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For Adults and Pediatric patients: For S.C. & IV use only. The treatment and dosage has to be initiated and adjusted individually for each patient, under the supervision of physicians experienced in the management of patients with the above indications.
Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patients: In patients with chronic renal failure the medicinal product has to be administered intravenously. Anaemia symptoms and sequelae may vary with age, gender, and co-morbid medical conditions; a physician´s evaluation of the individual patient´s clinical course and condition is necessary. This drug should be administered in order to increase haemoglobin to not greater than 12 g/dl (7.5 mmol/l). A rise in haemoglobin greater than 2 g/dl (1.25 mmol/l) over a four week period should be avoided. If it occurs, appropriate dose adjustments should be made as provided. Due to intra‑patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dl (6.2 mmol/l) to 12 g/dl (7.5 mmol/l). In paediatric patients the recommended target haemoglobin range is between 9.5 and 11 g/dl (5.9‑6.8 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.5 mmol/l) should be avoided. If the haemoglobin is rising by more than 2 g/dl (1.25 mmol/l) per month, or if the sustained haemoglobin exceeds 12 g/dl (7.5 mmol/l) reduce the epoetin alfa dose by 25%. If the haemoglobin exceeds 13 g/dl (8.1 mmol/l), discontinue therapy until it falls below 12 g/dl (7.5 mmol/l) and then reinstitute epoetin alfa therapy at a dose 25% below the previous level. Patients should be monitored closely to ensure that the lowest approved dose of epoetin alfa is used to provide adequate control of anaemia and of the symptoms of anaemia. Iron status should be evaluated prior to and during treatment and iron supplementation administered if necessary. In addition, other causes of anaemia, such as vitamin B12 or folate deficiency, should be excluded before instituting therapy with epoetin alfa. Non response to epoetin alfa therapy may have the following causes: iron, folate, or vitamin B12 deficiency; aluminium intoxication; intercurrent infections; inflammatory or traumatic episodes; occult blood loss; haemolysis, and bone marrow fibrosis of any origin.
Adult haemodialysis patients: The treatment is divided into two stages:
Correction phase: 50 IU/kg 3 times per week by the intravenous route. When a dose adjustment is necessary, this should be done in steps of at least four weeks. At each step, the increase or reduction in dose should be of 25 IU/kg 3 times per week.
Maintenance phase: Dosage adjustment in order to maintain haemoglobin values at the desired level: Hb between 10 and 12 g/dl (6.2‑7.5 mmol/l). The recommended total weekly dose is between 75 and 300 IU/kg by the intravenous route. The clinical data available suggest that those patients whose initial haemoglobin is very low (< 6 g/dl or < 3.75 mmol/l) may require higher maintenance doses than those whose initial anaemia is less severe (Hb > 8 g/dl or > 5 mmol/l).
Paediatric haemodialysis patients: The treatment is divided into two stages:
Correction phase: 50 IU/kg 3 times per week by the intravenous route. When a dose adjustment is necessary, this should be done in steps of 25 IU/kg 3 times per week at intervals of at least 4 weeks until the desired goal is achieved.
Maintenance phase: Dosage adjustment in order to maintain haemoglobin values 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. The clinical data available suggest that those paediatric patients whose initial haemoglobin is very low (< 6.8 g/dl or < 4.25 mmol/l) may require higher maintenance doses than those whose initial haemoglobin is higher ( > 6.8 g/dl or > 4.25 mmol/l).
Adult peritoneal dialysis patients: The treatment is divided into two stages: Correction phase: Starting dose of 50 IU/kg 2 times a week by the intravenous route.
Maintenance phase: Dosage adjustment in order to maintain haemoglobin values at the desired level: Hb between 10 and 12 g/dl (6.2‑7.5 mmol/l). Maintenance dose between 25 and 50 IU/kg 2 times per week into 2 equal injections.
Adult patients with renal insufficiency not yet undergoing dialysis: The treatment is divided into two stages:
Correction phase: Starting dose of 50 IU/kg 3 times per week by the intravenous route, followed if necessary by a dosage increase with 25 IU/kg increments (3 times per week) until the desired goal is achieved (this should be done in steps of at least four weeks).
