Drospirenone ethinyl estradiol tablets

Pharmacological effects The contraceptive effect of combined oral contraceptives (COCs) is based on the interaction of multiple factors, the most important of which are the inhibition of ovulation and changes in cervical secretions. In addition to the contraceptive effect, COCs have many favorable properties, despite the unfavorable properties mentioned in (Warnings and Adverse Reactions): more regular menstrual cycles, less dysmenorrhea, and less bleeding. The latter can reduce the occurrence of iron deficiency. A large prospective 3-group cohort study showed that the use of low-dose estrogens (ethinyl estradiol) drospirenone has other favorable properties besides contraception. Drospirenone has anti-mineralocorticoid activity, which can prevent weight gain and other symptoms caused by fluid retention. It antagonizes sodium retention associated with estrogen, provides good tolerability, and has a positive effect on premenstrual syndrome (PMS). In combination with ethinyl estradiol, drospirenone increases high-density lipoprotein (HDL) levels and shows a favorable lipid profile. The anti-androgenic activity of drospirenone has a favorable effect on the skin, reducing acne lesions and sebum production. In addition, drospirenone does not antagonize the increase in sex hormone binding globulin (SHBG) associated with ethinyl estradiol, which favors binding to endogenous androgens and inactivating them. Drospirenone It does not have any androgenic, estrogenic, glucocorticoid, or antiglucocorticoid activity. This property, combined with its anti-mineralocorticoid and anti-androgenic properties, makes the biochemical and pharmacological properties of drospirenone very similar to those of natural progestins. In addition, there is evidence that the risk of endometrial and ovarian cancer is reduced. Moreover, higher doses of COCs (ethinylestradiol 0.05 mg) have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease, and ectopic pregnancy. Whether this also applies to lower doses of COCs remains to be confirmed. Toxicology studies Routine preclinical tests for repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity have shown no particular risk to humans. However, it must be remembered that sex steroids may promote the growth of certain hormone-dependent tissues and tumors.

This product is a compound preparation, and its components are: each tablet contains 3 mg of drospirenone and 0.03 mg of ethinyl estradiol.

Light yellow film-coated tablets, appear white after removing the coating.

Female contraception

It is unlikely that a woman will become pregnant if she takes a COC as described in the guidelines. However, if these guidelines are not followed before the first withdrawal bleeding, or if withdrawal bleeding does not occur for two consecutive times, pregnancy must be excluded before continuing to take the COC. Laboratory tests The use of steroidal contraceptives may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma (carrier) protein levels such as corticosteroid binding globulin and lipid/lipoprotein fractions, carbohydrate metabolism parameters, and coagulation and fibrinolysis parameters. Changes usually remain within normal laboratory test ranges. Drospirenone causes an increase in plasma renin activity, and its mild antimineralocorticoid activity induces an increase in plasma aldosterone levels. Studies on the effects on the ability to drive and use machinery have not been conducted. No effects of COCs on the ability to drive and use machinery have been observed. Store all medications out of the reach of children. Route of administration Oral administration How to take This product has a contraceptive failure rate of about 1% per year with combined oral contraceptives if taken correctly. The contraceptive failure rate increases if a dose is missed or if the method of administration is incorrect. The tablets must be taken in the order indicated on the package, at approximately the same time each day, with a small amount of liquid. Take 1 tablet daily for 21 consecutive days. The next pack of pills should be started 7 days after the last pill of the cycle, during which time there will usually be a withdrawal bleed. Bleeding usually starts 2-3 days after the last pill of the cycle is taken, and may not have ended when the next pack of pills is started. How to start taking this product · Women who have not used hormonal contraceptives (in the past month) before starting this product should start taking the pills on the first day of the woman's natural menstrual cycle (i.e. the first day of menstrual bleeding). It is also possible to start on days 2-5. In this case, it is recommended to add a barrier method of contraception during the first 7 days of the first pill cycle. · Women who are switching from another combined hormonal contraceptive (combined oral contraceptive/COC), vaginal ring or transdermal patch should preferably start taking this product on the second day after taking the last hormonal pill of the previous COC, or at the latest immediately after the end of the withdrawal period of the previous COC or the end of the use of non-hormonal pills. For women who have used vaginal rings or transdermal patches, it is best to start taking this product on the day of removal, but at the latest, it should be started on the next dose. · Women who are switching from a progestogen-only method (minipills, injections, implants) or from a progestogen-releasing intrauterine system (IUS) can switch from minipills to this product at any time (from implants or IUS should be on the day of removal, from injections should be on the next injection day), but in all these cases, it should be recommended to add a barrier method of contraception during the first 7 days of taking the drug. · Women who have had an abortion in early pregnancy can start taking the drug immediately. In this case, no other contraceptive method is needed. · For breastfeeding women after childbirth or abortion in mid-term pregnancy, see the method of taking the drug after delivery or mid-term abortion.

