Nedaplatin for Injection

Nedaplatin for Injection

Generic Name: Nedaplatin for Injection
Brand name: Jiebaishu
Composition:Diammine[(hydroxy-κO)acetato(2-)-κO]platinum
Chemical structure:

Molecular formula: C2H8N2O3Pt 
Molecular weight:303.17 g/mol

Description:
This product is a white or yellowish loose lump or powder.
Strength:25mg
Indications:
It is mainly used for treating head-neck carcinoma, small cell lung cancer, non-small cell lung cancer,
esophageal cancer, ovarian cancer and other solid tumors.
Dosage and administration:
Before use, it should be dissolved in certain amount of 0.9% sodium chloride injection, then diluted to 500ml,
intravenous drip should be administrated for above 1 hour, after which, intravenous drip of above 1000ml
should be given.  Recommended dosage: 80-100mg/m2 once, one time per course, next course begins after
3-4 weeks.
Precautions:
1. This product should be used as far as possible under guidance of the experience of tumor chemotherapy,
and choose the patient carefully, and should have the conditions to deal with the emergency.
2. Hearing impairment, bone marrow, liver and kidney dysfunction, combined infection and varicella patients
and elderly people.
3. This product has a strong inhibition of bone marrow and may cause abnormal function of liver and kidney.
During the application of this product, the function of blood, liver and kidney should be regularly checked and
the patient's general condition should be paid close attention to, if abnormal drug should be stopped and
disposed properly. For patients with low bone marrow function and renal insufficiency and those who have
been treated with cisplatin, the initial dosage should be reduced appropriately. If the product is administered
for a long time, there will be an increasing trend of side effects and may cause delayed adverse reactions.
4. Pay attention to the tendency of bleeding and the occurrence or aggravation of infectious diseases.
5. This product is mainly excreted by the kidney. In the process of applying this product, it is necessary to
ensure adequate urine volume to reduce the toxic damage to renal tubules in the urine. When necessary,
the appropriate use of mannitol, furosemide infusion and diuretic. The report of the application of furosemide
diuretics, can aggravate renal dysfunction, hearing impairment, so should be infusion to supplement water.
In addition, the difficulty of drinking water or the patients with nausea, vomiting, loss of appetite, diarrhea and
so on should be paid special attention.
6. attention should be paid to the adverse reactions of digestive tract, such as nausea, vomiting and loss of
appetite, and appropriate treatment.
7. The combination of other anti malignant tumor drugs (nitrogen mustard, metabolic antagonist, alkaloid,
antibiotic, etc.) and radiotherapy may aggravate bone marrow suppression.
8. patients of childbearing age should consider the effect of this product on the gonads.
9. this product is only intravenous drip, and should be avoided out of the blood vessel.
10. When the product is formulated, it can not be mixed with other antitumor drugs. It is also not suitable to
use amino acid infusion and acid infusion below pH5 (such as electrolyte infusion, 5% glucose infusion or
glucose sodium chloride infusion).
11. this product is not in contact with aluminum containing utensils. Direct sunlight should be avoided when
the product is stored and dripped.
12. of the products were in clinical trials abroad (632 cases), 2 cases died suddenly, and 1 cases died of
Adams-Stokes Syndrome, cerebral hypoxia syndrome caused by cardiac conduction block. 1 cases of
sudden death died of heart failure due to hypertension, and the other 1 died of coronary artery infarction
caused by previous myocardial infarction or hemorrhage due to brain metastasis. In the 1 cases of A J's
syndrome, the ST segment of ECG decreased after administration. It is suspected that the loss of appetite
and anemia caused by this product is the inducement of the attack. However, no autopsy found it, which can
not show that this product is related to it.

Pharmacology and toxicology:
Nedaplatin is a cisplatin analogue. After the product enters the cell, the bond between alcohol and oxygen on
the glycolate ligand breaks, and the combination of water and platinum leads to the formation of ionic
substances (active substances or hydrates). Then, the fractured glycolic acid ester ligand became unstable
and released, producing a variety of ionic substances, binding to DNA. This product is combined with cisplatin
in the same way as DNA, and inhibits DNA replication, thus producing antitumor activity. In addition, it has
been confirmed that the base site of this product is the same as cisplatin when it reacts with DNA. Toxicology
research: Repeated dose toxicity: Weekly the rats were 2 times a month, every day (a) for 1 consecutive
months, the weekly dosing for 6 months and the dog once a week for 6 weeks intravenous injection of drug
toxicology research results show that the toxicity of cisplatin and similar major toxicity the target organ for
blood (RBC, thrombocytopenia), kidney, pancreas. Genotoxicity: the Ames test is positive, and the
chromosome aberration test in vitro (human lymphocytes) and in vivo (mouse bone marrow cells) shows that
this product can cause chromosome aberration rate to increase significantly. Reproductive toxicity: there is
teratogenicity when the dose of the intravenous injection of this product is 500 u g/kg in the stage of organ
formation in rabbits, and the dose of no influence on fetus is 250 mu g/kg. When the dosage of the rats was
540 mu g/kg, it could cause the delayed ossification of fetal rats, but had no obvious effect on its shape,
skeletal system and development.

Pharmacokinetics:
Intravenous infusion of tumor patients with nedaplatin 80mg/m2 or 100mg/m2, in vivo dynamic, the product
of the method for direct determination of total platinum by atomic absorption spectrometry. The results show
that nedaplatin single intravenous drip, reduce bipolar platinum concentration in plasma, t1/2 alpha is about
0.1-1 hours, t1/2 beta is about 2-13 hours, AUC increases with the increase of dosage. This product is mainly
free in the form of plasma. Animal tests show that the product is more distributed in the kidney and bladder,
and the concentration of the tissue is higher than the plasma concentration. The excretion of this product is
mainly urinary excretion, and the recovery rate of platinum in urine for 24 hours is between 40-69%.

Storage:
Protect from light, and keep air-tightly

Packs:
Neutral borosilicate glass control injection vial, 10mg/ vial, 5 vial / box.

Shelf-life:24 months