General: In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Recormon should be used with caution in the presence of refractory anemia with excess blasts in transformation, epilepsy, thrombocytosis and chronic liver failure. Folic acid and vitamin B12 deficiencies should be ruled out as they reduce the effectiveness of Recormon.
In order to ensure effective erythropoiesis, iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary and conducted in accordance with therapeutic guidelines.
Recormon contains phenylalanine as an excipient. Therefore this should be taken into consideration in patients affected with severe forms of phenylketonuria.
The indication for Recormon treatment of nephrosclerotic patients not yet undergoing dialysis should be defined individually as a possible acceleration of progression of renal failure cannot be ruled out with certainty.
Lack of effect: The most common reasons for incomplete response to ESAs are iron deficiency and chronic inflammation (e.g. due to uremia or advanced metastatic cancer). The following conditions may also compromise the effectiveness of ESAs therapy: chronic blood loss, bone marrow fibrosis, severe aluminium overload due to treatment of renal failure, folic acid or vitamin B12 deficiencies, and hemolysis. If all the conditions mentioned are excluded and the patient has a sudden drop of hemoglobin associated with reticulocytopenia and anti-erythropoietin antibodies, examination of the bone marrow for the diagnosis of Pure Red Cell Aplasia (PRCA) should be considered. If PRCA is diagnosed, therapy with epoetin beta must be discontinued and patients should not be switched to another ESA.
Pure red cell aplasia caused by neutralizing anti-erythropoietin antibodies has been reported in association with erythropoietin therapy, including Recormon. These antibodies have been shown to cross-react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to Recormon (see Adverse Reactions).
Effect on tumor growth: Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumor cells. As with all growth factors, there is a concern that epoetins could stimulate the growth of any type of malignancy.
A controlled clinical study in which epoetin beta was administered to patients with head and neck cancer, has shown a shorter locoregional progression free survival in patients receiving epoetin beta. Another clinical study in breast cancer designed to show a positive effect of epoetin beta on overall survival compared to untreated controls, showed no statistically significant effects in terms of overall survival or tumor progression. Furthermore, meta-analysis data from randomized, controlled clinical studies with epoetin beta in treatment of anemia in cancer patients (12 studies, 2301 patients; including the two studies mentioned previously) did not show any statistically significant negative effects on survival or tumor progression (see Pharmacology: Pharmacodynamics: Clinical / Efficacy Studies under Actions).
In CKD patients and patients with cancer receiving chemotherapy an increase in blood pressure (hypertensive episodes) or aggravation of existing hypertension, especially in cases of rapid Hb increase can occur. Increases in blood pressure can be treated with antihypertensive drugs. If blood pressure rises cannot be controlled by drug therapy, a transient interruption of Recormon therapy is recommended. Particularly at the beginning of therapy, regular monitoring of the blood pressure is recommended, including between dialyses in patients with renal anemia. In patients with CKD, hypertensive crisis with encephalopathy-like symptoms may also occur in individual patients with otherwise normal or low blood pressure. This requires the immediate attention of a physician and intensive medical care. Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning sign.
Severe aluminium overload due to treatment of renal failure may compromise the effectiveness of Recormon.
In CKD patients an increase in heparin dose during hemodialysis is frequently required during the course of therapy with Recormon as a result of the increased Hb. Occlusion of the dialysis system is possible if heparinization is not optimal. Early shunt revision and thrombosis prophylaxis by administration of acetylsalicylic acid, for example, should be considered in CKD patients at risk of shunt thrombosis.
In CKD patients there may be a moderate dose-dependent rise in the platelet count within the normal range during treatment with Recormon, especially after intravenous administration. This regresses during the course of continued therapy. It is recommended that the platelet count be monitored regularly during the first 8 weeks of therapy.
In patients in an autologous blood pre-donation programme there may be an increase in platelet count, mostly within the normal range. Therefore, it is recommended that the platelet count be determined at least once a week in these patients. If there is an increase in platelets of more than 150 x 109/l or if platelets rise above the normal range, treatment with Recormon should be discontinued.
For use of Recormon in an autologous pre-donation program, the official guidelines on principles of blood donation must be considered, in particular: only patients with a PCV ≥ 33 % (hemoglobin ≥ 11 g/dl [6.83 mmol/l]) should donate; special care should be taken with patients below 50 kg weight; the single volume drawn should not exceed approx. 12 % of the patient's estimated blood volume.
Treatment should be reserved for patients in whom it is considered of particular importance to avoid homologous blood transfusion taking into consideration the risk/benefit assessment for homologous transfusions.
In patients treated for anemia of prematurity, there may be a slight rise in platelet counts, particularly up to day 12 - 14 of life, therefore platelets should be monitored regularly.
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. 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, Recormon 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 Recormon, treatment with Recormon must not be restarted in this patient at any time.
Laboratory tests: Platelet counts and haematocrit/haemoglobin levels should be monitored at regular intervals in all patients.
In patients with chronic kidney disease, serum potassium elevation has been reported in patients receiving Recormon, though causality has not been established. If an elevated or rising potassium level is observed then consideration should be given to interrupt Recormon administration until the level has been corrected.
Drug Abuse and Dependence: Misuse by non-anemic persons may lead to an excessive increase in Hb. This may be associated with life-threatening complications of the cardiovascular system.
There are no reports on dependence when using epoetin beta.
Ability to Drive and Use Machines: Recormon has no or negligible influence on the ability to drive and use machines.
Renal Impairment: (see General as previously mentioned).
Hepatic Impairment: (see Special Dosage Instructions under Dosage & Administration).
Use in Children: Clinical registration trials have been performed in children and adolescents with anemia due to chronic kidney disease and in neonates for prevention of anaemia due to prematurity.
In the indication anemia due to chronic kidney disease, Recormon should not be used in infants (i.e. below 2 years of age) (see Special Dosage Instructions under Dosage & Administration, General as previously mentioned).
In the indications anaemia in cancer patients receiving chemotherapy and treatment for increasing the amount of autologous blood, Recormon is not indicated in the pediatric population.
Use in Elderly: (see Special Dosage Instructions under Dosage & Administration).