / l. Increase hemoglobin concentration should be avoided more 120 g / l; the following information provides guidance on dose adjustment in the case of, If the hemoglobin exceeds 120 g / l.

The recommended initial dose of the drug – 500 g (6.75 mg / kg) 1 once every 3 weeks either by 2.25 mg / kg 1 once a week. If clinical response (fatiguability, hemoglobin content) through 9 weeks was inadequate, further therapy may be ineffective. The use of Aranespa stop after about 4 weeks after completing chemotherapy.

After reaching the target hemoglobin drug dose should be reduced by 25-50%, to adequately control symptoms of anemia by using minimum approved doses of Aranespa. Dose titration is possible between 500 g, 300 mcg and 150 g.

Should carefully monitor the status of patients. If the level of hemoglobin in the patient exceeds 120 g / l, drug dose should be reduced by 25-50%. If the hemoglobin exceeds 130 g / l, You must suspend the application Aranespa. After lowering the hemoglobin to 120 g/l or lower, therapy can be resumed, drug dose should be reduced by 25% from previous.

If the hemoglobin exceeds 20 g/l for 4 of the week, There is a need to reduce the dose of the drug to the 25-50%

Rules of conduct and treatment of injection drug

Aranesp is a sterile product, manufactured without preservatives. One syringe should be no more than one dose. Any number of drug, remaining in a filled syringe, be destroyed.

To make p/injection preparation required: a new prefilled syringe, containing Aranesp and wetted with alcohol swabs or similar materials.

Preparing to injection drug Aranesp

1. Prefilled syringes to get it out of the fridge, do not shake. Leave the syringe at room temperature approximately 30 m (to improve tolerability of injections). Not permitted heating of syringe pre-filled in other ways (eg, in a microwave oven or in hot water).

2. Remove the cap of the syringe immediately before injection.

3. Verify that the dosage in a filled syringe dose, appointed doctor.

4. Check the expiration date of the drug in a filled syringe on the label. You should not use a prefilled syringe, If the last day of the specified month expired.

5. Before the introduction of the solution of the drug Aranesp should check for the presence of visible particles. You can only use colorless, transparent or slightly opalesciruûŝego (“Pearl”) solution. Do not shake.

6. Wash hands thoroughly.

7. Select Comfort, well-lit place and clean surface, where it is possible to arrange all the necessary materials so, that they are easily accessible.

Immediately before injection

1. Hold the cylinder of a syringe, carefully remove the CAP from the needle, do not unscrew. Push it in a straight line, avoid touching the needle and not pushing the syringe plunger. If the inside of the syringe pre-filled visible air bubbles, There is no need to remove them before injection. A solution with air bubbles cannot cause harm. The syringe is now ready for use.

2. Best places for drug administration are: upper thigh area; and belly, except for the area around the navel. Every time you should change the injection site, to avoid pain in one area. If the injection makes another person, then for the introduction of the drug, you can also use the back surface of the shoulder.

If the scope, where it is expected to do the injection, flushed or otekla, You can change its.

The introduction of the drug

1. Disinfect the skin, without pressure, using moistened with alcohol swab, and take skin fold your thumb and index finger.

2. Insert the needle into the skin completely (the doctor or nurse should instruct the patient to perform this procedure).

3. Gently pull the syringe plunger, to make sure, that did not happen the puncture of a vessel. If the inside of the syringe blood appears, remove the needle and insert it in another location.

4. Gently and slowly enter the solution, hold the skin in the crease.

5. After the imposition of a solution remove the needle and let go of a skin fold.

6. If blood will, gently wipe it with a cotton swab. Do not rub the injection site. If necessary,, You can stick with his band.

Patients should be warned about, What if I have problems with the introduction of the drug should contact their doctor or nurse.

Destruction of used syringes

Do not wear the back cap on the needle of a syringe used.

Dispose of the used syringe should be in accordance with the generally accepted rules.

Side effect

Allergic reactions: rarely – dyspnoea, skin rashes and urticaria.

Patients with chronic renal insufficiency

Cardio-vascular system: often (> 1%, ≤ 10%) – arterial hypertension, vascular access thrombosis.

However, when analyzing the results of the study on the safety of such reactions were not associated with changes in hemoglobin (<120 g / l, compared with >120 g / l) or with the speed increase hemoglobin (< 10, from 10 to < 20, from 20 to < 30 and ≥ 30 g/l hemoglobin within 4 weeks).

CNS: often (> 1%, ≤ 10%) -headache; very rarely-seizures.

