Approval date: April 10, 2007
Revise date: Sept.29, 2019
Leaflet of Recombinant Human Erythropoietin Injection (CHO cell)
Please read the instructions carefully and use the drug under the guidance of doctors. Athletes should use it with caution
This product may lead to increased mortality and risks of patients to experience severe cardiovascular events, thrombotic events and apoplexy and can stimulate tumor growth of patients. (For details, see Precautions)
Generic name: Recombinant Human Erythropoietin Injection (CHO cell)
Trade name: EPOSINO
English name: Recombinant Human Erythropoietin Injection (CHO cell)
Chinese Pinyin: Chongzu Ren Cuhongsu Zhusheye (CHO cell)
This product is colorless and transparent liquid with pH6.9±0.5.
[Dosage and Administration]
This product should be administered through subcutaneous and intravenous way 2-3 times per week under physicians’ direction. Dosage can be changed according to anemia status, age, and other related factors of patients.
If the hematocrit has reached 30-33vol/% and/or the hemoglobin has reached 100-110g/l, the maintenance treatment period starts. The dosage should be 2/3 of the initial dosage on this stage. The hematocrit should be monitored once every 2-4 weeks so as to adjust the dosage to maintain hematocrit and hemoglobin at the proper level as well as to avoid erythropoesis to be formed too quickly.
2. Red blood cell mobilization during surgical perioperative period.
Suitable for use by elective surgical patients with preoperative hemoglobin value in the 100-130 g / L of (except for cardiovascular surgery patients), using a dose 150IU/ kg of body weight subcutaneously, three times a week, from 10 days prior to surgery patients to 4 days after application. It can relieve anemia during and after surgery and reduce the demand for allogeneic blood transfusion, speed up the recovery of postoperative anemia tend. In order to prevent iron deficiency during the drug use period, iron should be supplemented at the same time.
1．Common reactions: A few may have headache, low fever and fatigue and only few may have muscle pain and arthralgia at the initial stage of drug administration. But most of the side reactions may be relieved through the treatment and no need to discontinue the use of the drug. If the above –mentioned symptoms still exist, stopping using the drug may be considered.
3. Cardiovascular System: Hypertension or other symptoms caused by the exacerbation of existing hypertension and hypertensive encephalopathy may occur such as headache, disturbance of consciousness, convulsion and sometimes even encephalorrhagia. Therefore, blood pressure should be monitored periodically, the drug dosage may be decreased or stopped, and the depressor drug may also be adjusted.
5. Liver: Hepatic function impairment may occur, GOP and GPT sometimes may rise up.
2. Those allergic to this product or to other erythropoietin agents, those allergic to human serum albumin.
2. During the treatment with “EPOSINO”, the hematocrit should be checked regularly (once a week at the early stage and once every two weeks in the maintenance period). The hematocrit should be maintained under 36vol/% to avoid the formation of extraordinary erythropoiesis.If excessive red blood cell growth is found, suitable treatment shall be taken such as stopping the use of EPOSINO temporarily. When using 36000IU /syringe, check the hemoglobin regularly (once every one to two weeks). When the hemoglobin is higher than 120g/L, the administration is not recommended to continue. In case of excessive red blood cell growth, take appropriate measures.
3. In CRF patients receiving treatment, it’s rarely seen to have worse hemoporphyrin. Hematoporphyrin patients should use recombinant human erythropoietin with caution. During treatment, absolute or functional iron deficiency may occur. In functional iron deficiency, the ferritin levels is normal, but transferrin saturation can decrease, the reason may be that stored iron in the body cannot be quickly mobilized and released to meet the increased demand for iron under the effect of erythropoietin to stimulate the bone marrow hemopoiesis. Transferrin saturation should be ≥ 20%, ferritin should be ≥ l00ng/ml. Before and during treatment with the drug, patients should receive iron status assessment, indicators include: transferrin saturation (mean ratio of serum iron and transferrin bondability) and serum ferritin. In fact, all patients eventually need to supplement iron to increase or maintain transferrin saturation to meet the need of erythropoiesis promoted by the product. Surgery patients using this product should be supplemented with iron throughout the course of treatment to support erythropoiesis and avoid depletion of iron stores.
4. This product can cause increased blood pressure during treatment, so the blood pressure should be adequately controlled before treatment. In early treatment, when the hematocrit increases, about 25% of dialysis patients need to start or strengthen anti-hypertensive treatment. During treatment with the drug, blood pressure of patients should be strictly monitored and controlled. Patients should be informed of antihypertensive treatment and the importance of dietary restrictions. If blood pressure is difficult to control, reducing or stop using this product can reduce the hemoglobin.
If at any time within two weeks, hemoglobin increases by more than lg/dL, it’s recommended to reduce the product's dose, because aggravation of high blood pressure may be related to the rapid growth of hemoglobin.。For patients with CRF receiving hemodialysis treatment have clinically significant ischemic heart disease or congestive heart failure, the dosage of the product should be carefully adjusted to achieve and maintain hemoglobin levels between the 10-12g/dL.
5. For patients with a history of seizures or blood disease (such as sickle-cell anemia disease, myelodysplastic syndrome or high-blood clotting disorder) , the drug safety and effectiveness remain unclear.
In view of the increased risk of epilepsy during first 90 days of treatment, blood pressure and neurological aura symptoms should be closely monitored. In the meantime, patients should avoid engaging in potentially hazardous activities such as driving or operating heavy machinery.
6. During hemodialysis, the patients taking the drug needs to be strengthened with heparin anticoagulation treatment to prevent artificial thrombus coagulation of kidney. In treatment of adult patients with CRF associated with ischemic heart disease or of congestive heart failure, compared with standard hematocrit of 30%, patients with standard hematocrit of 42% (normal hematocrit) have higher risks of thrombus events ( including vascular access thrombosis). Patients previously with cardiovascular disease should be closely monitored.
8. Folic and VitaminB12 insufficiency and ultra-high aluminum may reduce efficacy of EPOSINO.
[Drug administration by pregnant women or in lactation]
[Drug administration by children]
[Drug administration by aged patients]
[Pharmacology and Toxicology]
2.2 Subacute toxicity and chronic toxicity
2.2.2 Dog: Subacute toxicity and chronic toxicity test on female and male dog receiving intravenous or intraperitoneal injection in the 4th week, 13th week and 52nd week shows that plethora is caused due to excessive pharmacological action after administration of the drug in the 4th week, 13th week and 52nd week at the dosage of 200IU/kg/day, 100IU/kg/day and 20IU/kg/day respectively, and long-term administration of the drug can result in fibrosis of marrow and change of kidney structure.
Drug injected subcutaneously is absorbed slowly, concentration of erythropoietin in serum rises 2 hours later, it takes 18 hours for the drug concentration in blood to reach the peak value, bone marrow is special takein organ, the drug is mainly taken by liver and kidney, the drug is mostly metabolized in the body after administration, animal (rat) test shows that a small amount of EPO was also degraded in kidney, bone marrow and spleen, in addition to liver, Kidney was not the main organ for eliminating EPO, anemia patients using EPO excrete less than 10% of the drug in original form through the kidney.
Store and transport at 2-8℃, protect from light
Pre-filled syringe, 1 syringe/small carton, 6 syringes/ medium carton
“Chinese Pharmacopoeia” Version 2015, Volume 3
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