Approval date: April 29, 2010
Revise date: Sep.29, 2019
Instructions of recombinant human granulocyte colony- stimulating factor injection
Please read the instructions carefully and use the drug under the guidance of doctors.
Generic name: Recombinant human granulocyte colony-stimulating factor injection
Trade name: White-C
English name: Recombinant human granulocyte colony- stimulating factor injection
Chinese Pinyin: Chongzu Ren Lixibao Cijiyinzi Zhusheye
Recombinant human granulocyte colony-stimulating factor, obtained by recombinant genetic E.coli seed expression and purification.
Auxiliary materials: Mannitol, Polysorbate 80, Sodium acetate and Acetic acid
Colorless and transparent liquid
Granulocytopenia resulting from chemotherapy
For cancer patients taking bone marrow suppression drugs, especially after the treatment with some strong bone marrow deprivation chemical drugs, the injection of this drug can prevent granulocytopenia, lighten the degree of granulocytopenia, shorten duration of granulocytopenia and speed up the recovery of the granulocytes, consequently reducing the risk of combined infection.
(1) 75μg/0.5ml/pre-filled syringe (4.5×106IU/0.5ml/pre-filled syringe),
(2) 150μg/0.5ml/pre-filled syringe) (9.0×106IU/0.5ml/pre-filled syringe),
(3) 300μg/ml/pre-filled syringe (1.8×107IU/1ml/pre-filled syringe)
[Dosage and administration]
Used for chemotherapy-induced neutropenia. For adult patients with neutrophilic granulocyte count falling to less than 1000/mm3 (white blood cell count is 2000/mm3) after chemotherapy, take the drug once a day through subcutaneous or intravenous injection at 2~5μg/kg after starting chemotherapy; For children patients with neutrophilic granulocyte count falling to less than 500/mm3 (white blood cell count is 1000/mm3) after chemotherapy, take the drug once a day through subcutaneous or intravenous injection at 2~5μg/kg after starting chemotherapy When neutrophilic granulocyte count returns to more than 5000/mm3 (white blood cell count is 10000/mm3), stop the drug administration.
2. Neutropenia syndrome caused by chemotherapy for acute leukemia
Leukemia patients with white blood cell count of less than 1000/mm3，there is obvious reduction of myeloblast in bone marrow and no myeloblast is seen in peripheral blood after chemotherapy, adult patients take the drug once a day through subcutaneous or intravenous injection at 2~5μg/kg, children patients take the drug once a day through subcutaneous or intravenous injection at 2~5μg/kg. When neutrophilic granulocyte count returns to more than 5000/mm3 (white blood cell count is 10000/mm3), stop the drug administration.
1. Musculo-skeletal system: sometimes muscle aches, bone pain, back pain, chest pain may happen .
2. Digestive system: Sometimes it has the phenomenon of loss of appetite, or rise of liver glutamate pyruvate transaminase and glutamic-oxalacetic transaminase.
3. Others: Some people will have fever, headache, fatigue, skin rash, ALP, LDH increase.
4. Very few people will have shock, interstitial pneumonia, adult respiratory distress syndrome, naive cells increase.
1. Those who are allergic to granulocyte colony-stimulating factor and other agents expressed by E. coli are forbidden to take the drug.
2. Those with severe liver, kidney, heart, lung function impairment are forbidden to take the drug.
3. Myeloid Leukemia patients with no obvious reduction of immature granulocytes in bone marrow or immature granulocytes detected in peripheral blood.
1. This product should be taken 24-48 hours after the administration of chemotherapeutic drugs .
2. Hemogram should be monitored twice a week during the use of the drug, especially the change in number of neutrophilic granulocytes.
3. For malignant proliferation of myeloid cell system, (acute myeloid leukemia, etc.) This product should be used with caution.
4. Safety and efficacy for long-term use of the drug has not been established, there have been report of spleen enlargement.