Maintenance phase: Appropriate adjustment of dose should be made in order to maintain haemoglobin values at the desired level: Hb between 10 and 12 g/dl (6.2‑7.5 mmol/l). Extending dose intervals may require an increase in dose. The maximum dosage should not exceed 150 IU/kg 3 times per week.
Patients with chemotherapy induced anaemia: Epoetin alfa should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin concentration ≤ 10 g/dl (6.2 mmol/l)). Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary. Due to intra‑patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management with consideration for the haemoglobin target range of 10 g/dl (6.2 mmol/l) to 12 g/dl (7.5 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.5 mmol/l) should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceed 12 g/dl (7.5 mmol/l) are described below. Epoetin alfa therapy should be continued until one month after the end of chemotherapy. The initial dose is 150 IU/kg given subcutaneously 3 times per week. Alternatively, epoetin alfa can be administered at an initial dose of 450 IU/kg subcutaneously once weekly. – If haemoglobin has increased by at least 1 g/dl (> 0.62 mmol/l) or the reticulocyte count has increased ³ 40,000 cells/μl above baseline after 4 weeks of treatment, the dose should remain at 150 IU/kg 3 times a week or 450 IU/kg once weekly. – If the haemoglobin increase is < 1 g/dl (< 0.62 mmol/l) and the reticulocyte count has increased < 40,000 cells/μl above baseline, increase the dose to 300 IU/kg 3 times per week. If after an additional 4 weeks of therapy at 300 IU/kg 3 times per week, the haemoglobin has increased ³ 1 g/dl (³ 0.62 mmol/l) or the reticulocyte count has increased ³ 40,000 cells/μl the dose should remain at 300 IU/kg 3 times per week. However, if the haemoglobin has increased < 1 g/dl (< 0.62 mmol/l) and the reticulocyte count has increased < 40,000 cells/μl above baseline, response to epoetin alfa therapy is unlikely and treatment should be discontinued. Patients should be monitored closely to ensure that the lowest approved dose of epoetin alfa is used to provide adequate control of the symptoms of anaemia.
Dosage adjustment to maintain haemoglobin concentration between 10 g/dl‑12 g/dl (6.2‑7.5 mmol/l): -If the haemoglobin is rising by more than 2 g/dl (1.25 mmol/l) per month, or if the haemoglobin exceeds 12 g/dl (7.5 mmol/l), reduce the epoetin alfa dose by about 25 to 50%. If the haemoglobin exceeds 13 g/dl (8.1 mmol/l), discontinue therapy until it falls below 12 g/dl (7.5 mmol/l) and then reinstitute epoetin alfa therapy at a dose 25% below the previous dose.
Adult surgery patients in an autologous predonation programme: This product should be given by the intravenous route. At the time of donating blood, this product should be administered after the completion of the blood donation procedure. Mildly anaemic patients (haematocrit of 33‑39%) requiring predeposit of ³ 4 units of blood should be treated with this product at a dose of 600 IU/kg body weight 2 times weekly for 3 weeks prior to surgery. Using this regimen, it was possible to withdraw ≥ 4 units of blood from 81% of epoetin alfa‑treated patients compared to 37% of placebo-treated patients. Epoetin alfa therapy reduced the risk of exposure to homologous blood by 50% compared to patients not receiving epoetin alfa. All patients being treated with this product should receive adequate iron supplementation (e.g. 200 mg oral elemental iron daily) throughout the course of treatment. Iron supplementation should be started as soon as possible, even several weeks prior to initiating the autologous predeposit, in order to achieve high iron stores prior to starting therapy.
