Aranesp 40mcg

treatment of symptomatic anemia in adults and children suffering from chronic renal failure (CRF),

therapy of symptomatic anemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.

Treatment with Aranesp should be carried out by doctors who have experience in prescribing for the above-mentioned indications.

Aranesp is delivered ready for use in pre-filled syringes (PZS). Instructions for the use of the drug, its handling and the procedure for its destruction are given in the section "Special instructions".

Treatment of symptomatic anemia in combination with chronic renal failure in adults and children.

The symptoms of anemia and the effects can vary depending on patients ' age, gender, and disease severity, in each case required the analysis of individual clinical data of the patient by the attending physician.

Aranesp can be used n / a or IV to increase the level of hemoglobin, but not higher than 120 g/l. In patients who are not on dialysis, the subcutaneous route of administration is preferred, since it avoids peripheral vein punctures.

The level of hemoglobin in patients is subject to individual fluctuations, including sometimes above or below the desired target values. If the hemoglobin level deviates beyond the target values, the dose is modified, and the target value should be considered as the range from 100 to 120 g/l. A persistent increase in the level of hemoglobin above 120 g / l should be avoided, instructions for dose modification at hemoglobin values above 120 g / l are presented below. You should also avoid increasing the level of hemoglobin by more than 20 g / l over a 4-week period. In this case, a dose adjustment is also necessary.

Treatment with Aranesp includes two stages — the correction phase and the maintenance phase. Recommendations for use and dosage in adults and children are given separately in the instructions. The use in children under the age of 1 year has not been studied.

Adult patients with chronic renal failure

Correction phase. The initial dose for n / a or intravenous administration should be 0.45 mcg/kg of body weight with a single weekly administration. Alternatively, for patients who do not receive dialysis, it is allowed to administer the drug in an initial dose of 0.75 mcg/kg of body weight every two weeks. If the increase in the concentration of hemoglobin is insufficient (less than 10 g / l for 4 weeks), the dose of the drug is increased by approximately 25%. Increasing the dose of the drug should not be carried out more often than once every four weeks.

If the increase in hemoglobin content exceeds 20 g / l in 4 weeks, the dose of the drug should be reduced by about 25%. If the hemoglobin level exceeds 120 g/l, the possibility of reducing the dose of the drug should be considered. If the hemoglobin content continues to increase, the dose should be reduced by about 25%. If the hemoglobin continues to increase after a dose reduction, it is necessary to temporarily stop using the drug until the hemoglobin level begins to decrease, after which you can resume therapy, and the dose of the drug should be reduced by about 25% of the previous dose.

Hemoglobin should be measured weekly or biweekly until it stabilizes.

In the future, the intervals between hemoglobin measurements can be increased.

The maintenance phase. In the maintenance phase of treatment, you can continue to administer Aranesp once a week or switch to administration once every two weeks. When transferring patients on dialysis from weekly injections to a once-every-two-week regimen, the initial dose should be twice the dose administered once a week. For patients who do not receive dialysis, after reaching the required hemoglobin concentration against the background of prescribing the drug every two weeks, its n / A administration can be performed once a month using the initial dose, twice the previous dose, administered every two weeks.

Titration of the dose to maintain the required hemoglobin concentration should be performed as often as required.

If optimization of the Aranespa dose is necessary to maintain the required hemoglobin level, it is recommended to increase it by approximately 25%.

If there is an increase in the level of hemoglobin more than 20 g/l for 4 weeks, the dose of the drug should be reduced by approximately 25%, depending on the rate of increase. If the hemoglobin content exceeds 120 g / l, you should consider reducing the dosage of the drug. If the hemoglobin content continues to increase, the dose should be reduced by about 25%. If after reducing the dose, hemoglobin continues to rise, you need to temporarily stop using the product prior to the reduction of hemoglobin level, and then resume therapy, and dosage of the drug should be reduced by approximately 25% of previous dose

Should be careful monitoring of patients for adequate correction of anemia with the use of the minimum approved dose Aranesp.

