EPO (Erythropoietin) 3000IU/vial,5vials/kit
For treating anemia caused by renal insufficiency and applicable to dialysis patients and nondialysis patients

Recombinant Human Erythropoietin For Injection
[Description]
Erythropoietin is a glycoprotein which stimulates red blood cell production. It is produced in the kidney and stimulates the division and differentiation of committed erythroid progenitors in the bone marrow. CLONEPO, a 165 amino acid glycoprotein manufactured by recombinant DNA technology, has the same biological effects as endogenous erythropoietin. It has a molecular weight of 36000—45000 daltons. rhEPO for injection is a freeze-dried preparation prepared from recombinant proteins expressed by Chinese Hamster Ovarian(CHO) cells containing recombinant plasmids of the human erythropoietin gene. The recombinant proteins are isolated, purified and lyophilized after cultivations of the transfected CHO cells. The preparation contains a stabilizer, but free of preservatives and antibiotics.
[Strength]
1000IU/vial;2000IU/vial; 3000IU/vial;4000IU/vial
[Pharmacology] EPO is a kind of glycoprotein mainly produced by kidney, which can stimulate the proliferation and differentiation of erythroid progenitors, increase CFU-E & BFU-E colony formation.
[Pharmacokinetics] Following subcutaneous administration of rhEPO, absorption is slow. Rise in serum erythropoietin concentration are detectable 2 hours later and reach main peak level at about 18 hours. Bone marrow is a specific organ for ingesting, and the drug is mainly ingested by liver and kidney. After subcutaneous administration, large portion of rhEPO is metabolized in body. As experiments on animals(rats) exhibited that small portion is degraded in kidney, bone marrow and spleen, except in liver. Kidney is not the main role in the excretion of recombinant erythropoietin, for anemia patients with recombinant erythropoietin therapy, below 10% of recombinant erythropoietin is excreted unchanged in the urine.
[Indication] Anemia associated with Chronic Renal Failure(CRF).
Anemia in cancer patient on Chemotherapy or radiation therapy.
[Dosage and Administration]
CLONEPO should be administered under the guidance of a qualified physician. It may be given either as an IV or SC injection after dissolved in 1ml sterile water for injection. The recommended range for the starting dose of CLONEPO is 100 to 150IU/kg weekly total, given in 2-3 divided doses for patients on hemodialysis, or 75 to 100IU/kg weekly total, given in 2-3 divided doses for patients on peritoneal dialysis and patients not on dialysis. If Hct increased by less than 0.5vol% per week, the dose should be increased by 15 to 30IU/kg after four weeks of therapy. Hct should approach 30 to 33vol%, but not more than 36vol%. The dosage of CLONEPO must be individualized to maintain the Hct between 30 to 33vol% or Hb between 100 to 110g/L. The suggested dose of CLONEPO should be reduced to 2/3 of therapy dose, and regulate the dose according to Hct range.
[Auxiliary drug]
During rhEPO therapy, iron will be deficient as the consumption of iron stores, so majority of the patients require supplemental iron to increase or maintain transferrin saturation to levels which will adequately support erythropoiesis stimulated by rhEPO. If ferritin in serum is lower than 100ng/ml or transferrin saturation lower than 20%, drugs rich in iron should be applied in routine way every day.
[Contraindications]
rhEPO is contraindicated in patients with: 1.Uncontrolled hypertension. 2.Known hypersensitivity to mammalian cell-derived products. 3.Known hypersensitivity to human albumin. 4.Concurrent infection should not use this product until the infection is cured.
[Warnings]

1. During therapy with rhEPO, hematology examination should be monitored regularly (once weekly for starting therapy, and once two weeks for maintenance period). It should be withdrawl if excess erythropoiesis is monitored (Hct≥36vol%).
2. .Modest increases were possiblely seen in serum potassium when treated with rhEPO, dose adjustment should be under the guidance of a qualified physician.
3. .For patients with thrombotic diseases, such as myocardial infarction, pulmonary embolism, cerebrovascular infarction, rhEPO should be used with caution.
4. .rhEPO should not be used for any sports activities.

[Lack or loss of response]
The following etiologies should be considered when patients are lack or loss of response:
1.Iron deficiency.
2.Underlying infectious, inflammatory, or malignant processes.
3. Deficiencies of folic acid or vitamin B12.
4.Severe excessive aluminium.
[Carcinogenesis, Mutagenesis]
Carcinogenic potential of rhEPO has not been evaluated. rhEPO does not induce bacterial gene mutation (Ames Test), chromosomal aberrations in mammalian cells or micronuclei in mice.
[Pregnancy Category C]
rhEPO has been shown to have adverse effects in rats when given in doses 5 times the human dose. There are no adequate and well-controlled studies in pregnant women. rhEPO should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.
[Nursing Mothers]
It is not known whether rhEPO is excreted in human milk.
[Pediatric Use] The safety in premature infants, newborns and infants has not been established.
[Geriatric Use]
Blood pressure and Hct should be monitored carefully in eldly patients, and the dose and administration frequency should be appropriate adjusted.
[Drug Interaction] None known.
[Overdose] May lead to excessive hematocrit, then caused some kind of fatal cardiovascular complications.
[Adverse Reactions]
1.Common reactions: In the initial use of this product, headache, low fever and fatigue may occur in minor patients, in a few cases myalgia and arthralgia may appear. Most of these adverse reactions may improve with symptomatic treatment and need not discontinue the treatment. If the adverse reactions persist, cessation shall be considered in a few cases.
2.Allergic reactions: In rare cases allergic reactions may appear after injection, such as skin rash, urticaria, or allergic shock. Thus for the initial or renew use of CLONEPO, reduction dosage is recommended initially. If there is no abnormal reactions observed, full dosage can be used. If any allergic reactions occurs, rhEPO should be immediately discontinued and appropriate therapy initiated.
3.Cardiovascular and cerebrovascular system: Increases in blood pressure, exacerbation of hypertension, and hypertensive encephalopathy which causes headache, conscious disturbance and spasm, even intracerebral hemorrhage. So the blood pressure should be monitored carefully during CLONEPO therapy, the dose should be decreased or withdrawl if necessary.
4.Blood system: The blood viscosity increases with Hct increasing. It should be cautious to avoid thrombopoiesis.
5.Liver: There have been rare books of GOT and GPT elevation.
6.Gastrointestinal system: On occasion, nausea, vomit, anorexia and diarrhea have been observed.
[Notes]
1. Examine carefully for possible damage of vial before use.
2. Do not use if the powder can not be dissolved completely.
3. Use upon doctor’s prescription only.
[Storage] Store at 2 ~ 8°C in dark
[Shelf life] 2 years
[National drug License No.]
NDC S19991023(1000IU), NDC S19980080(2000IU),
NDC S19991024(3000IU); NDC S19991025(4000IU).
[Manufacturer]
Name: Shanghai Chemo Wanbang Biopharma Co., Ltd,
Address: 1098, Yuegong Road, Jinshan Industrial zone, Shanghai 201506, P.R.China