Medicinal Products

BINOCRIT 5000 IU / 0.5 mL

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Epoetin alfa
laboratory: Sandoz Gmbh

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

Indication

Treatment of symptomatic anemia associated with chronic renal failure (CKD) in adults and children:

- Treatment of anemia secondary to chronic renal insufficiency in children and adult patients with hemodialysis and adult patients on peritoneal dialysis (see Warnings and precautions for use ).

- Treatment of severe anemia of renal origin accompanied by clinical symptoms in adult patients with renal insufficiency who have not yet been dialyzed (see Warnings and precautions for use ).

Treatment of anemia and reduction of transfusion requirements in adult patients treated with chemotherapy for solid tumors, malignant lymphomas or multiple myeloma and at risk of transfusion due to their general condition (eg, cardiovascular status, pre-existing anemia) existing at the beginning of chemotherapy).

Binocrit can be used to increase autologous blood donation in patients participating in a deferred autologous transfusion program. If used in this indication, the benefits should be weighed against the reported risk of thromboembolic events. Treatment should be given only in patients with moderate iron-deficient anemia (hemoglobin (Hb) level of 10-13 g / dl (6.2-8.1 mmol / l)), if blood savings are not available or not sufficient when the planned major non-urgent procedure requires a large volume of blood (4 or more blood units in women, 5 units or more in men).

Binocrit can be used to reduce exposure to homologous blood transfusions in non-iron deficient adult patients undergoing major scheduled orthopedic surgery with a presumed high risk of transfusion complications. Use should be restricted to patients with moderate anemia (eg, 10-13 g / dl or 6.2-8.1 mmol / l Hb) who do not have access to a delayed autologous where blood losses of 900 to 1800 ml are expected.

Dosage BINOCRIT 5000 IU / 0.5 mL Solution for injection Box of 1 pre-filled syringe 0.5 mL

Treatment with Binocrit should be initiated under the supervision of physicians experienced in the management of patients with the above indications.

Dosage

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

In patients with chronic renal failure, the drug should be administered intravenously (see Warnings and Precautions ).

The symptoms and sequelae of anemia may vary according to age, gender and the overall impact of the disease; an assessment by the physician of the state of health and the clinical course of each patient is necessary.

The target hemoglobin level is 10 to 12 g / dl (6.2-7.5 mmol / l) in adults and 9.5 to 11 g / dl (5.9-6.8 mmol / l) ) in children.

Any hemoglobin level permanently greater than 12 g / dl (7.5 mmol / l) should be avoided. If the hemoglobin level rises above 2 g / dl (1.25 mmol / l) per month or if it consistently exceeds 12 g / dl (7.5 mmol / l), the dose should be reduced 25% epoetin alfa. If the hemoglobin level exceeds 13 g / dl (8.1 mmol / l), treatment should be discontinued until the level falls below 12 g / dl (7.5 mmol / l) after the epoetin alfa treatment can be reinstated at a 25% lower dose.

Due to intra-patient variability, it may occasionally occur that hemoglobin levels above or below the desired level are observed.

Patients should be closely monitored to ensure that the lowest possible dose of epoetin alfa is used and that anemia and symptoms of anemia can be adequately controlled.

The state of the iron stores should be assessed before and during treatment and additional iron supplementation should be given when needed. In addition, before starting treatment with epoetin alfa, other causes of anemia, such as vitamin B 12 or folate deficiency, should be eliminated. Failure to respond to epoetin alfa treatment should lead to a search for the causes. These may be: iron deficiency, folic acid or vitamin B 12 ; aluminum intoxication; intercurrent infections; inflammatory syndromes or trauma; occult bleeding; hemolysis and medullary fibrosis of any origin.

Adult patients on hemodialysis:

The treatment takes place in two phases:

Corrective phase:

50 IU / kg 3 times a week intravenously. If a dose adjustment is necessary, it is recommended to proceed in increments of at least 4 weeks. At each level, the recommended dose increase or decrease is 25 IU / kg 3 times a week.

Maintenance phase:

The dosage is adjusted to maintain hemoglobin at the desired level: Hb between 10 and 12 g / dl (6.2-7.5 mmol / l).

The recommended total weekly dose is 75 to 300 IU / kg administered in doses of 25-100 IU / kg three times a week intravenously.

Available clinical data suggest that patients with very low initial hemoglobin levels (<6 g / dl or 8 g / dl or> 5 mmol / l).

Children in hemodialysis:

The treatment takes place in two phases:

Corrective phase:

50 IU / kg 3 times a week intravenously. If a dose adjustment is necessary, it is recommended to proceed in increments of 25 IU / kg 3 times weekly, with an interval of at least 4 weeks between each adjustment, until the desired end is reached.