After any change in the dose or mode of administration, the hemoglobin content should be monitored every 1 or 2 weeks. Dose changes during the maintenance phase should be performed no more than once every 2 weeks.

If the route of administration of the drug is changed, the same doses of the drug should be used and the hemoglobin concentration should be monitored once every 1-2 weeks in order to maintain the required hemoglobin level.

Adult patients receiving weekly 1, 2 or 3 injections of rfEPO can be switched to a single weekly administration of Aranespa or its administration once every two weeks. The initial weekly dose of Aranespa (mcg/week) is determined by dividing the total weekly dose of rfEPO (IU/week) by 200. The initial dose of Aranespa (mcg / 2 weeks) with a biweekly administration regimen is determined by dividing the total cumulative dose of rfEPO administered over a 2-week period by 200. Due to the known individual variability, individual patients may need to titrate the doses until the optimal therapeutic effect is obtained. When replacing RCHEPO with the drug Aranesp, the measurement of hemoglobin levels should be performed at least once a week or every two weeks, and the method of administration of the drug should remain unchanged

Children with chronic renal failure

Correction phase. For children aged 11 years and older, the initial dose for n / a or intravenous administration of the drug is 0.45 mcg/kg of body weight in the form of a single injection once a week. In patients who do not receive dialysis, an initial dose of 0.75 mcg/kg, n/a once every two weeks can be used. If the increase in the level of hemoglobin is not enough (less than 10 g / l for a 4-week period), it is necessary to increase the dose of the drug by about 25%. An increase in the dose should be carried out no more than once every four weeks.

If the increase in the hemoglobin content exceeds 20 g / l in 4 weeks, the dose of the drug should be reduced by about 25%, depending on the degree of increase in the hemoglobin level. If the hemoglobin level exceeds 120 g/l, the possibility of reducing the dose of the drug should be considered. If the hemoglobin content continues to increase, the dose should be reduced by about 25%. If after reducing the dose, hemoglobin continues to rise, you need to temporarily stop using the product prior to the reduction of hemoglobin level, and then resume therapy, and the dose should be reduced by approximately 25% from the previous rate.

Hemoglobin should be measured weekly or every 2 weeks until it stabilizes.

In the future, the intervals between hemoglobin measurements can be increased.

There are no recommendations regarding the correction of hemoglobin levels in children aged 1 to 10 years.

The maintenance phase. In children 11 years and older in the maintenance phase of therapy, the administration of Aranespa can be continued in the mode of 1 time per week or 1 time every two weeks. Patients on dialysis, when transferring them from the Aranespa dosage regimen once a week to the once-every-two-week regimen, should initially receive a dose equivalent to twice the once-a-week administration regimen. If the patient is not on dialysis, after reaching the target level of hemoglobin in the dosage regimen of the drug 1 every two weeks, Aranesp can be prescribed once a month, with the initial dosage should be twice the dose that was used in the regimen 1 every two weeks

For children aged 1 to 18 years, clinical data have shown that patients receiving RCHEPO two or three times a week can be switched to Aranesp administered once a week, and patients receiving RCHEPO once a week can be switched to a biweekly regimen. The initial dosage of Aranespa for children (mcg/week) administered weekly can be determined by dividing the total weekly dose of rfEPO (IU / week) by 240. The initial dosage of Aranespa when administered every 2 weeks (mcg/ every 2 weeks) can be determined by dividing the total dose of RCHEPO for a two-week period by 240. Due to individual differences, it is necessary to select the optimal therapeutic dose for individual patients. When replacing RCHEPO with Aranesp, the hemoglobin level should be monitored every 1-2 weeks, and the same method of administration of the drug should be used

Titration of the dose to maintain the required hemoglobin concentration should be performed as often as required.

If optimization of the Aranespa dose is necessary to maintain the required hemoglobin level, it is recommended to increase it by approximately 25%.

