Dimia, 28 pcs., 3 mg+0.02 mg, film-coated tablets

Instructions for use DIMIA® (DIMIA®)

If any of the conditions/risk factors listed below exist, the benefit of taking combined oral contraceptives should be assessed individually for each woman and discussed with her before starting use. If an adverse event worsens or if any of these conditions or risk factors occur, the woman should contact her doctor to decide whether to continue or interrupt the combined oral contraceptive.

In the case of suspected or established venous or arterial thromboembolism, combined hormonal contraceptives should be discontinued. If anticoagulant therapy is initiated, adequate alternative contraception should be initiated to avoid the teratogenic effects of anticoagulant therapy (coumarins).

The use of any combined oral contraceptive increases the risk of venous thromboembolism (VTE). Drugs containing levonorgestrel, norgestimate, or norethisterone are associated with the lowest risk of VTE. Other drugs, such as Dimia®, have twice the risk. The decision to use a drug that is not included in the list with the lowest risk should be made only after a conversation with the woman. Make sure she understands the risk of VTE when taking Dimia®, how it is affected by her risk factors, and that the greatest risk of developing VTE is observed in the first year of using the drug. In addition, there is evidence that the risk increases when combined hormonal contraceptives are resumed after a break of 4 weeks or more.

Over the course of a year, VTE develops in approximately 2 in 10,000 women who are not pregnant and not taking combined hormonal contraceptives. However, a woman's individual risk may be much higher, given her risk factors.

It is estimated1 that of 10,000 women using combined hormonal contraceptives containing drospirenone, 9–12 will develop VTE within a year (compared with approximately 62 women using combined hormonal contraceptives containing levonorgestrel).

In both cases, the number of VTEs per year is less than the number expected during pregnancy or the postpartum period.

VTE can be fatal in 1-2% of cases.

In very rare cases, thrombosis of other vessels (for example, hepatic, mesenteric, renal or retinal veins and arteries) has been reported in patients taking combined hormonal contraceptives.

1 These incidence rates were obtained by analyzing a pool of data from epidemiological studies using relative risks for different drugs compared with combined hormonal contraceptives containing levonorgestrel.

2 The median range of 5–7 cases per 10,000 woman-years, based on the magnitude of the relative risk for levonorgestrel-containing combined hormonal contraceptives compared with non-drug-related events, is approximately 2.3–3.6.

Risk factors for developing VTE

The risk of developing venous thromboembolic complications when using combined hormonal contraceptives may increase significantly in women with additional risk factors, in particular those with multiple risk factors (see Table 1).

Dimia® is contraindicated in women with multiple risk factors that place the patient at high risk of developing venous thrombosis. If a woman has more than one risk factor, a situation may arise in which the risk increases to a greater extent than with a simple summation of individual factors:

• in this case, the overall risk of developing VTE should be taken into account. If the benefit/risk ratio is assessed as unfavorable, the use of combined hormonal contraceptives should be abandoned.

Table 1. Risk factors for developing VTE

There is no consensus on the possible role of varicose veins and superficial vein thrombophlebitis in the development or progression of venous thrombosis.

The increased risk of thromboembolism during pregnancy and especially in the first 6 weeks of the postpartum period should be taken into account.

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

If symptoms occur, the woman should seek emergency medical attention and notify the health care provider that she is using a combined hormonal contraceptive.

Symptoms of deep vein thrombosis (DVT):

• unilateral swelling of the lower limb and/or foot or the presence of swelling along the vein in the lower limb;
• pain or tenderness in the lower extremity that may only be felt when standing or walking;
• increased temperature of the affected lower limb, redness or discoloration of the skin of the lower limb.

Symptoms of pulmonary embolism (PE):

• sudden onset of unexplained shortness of breath or rapid breathing;
• sudden cough, which may be accompanied by hemoptysis;
• sharp chest pain;
• severe dizziness;
• fast or irregular pulse.

Some of the symptoms reported (eg, shortness of breath, cough) are nonspecific and for this reason may be misinterpreted as more common or less severe conditions (eg, respiratory tract infections).

Other signs of vascular occlusion may include:

• sudden pain, swelling and slight cyanosis of the limb.

