Medicinal Products

ARANESP 100 micrograms

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Darbepoetine alfa
laboratory: Amgen Europe BV

Injectable solution
Box of 1 pre-filled syringe with 0.5 mL safety system
All forms

Indication

Treatment of symptomatic anemia related to chronic renal failure (CRF) in adults and children.

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

Dosage ARANESP 100 micrograms Solution for injection Box of 1 pre-filled syringe with 0.5 mL safety system

Aranesp treatment should be initiated by physicians who have experience with the indications mentioned above.

Aranesp is presented in a pre-filled syringe ready for injection. Instructions for use, handling and disposal are given in the Instructions for Use, Handling and Disposal section .

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

The symptoms and consequences of anemia may vary depending on age, sex and the overall clinical picture; It is necessary for a doctor to evaluate the disease and its evolution. Aranesp can be administered subcutaneously or intravenously to increase hemoglobin to a maximum of 12 g / dl (7.5 mmol / l). The subcutaneous route is preferred in patients who are not hemodialysis, in order to preserve the peripheral veins.

Due to intra-individual variability, point concentrations of hemoglobin can be observed below and above the desired values. The variability of hemoglobin level should be controlled by adjusting the dosage, relative to the target hemoglobin level between 10 g / dl (6.2 mmol / l) and 12 g / dl (7.5 mmol / l) . Maintaining a hemoglobin level above 12 g / dl (7.5 mmol / l) should be avoided; recommendations for dosage adjustment when the hemoglobin level exceeds 12 g / dl (7.5 mmol / l) are detailed below. An increase of hemoglobin above 2 g / dl (1.25 mmol / l) over a period of 4 weeks should be avoided. If this occurs, the dosage should be adjusted.

Treatment with Aranesp is divided into two phases - corrective phase and maintenance phase. Treatment modalities are presented separately for adults and children. Treatment of children under 1 year old has not been studied:

Adults with chronic renal failure

Corrective phase

The initial dose is 0.45 μg / kg body weight administered subcutaneously or intravenously as a single weekly injection. In non-dialysis patients, an initial dose of 0.75 μg / kg can be administered subcutaneously as a single injection once every two weeks. If the increase in hemoglobin is insufficient (less than 1 g / dl [0.6 mmol / l] in four weeks), the dose may be increased by approximately 25%. The dosage should not be increased more than once every four weeks.

If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) over a four-week period, reduce the dose by approximately 25% from the previous dose, depending on the dose. importance of this increase. If the hemoglobin level is greater than 12 g / dl (7.5 mmol / l), a dose reduction should be considered. If the hemoglobin level continues to increase, the dose should be reduced by approximately 25%. If, after this dose reduction, the hemoglobin level still increases, the administration should be temporarily suspended until the hemoglobin level begins to decrease. The treatment will then be resumed at a dose of 25% lower than the previous dose.

The hemoglobin level should be measured once a week or every two weeks until it has stabilized. Then the hemoglobin level can be measured at longer intervals.

Maintenance phase

During the maintenance phase, Aranesp can continue to be administered as a single weekly injection or once every two weeks. Dialysis patients treated with an Aranesp injection every 2 weeks should receive an initial dose of Aranesp equivalent to twice the weekly dose previously administered. In non-dialysis patients, once the target hemoglobin level is reached by one dose every two weeks, Aranesp can be administered by subcutaneous injection once a month using an initial dose equivalent to twice the dose used every two weeks. The dose administered should be evaluated to maintain the target hemoglobin level.

If a dose adjustment is necessary to maintain hemoglobin at the desired level, it is recommended to increase or decrease the dose by approximately 25% from the previous dose.

If the hemoglobin level increases by more than 2 g / dl (1.25 mmol / l) over a period of 4 weeks, reduce the dose by approximately 25% depending on the significance of this increase. If the hemoglobin level is greater than 12 g / dl (7.5 mmol / l), a dose reduction should be considered. If the hemoglobin level continues to increase, the dose should be reduced by approximately 25%. If, after this dose reduction, the hemoglobin level still increases, the administration should be temporarily suspended until the hemoglobin level begins to decrease. The treatment will then be resumed at a dose of 25% lower than the previous dose.

Patients should be closely monitored to ensure that the appropriate minimum dose of Aranesp is used to control the symptoms of anemia.

After each dose or schedule adjustment, the hemoglobin level should be checked once a week or every two weeks. During the maintenance phase, the dosage should not be changed more than once every two weeks.

When the route of administration is changed, the same dose should be used and the hemoglobin should be monitored once a week or every two weeks to adjust the dose to maintain the desired level.

