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®

If any of the conditions, diseases or risk factors listed below currently exist, the potential risks and expected benefits of using COCs, including the combination of drospirenone + ethinyl estradiol, should be carefully weighed in each individual case and discussed with the woman before starting taking the drug. If any of these conditions, diseases or risk factors worsen, intensify or appear for the first time, a woman should consult her doctor to decide whether to stop taking the drug.

Risk of developing VTE and ATE

The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of VTE and ATE (such as DVT, PE, myocardial infarction, cerebrovascular disorders). These diseases are rare.

The increased risk of developing VTE associated with the use of COCs is due to the presence of estrogen in its composition. Drugs containing levonorgestrel, norgestimate, or norethisterone as a progestogen component are associated with the lowest risk of VTE.

When using other COCs, such as the combination of drospirenone + ethinyl estradiol, the risk of developing VTE is 2 times higher. The choice of a COC with a higher risk of VTE should only be made after consultation with the woman to ensure that she fully understands the risk of VTE associated with the contraceptive, the effect of the drug on her existing risk factors and that the risk of developing VTE maximum in the first year of taking such drugs. The increased risk of developing VTE is present primarily during the first 3 months.

An increased risk is also observed when COC use is resumed (after a break between doses of the drug of 4 weeks or more).

VTE can be life-threatening or lead to death (in 1-2% of cases).

VTE, manifested as DVT or PE, can occur with all COCs. It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels.

Symptoms of DVT include the following:

unilateral swelling of the lower limb or along a vein in the lower limb, pain or discomfort in the lower limb only in an upright position or when walking, local increase in temperature in the affected lower limb, redness or discoloration of the skin on the lower limb.

Symptoms of pulmonary embolism

: difficulty or rapid breathing, sudden cough, including coughing up blood, sharp chest pain that may get worse with deep breaths, anxiety, severe dizziness, fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more common and less severe conditions (eg, respiratory tract infection).

ATE can lead to stroke, vascular occlusion, or myocardial infarction.

Symptoms of a stroke

: sudden weakness or numbness of the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech or understanding, sudden loss of vision on one or both sides, sudden difficulty walking, dizziness, loss of balance or coordination, sudden , severe or prolonged headache for no apparent reason, loss of consciousness or fainting with or without a seizure.

Other signs of vascular occlusion

: sudden pain, swelling and slight cyanosis of the extremities, “acute” abdomen.

Symptoms of myocardial infarction include

: pain, discomfort, feeling of pressure, heaviness, compression or bursting in the chest, arm or chest, discomfort radiating to the back, jaw, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.

ATE can be life-threatening or fatal.

In women with a combination of several risk factors or high severity of one of them, the possibility of their mutual reinforcement should be considered. In such cases, the degree of increase in risk may be higher than with a simple summation of factors. In this case, taking Dimia® is contraindicated (see section “Contraindications”).

The risk of developing thrombosis (venous and/or arterial) and thromboembolism increases:

-with age;

- for smokers (with an increase in the number of cigarettes or an increase in age, the risk increases, especially in women over 35 years old);

in the presence of:

-obesity (body mass index (BMI) more than 30 kg/m2);

-family history (for example, if there is a family history of venous or arterial thrombosis/thromboembolism in close relatives or parents under the age of 50 years). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking COCs;

- in case of prolonged immobilization, serious surgery, any operation on the lower extremities, in the pelvic area or neurosurgical surgery, extensive severe trauma. In these situations, you should stop taking the COC (in the case of a planned operation, at least 4 weeks before it) and not resume it for two weeks after the end of immobilization.

Temporary immobilization (eg, air travel longer than 4 hours) may also be a risk factor for VTE, especially if other risk factors are present:

- dislipoproteinemia;

- arterial hypertension:

-migraine;

- heart valve diseases;

- atrial fibrillation.

About 9-12 out of 10,000 women taking COCs containing drospirenone may develop VTE within a year, compared with about 6 in 10,000 women for COCs containing levonorgestrel.

The possible role of varicose veins and thrombophlebitis of superficial veins in the development of VTE remains controversial.

The increased risk of thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, 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 COCs (which may precede cerebrovascular events) is grounds for immediate discontinuation of these drugs.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia. antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When assessing the benefit-risk ratio, it should be taken into account that adequate treatment of the relevant condition/disease can reduce the associated risk of thrombosis.