With retinal vascular occlusion, symptoms may range from blurred vision without pain to progressive vision loss. In some cases, sudden loss of vision may occur.

Risk of developing arterial thromboembolism (ATE)

The results of epidemiological studies have linked the use of combined hormonal contraceptives with an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular accident (for example, transient ischemic attack, stroke). Arterial thromboembolic complications can be fatal.

Risk factors for developing ATE

The risk of developing arterial thromboembolic complications or cerebrovascular accidents during the use of combined hormonal contraceptives increases in the presence of risk factors (see Table 2). Dimia® is contraindicated in women with one serious or multiple risk factors for the development of ATE, on the basis of which she can be classified as a high risk group for the development of arterial thrombosis. If a woman has multiple risk factors, it is possible that the increase in risk is greater than the sum of the individual factors, in which case the magnitude of the overall risk should be considered. Combined hormonal contraceptives should not be prescribed if the benefit/risk ratio is assessed as negative.

Table 2. Risk factors for developing ATE

Symptoms of ATE

If symptoms occur, the woman should seek emergency medical attention and notify the health care provider that she is using a combined hormonal contraceptive.

Symptoms of acute cerebrovascular accident:

• sudden numbness or weakness of the muscles of the face, upper or lower extremities, especially on one side of the body;
• sudden disturbance in gait, dizziness, loss of balance or coordination;
• sudden onset of confusion, difficulty speaking or understanding;
• sudden loss of vision in one or both eyes;
• sudden onset of severe or prolonged headache without a known cause;
• loss of consciousness or fainting with or without convulsions.

The temporary nature of the symptoms indicates that this phenomenon is a transient ischemic attack (TIA).

Symptoms of a heart attack may include:

• pain, discomfort, a feeling of pressure, heaviness, a feeling of tightness or fullness in the chest, upper limb or below the sternum;
• discomfort radiating to the back, lower jaw, throat, arm, stomach;
• feeling of fullness in the stomach, indigestion, or choking;
• sweating, nausea, vomiting, or dizziness;
• a state of extreme weakness, anxiety or shortness of breath;
• fast or irregular pulse.

Tumors

Some epidemiological studies have reported an increased risk of cervical cancer in women receiving combined oral contraceptives for more than 5 years. However, there is no consensus on the extent to which sexual behavior and other factors, such as the human papillomavirus (HPV), influence this disease.

A meta-analysis of the results of 54 epidemiological studies found a slight increase in the relative risk (RR = 1.24) of breast cancer in women taking combined oral contraceptives. The risk gradually decreases over 10 years after stopping combined oral contraceptives. Because Breast cancer is rare in women under 40 years of age, and an increase in the number of diagnosed cases of breast cancer in users of combined oral contraceptives has little effect on the overall likelihood of breast cancer. These studies did not find sufficient evidence of causality. The increased risk may result from earlier diagnosis of breast cancer in combined oral contraceptive users, the biological effects of combined oral contraceptives, or a combination of both. Diagnosed breast cancer in women who had ever taken combined oral contraceptives was clinically less severe than cancer in women who had never taken combined oral contraceptives.

In rare cases, benign liver tumors and, even more rarely, malignant liver tumors have been reported in women taking combined oral contraceptives. In some cases, these tumors were life-threatening due to intra-abdominal bleeding. In women taking combined oral contraceptives, if there is severe upper abdominal pain, liver enlargement, or signs of intra-abdominal bleeding, a liver tumor should be considered in the differential diagnosis.

When taking combined oral contraceptives with the highest hormone content (50 mcg ethinyl estradiol), the risk of endometrial and ovarian cancer is reduced. However, it has not yet been proven whether this applies to combined oral contraceptives with low hormone content.

Other states

The progestogen component of the drug Dimia® is an aldosterone antagonist that retains potassium in the body. In most cases, an increase in potassium levels is not expected. However, in a clinical study in some patients with mild to moderate kidney disease who were taking potassium-sparing medications, serum potassium levels increased slightly while taking drospirenone. Therefore, it is recommended to monitor serum potassium levels during the first cycle of treatment in patients with renal failure whose pre-treatment serum potassium concentrations were at the ULN level and, especially, while taking potassium-sparing drugs.