Local reactions: often (> 1%, ≤ 10%) – pain at the site of subcutaneous injections (been recorded more often, than when applying rčÈpo). Discomfort at the injection site, usually, was easy and temporary and developed, mainly, After the first injection.

From the hematopoietic system: in some cases – collective krasnokletočnaâ Aplasia (PKKA), caused by neutralizing the influence of anti-èritropoètinovyh antibodies.

Patients with cancer

Incidence of hypertension and cardiovascular phenomena were compared in cancer patients, placebo, rčÈpo or Aranesp, When Aranesp injected p/. Besides, similar adverse reactions were not associated with either the content of hemoglobin (< 130, compared with >130 g / l), Neither speeds increase hemoglobin (> 20 g/l for 4 weeks).

Generally, adverse effects when applying Aranespa in cancer patients, receiving concomitant chemotherapy, consistent with the underlying disease and used for its treatment of chemotherapy.

From the blood coagulation system: increase in the rate of thromboembolic complications, including deep vein thrombosis and pulmonary embolism, compared to patients, placebo.

Cardio-vascular system: often (> 1%, ≤ 10%) -Embolic reactions.

On the part of the musculoskeletal system: often (> 1%, ≤ 10%) -arthralgia.

Local reactions: often (< 5%) – pain at the injection site. Discomfort at the injection site was, usually, light and time.

From the body as a whole: often (> 1%, ≤ 10%) – peripheral edema.

Contraindications

is badly controlled arterial hypertension;

-hypersensitivity to darbèpoètinu alpha, rčÈpo or any of the preparation components.

FROM caution should use the drug in patients with liver diseases, sickle-cell anemia, epilepsy.

Pregnancy and lactation

There are no adequate and well-controlled clinical studies on the safety of the drug during pregnancy has not been. With caution and after a careful assessment of the expected benefits of therapy to the mother and the potential risk to the fetus should designate product for pregnant women.

If necessary, the appointment during lactation breastfeeding should be discontinued.

IN experimental research in rats, rabbits, there was no direct damaging effects of the drug on the course of pregnancy, the embryonic development of the foetal/, at birth or postnatal development. Penetrates through the placental barrier in minimal concentrations.

Cautions

To confirm the efficacy of erythropoiesis in all patients should determine iron content before and during treatment with a view to the appointment of, in case of need, complementary therapy drugs iron.

When no response to the application Aranespa should identify the cause. Efficacy of erythropoiesis stimulating substances decreases when there is a shortage of iron, folic acid or vitamin b₁₂, as a consequence, their content must be adjusted. Èritropoètičeskij response can also be attenuated in the presence of opportunistic infections, the symptoms of inflammation or injury cases, hidden blood loss, hemolysis, heavy aluminum intoxication, related hematological diseases or bone marrow fibrosis. The number of reticulocytes to be regarded as one of the evaluation parameters. If the typical reasons for absence of response excluded, and the patient is detected retikulozitopenia, should undertake a study of the bone marrow. If the pattern matches the bone marrow picture PKKA, We recommend that you perform a study on the presence of antibodies to èritropoètinu.

PKKA, caused by neutralizing the influence of antièritropoètinovyh antibodies, has been described in connection with the use of recombinant eritropoetinov, including alpha darbèpoètin. It has been shown, that these antibodies cross-react with all èritropoètinami. In the case of diagnosis PKKA, treatment with Aranesp must stop without a subsequent transfer of the patient to the therapeutic regimen, includes other recombinant erythropoietin.

In all studies Aranespa criterion for exclusions were active liver disease, thus, data on the use of drugs in patients with impaired liver function is missing. Unnecessarily. the liver is by deducing the darbèpoètina alpha and rčÈpo, patients with pathology of the liver medication should be administered with caution.

Aranespom abuse in healthy individuals can lead to excessive increase of hematocrit. Similar phenomena can be associated with life-threatening complications from the circulatory system.

The protective needle cap on the prefilled syringe contains in its composition the dehydrated natural rubber (a derivative of latex), that may cause an allergic reaction.

While maintaining the level of hemoglobin in patients with chronic renal insufficiency, its concentration should not exceed the specified upper bound . In clinical trials, When you reach the target hemoglobin more 120 g/l with the use erythropoiesis stimulating drugs, patients experienced an increased risk of mortality and the development of serious complications from the circulatory system. During the controlled clinical studies failed to detect significant benefits from the use of èpoètinov, If hemoglobin concentration, exceed the level of, necessary to control symptoms of anemia and eliminate the need for blood transfusions

Patients with chronic renal insufficiency

The use of additional iron therapy is recommended for all patients, whose serum ferritin concentration does not exceed 100 ug / L or the transferrin saturation level below 20%.

