| Primary information |
|---|
| ID | 1635 |
| ThPP ID | Th1141 |
| Therapeutic Peptide/Protein Name | Epoetin zeta |
| Sequence | APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYA view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 18200 (unglycosylated), 30600 (glycosylated) |
| Chemical Formula | C809H1301N229O240S5 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | For subcutaneous dose: 7.37 hours |
| Description | Recombinant (CHO cell derived) erythropoietin with a sequence identicle to the Epoietin alfa. The molecular weight of the glycosylated protein is 30.6 kDa, of which nearly 40% is contributed by carbohydrates. The oligosaccharide chains are subject to posttranslational modifications and display heterogeneity. |
| Indication/Disease | For use in the treatment of symptomatic anaemia associated with chronic renal failure (CRF) in adult and paediatric patients. Also for use in the 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). Also for used to increase the yield of autologous blood from patients in a predonation program. When administered subcutaneously, Epoetin Zeta is equivalent to Epoetin Alfa in terms of clinical effectiveness. |
| Pharmacodynamics | Used in the treatment of anemia. Involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. |
| Mechanism of Action | Binding of erythropoietin to the erythropoietin receptor leads to receptor dimerization, which facilitates activation of JAK-STAT signaling pathways within the cytosol. Activated STAT (signal transducers and activators of transcription) proteins are then translocated to the nucleus where they serve as transcription factors which regulate the activation of specific genes involved in cell division or differentiation. |
| Toxicity | N.A. |
| Metabolism | N.A. |
| Absorption | N.A. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | N.A. |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | Erythropoietin receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Retacrit |
| Company | Norbitec |
| Brand Discription | Human erythropoietin is a single chain, monomeric, glycosylated polypeptide of 165 amino acids. Erythropoietin for clinical use is produced by recombinant DNA technology using mammalian cells as expression system. All epoetins in clinical use have an amino acid sequence similar to endogenous erythropoietin but differ in the glycosylation pattern. Glycosylation influences pharmacokinetics and may affect efficacy and safety, particularly immunogenicity. The active substance in SB309 (Epoetin zeta) is a recombinant human erythropoietin (rhEPO) of identical primary structure produced in Chinese Hamster Ovary (CHO) cells. The molecular weight of the glycosylated protein is 30.6 kDa. The oligosaccharide chains are subject to posttranslational modifications and display heterogeneity to a certain extent. To support the claim that Retacrit is biosimilar to the reference medicinal product Erypo with regard to quality, safety and efficacy, the applicant has submitted a comparability exercise for a similar biological medicinal product versus the reference medicinal product. The main clinical data for the application submitted by the applicant consists of two pharmacokinetic (PK) trials comparing the PK profiles of SB309 and Erypo after single dose administration, and two phase III trials (one correction phase study and one maintenance phase study) comparing efficacy and safety of intravenously (IV) administered SB309 and Erypo in patients with renal anaemia. |
| Prescribed for | Treatment of anaemia associated with chronic renal failure in adult and paediatric patients on haemodialysis and adult patients on peritoneal dialysis. Treatment of severe anaemia 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). Retacrit 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 (haemoglobin (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). |
| Chemical Name | N.A. |
| Formulation | The drug product is presented as a solution for injection in pre-filled syringes in the following strengths: 3,333 IU/ml (presentation of 0.3, 0.6 and 0.9 ml), 10,000 IU/ml (presentations of 0.4, 0.5, 0.6, 0.8 and 1 ml) and 40,000 IU/ml (presentations of 0.5, 0.75 and 1 ml), with all strengths exhibiting the same qualitative composition. |
| Physcial Appearance | Retacrit [epoetin zeta (INN)] solution for injection in pre-filled syringes contains recombinant human erythropoietin (rhu-EPO, epoetin) as drug substance and water for injection, sodium monohydrogen phosphate, sodium dihydrogen phosphate, sodium chloride, calcium chloride, polysorbate 20, glycine, |
| Route of Administration | N.A. |
| Recommended Dosage | 50 IU/kg (International Units per kilogram), 3 times a week. If the solution is given into a vein, it should be injected over 1-5 minutes. |
| Contraindication | Hypersensitivity to the active substance or to any of the excipients. Patients who develop Pure Red Cell Aplasia (PRCA) following treatment with any erythropoietin must not receive Retacrit or any other erythropoietin, Uncontrolled hypertension, In the indication increasing the yield of autologous blood: myocardial infarction or stroke in the month preceding treatment, unstable angina pectoris, increased risk of deep venous thrombosis such as history of venous thromboembolic disease. Patients who for any reason cannot receive adequate antithrombotic prophylaxis. |
| Side Effects | Flu-like symptoms, headache, joint pain, feeling of weakness, tiredness and dizziness. Respiratory tract congestion, such as stuffy nose and sore throat, has been reported in patients with kidney disease not yet on dialysis. Increased blood pressure. Chest pain, breathlessness, painful swelling in the leg which may be symptoms of blood clots (pulmonary embolism, deep vein thrombosis). Stroke (insufficient blood supply to the brain, which may lead to inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or an inability to see one side of the visual field). Skin rash and swelling around the eyes (oedema), which may result from an allergic reaction. Blood clot in an artificial kidney. |
| Useful Link | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000872/WC500054374.pdf http://www.drugs.com/international/epoetin-zeta.html https://www.medicines.org.uk/emc/PIL.21691.latest.pdf https://www.medicines.org.uk/emc/medicine/21313 http://ec.europa.eu/health/documents/community-register/2007/2007121835169/anx_35169_en.pdf |
| PubMed ID | 20369312, 18208642 |
| 3-D Structure | Th1141 (View) or (Download) |