Safety Summary The most commonly reported adverse reactions for this product are nausea and breast pain. These adverse reactions have occurred in more than 6% of users. Serious adverse reactions include arterial and venous thromboembolism. List of Adverse Reactions The incidence of adverse reactions reported in clinical trials of this product (a total of 4897 cases) is summarized in the table below. In each frequency group, adverse reactions are listed in descending order of severity. Frequency is defined as common (≥1/100 to adverse events in clinical trials using the MedDRA dictionary (version 12.1). Different MedDRA terms expressing the same medical phenomenon are combined into one adverse reaction to avoid diluting or masking the true effect. *- The incidence estimate comes from epidemiological studies. The incidence in the combined oral contraceptive group is borderline very rare. *- "Arterial and venous thromboembolic events" includes the following medical entities: peripheral deep vein occlusion, thrombosis and embolism/pulmonary vascular occlusion, thrombosis, embolism and infarction/myocardial infarction/cerebral infarction and non-hemorrhagic stroke. For arterial and venous thromboembolic events and migraine, see also

As required by the FDA and FDA's Warnings and Warnings (see ), a complete medical history and physical examination should be obtained and reviewed regularly. Periodic medical evaluations are also important because contraindications (e.g., transient ischemic attack) or risk factors (e.g., family history of venous or arterial thrombosis) may first appear during COC use. The frequency and nature of these medical evaluations should be based on established clinical practices and tailored to the individual woman, but should generally focus on blood pressure, breast, abdominal, and pelvic organs, including cervical cytology. Women should be informed that oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases. Reduced efficacy if missed doses occur (see Combined oral contraceptives (COCs) should not be used in any of the following situations. If any of the following situations occur for the first time during COC use, the drug must be discontinued immediately. Presence of, or history of, venous or arterial thrombosis/thromboembolism (e.g., deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular accident Presence of prodromal symptoms or relevant medical history of thrombosis (e.g., transient ischemic attack, angina pectoris) Presence of severe or multiple risk factors for venous or arterial thrombosis (see