Maintenance phase:

The dosage is adjusted to maintain hemoglobin at the desired level: Hb between 9.5 and 11 g / dl (5.9-6.8 mmol / l).

Generally, children under 30 kg require higher maintenance doses than children over 30 kg and adults.

For example, the following maintenance doses were used in clinical trials after 6 months of treatment:

Dose (IU / kg 3 times a week)

Weight (kg)

Median dose

Usual maintenance dose

<10

100

75-150

10-30

75

60-150

> 30

33

30-100

Available clinical data suggest that children with very low initial hemoglobin levels (<6.8 g / dl or 6.8 g / dl or> 4.25 mmol / l).

Adult patients on peritoneal dialysis: The treatment is divided into two phases:

Corrective phase:

The initial dose is 50 IU / kg twice a week intravenously.

Maintenance phase:

The dosage is adjusted to maintain hemoglobin at the desired level: Hb between 10 and 12 g / dl (6.2-7.5 mmol / l). The maintenance dose is between 25 and 50 IU / kg twice a week in 2 equal injections).

Adult patients with renal insufficiency who have not yet been dialyzed: Treatment takes place in two phases:

Corrective phase:

The starting dose is 50 IU / kg 3 times a week intravenously followed, if necessary, by an increase in the dose of 25 IU / kg (3 times per week) until the desired end is achieved (by level of at least 4 weeks).

Maintenance phase:

The dosage is adjusted to maintain hemoglobin at the desired level: Hb between 10 and 12 g / dl (6.2-7.5 mmol / l). The maintenance dose is between 17 and 33 IU / kg 3 times a week intravenously.

The maximum dosage should not exceed 200 IU / kg 3 times a week.

Treatment of anemia induced by chemotherapy:

Epoetin alfa should be administered subcutaneously to patients with anemia (hemoglobin ≤ 10 g / dl [6.2 mmol / l], for example). The symptoms and sequelae of anemia may vary according to age, gender and the overall impact of the disease; an assessment by the physician of the state of health and the clinical course of each patient is necessary.

Due to intra-patient variability, it may occasionally occur that hemoglobin levels above or below the desired level are observed. This variability in hemoglobin levels should be managed by adjusting the dose to maintain a target range of 10 g / dl (6.2 mmol / l) to 12 g / dl (7.5 mmol / l). Any hemoglobin level permanently greater than 12 g / dl (7.5 mmol / l) should be avoided; recommendations for action in the event of hemoglobin levels greater than 12 g / dl (7.5 mmol / l) are described below.

Patients should be closely monitored to ensure that the lowest possible dose of epoetin alfa is used and that the symptoms of anemia can be adequately controlled.

Epoetin alfa should be given for another month after the end of chemotherapy.

The initial dose is 150 IU / kg subcutaneously 3 times a week. Alternatively, epoetin alfa should be administered subcutaneously at the initial dose of 450 IU / kg once a week.

- If the hemoglobin has increased by at least 1 g / dl (> 0.62 mmol / l) or if the reticulocytes have increased by at least 40 000 cells / μl compared to the initial values, after 4 weeks of treatment the dose should be maintained at 150 IU / kg 3 times weekly or 450 IU / kg once a week.

- If the increase in hemoglobin is less than 1 g / dl (<0.62 mmol / l) and the reticulocytes have increased by less than 40 000 cells / μl from baseline, the dose should be increased to 300 IU / kg 3 times a week. If after 4 additional weeks of treatment at 300 IU / kg 3 times weekly, hemoglobin increased by at least 1 g / dl (≥0.62 mmol / l) or if reticulocytes increased by at least 40 000 cells / μl, the dose of 300 IU / kg 3 times a week should be maintained. However, if hemoglobin increased by <1 g / dl (<0.62 mmol / l) and reticulocytes increased by less than 40, 000 cells / μl from baseline, the response to treatment with epoetin alfa is unlikely and treatment should be discontinued.

Dosage adjustment to maintain the hemoglobin level between 10 g / dl and 12 g / dl (6.2-7.5 mmol / l): If the hemoglobin level increases by more than 2 g / dl (1.25 mmol / l) per month or if the hemoglobin level exceeds 12 g / dl (7.5 mmol / l), the dose should be reduced by approximately 25-50%. If the hemoglobin level exceeds 13 g / dl (8.1 mmol / l), treatment should be discontinued until the level falls below 12 g / dl (7.5 mmol / l). treatment with epoetin alfa may be reinstituted at a 25% lower dose.

Autologous transfusion programmed in adult patients undergoing surgery:

Binocrit should be administered intravenously.

At the time of blood donation, Binocrit must be administered once the donation procedure is complete.