Clinical trials have shown that adult patients receiving r-HuEPO once, twice or three times a week may receive Aranesp once weekly or once every 2 weeks. The initial weekly dose of Aranesp (μg / week) can be calculated by dividing the total weekly dose of r-HuEPO (IU / week) by 200. The initial dose of Aranesp administered every 2 weeks (μg / 2 weeks) can be calculated by dividing by 200 the total dose of r-HuEPO administered over a 2-week period. Due to individual variability, the search for the optimal therapeutic dose should be done for each patient. When replacing r-HuEPO with Aranesp, the hemoglobin level should be monitored once a week or every two weeks and the same route of administration should be used.

Children with chronic renal failure

Corrective phase

In children> 11 years of age, the initial dose is 0.45 μg / kg body weight administered subcutaneously or intravenously as a single injection once weekly. In non-dialysis patients, an initial dose of 0.75 μg / kg can be administered subcutaneously as a single injection once every two weeks. If the increase in hemoglobin is insufficient (less than 1 g / dl [0.6 mmol / l] in four weeks), the dose may be increased by approximately 25%. The dosage should not be increased more than once every four weeks.

If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) over a four-week period, reduce the dose by approximately 25% from the previous dose, depending on the level. increase. If the hemoglobin level is greater than 12 g / dl (7.5 mmol / l), a dose reduction should be considered. If the hemoglobin level continues to increase, the dose should be reduced by approximately 25%. If, after this dose reduction, the hemoglobin level still increases, the administration should be temporarily suspended until the hemoglobin level begins to decrease. The treatment will then be resumed at a dose of 25% lower than the previous dose.

The hemoglobin level should be measured once a week or every two weeks until it has stabilized. Then the hemoglobin level can be measured at larger intervals.

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

Maintenance phase

In children from 11 years of age, during the maintenance phase, Aranesp can continue to be administered as a single weekly injection or once every two weeks. Dialysis patients treated with an Aranesp injection every 2 weeks should receive an initial dose of Aranesp equivalent to twice the weekly dose previously administered. In non-dialysis patients, once the target hemoglobin level is reached by one dose every two weeks, Aranesp can be administered by subcutaneous injection once a month using an initial dose equivalent to twice the dose used every two weeks.

In patients aged 1 to 18 years, clinical data available in children have shown that patients receiving r-HuEPO two or three times a week can receive Aranesp once a week, and those receiving r-HuEPO once a week could benefit from Aranesp once every two weeks. The initial weekly dose of Aranesp (μg / week) in pediatrics can be calculated by dividing the total weekly dose of r-HuEPO (IU / week) by 240. The initial dose of Aranesp (μg / week) to be administered every two weeks in pediatrics can be calculated by dividing the total dose of r-HuEPO (IU / week) over two weeks by 240. Due to individual variability, the search for the optimal therapeutic dose should be performed for each patient. When replacing r-HuEPO with Aranesp, the hemoglobin level should be monitored once a week or every two weeks and the same route of administration should be used.

The dose administered should be periodically evaluated to maintain the target hemoglobin level.

If a dose adjustment is necessary to maintain hemoglobin at the desired level, it is recommended to increase or decrease the dose by approximately 25% from the previous dose.

If the hemoglobin level increases by more than 2 g / dl (1.25 mmol / l) in 4 weeks, reduce the dose by approximately 25% depending on the importance of this increase. If the hemoglobin level is greater than 12 g / dl (7.5 mmol / l), a dose reduction should be considered. If the hemoglobin level continues to increase, the dose should be reduced by approximately 25%. If, after this dose reduction, the hemoglobin level still increases, the administration should be temporarily suspended until the hemoglobin level begins to decrease. The treatment will then be resumed at a dose of 25% lower than the previous dose.

Patients should be closely monitored to ensure that the appropriate minimum dose of Aranesp is used to control the symptoms of anemia.

After each adjustment in dose or rate of administration, the hemoglobin level should be checked once a week or every two weeks. During the maintenance phase, the dosage should not be changed more than once every two weeks.

When the route of administration is changed, the same dose should be used and hemoglobin should be monitored once a week or every two weeks to adjust the dose to maintain the desired hemoglobin level.

Treatment of symptomatic anemia induced by chemotherapy in cancer patients

Aranesp should be administered subcutaneously to patients with anemia (eg, hemoglobin ≤ 10 g / dl (6.2 mmol / l)) to achieve a hemoglobin level not exceeding 12 g / dl (7.5 mmol / l). The symptoms and consequences of anemia may vary depending on age, sex and the overall clinical picture; It is necessary for a doctor to evaluate the disease and its evolution.