Precautions for children: This product can only be used after menarche. There is no data showing that the dosage needs to be adjusted. Precautions for pregnancy and lactation: This product is contraindicated during pregnancy. If pregnancy occurs during the use of this product, the medication must be discontinued. However, a large number of epidemiological studies have shown that the incidence of birth defects in infants born to women who took COCs before pregnancy has not increased, and the teratogenic effects of women who took COCs during early pregnancy have not increased. There was a case of a child born with esophageal atresia. The causal relationship between this event and this product is unclear. The data on taking this product during pregnancy are very limited, and no conclusions can be drawn on adverse effects on pregnancy, fetal or neonatal health. There is no relevant epidemiological data to date. Lactation Lactation may be affected by COCs because they can reduce milk secretion and change the composition of milk. Therefore, COCs are usually not recommended before lactating women are completely weaned. Small amounts of contraceptive steroid hormones and/or their metabolites may be secreted from breast milk. Other clinical conditions associated with circulatory adverse events include diabetes, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell disease. During COC use, the frequency or pain of migraine attacks increases (which may be a prodromal symptom of cerebrovascular accident), which may require immediate discontinuation of COC. Biochemical factors that suggest a possible inherited or acquired predisposition to venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulants). When weighing the benefits and risks, doctors should take into account that adequate treatment of a condition may reduce the risk of associated thrombosis, and that the risk of thrombosis associated with pregnancy is higher than that associated with the use of low-dose COCs (ethinyl estradiol·tumor). The most important risk factor for cervical cancer is persistent HPV infection. Some epidemiological studies have shown that long-term use of COCs can further increase this risk. However, there has been controversy as to the extent to which this result should be attributed to confounding effects, such as cervical screening and sexual behavior including the use of barrier contraceptive measures. A meta-analysis of 54 epidemiological studies showed that women who are currently using COCs have a slightly increased relative risk of being diagnosed with breast cancer (RR=1.24). The increased risk gradually disappears within 10 years after stopping COC use. Because breast cancer rarely occurs in women under 40 years old, the number of increased breast cancer diagnoses in current and recent COC users is small relative to the overall risk of breast cancer. This These studies do not provide causal evidence. The observed increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs, or both. Breast cancer in former COC users is often clinically at an earlier stage than in those who have never used COCs. Rare benign liver tumors and, even more rarely, malignant liver tumors have been reported in COC users. In individual cases, these tumors have caused life-threatening intra-abdominal hemorrhage. Liver tumors should be considered in the differential diagnosis of women taking COCs who present with severe epigastric pain, liver enlargement, or signs of intra-abdominal hemorrhage. Malignant tumors may be life-threatening or result in death. Other situations In patients with renal insufficiency, the ability to excrete potassium is limited. In a clinical study, drospirenone was shown to have no effect on serum potassium concentrations in patients with mild or moderate renal impairment. Only in patients with renal impairment whose serum potassium was in the upper normal range before treatment and who were taking potassium-sparing diuretics, in theory, should drospirenone be used. There may be a risk of hyperkalemia. Women with hypertriglyceridemia or a family history of COCs may be at increased risk of pancreatitis when taking COCs. Although mild increases in blood pressure have been reported in many women taking COCs, clinically significant increases are rare. The increase in blood pressure induced by ethinyl estradiol when used by other COCs in normotensive women may be counteracted by the antimineralocorticoid effects of drospirenone. However, if persistent clinically significant hypertension occurs during the use of a COC, the physician should carefully consider discontinuing the COC and treating the hypertension. If blood pressure returns to normal after antihypertensive treatment, COCs may be resumed when the physician considers it appropriate. The following conditions have been reported to occur or worsen during pregnancy and while taking COCs, but the evidence for an association with COC use is inconclusive: jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes gestationis; hearing loss associated with otosclerosis. In women with hereditary angioedema, exogenous estrogens may induce or worsen symptoms of angioedema. Acute or chronic liver dysfunction requires discontinuation of COC use until liver function tests return to normal. COCs should be discontinued in the event of recurrence of cholestatic jaundice that first occurred during pregnancy or during previous use of sex steroids. Although COCs may affect peripheral insulin resistance and glucose tolerance, there is no evidence that low-dose COCs (ethinylestradiol, Crohn's disease and ulcerative colitis) are associated with COC use. Chloasma occasionally occurs, especially in women with a history of chloasma gestationis. Women who are prone to chloasma should avoid exposure to sunlight or ultraviolet radiation while taking COCs. Each tablet contains 46 mg of lactose. This should be considered for patients who cannot ingest lactose due to the rare hereditary conditions of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Medical examination/consultation Before taking a COC for the first time or again, follow the contraindications (see Women should be advised to take chloasma). Women should start taking it on the 21st to 28th day after childbirth or miscarriage in the second trimester. If started later, women should be advised to use a barrier contraceptive method during the first 7 days of taking the medicine. However, if sexual intercourse has already occurred, the possibility of pregnancy should be ruled out before starting to take this product, or it should be taken until the first menstrual period. Treatment of missed pills If the user forgets to take the pill within 12 hours, the contraceptive protection will not be reduced. Once the woman remembers, she must take it immediately, and the next pill should be taken at the regular time. If the time of forgetting to take the pill exceeds 12 hours, the contraceptive protection may be reduced. The following two basic principles can be followed in the treatment of missed pills: 1. In any case, the pill should not be stopped for more than 7 days. 2. It is necessary to take it continuously for 7 days to maintain adequate suppression of the hypothalamic-pituitary-ovarian axis. Therefore, the following advice can be given in daily medication: · In the first week, users should take the missed pills as soon as they remember, even if it means taking two pills at the same time. Then continue at the regular time. Continue to take the pills. In addition, a barrier method of contraception such as condoms should be used for the next 7 days. If sexual intercourse has occurred within the previous 7 days, the possibility of pregnancy should be considered. The more pills missed and the closer to the regular pill-free period, the higher the risk of pregnancy. · In week 2, the woman should take the missed pills as soon as she remembers, even if this means taking two pills at the same time. Then continue taking the pills at the regular time. If the woman has taken the pills correctly in the 7 days before the first missed pill, she does not need to use additional contraceptive measures. However, if this is not the case, or if more than one pill is missed, she should be advised to use additional contraceptive measures for 7 days. · In week 3, because it is close to the pill-free period, the risk of reduced contraceptive reliability increases. However, it is still possible to prevent a reduction in contraceptive protection by adjusting the pill-taking schedule. If the woman has taken the pills correctly in the 7 days before the first missed pill, the woman does not need to use additional contraceptive measures if she follows either of the following two suggestions. If this is not the case, the woman is advised The woman follows the first of these two recommendations and uses additional contraceptive measures for the next 7 days. 1. The user should take the missed pill as soon as she remembers, even if this means taking two pills at the same time. Then continue taking the pills at the regular time. Start the next pack of pills immediately after the current pack is finished, i.e. there is no pill-free period between packs. The user is unlikely to have withdrawal bleeding until the second pack is finished, but spotting or breakthrough bleeding may occur between pill-free periods. 2. The woman may also be advised not to continue taking the pills for that cycle. The woman should take a 7-day pill-free period that includes the number of days she missed, and then start taking the next pack of pills. If the woman misses a pill and does not have withdrawal bleeding during the first normal pill-free period that follows, the possibility of pregnancy should be considered. [u]Advice for those who experience gastrointestinal disturbances[/u]If severe gastrointestinal disturbances occur, absorption may be incomplete and additional contraceptive measures should be used. If it occurs within 3-4 hours of taking the pills, If a woman does not want to change her regular dosing schedule, she must take the pills from the next pack. [u]How to change or delay her period[/u] To delay her period, a woman can take one pack of pills and then continue to take the next pack without a pill-free interval. She can delay her period until any time before the second pack is finished, if she wishes. Breakthrough bleeding or spotting may occur with extended dosing. She can resume regular dosing after the usual 7-day pill-free interval. If she wishes to change her current period to another day of the week, she can be advised to shorten the pill-free interval to the time she wishes. The shorter the pill-free interval, the greater the risk of not having withdrawal bleeding and of having breakthrough bleeding and spotting during the next pack (as described for delaying a period). Use in special populations Patients with impaired liver function Women with severe liver disease should not use this product: see Elderly Precautions: Not applicable. This product should not be used after menopause.

