Exemestane Tablets

Pharmacological action: The growth of breast cancer cells can depend on the presence of estrogen. The estrogen (estrone and estradiol) in the circulation of postmenopausal women is mainly converted from androgens (androstenedione and testosterone) in the adrenal glands and ovaries by aromatase in peripheral tissues. Preventing estrogen production by inhibiting aromatase is an effective selective treatment for postmenopausal hormone-dependent breast cancer. Exemestane is an irreversible steroid aromatase inactivator. It is similar in structure to androstenedione, the natural substrate of the enzyme, and is a pseudo-substrate of aromatase. It can inactivate the active site of the enzyme by irreversibly binding to it (this effect is also called self-destructive inhibition), thereby significantly reducing the level of estrogen in the blood circulation of postmenopausal women, but has no significant effect on the biosynthesis of corticosteroids and aldosterone in the adrenal glands. At a concentration 600 times higher than the concentration that inhibits aromatase, it has no significant effect on other enzymes in the steroidogenesis pathway. Toxicology study: Single-dose toxicity: Death occurred in mice when the single oral dose reached 3200 mg/kg (calculated by body surface area, about 640 times the clinically recommended dose for humans). Death occurred in rats and dogs when the single doses were 5000 mg/kg and 3000 mg/kg, respectively (calculated by body surface area, about 2000 times and 4000 times the clinically recommended dose for humans, respectively). Convulsion occurred in mice and dogs when the single doses were 400 mg/kg and 3000 mg/kg, respectively (calculated by body surface area, about 80 times and 4000 times the clinically recommended dose for humans, respectively). In clinical studies, healthy people showed good tolerance when the single dose of this product reached 800 mg/kg and patients with advanced breast cancer were given a dose of up to 600 mg for 12 consecutive weeks. Reproductive toxicity: Rats were given this product from 14 days before mating to 15-20 days of pregnancy, and continued to be given for 21 days during lactation. When the dose was 4 mg/kg/day (calculated by body surface area, equivalent to 1.5 times the clinically recommended dose for humans), the placenta weight increased; when the dose was greater than or equal to 20 mg/kg/day, the pregnancy period was prolonged, and delivery was abnormal or difficult. At the same time, an increase in reabsorbed fetuses, a decrease in the number of live fetuses, a decrease in fetal weight, and delayed ossification were also observed. When the dose was less than or equal to 810 mg/kg (calculated by body surface area, about 320 times the clinically recommended dose for humans) during the organogenesis period of pregnant rats, no obvious teratogenic effect was observed. When the rabbit was given a dose of 90 mg/kg/day during the organogenesis period (calculated by body surface area, it is about 70 times the recommended clinical dose for humans), the placenta weight decreased; when the dose was 270 mg/kg/day, abortion, increased fetal absorption and decreased fetal weight occurred; when the dose was less than or equal to 270 mg/kg/day (calculated by body surface area, it is about 210 times the recommended clinical dose for humans), the malformation rate of rabbits did not increase. There is currently no clinical research data on the effects of this product on pregnant women. If this product is taken during pregnancy, the patient should be informed of the potential harm of this product to the fetus and the potential risk of abortion. When male rats were given 500 mg/kg/day (calculated by body surface area, it is about 200 times the recommended clinical dose for humans) 63 days before mating and during the cage period, the fertility of female rats that were not given the drug that were mated with them was reduced. When the dose of this product is 20mg/kg/day (calculated by body surface area, equivalent to 8 times the clinically recommended dose for humans), it has no effect on the fertility parameters of female rats (such as ovarian function, mating behavior, and pregnancy rate), but reduces the average litter size. In addition, in general toxicity studies, when the dose is 3-20 times the clinically recommended dose for humans, calculated by body surface area, mice, rats, and dogs all show ovarian changes to varying degrees, including hyperplasia, increased number of ovarian cysts, and decreased number of corpora lutea. After rats were given 1mg/kg of radiolabeled 14C-exemestane orally, it was found that it could pass through the placenta, and radioactive exemestane appeared in breast milk 15 minutes after administration. At the above dose, 24 hours after a single dose, the concentrations of this product and its metabolites in maternal and fetal blood were equivalent. It is not known whether this product is secreted through human breast milk. Because many drugs can be secreted through breast milk, lactating women should use this product with caution. Genotoxicity: This product did not show mutagenicity in the Ames test and the V79 Chinese hamster lung cell test. It showed mutagenicity in human lymphocytes without metabolic activation in vitro, but the mouse micronucleus test was negative. This product did not increase the unscheduled DNA synthesis in rat hepatocytes. Carcinogenicity: There is currently no research data on the carcinogenicity of this product.

Exemestane

This product is a white sugar-coated tablet, which appears white after removing the sugar coating.

It is indicated for postmenopausal patients with advanced breast cancer whose disease has progressed after treatment with tamoxifen.

One tablet (25 mg) is taken orally once a day after meals. No dosage adjustment is required for patients with mild hepatic and renal insufficiency.

The main adverse reactions of this product are: nausea, dry mouth, constipation, diarrhea, dizziness, insomnia, rash, fatigue, fever, edema, pain, vomiting, abdominal pain, increased appetite, weight gain, etc. In addition, the literature also reports hypertension, depression, anxiety, dyspnea, and cough. Others include decreased lymphocyte counts and abnormal liver function indicators (such as alanine transferase, etc.). In clinical trials, only 3% of patients terminated treatment due to adverse reactions, mainly within the first 10 weeks of exemestane treatment; termination of treatment due to adverse reactions in the later period is uncommon (0.3%).

Patients who are allergic to this product or its excipients are prohibited from using this product. Pregnant and lactating women are prohibited from using this product. Children are prohibited from using this product.

Precautions for children: The efficacy and safety of this product in pediatric patients have not been evaluated. It is not recommended for use in children. Pregnancy and lactation precautions: Pregnant women: Pregnancy category X. Exemestane may be fetotoxic when used in pregnant women, and no clinical benefit has been demonstrated in premenopausal women with breast cancer. Exemestane is contraindicated in women who are pregnant or who may become pregnant. Exemestane has not been adequately and well-controlled in pregnant women. Oral administration of 1 mg/kg of exemestane to rats revealed that 14C-labeled exemestane can cross the placenta. The concentrations of exemestane and its metabolites in the blood of maternal rats and embryos are roughly equal. Rats were orally administered exemestane from 14 days before mating until the 15th or 20th day of pregnancy, and then exemestane was re-administered from the 21st day of lactation. When the dose of exemestane reached 4 mg/kg/day (approximately 1.5 times the recommended human dose, calculated in mg/m2), an increase in placental weight was observed. Precautions for the elderly: There are no special precautions for the use of this product in elderly patients. See [Dosage and Administration].

This product should not be used in combination with estrogen drugs to avoid antagonizing the pharmacodynamic effects of this product; Exemestane is mainly metabolized by cytochrome P-4503A4 (CYP3A4), but when used in combination with a strong CYP3A4 inhibitor (ketoconazole), the pharmacokinetics of this product did not change, so it seems that CYP2 enzyme inhibitors have no significant effect on the pharmacokinetics of this product. However, the possibility that known CYP3A4 inducers reduce the level of exemestane in plasma cannot be ruled out.

Keep away from light, seal tightly and store in a cool place.

25 mg

24 months

Tongfang Pharmaceutical Group Co., Ltd.

• Founded in:

  1993-12-08

• Address:

  No. 23, Xikang Road, Badaling Town, Yanqing District, Beijing (Yanqing Park, Zhongguancun Science Park)

• Tax NO.:

  91110000103044655Y

• Registered Funds:

  200 million yuan

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