Women with hypertriglyceridemia or a hereditary predisposition to it may have an increased risk of pancreatitis when taking combined oral contraceptives.

Although small increases in blood pressure were observed in many women taking combined oral contraceptives, clinically significant increases were rare. Only in these rare cases is immediate cessation of combined oral contraceptives justified. If, when taking combined oral contraceptives in patients with concomitant arterial hypertension, blood pressure constantly increases or significantly elevated blood pressure cannot be corrected with antihypertensive drugs, the use of combined oral contraceptives should be discontinued. After normalization of blood pressure with the help of antihypertensive drugs, combined oral contraceptives can be resumed.

The following diseases appeared or worsened both during pregnancy and when taking combined oral contraceptives, but the evidence for their relationship with taking combined oral contraceptives is inconclusive:

• jaundice and/or itching associated with cholestasis, gallstones;
• porphyria;
• systemic lupus erythematosus;
• hemolytic-uremic syndrome;
• Sydenham's chorea;
• herpes during pregnancy;
• otosclerosis with hearing loss.

In women with hereditary angioedema, exogenous estrogens may induce or worsen symptoms of edema.

Acute or chronic liver disease may be an indication to discontinue combined oral contraceptives until liver function tests normalize. Recurrence of cholestatic jaundice and/or pruritus associated with cholestasis, which developed during a previous pregnancy or with earlier use of sex hormones, is an indication for discontinuation of combined oral contraceptives.

Although combined oral contraceptives may affect peripheral insulin resistance and glucose tolerance, changes in treatment regimen in patients with diabetes mellitus while taking low-hormone combined oral contraceptives (containing <0.05 mg ethinyl estradiol) are not indicated. However, women with diabetes should be closely monitored, especially in the early stages of taking combined oral contraceptives.

While taking combined oral contraceptives, an increase in endogenous depression, epilepsy, Crohn's disease and ulcerative colitis was observed.

Chloasma may occur from time to time, especially in women who have a history of chloasma during pregnancy. Women who tend to develop chloasma should avoid exposure to the sun or ultraviolet radiation while taking combined oral contraceptives.

Active coated tablets contain 48.53 mg of lactose monohydrate, placebo tablets contain 37.26 mg of anhydrous lactose per tablet. Patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should not take Dimia®.

Placebo tablets contain the dye "sunset yellow", which can cause allergic reactions.

The drug contains soy lecithin. Patients with hypersensitivity to peanuts or soy should not take Dimia®.

Medical checkup

Before starting or re-using Dimia®, obtain a complete medical history (including family history) and exclude pregnancy. Blood pressure should be measured and a medical examination should be performed, guided by contraindications and precautions. It is important to draw a woman's attention to the risk of venous and arterial thrombosis, including the risk from the use of Dimia® compared to other combined oral contraceptives, to the symptoms of VTE and ATE, as well as to established risk factors and actions taken in case of suspected thrombosis.

A woman should be reminded to carefully read the instructions for use and adhere to the recommendations contained therein. The frequency and content of the survey should be based on existing practice guidelines.

Women should be reminded that oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of combined oral contraceptives may be reduced, for example, if active pills are missed, gastrointestinal problems occur while taking active pills, or other medications are taken at the same time.

Insufficient cycle control

As with other combined oral contraceptives, acyclic bleeding (spotting or breakthrough bleeding) may occur, especially in the first months of use. Therefore, any irregular bleeding should be assessed after a three-month adaptation period.

If acyclic bleeding recurs or begins after several regular cycles, the possibility of developing disorders of a non-hormonal nature should be taken into account and measures should be taken to exclude pregnancy or malignant neoplasms, including therapeutic and diagnostic curettage of the uterine cavity.

Some women do not experience withdrawal bleeding while taking placebo pills. If combined oral contraceptives are taken according to the instructions for use, it is unlikely that the woman is pregnant. However, if the rules of administration were violated before the first missed menstrual-like withdrawal bleeding, or if two bleedings were missed, pregnancy should be excluded before continuing to take the drug.

Impact on the ability to drive vehicles and operate machinery

Studies of the effect of the drug on the ability to drive vehicles or operate machinery have not been conducted. Among women taking combined oral contraceptives, there was no effect of these drugs on the ability to drive vehicles or operate machines.