Interactions Interactions of other drugs (enzyme inducers, certain antibiotics) with oral contraceptives may result in breakthrough bleeding and/or contraceptive failure. Women taking these drugs should temporarily add a barrier method of contraception or choose an alternative contraceptive method in addition to their COCs. A barrier method of contraception should be used during concomitant use of microsomal enzyme-inducing drugs and for 28 days after discontinuation. Women taking concomitant antibiotics (except rifampicin and griseofulvin) should use a barrier method of contraception until 7 days after discontinuation. If a barrier method of concomitant contraception is used beyond the last tablet in the COC pack, the next pack should be started without the usual break. Substances that reduce the effectiveness of COCs (enzyme inducers and antibiotics) Enzyme induction (increased hepatic metabolism): Drug interactions with drugs that induce microsomal enzymes can result in increased clearance of sex hormones (such as phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly oxcarbazepine, topiramate, felbamate, griseofulvin, and products containing St. John's wort). HIV protease (e.g., ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine), and their combination, have been reported to have potential effects on hepatic metabolism. Antibiotics (affecting enterohepatic circulation): Clinical reports suggest that the use of certain antibiotics (e.g., penicillins, tetracyclines) may reduce the enterohepatic circulation of estrogens, resulting in decreased serum ethinylestradiol concentrations. Substances that affect the metabolism of combined hormonal contraceptives (enzyme inhibitors) The production of the major metabolites of drospirenone in human plasma does not involve the cytochrome P450 system. Therefore, inhibitors of this enzyme system are unlikely to affect the metabolism of drospirenone. Effects of COCs on Other Drugs Oral contraceptives may affect the metabolism of certain other drugs, so that their plasma and tissue concentrations may be increased (e.g., cyclosporine) or decreased (e.g., lamotrigine). Based on in vitro inhibition studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin, and midazolam as labeled substrates, it can be concluded that drospirenone is unlikely to interact with the metabolism of other drugs at a dose of 3 mg. Other interactions When used with other drugs that can increase serum potassium concentrations, women taking this product may theoretically have increased serum potassium levels. This class of drugs includes angiotensin II receptor antagonists, potassium-sparing diuretics and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone (combined with ethinyl estradiol) with ACE antagonists or indomethacin, no clinically significant or statistically significant changes in serum potassium concentrations were observed. Note: The prescribing information of concomitant medications should be consulted to detect possible interactions. Interactions between other drugs (enzyme inducers, certain antibiotics) and oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure (see). Phase III clinical trials conducted in China showed that 163 (28.6%) of the 570 patients in the Yasmin group in the entire clinical trial had drug-related adverse events. The three most common treatment-related adverse events (incidence greater than or close to 5%) were irregular uterine bleeding (36 cases, or 6.3%), nausea (27 cases, or 4.7%), and mood swings (32 cases, or 5.6%). These events are known adverse reactions of combined oral contraceptives. In the trial, the serious adverse events that were definitely related to the trial drug in the Yasmin group were 2 cases (0.4%) of pregnancy, and both patients had a record of missing or delaying the medication before the pregnancy was discovered. No other serious adverse reactions occurred in patients taking Yasmin.

Store below 30°C.

21 tablets (drospirenone 3mg ethinylestradiol 0.03mg)

36 months