Due to intra-individual variability, point concentrations of hemoglobin can be observed below and above the desired values. The variability in hemoglobin levels should be controlled by adjusting the dosage to the target hemoglobin level between 10 g / dl (6.2 mmol / l) and 12 g / dl (7.5 mmol / l). Maintaining a hemoglobin level greater than 12 g / dl (7.5 mmol / l) should be avoided; recommendations for dosage adjustment when the hemoglobin level exceeds 12 g / dl are detailed below.

The recommended starting dose is 500 μg (6.75 μg / kg body weight), administered once every three weeks, or 2.25 μg / kg body weight administered once a week. If the clinical response (fatigue, hemoglobin) is not satisfactory after nine weeks of treatment, continued treatment may be ineffective.

Aranesp treatment should be discontinued approximately four weeks after the end of chemotherapy.

Once the individual therapeutic goal is reached, the dose should be reduced by 25 to 50% to ensure that the appropriate minimum dose of Aranesp is used to maintain hemoglobin levels to control the symptoms of anemia. . The choice of a dose of 500 μg, 300 μg or 150 μg should be considered.

Patients should be closely monitored. If the hemoglobin level exceeds 12 g / dl (7.5 mmol / l), the dose should be reduced by approximately 25-50%. Aranesp treatment should be temporarily discontinued if the hemoglobin level exceeds 13 g / dl (8.1 mmol / l). Treatment will be resumed at approximately 25% lower than the previous dose when the hemoglobin level has dropped to 12 g / dl (7.5 mmol / l) or less.

If the hemoglobin level increases by more than 2 g / dl (1.25 mmol / l) over a period of four weeks, the dose should be reduced by 25 to 50%.

Against indications

Known hypersensitivity to darbepoetin alfa, r-HuEPO or any of the excipients.

Poorly controlled high blood pressure

Aranesp side effects

Overview

Cases of serious allergic reactions including anaphylactic reactions, angioedema, allergic bronchospasm, skin rash, and urticaria have been reported with darbepoetin alfa.

Experience from clinical trials

Chronic renal failure patients

The data are from controlled studies involving 1357 patients, 766 treated with Aranesp and 591 treated with r-HuEPO. In the Aranesp-treated group, 83% were dialyzed and 17% were not dialysed.

Injection site pain has been reported as attributable to treatment in studies where Aranesp was administered subcutaneously. This observation was more frequent than with r-HuEPO. Discomfort at the injection site was usually mild and transient and occurred most often after the first injection.

The incidence of adverse reactions considered to be related to Aranesp treatment in controlled clinical studies is:

MedDRA classification by organ system

Incidence in patients

Side effects

Cardiac disorders

Very Common (≥1 / 10)

Hypertension

Skin and subcutaneous tissue disorders

Frequent (≥1 / 100 to <1/10)

Rash / erythema

Vascular disorders

Uncommon (≥ 1 / 1, 000 to <1/100)

Thromboembolic events

General disorders and administration site conditions

Frequent (≥1 / 100 to ≤1 / 10)

Pain at the injection site

Cancer patients

Adverse events were determined based on the pooled data from seven randomized, double-blind, placebo-controlled studies with a total of 2112 patients (1200 under Aranesp and 912 under placebo). Patients with solid tumors (eg lung, breast, colon or ovarian cancer) or lymphoid malignancies (eg lymphoma, or multiple myeloma) were included in these clinical studies.

The incidence of adverse reactions considered to be related to Aranesp treatment in controlled clinical studies is:

MedDRA classification by organ system

Impact

Side effects

Skin and subcutaneous tissue disorders

Frequent (≥1 / 100 to <1/10)

Rash / erythema

Vascular disorders

Frequent (≥1 / 100 to <1/10)

Thromboembolic events including pulmonary embolism

General disorders and administration site conditions

Very Common (≥1 / 10)

Edema

Frequent (≥1 / 100 to <1/10)

Pain at the injection site

Post marketing experience

The following side effects have been reported after the marketing of Aranesp:

• Pure red cell aplasia. Isolated cases of erythroblastopenia due to neutralizing antibodies to erythropoietin have been reported mainly in patients treated subcutaneously for chronic renal failure.In case of diagnosed erythroblastopenia, treatment with Aranesp should be discontinued and patients should not be treated with other recombinant erythropoietin (see Warnings and Precautions ).

• Allergic reactions, including anaphylactic reactions, angioedema, rash, and urticaria.

• Convulsions.

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