Dimia

Trade name: Dimia International name: Drospirenone + Ethinyl estradiol (Drospirenone + Ethinyl estradiol) Pharmacological group: combined contraceptive (estrogen + gestagen) Pharmacological group according to ATC: G03AA12. Drospirenone and estrogens Pharmacodynamics: Low-dose monophasic oral contraceptive with anti-MKS and antiandrogenic action. The contraceptive effect is due to a number of factors, the most important of which are inhibition of ovulation and changes in the viscosity of cervical mucus. The endometrium remains unprepared for egg implantation. As a result of the increased viscosity of the cervical mucus, it is difficult for sperm to penetrate into the uterine cavity. Drospirenone has anti-MKS activity, which can prevent weight gain and other symptoms associated with fluid retention (prevents Na+ retention caused by estrogens, provides very good tolerability and has a positive effect on premenstrual syndrome). In combination with ethinyl estradiol, it improves the lipid profile and increases the concentration of HDL. It has antiandrogenic activity, which leads to a reduction in the formation of acne and a decrease in the production of sebaceous glands, and does not affect the increase in the formation of sex hormone-binding globulin caused by ethinyl estradiol (inactivation of endogenous androgens). Drospirenone is devoid of any androgenic, estrogenic, GCS and anti-GCS activity. This, in combination with anti-MKS and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone. Like all combined oral contraceptives, it has a positive non-contraceptive effect: menstrual bleeding becomes lighter and shorter, which reduces the risk of anemia, pain is less pronounced or disappears completely.

Pharmacokinetics: Drospirenone: when taken orally, it is rapidly and almost completely absorbed. After a single oral dose, Cmax is 35 ng/ml, TCmax is 1-2 hours. Bioavailability is 76-85%. Food intake does not affect bioavailability. After oral administration, a two-phase decrease in serum concentration is observed with T1/2 - 1.6±0.7 hours and 27±7.5 hours. It binds to serum albumin and does not bind to sex hormone-binding globulin (the increase in its concentration induced by ethinyl estradiol does not affect the degree of its binding with plasma proteins), and corticosteroid binding globulin. The average apparent volume of distribution is 3.7±1.2 l/kg. Metabolized in the liver with virtually no involvement of the cytochrome P450 system (slightly with the participation of cytochrome CYP3A4). The majority of metabolites in plasma are represented by acid forms of drospirenone, derivatives with an open lactone ring, and 4,5-dihydro-drosperinone-3-sulfate. The rate of metabolic clearance of drospirenone is 1.5±0.2 ml/min/kg. Unchanged, it is excreted only in trace amounts. Metabolites are excreted in feces and urine in a ratio of 1.2:1.4. T1/2 for metabolites is 40 hours. During cyclic treatment, the maximum Css of drospirenone in the blood serum is achieved between the 7th and 14th day of treatment and is 60 ng/ml. A further slight increase in serum concentration is observed after 1-6 cycles of administration. Ethinyl estradiol: After oral administration, it is rapidly and completely absorbed. TCmax after a single dose of 30 mcg - 1-2 hours, Cmax - 100 pg/ml. It has a “first pass” effect through the liver with high individual variability. Absolute bioavailability is 36-59%. Concomitant food intake reduces bioavailability in approximately 25% of people. The apparent volume of distribution is 5 l/kg, binding to plasma proteins is about 98%. It undergoes presystemic conjugation in the mucous membrane of the small intestine and in the liver. It is primarily metabolized by aromatic hydroxylation, resulting in the formation of various hydroxylated and methylated metabolites, presented both as free metabolites and as conjugates with glucuronic and sulfuric acids. Metabolized completely, the rate of metabolic clearance is 2.3-7 ml/min/kg (practically not excreted unchanged). Metabolites are excreted in urine and bile in a ratio of 4:6. T1/2 - 6.8-26.1 hours, T1/2 of metabolites - 24 hours. Css is achieved during the second half of the treatment cycle.

Indications for use: Contraception.

