Dienogest Tablets

Pharmacological action: Dienogest is a 19-nortestosterone derivative. It has no androgenic activity, but has anti-androgenic activity, which is about one-third of that of cyproterone acetate. The affinity of dienogest for binding to the human uterine progesterone receptor is only 10% of that of progesterone. Although its affinity for the progesterone receptor is low, it has a strong progestin effect in vivo. Dienogest has no obvious androgenic, mineralocorticoid, and glucocorticoid activity in vivo. Dienogest plays a role in endometriosis by reducing the endogenous production of estradiol, thereby inhibiting the stimulation of estradiol on the normal and ectopic endometrium. When administered continuously, dienogest leads to an endocrine environment of low estrogen and high progesterone, causing endometrial tissue decidualization, thereby reducing endometriotic lesions. Toxicological studies: The results of the Ames test, the in vitro chromosome aberration test of Chinese hamster lung cells and human lymphocytes, the mouse lymphoma cell test, and the in vivo bone marrow micronucleus test of mice were negative. Reproductive toxicity In the rat fertility and early embryonic development test, female rats were given dienogest 0.3, 1, 0, 3.0 mg/kg/day from 15 days before mating to the 7th day of pregnancy. At the dose of 3.0 mg/kg/day, the fertility index of female rats decreased, the average number of implantations decreased, and the post-implantation loss rate increased. In the rat embryo-fetal development toxicity test, no embryotoxicity and teratogenicity were observed at a dose of 3.0 mg/kg/day for dienogest: In the rabbit embryo-fetal development toxicity test, no teratogenicity was observed at a dose of 3.0 mgikg/day for dienogest, and the post-implantation loss rate increased at a dose of 3.0 mg/kg/day, and no significant effect was observed at a dose of 1.0 mg/kg/day. In the rat perinatal toxicity test, dienogest at a dose of 1 mg/kg/day can cause a decrease in the estrus frequency, mating index, and fertility index of the F1 generation, accompanied by a decrease in the number of implantations and the number of F2 generations, and no significant effect was observed at a dose of 0.3 mg/kg/day. The above fertility suppression is the result of ovulation inhibition and prolonged pregnancy, which is related to the progestin activity of dienogest. In the 104-week carcinogenicity study in mice, mice were orally given dienogest 5, 15, 50 mg/kg/day (male) and 10, 30, 100 mg/kg/day (female). The exposure of female mice was equivalent to 1.1, 3.5, and 10.6 times the exposure of women given 3 mg. The incidence of uterine stromal polyps in female mice increased at a dose of 100 mg/kg. In the 104-week carcinogenicity study in rats, female rats were orally given dienogest 1, 3, and 10 mg/kg/day, which was equivalent to 0.2, 1.4, and 6.1 times the exposure of women given 3 mg. No carcinogenicity was observed. It should be remembered that sex steroids can promote the growth of certain hormone-dependent tissues and tumors.

The main ingredient of this product is dienogest. Chemical name: 17-hydroxy-3-oxo-19-nor-17α-pregnane-4.9-diene-21-nitrile Molecular formula: C20H25NO2 Molecular weight: 311.42

This product is white or off-white tablets.

Treat endometriosis.

Oral, one tablet per day, without interruption, preferably at the same time every day, take with water when needed. This product can be taken after meals or on an empty stomach. The tablets must be taken continuously, regardless of whether vaginal bleeding occurs. If you finish one box, start taking the next box without interruption. You can start treatment with this product on any day of the menstrual cycle. Before starting treatment, you need to stop any hormonal contraceptive method. If you need contraception, you should use non-hormonal contraceptive methods (such as barrier contraception). Management of missed tablets. The efficacy of dienogest tablets is weakened in the event of missed tablets, vomiting and/or diarrhea (if it occurs within 3 hours after taking the medicine). In the case of missing 1 or more tablets, once you remember, the patient should take 1 tablet as soon as possible, and then should continue to take it at the previous time on the next day. If the tablet is not absorbed due to vomiting or diarrhea, you should also take one tablet.