If the increase in the hemoglobin content exceeds 20 g / l in 4 weeks, the dose of the drug should be reduced by about 25%, depending on the degree of increase in the hemoglobin level. If the hemoglobin level exceeds 120 g/l, the possibility of reducing the dose of the drug should be considered. If the hemoglobin content continues to increase, the dose should be reduced by about 25%. If the hemoglobin continues to increase after a dose reduction, it is necessary to temporarily stop using the drug until the hemoglobin level begins to decrease, after which you can resume therapy, and the dose of the drug should be reduced by about 25% of the previous dose.

Patients should be carefully monitored to ensure that the minimum approved doses of Aranespa used provide adequate control of anemia symptoms.

After any change in the dose or mode of administration, the hemoglobin content should be monitored every 1 or 2 weeks. Dose changes during the maintenance phase should be performed no more than once every 2 weeks.

If the route of administration of the drug is changed, the same doses of the drug should be used and the hemoglobin concentration should be monitored once every 1-2 weeks in order to maintain the required hemoglobin level.

Treatment of symptomatic anemia induced by chemotherapy in patients with cancer

In patients with anemia (for example, with a hemoglobin concentration equal to or lower than 100 g / l) Aranesp can be used n/a to increase the level of hemoglobin (but not higher than 120 g/l). The symptoms and consequences of anemia depend on the age of the patients, their gender and the severity of the disease. In each case, it is necessary to analyze the individual clinical data of the patient by the attending physician.

Since the content of hemoglobin in the blood is an individual indicator, which is characterized by a pronounced variety, in some patients its content may either exceed the target level or be less than it. In this case, it helps to adjust the dosage of the drug, taking into account the fact that the target level of hemoglobin is from 100 g / l to 120 g/l. An increase in the hemoglobin concentration of more than 120 g/l should be avoided, the following is a guide for dose adjustment if the hemoglobin content exceeds 120 g/l.

The recommended initial dose of the drug is 500 mcg (6.75 mcg/kg) once every 3 weeks or 2.25 mcg/kg once a week. If the clinical response (fatigue, hemoglobin content) is inadequate after 9 weeks, further therapy may be ineffective. Application Aranesp stop approximately four weeks after completion of chemotherapy.

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

Patients should be carefully monitored. If the patient's hemoglobin level exceeds 120 g / l, the dose of the drug should be reduced by 25-50%. If the hemoglobin content exceeds 130 g / l, the use of Aranespa should be temporarily discontinued. After reducing the level of hemoglobin to 120 g / l or lower, therapy can be resumed, the dosage of the drug should be approximately 25% less than the previous one.

If the increase in the level of hemoglobin exceeds 20 g/l for 4 weeks, you should reduce the dosage of the drug by 25-50%.

hypersensitivity to darbepoetin alfa, rfEPO or to any component of the drug,

uncontrolled arterial hypertension.

With caution: liver diseases, sickle cell anemia.

Use Aranesp 40mcg (polysorbate 80) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Aranesp 40mcg (polysorbate 80) comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Aranesp 40mcg (polysorbate 80) refilled.
• Aranesp 40mcg (polysorbate 80) is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Aranesp 40mcg (polysorbate 80) at home, a health care provider will teach you how to use it. Be sure you understand how to use Aranesp 40mcg (polysorbate 80). Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Aranesp 40mcg (polysorbate 80) if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Do not shake Aranesp 40mcg (polysorbate 80). Do not use Aranesp 40mcg (polysorbate 80) if it has been shaken.
• Do not use Aranesp 40mcg (polysorbate 80) if it has been frozen.
• Do not dilute or mix Aranesp 40mcg (polysorbate 80) with any other solutions or medicines.
• Discard any unused portion of medicine left in the vial or syringe.
• Use only disposable syringes and needles. Use the syringes and needles only once and dispose of them in a puncture-proof container as instructed by your health care provider.
• Choose a new site each time you inject Aranesp 40mcg (polysorbate 80). Do not inject into an area that is tender, red, bruised, hard, swollen, or has scars or stretch marks.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Aranesp 40mcg (polysorbate 80), contact your doctor right away.