Contraindications: Hypersensitivity, thrombosis (venous and arterial) currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders), conditions preceding thrombosis (including transient ischemic attacks , angina pectoris) currently and in history, diabetes mellitus with vascular complications, the presence of severe or multiple risk factors for venous or arterial thrombosis, incl. complicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of the cerebral vessels or coronary arteries, uncontrolled arterial hypertension, major surgery with prolonged immobilization, smoking over the age of 35 years, liver failure, severe liver disease (until normalization of liver tests) in present or in history, liver tumors (benign or malignant), incl. history, severe or acute renal failure, hormone-dependent malignant diseases of the genital organs or mammary glands or suspicion of them, vaginal bleeding of unknown origin, pregnancy or suspicion of it, lactation.

With caution: Risk factors for the development of thrombosis and thromboembolism: smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine, heart valve defects, prolonged immobilization, major surgical interventions, extensive trauma, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident in young people). age in any of the immediate family), diseases that may cause peripheral circulatory disorders: diabetes mellitus, SLE, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of the superficial veins, hereditary angioedema, hypertriglyceridemia, liver diseases, diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (including jaundice and/or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes of pregnant women, chorea minor ( Sydenham's disease), Sydenham's chorea, chloasma), postpartum period.

Dosage regimen: Orally, 1 tablet, in the order indicated on the package, every day at approximately the same time with a small amount of water, continuously for 21 days. Each subsequent package begins after a 7-day break, during which menstrual-like bleeding is observed. It usually starts 2-3 days after taking the last tablet and may not end until you start taking a new package. If you have not taken any hormonal contraceptives in the previous month, take the drug on the first day of the menstrual cycle (the first day of menstrual bleeding). It is possible to start taking it on days 2-5 of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the tablets from the first package. When switching from taking other combined oral contraceptives, it is preferable to start taking the drug the next day after taking the last active tablet from the previous package, but no later than the next day after the usual 7-day break in taking (for drugs containing 21 tablets) or after taking the last inactive tablet (for drugs containing 28 tablets per package). When switching from contraceptives containing only gestagens (mini-pills, injection forms, implant): you can switch from a mini-pill on any day (without a break), from an implant - on the day of its removal, from an injection form - from the day you should the next injection was given. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. After an abortion in the first trimester of pregnancy, you can start taking it immediately. If this condition is met, there is no need for additional contraceptive protection. After childbirth or abortion in the second trimester of pregnancy, it is recommended to start taking the drug on days 21-28. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. If you have sexual intercourse, pregnancy should be excluded before starting to take the drug or you must wait until your first menstruation. Taking missed pills: if the delay in taking a pill is less than 12 hours, contraceptive protection is not reduced. It is necessary to take the tablet as soon as possible, the next one is taken at the usual time. If the delay in taking the pills is more than 12 hours (the interval since the last pill was taken is more than 36 hours), contraceptive protection may be reduced. If you miss taking the drug for 1-2 weeks, you must take the last missed tablet as soon as possible (even if this means taking 2 tablets at the same time). The next tablet is taken at the usual time. Additionally, a barrier method of contraception must be used for the next 7 days. If sexual intercourse took place within 1 week before missing a pill, the possibility of pregnancy must be taken into account. The more pills you miss and the closer this skip is to the 7-day break in taking the drug, the higher the risk of pregnancy. If you miss a dose of the drug by 3 weeks, you must take the last missed tablet as soon as possible (even if this means taking 2 tablets at the same time). The next tablet is taken at the usual time. Additionally, a barrier method of contraception must be used for the next 7 days. In addition, taking tablets from a new package should be started as soon as the current package is finished, i.e. nonstop. Most likely, bleeding is “spotting”, spotting or uterine bleeding is “spotting”, spotting from the vagina or uterine bleeding is “breakthrough”. You should resume taking the drug from a new pack after the usual 7-day break. To postpone the start of menstruation to another day of the week, you should shorten the next break in taking pills by as many days as you need to postpone the start of menstruation. The shorter the interval, the higher the risk of spotting and breakthrough bleeding while taking the second package (as well as in the case of delaying the onset of menstruation).