Adverse reactions to dienogest tablets are most common in the first month after the start of treatment and gradually decrease as treatment continues. Changes in bleeding patterns may occur, such as spotting, irregular bleeding, or amenorrhea. The following adverse reactions have been reported in users of dienogest tablets. Current or past severe liver disease in which liver function values have not returned to normal Current or past liver tumors (benign or malignant) Known or suspected sex hormone-dependent malignancies Vaginal bleeding of unknown cause Allergy to active substances or excipients For patients with current or past severe liver disease, dienogest tablets are contraindicated. For patients with renal impairment, there are no data to suggest that dose adjustments are needed.

Dienogest should not be used in the following cases, which are partly derived from information on other progestogen preparations. If any of the following occur during the use of Dienogest, the drug must be discontinued immediately. New active venous thromboembolic disease Current or previous arterial and cardiovascular disease (such as myocardial infarction, cerebrovascular accident, ischemic heart disease) Diabetes with vascular disease potential. Rare cases of benign liver tumors have been reported in users of hormonal drugs (such as the substances contained in Dienogest). Cases of malignant liver tumors are even rarer. In individual cases, these tumors can cause life-threatening intra-abdominal bleeding. When women taking Dienogest experience severe upper abdominal pain, liver enlargement, or signs of intra-abdominal bleeding, the presence of liver swelling and pain should be considered in the diagnosis. Changes in bone mineral density (BMD) in osteoporosis In an uncontrolled clinical trial, 111 adolescent female patients (12-18 years old) took dienogest tablets. During the 12-month treatment period, the lumbar spine bone mineral density (BMD) decreased: from baseline to the end of treatment, the average decrease in lumbar spine (L2-L4) BMD was 1.2%, ranging from -6% to 5% (95% confidence interval: -1.70%--0.78%, n=103.) At the end of treatment, the subgroup of patients with reduced bone mineral density at the end of treatment was re-measured at the end of treatment. There was a trend of recovery (the subgroup had an average decrease of 2.3% compared with baseline at the end of treatment, and a decrease of 0.6% compared with baseline 6 months after the end of treatment, ranging from -9% to 6% (95% confidence interval: -1.20%-0.06%. n=60). Decreased bone density is an issue that needs to be considered during adolescence and early adulthood, a critical period of bone growth. It is unclear whether decreased bone density in this population will reduce peak bone mass and increase the risk of future fractures. Because endogenous estrogen levels are reduced after taking dienogest, physicians should weigh the benefits and potential risks before prescribing for each patient at risk of fracture. Adequate intake of calcium and vitamin D, whether through food or supplements, is very important for the bone health of women of all ages. No effect of dienogest on bone density in adult women has been observed. Other situations: Patients with a history of depression should be carefully observed, and if depression recurs to a severe degree, the drug should be discontinued. Dienogest tablets generally do not affect It affects the blood pressure of normotensive women. However, if persistent clinically significant hypertension occurs during the use of dienogest tablets, dienogest tablets should be discontinued and the hypertension should be treated. Cholestatic jaundice and/or pruritus that occurred during pregnancy or previous use of sex hormone drugs recurs while taking dienogest tablets and dienogest tablets need to be discontinued. Dienogest tablets may have a slight effect on peripheral insulin resistance and glucose tolerance. Women with diabetes, especially those with a history of gestational diabetes, should be carefully observed during the use of dienogest tablets. Chloasma may sometimes occur, especially in women with a history of chloasma during pregnancy. Women who are prone to chloasma should avoid exposure to sunlight or ultraviolet radiation while using dienogest tablets. Contraception using progestin-only preparations Users of dienogest are more likely to develop an ectopic pregnancy than users of combined oral contraceptives. Therefore, in women with a history of ectopic pregnancy or impaired fallopian tube function, the decision to use dienogest tablets should be made only after a careful balance of the benefits and risks. During the use of dienogest tablets, persistent follicles (often called functional ovarian cysts) may occur. Most of these follicles are asymptomatic, but some are associated with pelvic pain. Lactose Each dienogest tablet contains 62.8 mg of lactose monohydrate. The lactose content in dienogest tablets should be considered for patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption who are on a lactose-free diet. Effects on the ability to drive and operate machines No effects on the ability to drive and operate machines have been observed in users of products containing dienogest.