Patients who are mildly anemic (33-39% hematocrit) requiring a prior blood sample of ≥ 4 units should be treated with Binocrit 600 IU / kg body weight twice weekly for 3 weeks prior to surgery.

All patients receiving Binocrit should receive adequate iron supplementation (eg, 200 mg oral elemental iron daily) for the duration of treatment. Administration of iron supplementation should be initiated as soon as possible, and even weeks before initiating autologous blood collection, in order to achieve high levels of iron stores prior to initiation of Binocrit therapy.

Treatment of adult patients to benefit from orthopedic surgery

scheduled major:

The subcutaneous route must be used.

The recommended dose is 600 IU / kg epoetin alfa, once a week for the 3 weeks prior to surgery (days D-21, D-14 and D-7), and the day of the procedure (D-Day). In cases where the time to surgery has to be reduced for medical reasons to less than 3 weeks, epoetin alfa must be administered daily at a dose of 300 IU / kg

10 consecutive days before the intervention, as well as the day of the intervention and during the 4 days following the intervention. During the preoperative haematological assessment, if the hemoglobin level reaches 15 g / dl (9.38 mmol / l) or more, epoetin alfa administration should be discontinued and the subsequent initial doses should not be administered.

It should be ensured that patients do not have iron deficiency at the start of treatment.

All patients treated with epoetin alfa should receive adequate iron supplementation (eg 200 mg / day oral Fe 2+ ) for the duration of epoetin alfa therapy. If possible, iron supplementation will be started before treatment with epoetin alfa to provide adequate iron stores.

Administration mode

Binocrit is a sterile product, but without preservatives, intended strictly for a single use. Administer the required quantity. This medication should not be given as an intravenous infusion or mixed with other medications.

1. Intravenous injection : in at least 1 to 5 minutes, depending on the total dose. In hemodialysis patients, a bolus injection may be performed during the dialysis session at the appropriate venous injection site of the dialysis line. Another possibility is to perform the injection following dialysis in the fistula needle tubing, followed by an injection of 10 ml of isotonic saline to rinse the tubing and ensure the passage correct product in the circulation.

A slower injection is preferable in patients who respond to treatment with flu-like symptoms.

2. Subcutaneous injection : A maximum volume of 1 ml per injection site should not be exceeded in a general way. In case of larger volume, use several injection sites. Injections are done at the level of the thighs or the anterior abdominal wall.

Against indications

- Hypersensitivity to the active substance or to any of the excipients.

- Patients who have developed PRCA following treatment with erythropoietin should not be treated with Binocrit or any other erythropoietin (see Warnings and Precautions for Use, "Pure Red Cell Aplasia").

- Uncontrolled hypertension.

- Patients who, for whatever reason, can not receive appropriate antithrombotic prophylaxis.

The use of epoetin alfa in the indication "increase autologous blood donation" is contraindicated

- in patients who have had a myocardial infarction or stroke during the month preceding the treatment, - or in case of unstable angina

- or in the event of increased risk of deep vein thrombosis, for example in the case of a history of venous thromboembolism.

If patients are scheduled for major scheduled orthopedic surgery and do not participate in a delayed autologous collection program, the use of epoetin alfa is contraindicated in patients with severe coronary artery disease, carotid artery disease, peripheral arteries, or cerebral, including in patients with a recent history of myocardial infarction or stroke.

Binocrit side effects

Overview

In cancer patients and patients with chronic renal failure, the most common adverse reaction during treatment with epoetin alfa is a dose-related increase in blood pressure or a worsening of existing hypertension. Blood pressure should be monitored, especially at the beginning of treatment (see Warnings and Precautions ). Other common adverse reactions observed in clinical trials of epoetin alfa were deep vein thrombosis, pulmonary embolism, seizures, diarrhea, nausea, headache, flu-like symptoms, pyrexia, rash and vomiting. Flu-like symptoms, including headache, arthralgia, myalgia and pyrexia, may occur especially at the start of treatment. The frequency of reactions may vary depending on the indication (see table below).

Serious adverse drug reactions include venous and arterial thromboses and emboli (in some cases fatal), such as deep vein thrombosis, pulmonary embolism, arterial thrombosis (including myocardial infarction and myocardial ischemia), retinal thromboses and thromboses of the shunt (including related to dialysis equipment). In addition, strokes (including cerebral infarction and cerebral hemorrhage) and transient ischemic attacks have been reported in clinical trials of epoetin alfa.

Cases of aneurysms have been reported.

Hypersensitivity reactions, including cases of rash, urticaria, anaphylactic reactions and angioedema, have been reported.

