Zidovudine Tablets

1. Pharmacological action: This product is an antiviral drug, which is highly active against retroviruses including human immunodeficiency virus (HIV) in vitro. It is phosphorylated by thymidine kinase in virus-infected cells to zidovudine triphosphate, which can selectively inhibit HIV reverse transcriptase, leading to termination of HIV chain synthesis and thus preventing HIV replication. 2. Toxicological action: Subacute toxicity and chronic toxicity: In a 6-month oral administration test in rats, anemia occurred in the group with the maximum daily dose of 500 mg/kg, but the plasma concentration at this time was equivalent to 100 times the clinical dose of patients. In two groups of monkeys taking the drug for 3 and 6 months, anemia occurred in the group with a daily dose of 34-300 mg/kg. At 6 months of the test, changes in the bone marrow and slight variations in the morphology of peripheral red blood cells were observed. Carcinogenicity, mutagenicity and reproductive toxicity: Three doses of zidovudine were given to mice and rats (60 mice and rats in each group), starting with 30, 60, and 120 mg/kg/day for mice and 80, 220, and 600 mg/kg/day for rats. After 90 days of administration, the dose was reduced to 20, 30, and 40 mg/kg/day due to anemia in mice. The high-dose group of rats was reduced to 450 mg/kg/day after 91 days and to 300 mg/kg/day after 279 days. In the mouse test, after 19 months, 7 high-dose groups had vaginal tumors, one medium-dose group had vaginal cancer, and no tumors were found in the low-dose group. In the rat test, after 20 months, two non-metastatic vaginal squamous cell carcinomas appeared in the high-dose group, and no vaginal tumors were found in the medium-dose and low-dose groups. No other tumors were found. The drug exposure amount that found tumors was about 3 times that of humans (100 mg every 4 hours) in mice and 24 times that of humans in rats, according to AUC. Two embryonic carcinogenicity tests were also conducted in mice. In one test, 20 mg/kg/day or 40 mg/kg/day of zidovudine was administered to mother mice from the 10th day of pregnancy until the mother mice gave birth, and the offspring were breastfed until 24 months after birth. The dose used in this test was about 3 times that of humans (according to AUC). An increase in vaginal tumors was found at 24 months, and no increase in tumors in other organs such as the liver and lungs was found. These findings are consistent with the results of standard carcinogenicity tests. In the second test, zidovudine was administered to mice at the maximum tolerated dose of 12.5 mg/day or 25 mg/day from 12 days of pregnancy to the 18th day. The incidence of lung, liver and female reproductive tract tumors in the offspring of the high-dose zidovudine group increased. The relationship between rodent carcinogenesis and human carcinogenesis is still unclear. Zidovudine is mutagenic in mouse 5178Y/TK/- lymphocytes, and the results of in vitro cell transformation tests are positive, the results of cytogenetic tests using human lymphocytes are positive, and the results of multiple-dose micronucleus tests in mice and rats are positive. The results of a single-dose cytogenetic test in rats were negative. Zidovudine was given to female and male rats in a reproductive test at a dose of 7 times that of humans (based on body surface area). According to the pregnancy rate, it did not affect fertility. Pregnancy: No evidence of mutagenicity was found in pregnant rats and rabbits at a dose of 500 mg/kg/day. Rats given 150 mg/kg/day or 450 mg/kg/day and rabbits given 500 mg/kg/day caused embryotoxicity, which was manifested as increased embryo resorption. In the teratogenicity test, the peak blood concentration of zidovudine given to rats was 66 to 226 times the steady-state peak concentration of the human dose (100 mg every 4 hours), and rabbits were 12 to 87 times that of humans. In an in vitro mouse fertilized oocyte test, zidovudine administration produced a dose-dependent reduction in blastocyst formation. In another teratogenicity test conducted in rats, a dose of 3000 mg/kg/day resulted in significant maternal toxicity and increased embryotoxicity. The peak blood concentration at this dose is 350 times that of humans (the estimated AUC is 300 times that of humans). In this test, no teratogenicity was found at doses below 600 mg/kg/day.

Zidovudine.

This product is white tablets.

Used to treat HIV (human immunodeficiency virus) infection.

Adults: If used in combination with other antiretroviral drugs, the recommended dose is 600 mg per day, taken in divided doses; if used alone, 500 mg/day or 600 mg/day is recommended, taken in divided doses (100 mg every 4 hours when awake). Children: The recommended dose for children aged 3 months to 12 years is 180 mg/m[sup]2[/sup] every 6 hours, and should not exceed 200 mg/m[sup]2[/sup] every 6 hours. Neonatal dosing: Start dosing 12 hours after birth until 6 weeks of age, orally 2 mg/kg/6 hours. Patient monitoring: Hematotoxicity is related to the bone marrow status before dosing, the dose, and the time of administration. Patients with poor bone marrow function, especially those with severe AIDS, should be monitored for anemia and white blood cell counts.

As the disease progresses, adverse reactions increase, and patients should be carefully monitored, especially when the disease progresses. 1. Bone marrow suppression: This product should be used with caution in people with poor bone marrow function, granulocytes [1000/mm3 or hemoglobin [9.5g/dl. For patients with severe AIDS, anemia and neutropenia are also the most obvious adverse reactions. There have been reports of pancytopenia anemia associated with the use of this product, and most people recover after stopping the drug. However, when this product is administered alone or in combination, if obvious anemia is found, the dose needs to be adjusted, the drug needs to be stopped and/or blood transfusions need to be performed. For patients with progressive HIV who are given this product, blood cell counts should be performed regularly. For patients with early HIV infection or asymptomatic patients, blood cells should be counted intermittently. If anemia or neutropenia occurs, the dose should be adjusted.

1. Patients who are allergic to this product are prohibited from using it. 2. Pregnant women and lactating women are prohibited from using it.

Precautions for children: Not yet clear. Precautions for pregnancy and lactation: Use with caution in pregnant women and prohibit use in lactating women. Precautions for the elderly: Not yet clear.

1. Combination with Ganciclovir: It may increase blood toxicity in some advanced patients. If these patients need to use combined medication, the dose should be reduced or one or both of the drugs should be discontinued to reduce liver toxicity. Patients using combined medication should undergo regular examinations including hemoglobin, hematocrit, white blood cell classification and count, etc. 2. Combination with α-interferon: Blood toxicity has been reported with combination use of α-interferon. As with the combined use of Ganciclovir, if necessary, the dose should be reduced or one or both of the drugs should be discontinued. Hematological parameters should be monitored regularly. 3. Myelosuppressive/cytotoxic drugs: There is a risk of increased blood toxicity when this product is used in combination with drugs that can affect RBC, WBC counts or cytotoxic drugs. 4. Probenecid: Probenecid inhibits

Keep away from light and store in a sealed container.

0.1g

24 months

Shanghai Shyndec Pharmaceutical Co., Ltd.

• Founded in:

  1996-11-27

• Address:

  No. 378, Jianlu Road, Pudong New Area, Shanghai

• Tax NO.:

  91310000630459924R

• Registered Funds:

  1,341,172,692 yuan

• Website:

  Log in to view

• Email:

  Log in to view