Precautions for children: Dienogest tablets are not suitable for use in children before menarche. The safety and efficacy of dienogest have been studied in an uncontrolled clinical trial for more than 12 months in 111 adolescent female patients (12-18 years old) with endometriosis (see Precautions). Therefore, doctors should prescribe it to adolescent female patients after weighing the benefits and potential risks. Precautions for pregnancy and lactation: Pregnancy should be excluded before starting to take dienogest tablets. Currently, there is limited data on the use of dienogest in pregnant women. Animal studies have not indicated direct or indirect adverse effects on reproductive toxicity (see [Pharmacology and Toxicology] section), but since endometriosis does not need to be treated during pregnancy, pregnant women should not be given dienogest tablets. Lactation medication is recommended not to use dienogest tablets for treatment during lactation. It is not clear whether dienogest is secreted into human milk, but animal data show that dienogest can be secreted in rat milk. The benefits of breastfeeding to the infant and the benefits of dienogest tablets to the mother must be weighed to decide whether to stop breastfeeding or discontinue treatment with dienogest tablets. Fertility According to existing data, ovulation is suppressed in most patients during treatment with dienogest tablets. However, dienogest tablets are not contraceptives. If contraception is required, non-hormonal contraceptive methods should be used (see [Usage and Use in Children]). According to existing data, the menstrual cycle returns to normal 2 months after stopping treatment with dienogest tablets. Precautions for the elderly: Elderly patients are not included in the applicable population for dienogest tablets.

Note: Consult your physician for concomitant medication information to determine potential drug interactions. Effects of Other Drugs on Dienogest Progestins, including dienogest, are primarily metabolized by the cytochrome P450 3A4 system (CYP3A4), which is located in the intestinal mucosa and liver. Therefore, inducers or inhibitors of CYP3A4 may affect progestin drug metabolism. Increased clearance of sex hormones due to enzyme induction may reduce the efficacy of dienogest tablets and may lead to adverse reactions such as changes in uterine bleeding patterns. Reduced clearance of sex hormones due to enzyme inhibition may increase exposure to dienogest and may lead to adverse reactions. Substances that increase the clearance of sex hormones I reduce effectiveness through enzyme induction, such as: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, as well as oxcarbazepine, topiramate, felbamate, griseofulvin, and drugs containing St. John's wort [Hypericum perforatum]. Enzyme induction occurs within a few days of taking the drug, with maximum enzyme induction occurring within a few weeks and may last for at least 4 weeks after stopping treatment. The effects of the CYP3A4 inducer rifampicin have been studied in postmenopausal women. Coadministration of rifampicin with estradiol/dienogest tablets resulted in a significant decrease in the steady-state plasma concentrations and systemic exposure of dienogest and estradiol. Systemic exposure to dienogest and estradiol, as measured by AUC1024, decreased by 83% and 44%, respectively. Substances that cause changes in sex hormone clearance: When used in combination with sex hormones, many HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors, including HCV inhibitors, increase or decrease the plasma concentrations of estrogens and progestins, and such changes may be clinically significant in some cases. Substances that reduce sex hormone clearance: Dienogest is a substrate of cytochrome P4503A4 (CYP3A4), and the clinical relevance of potential interactions with enzyme inhibitors is unknown. Concomitant use with strong CYP3A4 inhibitors may increase the plasma concentration of dienogest. Co-administration with the strong CYP3A4 inhibitor ketoconazole increased the AUC10-24 of dienogest at steady state by 2.9-fold. Co-administration with the moderate inhibitor erythromycin increased the AUCio2453 of dienogest at steady state by 1.6-fold. Effects of Dienogest on Other Drugs Based on in vitro inhibition studies, clinically relevant interactions of dienogest with other drugs metabolized by cytochrome P450 enzymes are unlikely. Interactions with Food A standardized high-fat meal did not affect the bioavailability of dienogest tablets. Laboratory Tests The use of progestins may affect the results of certain laboratory tests, including liver, thyroid, adrenal and renal function and (carrier) protein plasma levels, biochemical parameters such as corticosteroid binding globulin and lipid lipoprotein composition, carbohydrate metabolism parameters, and coagulation parameters and fibrinolysis parameters. The changes that occurred generally remained within the normal laboratory range.

Not exceeding 25°C. Store tightly closed in original packaging.

2mg*28 tablets

60 months