Hypertensive seizures accompanied by encephalopathies and seizures, requiring immediate medical attention and intensive care, also occurred during treatment with epoetin alfa in patients whose blood pressure was previously normal or low. Headaches of violent migraine type and sudden onset may be the alarm signal and should be the subject of special attention.

Very rare cases of erythroblastopenia with antibodies have been reported (<1 / 10, 000 cases per patient-year) after several months or years of treatment with epoetin alfa (see Warnings and Precautions ).

The overall safety profile of epoetin alfa was evaluated in 142 subjects with chronic renal failure and in 765 cancer patients who participated in double-blind, placebo-controlled clinical trials for product authorization. Adverse drug reactions reported in ≥ 0.2% of subjects in these epoetin alfa trials, as well as in additional clinical trials and pharmacovigilance trials, are listed below by organ system class and by frequency.

Frequencies are defined as follows: very common (≥1 / 10); frequent (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10 000, <1/1000); very rare (<1 / 10, 000); indeterminate frequency (can not be estimated based on available data).

Within each frequency group, adverse effects should be presented in order of decreasing severity.

Class of organ system

Frequency

Adverse reaction

Blood and lymphatic system disorders

Rare

Thrombocythemia (cancer patients)

Not known frequency

Erythroblastopenia with anti-erythropoietin antibodies 1

Thrombocythaemia (patients with chronic renal failure)

Immune system disorders

Not known frequency

Anaphylactic reaction

hypersensitivity

Nervous system disorders

Very common

Headache (cancer patients)

Frequent

Seizures (patients with chronic renal failure)

Headache (patients with chronic renal failure)

Rare

Cerebral haemorrhage 2

Seizures (cancer patients)

Not known frequency

Stroke 2

Hypertensive encephalopathy

Transient ischemic attack

Eye disorders

Not known frequency

Retinal thrombosis

Vascular disorders

Frequent

Deep vein thrombosis 2 (cancer patients)

Hypertension

Not known frequency

Deep vein thrombosis 2 (patients with chronic renal failure)

Arterial thrombosis

Hypertensive crisis

Respiratory, thoracic and mediastinal disorders

Frequent

Pulmonary embolism 2 (cancer patients)

Not known frequency

Pulmonary embolism 2 (patients with chronic renal failure)

Gastrointestinal disorders

Very common

nausea

Frequent

Diarrhea (cancer patients)

vomiting

Rare

Diarrhea (patients with chronic renal failure)

Skin and subcutaneous tissue disorders

Frequent

Skin rash

Not known frequency

Urticaria Quincke's Edema

Musculoskeletal and systemic disorders

Very common

Arthralgia (patients with chronic renal failure)

Frequent

Arthralgia (cancer patients)

Rare

Myalgia (cancer patients)

Not known frequency

Myalgia (patients with chronic renal failure)

Congenital, familial and genetic disorders

Not known frequency

porphyria

General disorders and administration site conditions

Very common

Pyrexia (cancer patients)

Flu-like symptoms (patients with chronic renal failure)

Frequent

Flu-like symptoms (cancer patients)

Not known frequency

Inefficient drug

Peripheral edema

Pyrexia (patients with chronic renal failure)

Reaction at the injection site

investigations

Not known frequency

Patient positive for anti-erythropoietin antibodies 1

Injury, poisoning and procedural complications

Frequent

Thrombosis of the shunt including dialysis equipment (patients with chronic renal failure)

1 Reactions whose frequency could not be estimated from clinical trials
2 Including cases whose outcome was fatal

Chronic renal failure patients

In patients with chronic renal failure, hemoglobin levels greater than 12 g / dl (7.5 mmol / l) may be associated with an increased risk of cardiovascular events, including death (see section 4.4). precautions for use ).

Shunt thrombosis has occurred in hemodialysis patients, particularly in patients who have a tendency to hypotension or who have complications with their arteriovenous fistula (eg, stenosis, aneurysms, etc.) (see section 5.2). caution and precautions for use ).

Cancer patients

An increased incidence of thromboembolic events has been reported in cancer patients receiving erythropoietin stimulating agents (ESA), including epoetin alfa (see Warnings and Precautions section ).

Patients to benefit from surgery

In patients scheduled for major scheduled orthopedic surgery with an initial hemoglobin level of 10 to 13 g / dl (6.2-8.1 mmol / l), the incidence of thromboembolic events (including most were deep vein thromboses), across all clinical trials, was found to be similar in the different groups treated with epoetin alfa and in the placebo group. Nevertheless, clinical experience is limited.

In patients with an initial hemoglobin level> 13 g / dl (8.1 mmol / l), the possibility that epoetin alfa treatment may be associated with an increased risk of post thromboembolic events -operative can not be excluded.

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