Recombinant Human Erythropoietin Injection (CHO cell)

[Product Name]

Recombinant Human Erythropoietin Injection (CHO cell)

[Character]

This product is colorless and transparent liquid with pH6.9±0.5.

[Composition]

Recombinant Human Erythropoietin

[Pharmacology and Toxicology]

1. Pharmacology: erythropoietin is a kind of active glycoprotein excreted by kidney. It acts on hematopoietic BFU-E in bone marrow and promotes its proliferation and differentiation. It can lead to obvious formation of stimulating colony through CFU-E. At high concentration, it can stimulate BFU-E and lead to the formation of colony.

2. Toxicology:

Acute toxicity: LD50 of injection in intravenous injection into mouse, rat, dog and 4 –day old immature rat is more than 2,000IU/kg.

Subacute toxicity and chronic toxicity

Rat: Subacute toxicity and chronic toxicity test on female and male rat 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 80IU/kg/day, 20IU/kg/day and 10IU/kg/day respectively, and long-term administration of the drug can result in fibrosis of marrow.

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 80IU/kg/day, 20IU/kg/day and 10IU/kg/day respectively, and long-term administration of the drug can result in fibrosis of marrow and change of kidney structure.

[Pharmacokinetics]

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 is not the main organ for eliminating EPO, anemia patients using EPO excrete less than 10% of the drug in original form through the kidney.

[Indications]

Anemia resulted from renal function insufficiency, including hemodialysis and non-hemodialysis

[Dosage and Administration]

This product shall be administered through subcutaneous and intravenous way 2-3 times per week under physicians’ instruction. Dosage can be changed according to anemia status, age, and other related factors of patients.

Treatment period: The initial dosage for the patients receiving hemodialysis is 100-150 IU/kg, and for those not on hemodialysis is 75-100 IU/kg per week. If hematocrit increase is not as expected (<0.5vol/week), the dosage can be changed after 4 weeks of initial treatment to increase the dose at15-30 IU/kg per week, but no more than 30 IU/kg per week. The expected rise of hematocrit shall be in the range of 30-33vol%, not higher than 34vol%.

Maintenance period: If the hematocrit has reached 30-33vol/% and or the hemoglobin has reached 100-110g/l, the maintenance treatment starts. The dosage shall be 2/3 of the initial dosage on this stage. The hematocrit shall 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.

[Side-effects]

1. Adverse 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 upon the treatment accordingly and there is no need to discontinue the use of the drug. If the above –mentioned symptoms still exist, stopping using the drug may be considered.

2. Allergic reactions: Allergic reactions such as skin rashes or urticaria, including allergic shock may occur rarely, therefor, it is advised that a small dosage of the drug shall be used as an initial dose as well as in the beginning of reuse of the drug, make sure no abnormal reactions occurs before the use of full dose as prescribed. If it does occur, the drug shall be stopped immediately and the proper treatment provided.

3. Cardiovascular System: Hypertension or other symptoms caused by the exacerbation of existing hypertension and hypertensive encephlaphathy may occur such as headache, disturbance of consciousness, convulsion and sometimes even encephalorrhagia. Therefore, blood pressure shall be monitored periodically, the drug dosage may be decreased or stopped, and the depressor drug may also be adjusted.

4. Hematological System: The blood viscosity may increase obviously as hematocrit rises. It shall be noted to prevent artificial renal hemo-agglutination.

5. Liver: Hepatic function impairment may occur; GOP and GPT sometimes may rise up.

6. Gastrointestinal System: Nausea, vomiting, anorexia and diarrhea may happen occasionally when the drug is used.

[Contra-indication]

Patients with uncontrollable severe hypertension

Those allergic to this product or to other erythropoietin agents

Those with combined infections, which shall be cured before the product is administered.

[Drug administration by pregnant women or in lactation]

The safety for pregnant women or in lactation is not certain.

[Drug administration by children]

The safety for premature infant, newborn baby and baby is not certain.

[Drug administration by aged patients]

For aged patients when EPOSINO is used, the blood pressure and hemotocrit shall be monitored frequently, and the dosage and times of administration shall be adjusted accordingly.

[Interaction]

not known yet

[Overdosage]

It may increase hematocrit too much and cause fatal complications of cardiovascular system

[Strengths]

2000IU, 3000IU, 4000IU, 6000IU/ml, 10000 IU/ml, API

[Package]

Pre-filled syringe or vial

[Storage]

Stored at 2-8℃

[License Number]

S20000007, S20000008, S20030083, S20030089.

[Manufacturer]

Shandong Kezing Bioproducts Co., Ltd.

Tangwangshan Road, MingShui Development Zone,

ZhangQiu, JiNan, China.

Zip Code: 250200

Tel: 86 0531 83310435