Warning

If any of the following conditions/risk factors exist, each woman should weigh the benefits of taking COCs against the possible risks and discuss them with her before she decides to start taking them. Have a discussion. If any of the following conditions or risk factors worsen, worsen, or appear for the first time, you should contact your doctor. The physician should decide whether the COC should be discontinued.

· Circulatory system diseases

Epidemiological studies have shown that the use of COCs is associated with arterial and venous thrombosis and thromboembolic diseases such as myocardial infarction, deep vein thrombosis, and pulmonary embolism. associated with an increased risk of cerebrovascular events. These events occur rarely.

The risk of venous thromboembolism (VTE) is highest within the first year of use. The risk is increased when starting a COC or when using the same or a different COC again (with a discontinuation interval lasting 4 weeks or longer). Data from a large prospective 3-arm cohort study showed that the increased risk occurred mainly in the first 3 months.

In short, the risk of venous thromboembolism in women who use COCs containing low-dose estrogen (< 50?g ethinyl estradiol) is 2-3 times higher than in women who do not use COCs and are not pregnant, but the risk is lower than that in pregnant women. and childbirth.

VTE can be life-threatening or cause death (1%-2%).

Epidemiological studies have shown that the risk of VTE in drospirenone-containing OCs is higher than that of levonorgestrel-containing OCs (i.e., second-generation oral contraceptives), which may be related to the risk of VTE in OCs containing desogestrel/gestodene. The risks with keto OCs (i.e., third-generation oral contraceptives) are comparable.

Venous thromboembolism (VTE) manifests as deep vein thrombosis and/or pulmonary embolism and may occur during the use of all COCs.

Extremely rare, thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral or retinal veins and arteries, has been reported in COC users. There is currently no consensus on whether the occurrence of these events is related to the use of COCs.

Symptoms of deep vein thrombosis (DVT) include: swelling of one leg or veins along the leg; pain or tenderness in the leg when standing or walking; increased warmth in the leg; itchiness of the skin on the leg Red or discolored.

Symptoms of pulmonary embolism (PE) may include sudden, unexplained shortness of breath or shortness of breath; a sudden cough that may be accompanied by bleeding; sharp chest pain that may be accompanied by increased deep breathing; anxiety; severe dizziness or vertigo; rapid or Irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are not pathognomonic and may be thought to result from other common or less severe events (eg, respiratory infection).

Arterial thromboembolic events may include cerebrovascular accident, vascular occlusion or myocardial infarction (MI). Symptoms of a cerebrovascular accident may include: Sudden numbness or weakness in the face, arms, or legs, especially on one side of the body; Sudden confusion, speech or comprehension problems; Sudden unilateral or bilateral vision impairment; Sudden visual impairment on one or both sides; Difficulty walking, dizziness, loss of balance or coordination; sudden, severe or unexplained long-term headache; loss of consciousness or fainting with or without epileptic seizures. Other signs of vaso-occlusion may include sudden pain, swelling and bluish discoloration of the extremities; acute abdominal pain.

Symptoms of myocardial infarction (MI) include: chest, arm or substernal pain, discomfort, pressure, heaviness, squeezing or fullness; discomfort radiating to the back and jaw , throat, arms, stomach; feeling of fullness, indigestion, or suffocation; sweating, nausea, vomiting, or dizziness; extreme weakness, anxiety, or shortness of breath; fast or irregular heartbeat.

Arterial thromboembolic events can be life-threatening or lead to death.

In women with multiple risk factors or in whom a single risk factor is severe, the possibility of a synergistic increased risk of thrombosis must be considered. This increased risk may be greater than the simple sum of the individual factors. If the risk-benefit assessment is negative, COCs should not be prescribed (see Contraindications).

The risk of venous or arterial thrombosis/thromboembolic events or cerebrovascular accidents may increase with:

- Increasing age;

- Obesity (weight Index exceeds 30 kg/m2);

- Positive family history (i.e., siblings or parents have suffered from venous or arterial thromboembolism at an earlier age). If a genetic predisposition is suspected, a specialist should be consulted before deciding to use any COC;

- Prolonged immobilization, major surgery, any leg surgery, or major trauma. In these cases, it is recommended to stop taking COCs (at least 4 weeks before elective surgery) and not resume taking COCs until two weeks after full recovery of activity.

- Smoking (the risk further increases with heavy smoking and age, especially women over 35 years old);

- Dyslipoproteinemia;

- Hypertension;

- Migraines;

- Valvular heart disease;

- Atrial fibrillation;

For varicose veins and superficial thrombophlebitis in venous thromboembolism, there is no consensus.

The increased risk of thromboembolism during the puerperium should be considered (see Medication in Pregnant and Lactating Women).

Other clinical conditions associated with adverse circulatory events include diabetes mellitus, 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 of migraine attacks or pain intensity increases (which may be a prodromal symptom of a cerebrovascular accident). This may require immediate discontinuation of COC.

Biochemical factors suggesting possible hereditary or acquired predisposition to venous or arterial thrombosis, including active protein C (APC) resistance, homocystinemia, and antithrombin III deficiency , protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulants).

When weighing the risks and benefits, physicians should consider that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk of thrombosis is higher with pregnancy than with the use of low-dose COCs ( Risks associated with ethinyl estradiol <0.05 mg).