Tumors

The most significant risk factor for the development of cervical cancer (CC) is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing CC with long-term use of COCs. However, the connection with taking COCs has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior patterns (less use of barrier methods of contraception, greater number of sexual partners).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years after stopping COC use. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the incidence of breast cancer in women who are currently taking COCs or have recently taken it is insignificant in relation to the overall risk of this disease. Its connection with COC use has not been proven. The observed increase in risk may also be a consequence of earlier diagnosis of breast cancer in women taking COCs (they are diagnosed with earlier clinical forms of breast cancer than women not taking COCs), the biological effects of COCs, or a combination of both of these factors.

In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors, which in some cases led to life-threatening intra-abdominal bleeding, was observed. In case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

Other states

Depressed mood and depression are well-known adverse reactions when using hormonal contraceptives (see section "Side effects"). Depression can be serious and is a well-known risk factor for suicidal behavior and suicide. Women should contact their doctor if they experience mood swings or symptoms of depression, including soon after starting Dimia®.

Clinical studies have shown no effect of drospirenone on plasma potassium concentrations in patients with mild to moderate renal failure. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at the upper limit of normal, while simultaneously taking medications that lead to potassium retention in the body. In women with an increased risk of developing hyperkalemia, it is recommended to monitor plasma potassium concentrations during the first cycle of taking Dimia®.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking COCs.

Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases have rarely been reported. However, if a persistent clinically significant increase in blood pressure develops while taking COCs, these drugs should be discontinued and treatment of arterial hypertension should be initiated. COC use can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy. The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; gestational herpes; hearing loss associated with otosclerosis. Cases of worsening the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis during the use of COCs have also been described.

In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal.

Recurrence of cholestatic jaundice, which developed for the first time during a previous pregnancy or previous use of sex hormones, requires discontinuation of COC use.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the dose of hypoglycemic drugs in diabetic patients using low-dose COCs (<0.05 mg ethinyl estradiol). However, women with diabetes mellitus should be carefully monitored while taking COCs.

Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking COCs.

Effect on liver function tests

In clinical studies involving patients receiving hepatitis C viral therapy (a combination of drugs containing ombitasvir, paritaprevir, ritonavir, dasabuvir, with or without ribavirin), increases in ALT activity more than 5 times the upper limit of normal were recorded more often in patients using ethinyl estradiol-containing COCs.

If a course of therapy with this combination of antiviral drugs is necessary, the patient taking the COC drospirenone + ethinyl estradiol should be switched to alternative methods of contraception (non-hormonal or progestogen-only contraceptives) before starting treatment. You can resume taking the combination of drospirenone + ethinyl estradiol no earlier than 2 weeks after the end of the course of therapy with antiviral drugs.

Laboratory tests

Taking COCs may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in the blood plasma, indicators of carbohydrate metabolism, parameters of coagulation and fibrinolysis. Changes usually do not go beyond normal values. Drospirenone increases plasma renin activity and aldosterone concentrations, which is associated with its antimineralocorticoid effect.

Medical examinations

Before starting or resuming taking the drug Dimia®, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough medical (including measurement of blood pressure, heart rate, determination of BMI) and gynecological examination (including examination of the mammary glands and cytological examination of the cervical epithelium), exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least once every 6 months.

The woman should be warned that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of COCs may be reduced in the following cases: if hormone-containing (white) tablets are missed, with vomiting and diarrhea, or as a result of drug interactions.

Poor control of the menstrual cycle

While taking COCs, irregular bleeding may occur (“spotting” and/or “breakthrough” bleeding), especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three drug cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough diagnostic evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop withdrawal bleeding while taking green pills that do not contain hormones; pregnancy should be ruled out before continuing to take the drug. This is of particular importance for women taking concomitant drugs with teratogenic effects. And although the onset of pregnancy while regularly taking Dimia® is unlikely, at the slightest suspicion of pregnancy a pregnancy test should be performed.

Soybeans

Dimia®, film-coated tablets, contains soy lecithin. Patients with peanut and soy allergies should not take this drug.

Sunset yellow dye

Placebo tablets contain sunset yellow, which may cause allergic reactions.