Side effects: Frequency: often (more than 1/100, less than 1/10), infrequently (more than 1/1000, less than 1/100), rarely (more than 1/10000, less than 1/1000). From the genitourinary system: acyclic vaginal bleeding (spotting or breakthrough bleeding), often - engorgement, tenderness of the mammary glands, infrequently - hypertrophy of the mammary glands, decreased libido, rarely - changes in the nature of vaginal secretion, discharge from the mammary glands, increased libido. From the nervous system: often - headache, decreased mood, emotional lability, infrequently - migraine. From the cardiovascular system: rarely - thrombosis (venous and arterial), thromboembolism. From the digestive system: often - nausea, abdominal pain, infrequently - vomiting, diarrhea. From the skin: infrequently - skin rash. Allergic reactions: infrequently - urticaria, rarely - erythema nodosum, erythema multiforme. Other: often - weight gain, infrequently - fluid retention, rarely - poor tolerance of contact lenses, weight loss, chloasma, especially if there is a history of chloasma in pregnancy.

Overdose: Symptoms: nausea, vomiting and slight vaginal bleeding. Treatment is symptomatic. There is no specific antidote.

Interaction: Drugs that induce microsomal liver enzymes: phenytoin, barbiturates, primidone, carbamazepine and rifampicin, rifabutin, oxcarbazepine, topiramate, felbamate, griseofulvin and drugs containing St. John's wort increase the clearance of sex hormones, which can lead to breakthrough bleeding or decreased reliability contraception. HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors and combinations thereof also have the potential to affect hepatic metabolism. Maximum induction of liver microsomal enzymes usually does not occur for 2–3 weeks, but may then persist for at least 4 weeks after drug therapy is stopped. Ampicillins and tetracyclines reduce the reliability of contraception (they reduce the enterohepatic circulation of estrogens). When taking drugs that affect the induction of liver enzymes simultaneously and for 28 days after their discontinuation, it is necessary to temporarily use a barrier method of contraception. While taking antibiotics (ampicillin, tetracycline) and for 7 days after their discontinuation, it is necessary to temporarily use a barrier method of contraception. If the concomitant prescription of drugs is started at the end of taking a package of an oral contraceptive, the next package should be started without the usual break in administration. In women receiving drugs that affect liver enzymes for a long time, it is necessary to consider the possibility of using other methods of contraception. Oral combined contraceptives may affect the metabolism of other drugs, leading to an increase (cyclosporine) or decrease (lamotrigine) in their plasma and tissue concentrations. There is a theoretical possibility of increasing the concentration of serum K+ in women receiving oral contraceptives simultaneously with other drugs that increase the concentration of K+ in the blood serum: ACE inhibitors, angiotensin II receptor blockers, some NSAIDs (for example, indomethacin), potassium-sparing diuretics and aldosterone antagonists. However, in a study evaluating the interaction of an ACE inhibitor with a drospirenone-estradiol combination in women with moderate hypertension, there was no significant difference between serum K+ concentrations in women receiving enalapril and placebo.