· 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. But there has been controversy over the extent to which this result is attributable to confounding effects such as cervical screening and sexual behavior including the use of barrier contraception.

A meta-analysis of 54 epidemiological studies showed that women currently using COCs had a slightly increased relative risk of being diagnosed with breast cancer (RR=1.24). Over the 10 years after COC use was stopped, the increased risk gradually disappeared. Because breast cancer rarely occurs in women under 40 years of age, the increased number of breast cancer diagnoses among current and recent COC users is small relative to the overall risk of breast cancer. These studies provide no evidence of cause and effect. The observed increased risk may be due to earlier breast cancer diagnosis in COC users, biological effects of COCs, or both. Compared with those who have never used COCs, the breast cancer of those who have used COCs is often at an earlier clinical stage.

Rare benign liver tumors and even rarer malignant liver tumors have been reported in users of COCs. In isolated cases, these tumors have caused life-threatening intra-abdominal bleeding. When women taking COCs experience severe epigastric pain, liver enlargement, or signs of intra-abdominal bleeding, liver tumors should be considered in the differential diagnosis.

Malignant tumors can be life-threatening or cause death.

· Other conditions

In patients with renal insufficiency, potassium excretion capacity is limited. In a clinical study, administration of drospirenone to patients with mild or moderate renal impairment showed no effect on serum potassium concentrations. Only patients with renal impairment whose pretreatment serum potassium is in the upper limit of the normal range and who are taking potassium-sparing diuretics are theoretically at risk for hyperkalemia.

For women with hypertriglyceridemia or a family history, taking COCs may increase the risk of pancreatitis.

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 in normotensive women taking other COCs may be antagonized by the antimineralocorticoid effects of drospirenone. However, if persistent clinically significant hypertension develops during use of a COC, physicians should carefully consider discontinuing the COC and treating the hypertension. If your blood pressure returns to normal after antihypertensive treatment, you can resume taking COC when your doctor considers it appropriate.

The following conditions have been reported to occur or worsen during pregnancy and while taking COCs, but the evidence associated with COC use is inconclusive: jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyrins disease; systemic lupus erythematosus; hemolytic uremic syndrome; chorea minor; herpes pregnancy; hearing loss associated with otosclerosis.

In women with hereditary angioedema, exogenous estrogens can induce or worsen the symptoms of angioedema.

Acute or chronic liver function abnormalities require discontinuation of COC until liver function indicators return to normal. COCs should be discontinued when cholestatic jaundice first occurs during pregnancy or during previous use of sex steroids.

Although COCs may affect peripheral insulin resistance and glucose tolerance, there is no evidence that patients with diabetes taking low-dose COCs (ethinyl estradiol <0.05 mg) need to change their treatment regimen. However, women with diabetes should be carefully observed while taking COCs.

Crohn's disease and ulcerative colitis are related to the use of COCs.

Chloasma occurs occasionally, especially in women with a history of chloasma of pregnancy. Women prone to chloasma should avoid exposure to sunlight or ultraviolet radiation while taking COCs.

Each tablet contains 46 mg of lactose. It should be considered in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption who are unable to consume lactose.

Medical examination/consultation

Before taking COC for the first time or again, a complete medical history and comprehensive examination should be collected in accordance with the requirements of contraindications (see Contraindications) and warnings (see Precautions). physical examination and regular reexamination.

Regular medical evaluation is also important because contraindications (e.g., transient ischemic attack, etc.) or risk factors (e.g., family history of venous or arterial thrombosis) may appear for the first time while taking COCs. The frequency and nature of these medical evaluations should be based on established clinical practice 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

The efficacy of COC may be reduced if doses are missed (see Dosage and Administration), gastrointestinal disorders (see Dosage and Administration), or when other drugs are taken at the same time (see Drugs interaction).

Impact on cycle control

Irregular bleeding (spotting or breakthrough bleeding) may occur in all COCs users, especially during the first few months of use. Therefore, evaluation of any irregular bleeding is only meaningful after an adaptation period of approximately 3 cycles.

If irregular bleeding persists or occurs after regular cycles, non-hormonal causes should be considered and appropriate diagnostic measures taken to rule out malignancy or pregnancy. These measures may include dilation and curettage.

Some women may not experience withdrawal bleeding during the withdrawal period. It is unlikely that women will become pregnant if COCs are taken as described in Dosage and Administration. However, if withdrawal bleeding does not occur for the first time without taking the medicine according to these methods, or if withdrawal bleeding does not occur twice, pregnancy must be ruled out before continuing to take COC.

·Laboratory tests

The use of steroidal contraceptives may affect the results of certain laboratory tests, including biochemical indicators of liver, thyroid, adrenal gland and renal function, plasma (carrier) Protein levels such as corticosteroid binding globulin and lipid/lipoprotein ratio, carbohydrate metabolism markers, and coagulation and fibrinolysis markers. Changes generally remain within the normal laboratory range. Drospirenone causes an increase in plasma renin activity and its mild antimineralocortic activity induces an increase in plasma aldosterone levels.

No studies have been conducted on the effects on the ability to drive or operate machinery. No effects of COC use on the ability to drive or operate machinery were observed.

Store all medications properly and out of the reach of children.