Although no cases of allergic reactions occurred in the clinical trials of this product but a small number of allergic reactions are found in similar foreign preparations (the incidence rate is <1/ 4000〕, it appeared as skin rash, urticaria, facial swelling, difficult breathing, tachycardia, and low blood pressure, most occurred within 30 minutes after taking the drug. The drug use should be immediately suspended, the symptoms quickly disappeared after treatment with the anti-histamine, corticosteroids, bronchial spasm agents and (or) epinephrine. Sensitizing drugs should not be used for these cases.
5. This product is only used under the guidance of doctors.
[Administration by pregnant and lactating women]
Safety during pregnancy has not been established. When there is proof that the potential benefits of drug use by pregnant women are greater than the potential risk to the fetus, the drug can be taken. Breast-feeding women should stop breast-feeding before treatment.
[Administration by Children]
Children should use it with caution and be properly monitored. As the drug safety for newborns and infants are not established, it’s recommended not to use the drug. Long-term toxic effects were not found in patients aged 4 months to 17 years taking the drugs everyday. No changes were found in their growth, development, sexual character and internal excretion.
[Drug use by Elderly patients]
Physiological function in elderly patients is relatively low, it is needed to observe the patient's condition, pay attention to dosage and intervals, and take care to use the drug. Its safety and efficacy has not been established.
Not fully known. Take care to use drugs that can promote the release of the white blood cell (such as lithium-agent).
When taking the drug at a dose exceeding the safe dose, there will be urine occult blood, urine protein showing positive, serum alkaline phosphatase activity obviously improved, but after five weeks of recovering, all the indicators can be back to normal. When injected at a dose much higher than the safe dose, there will be loss of appetite, lower weight, weakening of activity, as well as urine occult blood, urine protein showing positive, apparent pathological changes in liver. These changes could be eliminated or relieved after the recovery period.
The product is human granulocyte colony-stimulating factor (rhG-CSF) by the use of recombinant technology. Compared with natural products, biological activity in vivo and in vitro are basically the same. rhG-CSF is one of the major cytokines regulating granulopoiesis of bone marrow. It selectively acts on the granulocyte progenitor cells, promoting their proliferation, differentiation, and increase functions of undifferentiated granulocytes.
2.1 Acute toxicity: Mice were injected via caudal vein once at 5040μg/kg of this product, equivalent to 1000 times the dosage for general clinical injection. With continuous observation for 10 days, no toxic reactions were observed.
2.2 Sub-acute toxicity: Mice were injected for 4 weeks (intravenous, subcutaneous injection), 13 weeks (intravenous injection) at noneffective dose of 1μg/kg / day. If injected at more than l0μg/kg/day, bone resorption and bone formation in thigh bone endomembrane of posterior limb, ALP increase, spleen weight increase and so on can be seen. In 4 weeks and 13 weeks administration (intravenous) test, these phenomena disappeared after drug withdrawal. Monkey was injected for 4 weeks, 13 weeks (intravenous) at noneffective doses of 10μg/kg/day, lμg/kg/day or more, there was a sharp increase of white blood cells (15-28 times the number before the administration) after 4 weeks of administration at the dose of 1000μg/kg/day, which is considered the cause of death due to cerebral hemorrhage, while there was no death at dose of 1000μg/kg/day for 13 weeks. In addition, the reduction of proerythroblast in bone marrow, spleen enlargement and so on can be seen within different effective doses. After administration test for 13 weeks, the above phenomenon is back to normal. The test results in young mice are the same as adult mice, no difference was found in pharmacological effects and toxicity.