Necessary to control blood pressure in all patients, especially at the beginning of the application Aranespa. Patients should be aware of the importance of compliance with the guidelines for the use of antihypertensive drugs and dietary restrictions. If blood pressure difficult to control when carrying out the relevant procedures, can be reduced hemoglobin by reducing the dose of Aranesp or temporary interruption of the introduction.

In patients with chronic renal failure and clinical symptoms of ischemic heart disease or congestive heart failure, target hemoglobin levels should be determined individually. In these patients, the maximum content of hemoglobin should not exceed 120 g / l, except, when the severity of the symptoms (eg, angina) It requires a different solution.

During the application of Aranesp should be regular monitoring of serum potassium. Raising the potassium concentration has been described in several patients, receiving Aranesp, however, a causal relationship has not been established. When detecting the rising or increased potassium concentrations, introduction of Aranesp should be discontinued prior to normalization.

Patients, epilepsy, Aranesp should be administered with caution, tk. there are reports of seizures in patients with chronic renal failure, treated with Aranesp.

Patients with cancer

Effect on tumor growth. Erythropoietins are growth factors, that, mainly, It stimulates the production of red blood cells. Erythropoietin receptors may be expressed on the surface of various tumor cells. As with any growth factors, There is a suggestion that, that can stimulate tumor growth erythropoietins.

In several controlled clinical trials in cancer patients, receiving chemotherapy, was not shown, that èpoètiny can improve overall survival or reduce progression of tumors.

In controlled clinical trials Aranespa and other erythropoiesis stimulating drugs have been shown to:

– shortening time to progression in patients with head and neck cancer, receiving radiation therapy, When a target hemoglobin level set to 140 g / l. The use of erythropoiesis-stimulating drugs in these patients is not shown.

– reduction of the total survival rates and an increase in deaths from disease progression for the fourth month in patients with metastatic breast cancer, receiving chemotherapy, When the target hemoglobin range was installed 120 to 140 g / l.

– increased risk of death in patients with active malignant disease, but not receiving either radiation, Neither cytostatic treatment, When a target hemoglobin level set to 120 g / l. The use of erythropoiesis-stimulating drugs such patients not shown.

In patients with solid tumors or malignant lymphoproliferative disease with increased levels of hemoglobin above 120 g/l should strictly adhere to the recommended dose adjustment scheme to minimize the potential risk of thromboembolic phenomena. You also need to regularly monitor the number of platelets and hemoglobin concentration in the blood.

Effects on ability to drive vehicles and management mechanisms

There was no influence of the drug Aranesp on the ability to drive vehicles and handling equipment.

The results of experimental studies

In experimental studies in rats and dogs when introducing Aranespa reliably increased hemoglobin concentration, gematokrita, red blood cells and reticulocytes, that matches the expected pharmacological effect. Adverse events with the introduction of the drug in very high doses were seen as a result of enhanced pharmacological action (reduction of tissue blood flow due to increased blood viscosity). These were identified as mielofibrozy and hypertrophy of the spleen, as well as the expansion of the micro ECG in dogs, without cardiac arrhythmia and the effect on QT interval.

Aranesp did not possess any genotoxic potential and influence on cell proliferation of a number of negematologičeskogo no in vitro, nor in vivo. Studies on chronic toxicity was not observed tumorogennogo or unexpected response well-expressed none well-studied type fabrics. In extensive animal studies the carcinogenic potential of assessment darbèpoètina Alpha not animations.

Overdose

Aranesp is characterized by a wide range of therapeutic doses. Even at very high concentrations of the drug in the serum, There was no overdose symptoms.

Treatment: in the case of Polycythemia introduction Aranespa should temporarily stop. If there is clinical evidence can be performed flebotomiâ.

Drug Interactions

Clinical data, received to date, not contain guidance on the interaction of Aranespa with other substances. However it is known, that may be possible his interaction with drugs, characterized by a high degree of affinity for erythrocytes, such as ciclosporin, tacrolimus. While appointing darbèpoètina Alpha with any such drugs should monitor the level of their content in the serum with dose modification in case of increase in the concentration of hemoglobin.

In view of the fact, that studies were not conducted for compatibility, the drug Aranesp should not be confused or in the form of infusions, together with other medicines.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be kept out of the reach of children protected from the light spot, at a temperature of from 2 ° to 8 ° C.; Do not freeze. Shelf life – 2 year.

Before the outpatient use of Aranesp can be momentarily moved from storage conditions at room temperature (25 ° C) for a maximum period of 7 days. Once extracted from the fridge and reached room temperature (25 ° C) the syringe should be used within 7 days or destroy.