Adult patients scheduled for major elective orthopaedic surgery: The subcutaneous route of administration should be used. The recommended dose regimen is 600 IU/kg epoetin alfa, given weekly for three weeks (days 21, 14 and 7) prior to surgery and on the day of surgery (day 0). In cases where there is a medical need to shorten the lead time before surgery to less than three weeks, 300 IU/kg epoetin alfa should be given daily for 10 consecutive days prior to surgery, on the day of surgery and for four days immediately thereafter. When performing haematologic assessments during the preoperative period, if the haemoglobin level reaches 15 g/dl (9.38 mmol/l), or higher, administration of epoetin alfa should be stopped and further dosages should not be given. Care should be taken to ensure that at the outset of the treatment patients are not iron deficient. All patients being treated with epoetin alfa should receive adequate iron supplementation (e.g. oral iron substitution of 200 mg Fe2+ daily) throughout the course of epoetin alfa treatment. If possible, iron supplementation should be started prior to epoetin alfa therapy, to achieve adequate iron stores.
Method of administration: As with any other injectable product, check that there are no particles in the solution or change in colour. This is a sterile but unpreserved product and is for single use only. Administer the amount required. Do not administer by intravenous infusion or mixed with other medicinal products.
Intravenous injection: over at least one to five minutes, depending on the total dose. In haemodialysed patients, a bolus injection may be given during the dialysis session through a suitable venous port in the dialysis line. Alternatively, the injection can be given at the end of the dialysis session via the fistula needle tubing, followed by 10 ml of isotonic saline to rinse the tubing and ensure satisfactory injection of the product into the circulation. A slower injection is preferable in patients who react to the treatment with “flu‑like” symptoms.
Subcutaneous injection: a maximum volume of 1 ml at one injection site should generally not be exceeded. In case of larger volumes, more than one site should be chosen for the injection. The injections are given in the limbs or the anterior abdominal wall. In those situations in which the physician determines that a patient or caregiver can safely and effectively administer subcutaneously, instruction as to the proper dose and administration should be provided.
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Urinary Antispasmodic. Mirabegron 25 mg, 50 mg. PROLONG REL. TABS.: 30×25, 50 mg.
Adult. (include. elder. pts.) 50 mg once
daily with/without food.
Sympt. tmt. of urgency, incr. micturition
freq. and/or urgency incont. as may occur
in adult pts. with OAB syndr.
Creation date March 2020
Treatment of symptomatic anemia associated with chronic renal failure (CRF) in adult and pediatric patients:
– Treatment of anemia associated with chronic renal failure in pediatric and adult patients on haemodialysis and adult patients on peritoneal dialysis.
– Treatment of severe anemia of renal origin accompanied by clinical symptoms in adult patients with renal insufficiency not yet undergoing dialysis.
Treatment of anaemia and reduction of transfusion requirements in adult patients receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, and at risk of transfusion as assessed by the patient’s general status (e.g. cardiovascular status, pre-existing anaemia at the start of chemotherapy). The drug can be used to increase the yield of autologous blood from patients in a predonation programme. Its use in this indication must be balanced against the reported risk of thromboembolic events. Treatment should only be given to patients with moderate anaemia (hemoglobin (Hb) 10‑13 g/dl (6.2‑8.1 mmol/l), no iron deficiency), if blood saving procedures are not available or insufficient when the scheduled major elective surgery requires a large volume of blood (4 or more units of blood for females or 5 or more units for males). This product can be used to reduce exposure to allogeneic blood transfusions in adult non‑iron deficient patients prior to major elective orthopedic surgery, having a high perceived risk for transfusion complications. Use should be restricted to patients with moderate anaemia (e.g. Hb 10‑13 g/dl or 6.2 8.1 mmol/l) who do not have an autologous predonation programme available and with an expected moderate blood loss of 900 to 1800 ml. Good blood management practices should always be used in the perisurgical setting.
Hypersensitivity to the active substance or to any of the excipients.
Patients who develop Pure Red Cell Aplasia (PRCA) following treatment with any erythropoietin should not receive epoetin alfa or any other erythropoietin. Uncontrolled hypertension. All contraindications associated with autologous blood predonation programme should be respected in patients being supplemented with Binocrit. The use of Binocrit in patients scheduled for major elective orthopaedic surgery and not participating in an autologous blood predonation programme is contraindicated in patients with severe coronary, peripheral arterial, carotid or cerebral vascular disease, including patients with recent myocardial infarction or cerebral vascular accident. Surgery patients who for any reason cannot receive adequate antithrombotic prophylaxis.