2.3 Chronic toxicity: Given continuous subcutaneous injection of rhG at 180μg/kg for 29 days, the Beagle dog can have more obvious toxicity reactions primarily manifested as intermittent fever, loss of appetite, some animals have ECG II lead T-wave inversion deepened, injection -site skin thickened or with erythema, a high degree of edema in subcutaneous tissue, large Infiltration of inflammatory cells, focal necrosis, some animals had proliferation of primitive bone marrow cell, enlarged spleen and active spleen cell growth. AST and T-Bil have a transient increase, several animals had pathological changes in liver cells. However, the above changes can return to normal 30 days after stopping the drug use. Long-term administration at 60μg/kg can produce mild toxicity, such as fever, loss of appetite, irritating damage to local skin tissue of injection, reversible pathological changes in the bone marrow and spleen which is smaller than that caused by the dose of 180μg/kg. Long-term administration at doses of 20μg/kg produced no significant toxicity on the Beagle dogs, long-term subcutaneous injection of rhG-CSF at 20μg/kg is a safe dose for Beagle dogs, the dose is 4 times commonly used clinical dose of 5μg/kg. Continuous subcutaneous injection of rhG-CSF for 90 days produced toxicity on rats that significantly increased with the dose increase. 500μg/kg is dose of obvious toxicity. At this dose, body weight of animals increased more slowly than the control group after 1 week, body weight of male animals failed to return to normal level until the end of the experiment and the difference is significant. AST in 30 days had a transient increase beyond the normal range. In blood-related indicators, 30-day bone marrow granulocyte ratio is higher than the control group, and the erythrocyte ratio is relatively lower, granulocyte/erythrocyte ratio in bone marrow has significant difference. The organ coefficient of spleen was significantly higher than control group and other groups in 30 and 60 days. Reticulocytes are also higher than control group. No obvious abnormalities in other indicators. 100μg/kg can basically be regarded as the dose without toxic reaction, which is 20 times the commonly used clinical dose. Animals in this group had short-term weight reduction after 3 weeks and 4 weeks administration of drug, a transient increase of reticulocyte compared with the control group, granulocyte/erythrocyte ratio in bone marrow is apparently higher than control group in 30 days, which may be the drug efficacy response to granulocyte. 20μg/kg is a safe dose 4 times commonly used clinical dose. In 90 days of continuous administration of the drug, apparent toxic effects were not found on the animal,, only granulocyte/erythrocyte ratio in bone marrow is higher than the control group, which is considered the role of the drug efficacy.
2.4 Reproductive toxicity: 500μg/kg/day or more is noneffective dose for reproductive capacity of parental generation of animals, fetus, and newborn mice taking the drug (intravenous) respectively before pregnancy, during pregnancy and organ formation period. 100μg/kg/day or more and 4μg/kg / day is noneffective dose for reproductive capacity of parental generation of animals, and newborn mice taking the drug (intravenous) in the perinatal period and period of lactation. At 20μg/kg/day or more, it can be seen to inhibit the development of neonatal rats. In addition, 20μg/kg/day and 5μg/kg/day are noneffective dose for reproductive capacity of parental generation of animals and fetus taking the drug (intravenous) in rabbit organ formation period. At 80μg/kg/day, the mother animals had genitourinary bleeding accompanied with abortion, at the 20μg/kg/day or above, number of viable fetuses was reduced, No teratogenic effects were found in all tests.
2.5 Antigen: Antigenicity appeared when guinea pigs, rabbits and mice take immunostimulants (FCA or aluminum hydroxide gel) at the same time. While no antigenicity happened when administered alone. the antibody potency increased in the rabbit test of E. coli mutant protein antigen and the use of FCA. While antibody potency didn’t increased when this drug was used alone. In addition, in clinical trials, no antibodies against the drug and potency increase of mutant protein antibodies from Escherichia coli were found.
2.6 Others: Systemic allergic reaction test, mutagenicity test, local irritation test and pyrogenic test were normal.
This product, after intravenous or subcutaneous injection, was distributed mainly in the kidneys, bone marrow and plasma, degraded through amino acid metabolism, mainly excreted by urine. The half-life is 3.5 hours through subcutaneous injection, clearance rate is 0.5-0.7ml/min/kg.
[Storage] 2-8℃, protect from light
[Package] Pre-filled syringe, 1 pre-filled syringe/small carton
[Shelf life] 24 months.
[Standard based on] “Chinese Pharmacopoeia” edition 2015, volume 3
75μg/0.5ml/pre-filled syringe GYZZ S20010015
150μg/0.5ml/pre-filled syringe GYZZ S20010016
300μg/1ml/pre-filled syringe GYZZ S20103004
Shandong Kexing Bio-Products Co., Ltd.
Address: No.2666 Chuangye Road, Mingshui Development Zone, Zhangqiu, Jinan, Shandong, China.
Zip Codes: 250200