Zoledronic Acid for Injection

Pharmacological action: The pharmacological action of zoledronic acid is mainly to inhibit bone resorption. Its mechanism of action is not fully understood and may be related to multiple effects. Zoledronic acid can inhibit osteoclast activity in vitro, induce osteoclast apoptosis, and block osteoclast absorption of mineralized bone and cartilage by binding to bone. Zoledronic acid can also inhibit the enhanced osteoclast activity and bone calcium release caused by various stimulating factors released by tumors. Toxicological studies: Genetic toxicity: The results of the Ames bacterial reverse mutation test, the Chinese hamster ovary cell chromosome aberration test, the Chinese hamster gene mutation test and the rat micronucleus test were all negative. Reproductive toxicity: Female rats were subcutaneously injected with 0.01, 0.03 or 0.1 mg/kg/day of this product from 15 days before mating to the end of pregnancy (AUC is 0.07, 0.2 and 1.2 times that of 4 mg intravenous injection in humans). Animals in the high-dose group showed ovulation inhibition and decreased pregnancy rate. Animals in the medium-dose and high-dose groups showed increased pre-implantation loss, decreased number of implanted embryos and live fetuses, decreased survival rate of newborn mice, and dystocia and increased perinatal mortality in all dose groups. The cause of death of maternal mice may be related to the drug's inhibition of bone calcium mobilization, leading to perinatal hypocalcemia, which may be a common effect of bisphosphonates. Female rats were subcutaneously injected with 0.1, 0.2 or 0.4 mg/kg/day of this product during pregnancy (AUC is 1.2, 2.4 or 4.8 times that of human intravenous injection of 4 mg). Animals in the medium- and high-dose groups showed increased pre- or post-implantation loss, decreased number of live fetuses, and fetal skeletal, visceral and external deformities. The skeletal deformities of the fetuses in the high-dose group were manifested as unossified and incomplete ossification, thickened, bent or shortened bones, etc. Toxic reactions such as reduced lens size, cerebellar dysplasia, reduced or absent liver lobules, deformed lung lobes, vascular dilation, cleft palate, and edema were also observed in the high-dose group. The fetuses of animals in the low-dose group also showed skeletal deformities. In this experiment, the maternal animals in the high-dose group showed a decrease in body weight and food intake, indicating that the experiment has reached the highest drug exposure level. Pregnant rabbits were subcutaneously given 0.01, 0.03, and 0.1 mg/kg/day of this product (AUC is less than or equal to 0.5 times the intravenous dose of 4 mg in humans), and no toxicity of this product to the fetus was observed. Maternal death and abortion occurred in animals in each medication group (the dose was greater than or equal to 0.05 times the intravenous dose of 4 mg based on relative body surface area), which may be related to drug-induced hypocalcemia. Carcinogenicity: Routine lifetime carcinogenicity tests were conducted on mice and rats. Mice were orally given 0.1, 0.5, and 2.0 mg/kg/day of this product (the dose was greater than or equal to 0.002 times the intravenous dose of 4 mg in humans based on relative body surface area), and the incidence of Harderian (accessory lacrimal gland) adenoma in all medication groups increased. Rats were orally administered 0.1, 0.5, and 2.0 mg/kg/day of this product (calculated based on relative body surface area, the dose is less than or equal to 0.2 times the human intravenous dose of 4 mg), and no increase in tumor incidence was observed.

The main ingredient of this product is zoledronic acid.

Bone pain caused by osteolytic bone metastases of malignant tumors.

Intravenous drip: For adults, 4 mg each time, diluted with 100 ml 0.9% sodium chloride injection or 5% glucose injection, then intravenously dripped. The drip time should be no less than 15 minutes. The drug should be administered once every 3 to 4 weeks or as directed by a doctor.

The most common adverse reaction of this product is fever. Other adverse reactions mainly include: systemic reactions: fatigue, chest pain, leg edema, conjunctivitis; digestive system: nausea, vomiting, constipation, diarrhea, abdominal pain, dysphagia, anorexia; cardiovascular system: hypotension; blood and lymphatic system: anemia, hypokalemia, hypomagnesemia, hypophosphatemia, hypocalcemia, granulocytopenia, thrombocytopenia, pancytopenia; muscle and bone: bone pain, joint pain, muscle pain; kidney: increased serum creatinine value (related to the time of administration); nervous system: insomnia, anxiety, excitement, headache, lethargy; respiratory system: dyspnea, cough, pleural effusion; infection: urinary tract infection, upper respiratory tract infection; metabolic system: anorexia, weight loss, dehydration; others: flu-like symptoms, redness and swelling at the injection site, rash, itching, etc. The toxic and side effects of zoledronic acid are mostly mild and transient. In most cases, they will disappear automatically within 24 to 48 hours without special treatment.

1. It is contraindicated for patients who are allergic to this product or other bisphosphonates; 2. It is not recommended for patients with severe renal insufficiency; 3. It is contraindicated for pregnant and lactating women.

Precautions during pregnancy and lactation: This product is contraindicated for use by pregnant and lactating women.

This product should be used with caution when used in combination with aminoglycosides, because aminoglycosides have a synergistic effect in lowering blood calcium, which may prolong the duration of hypocalcemia. When used in combination with diuretics, it may increase the risk of hypocalcemia. When used in combination with thalidomide, it may increase the risk of renal dysfunction in patients with multiple myeloma.

Keep in a light-proof and airtight container.

4mg

Yangtze River Pharmaceutical Group Sichuan Hairong Pharmaceutical Co., Ltd.

• Founded in:

  2001-08-17

• Address:

  No. 802, South Section of Rainbow Avenue, Dujiangyan City, Chengdu City, Sichuan Province

• Tax NO.:

  91510181730231740X

• Registered Funds:

  50 million yuan

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