In all patients receiving Binocrit, blood pressure should be closely monitored and controlled as necessary. Binocrit should be used with caution in the presence of untreated, inadequately treated or poorly controllable hypertension. It may be necessary to add or increase antihypertensive treatment. If blood pressure cannot be controlled, Binocrit treatment should be discontinued.
Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning signal.
Epoetin alfa should also be used with caution in patients with epilepsy, history of seizures, or medical condition associated with a predisposition to seizure activity such as CNS infections and brain metastases. Epoetin alfa should be used with caution in patients with chronic liver failure.
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatiening or fatal, have been reported in association with epoetin treatment. More severe cases have been observed with long-acting epoetins. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Binocrit should be withdrawn immediately and an alternative treatment considered.
If the patient has developed a severe cutaneous skin reaction such as SJS or TEN due to the use of Binocrit, treatment with Binocrit must not be restarted in this patient at any time.
In all patients, haemoglobin levels should be closely monitored due to a potential increased risk of thromboembolic events and fatal outcomes when patients are treated at haemoglobin levels above the concentration range for the indication of use.
There may be a moderate dose-dependent rise in the platelet count within the normal range during treatment with epoetin alfa. This regresses during the course of continued therapy. In addition, thrombocythaemia above the normal range has been reported. It is recommended that the platelet count is regularly monitored during the first 8 weeks of therapy.
All other causes of anaemia should be evaluated and treated prior to initiating therapy with epoetin alfa, and when deciding to increase the dose.
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Increase in blood pressure or aggravation of existing hypertension. Diarrhoea, nausea, vomiting, pyrexia and headache. Influenza-like illness may occur especially at the start of treatment. Respiratory tract congestion, which includes events of upper respiratory tract congestion, nasal congestion and nasopharyngitis. Increase in thrombotic vascular events (TVEs). Venous and arterial thromboses, Hypertension, Cough, Rash, Arthralgia, Bone pain, Myalgia, Pain in Extrimity, Chills, Injection site reaction, Oedema Peripheral. Hypersensitivity reactions, including cases of rash, urticaria, anaphylactic reaction, and angioneurotic edema have been reported. Hypertensive crisis with encephalopathy and seizures, requiring the immediate attention of a physician and intensive medical care, have occurred also during epoetin alfa treatment in patients with previously normal or low blood pressure. Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning signal.
Severe cutaneous adverse reactions (SCARS) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment
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No evidence that indicates that treatment with epoetin alfa alters the metabolism of other medicinal products. Medicinal products that decrease erythropoiesis may decrease the response to epoetin alfa. Since cyclosporin is bound by red blood cells there is potential for medicinal product interaction. If epoetin alfa is given concomitantly with cyclosporin, blood levels of cyclosporin should be monitored and the dose of cyclosporin adjusted as the haematocrit rises. No evidence exists that indicates an interaction between epoetin alfa and granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) with regard to haematological differentiation or proliferation of tumour biopsy specimens in vitro. In female adult patients with metastatic breast cancer, subcutaneous co-administration of 40,000 IU/ml epoetin alfa with trastuzumab 6 mg/kg had no effect on the pharmacokinetics of trastuzumab.
Pregnancy and Lactation
Pregnancy: There are no or limited amount of data from the use of epoetin alfa in pregnant women.
Breast-feeding: It is not known whether epoetin alfa is excreted in human milk. Epoetin alfa should be used with caution in nursing women.
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The therapeutic margin of epoetin alfa is very wide. Overdose of epoetin alfa may produce effects that are extensions of the pharmacological effects of the hormone. Phlebotomy may be performed if excessively high haemoglobin or haematocrit levels occur. Additional supportive care should be provided as necessary.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage: Store and transport refrigerated (2°C‑8°C). Do not freeze or shake. Store in the original package in order to protect from light. For the purpose of ambulatory use, the patient may remove this product from the refrigerator and store it not above 25°C for one single period of up to 3 days.