Special instructions: A number of epidemiological studies have revealed a slight increase in the incidence of venous and arterial thrombosis and thromboembolism when taking combined oral contraceptives. Venous thromboembolism (VTE), manifesting as deep vein thrombosis and/or pulmonary embolism, can develop during the use of all combined oral contraceptives. The estimated incidence of VTE in women taking oral contraceptives with low doses of estrogens (less than 50 mcg ethinyl estradiol) is up to 4 per 10 thousand women per year, compared with 0.5-3 per 10 thousand women not using oral contraceptives. However, the incidence of VTE developing when taking combined oral contraceptives is less than the incidence associated with pregnancy (6 per 10 thousand pregnant women per year). In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, for example, the hepatic, mesenteric, renal arteries and veins, the central retinal vein and its branches, have been described. The connection with the use of combined oral contraceptives has not been proven. A woman should stop taking the drug and consult a doctor if symptoms of venous or arterial thrombosis develop, which may include unilateral leg pain and/or swelling, sudden severe chest pain, with or without radiation to the left arm, sudden shortness of breath, sudden coughing attack, any unusual, severe, prolonged headache, increased frequency or severity of migraines, sudden partial or complete loss of vision, diplopia, slurred speech or aphasia, dizziness, collapse with or without a partial seizure, weakness or very significant loss of sensation suddenly appearing on one side or in one part of the body, movement disorders, “acute” abdomen. The risk of thrombosis (venous and/or arterial) and thromboembolism increases: with age, in smokers (with increasing number of cigarettes smoked or increasing age, the risk further increases, especially in women over 35 years of age), with a family history (i.e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age), obesity (body mass index more than 30), dyslipoproteinemia, arterial hypertension, heart valve disease, atrial fibrillation, prolonged immobilization, major surgery, any surgery on the legs or extensive trauma. In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery at least 4 weeks before it) and not to resume use for 2 weeks after the end of immobilization. The increased risk of thromboembolism in the postpartum period should be taken into account. Circulatory abnormalities may also occur in diabetes mellitus, SLE, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia. An increase in the frequency and severity of migraine during the use of combined oral contraceptives (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs. Biochemical parameters that may be a sign of hereditary or acquired predisposition to venous or arterial thrombosis: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C and S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant). When considering the risk/benefit ratio, the physician should consider that adequate treatment of these conditions may reduce the associated risk of thrombosis and that the risk of thrombosis associated with pregnancy is greater than with the use of oral contraceptives. An increased risk of cervical cancer with long-term use of combined oral contraceptives has been reported in some epidemiological studies. Its connection with the use of combined oral contraceptives has not been proven. A meta-analysis of 54 epidemiological studies demonstrated that there is a slightly increased relative risk (RR=1.24) of developing breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. Its connection with the use of combined oral contraceptives has not been proven. The observed increased risk may be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives (breast cancer in women who had ever used combined oral contraceptives was clinically less severe than in women who had never used them). In rare cases, the development of liver tumors has been observed during the use of combined oral contraceptives. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis. K+ excretion may be reduced in patients with renal failure. In a clinical study, drospirenone had no effect on serum K+ concentrations in patients with mild to moderate renal impairment. The theoretical risk of developing hyperkalemia exists in cases where the serum concentration of K+ before treatment was at the upper limit of normal and while taking potassium-sparing drugs. In women with hypertriglyceridemia or a family history, an increased risk of pancreatitis cannot be excluded while taking combined oral contraceptives. Although slight increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. The relationship between taking combined oral contraceptives and a clinically significant increase in blood pressure has not been established. The anti-MCS effect of drospirenone may offset the increase in blood pressure caused by ethinyl estradiol, which is observed in normotensive women taking other types of combined oral contraceptives. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, discontinuation of the drug and treatment of arterial hypertension is necessary. Taking combined oral contraceptives can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy. Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using combined oral contraceptives. However, women with diabetes mellitus should be carefully monitored while taking combined oral contraceptives. Women prone to chloasma should avoid prolonged sun exposure and exposure to UV radiation while taking combined oral contraceptives. May affect biochemical indicators of liver, thyroid, adrenal and kidney function, as well as the amount of plasma transport proteins, such as corticosteroid binding globulin and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis. Changes usually occur within laboratory limits. Due to anti-MKS activity, drospirenone increases the activity of renin and aldosterone in blood plasma. Prescribing a combined contraceptive with anti-MCS and anti-androgenic properties may be especially useful for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. While taking combined oral contraceptives, irregular bleeding may occur (“spotting” or “breakthrough” bleeding), especially during the first months of use. Therefore, assessment of any irregular bleeding is only meaningful after an adaptation period of approximately 3 cycles. If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures taken to exclude malignancy or pregnancy. These may include diagnostic curettage. Some women experience withdrawal bleeding and pregnancy should be ruled out before continuing combined oral contraceptives. Before using the drug, it is necessary to conduct a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination of cervical mucus), and exclude pregnancy. In addition, disorders of the blood coagulation system should be excluded. The woman should be warned that the drug does not protect against HIV infection (AIDS) and other sexually transmitted diseases. In case of long-term use of the drug, it is necessary to carry out control examinations every 6 months.

Manufacturer: Gedeon Richter-RUS JSC, Hungary Registration certificate holder: Gedeon Richter (Hungary) JSC, Hungary Forms of release: film-coated tablets 3 mg + 0.02 mg, blister made of PVC/PE/PVDC - aluminum foil, film-coated tablets shell, blister made of PVC/PE/PVDC - aluminum foil Dispensing conditions: by prescription Registration data: LP-001179 dated 11/11/2011 Status of the registration certificate: valid (until 2021) Pharmaceutical article number: LP 001179-111111