Ask your health care provider any questions you may have about how to use Aranesp 40mcg (polysorbate 80).

Use: Labeled Indications

Anemia due to chemotherapy in patients with cancer: Treatment of anemia in patients with nonmyeloid malignancies when anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of 2 additional months of planned chemotherapy.

Anemia due to chronic kidney disease: Treatment of anemia due to chronic kidney disease, including patients on dialysis and patients not on dialysis.

Limitations of use: Aranesp 40mcg has not demonstrated improved quality of life, fatigue, or well-being. Aranesp 40mcg is not indicated for use under the following conditions:

- Cancer patients receiving hormonal therapy, therapeutic biologic products, or radiation therapy unless also receiving concurrent myelosuppressive chemotherapy

- Cancer patients receiving myelosuppressive chemotherapy when the expected outcome is curative

- Cancer patients receiving myelosuppressive chemotherapy when anemia can be managed by transfusion

- As a substitute for red blood cell (RBC) transfusion in patients requiring immediate correction of anemia

Off Label Uses

Myelodysplastic syndromes, lower-risk (symptomatic anemia management)

Data from 4 studies, a meta-analysis, and a systematic review support the use of Aranesp 40mcg (initially as a single agent and then in combination with growth-colony stimulating factor after single-agent failure) in the management of anemia in patients with lower-risk myelodysplastic syndromes.

Based on guidelines from the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH) for management of cancer-associated anemia with erythropoiesis-stimulating agents, erythropoiesis-stimulating agents may be an option for management of anemia in patients with lower-risk myelodysplastic syndromes who have an erythropoietin level ≤500 mU/mL.

See also:
What other drugs will affect Aranesp 40mcg?

No formal drug interaction studies have been conducted with Aranesp 40mcg.

General provisions

There have been reports of serious allergic reactions, including anaphylactic manifestations, angioedema, shortness of breath, rash and urticaria, associated with the use of darbepoetin alpha.

Data obtained in controlled trials

Patients with chronic renal failure. In controlled trials, out of 1,357 patients, 766 patients received Aranesp and 591 patients received recombinant human erythropoietin, 83% were on dialysis, and 17% were not.

Aranespa injection site pain was reported as associated with the use of the drug and was more frequently reported in the darbepoietin group than in the recombinant human erythropoietin group. The discomfort at the injection site was usually minor and transient, and was noted mainly after the first injection.

The frequency of adverse reactions considered to be associated with Aranesp treatment in controlled clinical trials was (Table 1):

Table 1

Cancer patients. Adverse reactions were determined based on combined data from seven randomized, double-blind, placebo-controlled Aranespa trials involving 2112 patients (Aranesp — 1200, placebo — 912). The clinical trials included patients with solid tumors (e.g. lung, breast, colon, ovarian) and lymphoid malignancies (e.g. lymphoma, multiple myeloma).

The frequency of adverse effects considered to be associated with Aranesp treatment in controlled clinical trials is as follows (Table 2):

Table 2

Post-registration security monitoring data

During the application Aranesp in routine clinical practice was reported about the development of the following adverse reactions:

- partial red cell aplasia. In some cases, neutralizing antibodies to erythropoietin mediating PKKA have been reported in connection with Aranesp therapy. Primarily, these messages are received for patients with chronic renal failure treated with the drug n/a. In case of confirmation of the diagnosis PKKA Aranesp therapy must be discontinued and patients should be transferred to another recombinant erythropoietin,

- allergic reactions, including anaphylactic reactions, angioedema, skin rash and urticaria. Frequency unknown, (cannot be estimated based on available data),

- convulsions. Frequency unknown, (cannot be estimated based on available data),

- increased blood pressure. The frequency is unknown (cannot be estimated based on available data).

Darbepoetin alpha is a drug with a wide therapeutic range. Even with a very high concentration of the drug in the blood serum, there were no symptoms of overdose.

In case of polycythemia, the introduction of Aranesp should be suspended (see "Method of administration and dose"). If there are clinical indications, a phlebotomy can be performed.

Darbepoetin Alfa