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

Use during pregnancy and breastfeeding

Dimia® is contraindicated during pregnancy.
If pregnancy occurs while using Dimia®, it should be stopped immediately. Extensive epidemiological studies have found neither an increased risk of birth defects in children born to women who took COCs before pregnancy, nor a teratogenic effect of COCs if taken unintentionally during pregnancy.

According to preclinical studies, it is impossible to exclude undesirable effects that affect the course of pregnancy and fetal development due to the hormonal action of the active components.

The drug Dimia® can affect lactation: reduce the amount of milk and change its composition. Small amounts of contraceptive steroids and/or their metabolites may be excreted in milk during COC use. These amounts may affect the child. The use of Dimia® during breastfeeding is contraindicated.

Use for liver dysfunction

Contraindicated:

• existing severe liver disease (or history) provided that liver function is not currently normalized;
• liver tumor (benign or malignant) currently or in history.

Use for renal impairment

Contraindicated:

• severe chronic or acute renal failure

Use in children

The use of the drug before menarche is not indicated.

special instructions

If you have any of the conditions/risk factors listed below, the benefits of taking COCs 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. The doctor must decide whether to stop taking the COC.

Circulatory disorders

Taking any combined oral contraceptive increases the risk of venous thromboembolism (VTE). The increase in the risk of VTE is most pronounced in the first year of a woman's use of a combined oral contraceptive.

Epidemiological studies have shown that the incidence of VTE in women without risk factors taking low-dose estrogens (<0.05 mg ethinyl estradiol) as part of a combined oral contraceptive is approximately 20 cases per 100,000 woman-years (for “second generation” levonorgestrel-containing COCs) or 40 cases per 100,000 woman-years (for desogestrel/gestodene-containing “third generation” COCs). Women who do not use COCs have an incidence of 5-10 VTE and 60 pregnancies per 100,000 woman-years. VTE is fatal in 1-2% of cases.

Data from a large, prospective, 3-arm study showed that the incidence of VTE in women with or without other risk factors for venous thromboembolism using the combination of ethinyl estradiol and drospirenone 0.03 mg + 3 mg was the same as the incidence of VTE in women using levonorgestrel-containing oral contraceptives and other PDAs. The risk of venous thromboembolism when taking Dimia® has not currently been established.

Epidemiological studies have also revealed an association between COC use and an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic events).

Very rarely, thrombosis of other blood vessels, such as veins and arteries of the liver, mesentery, kidney, brain or retina, has occurred in women taking oral contraceptives. There is no consensus regarding the connection of these phenomena with the use of hormonal contraceptives.

Symptoms of venous or arterial thrombotic/thromboembolic events or acute cerebrovascular accidents:

• unusual unilateral pain and/or swelling of the lower extremities;
• sudden severe pain in the chest, regardless of whether it radiates to the left arm or not;
• sudden shortness of breath;
• sudden onset of cough;
• any unusual severe, long-lasting headache;
• sudden partial or complete loss of vision;
• diplopia;
• impaired speech or aphasia;
• vertigo;
• collapse with or without partial epileptic seizures;
• weakness or very noticeable numbness that suddenly affects one side or part of the body;
• movement disorders;
• symptom complex “acute” abdomen.

Before starting to take COCs, a woman should consult a specialist.

The risk of venous thromboembolic disorders when taking COCs increases with:

• increasing age;
• hereditary predisposition (venous thromboembolism has ever occurred in siblings or parents at a relatively early age);
• prolonged immobilization, extensive surgery, any surgery on the lower extremities or major trauma. In such situations, it is recommended to stop taking the drug (in the case of planned surgery, at least four weeks in advance) and not to resume until two weeks have passed after complete restoration of mobility. If the drug is not stopped promptly, anticoagulant treatment should be considered;
• obesity (BMI more than 30 kg/m2);
• lack of consensus on the possible role of varicose veins and superficial thrombophlebitis in the appearance or exacerbation of venous thrombosis.

The risk of arterial thromboembolic complications or acute cerebrovascular accident when taking COCs increases with:

• increasing age;
• smoking (women over 35 years of age are strongly advised to quit smoking if they want to take COCs);
• dyslipoproteinemia;
• arterial hypertension;
• migraine without focal neurological symptoms;
• obesity (BMI more than 30 kg/m2);
• hereditary predisposition (arterial thromboembolism ever in siblings or parents at a relatively early age). If a hereditary predisposition is possible, a woman should consult a specialist before starting to take COCs;
• damage to the heart valves;
• atrial fibrillation.

Having one major risk factor for venous disease or multiple risk factors for arterial disease may also be a contraindication. Anticoagulant therapy should also be considered. Women taking COCs should be properly instructed to inform their physician if symptoms of thrombosis are suspected. If thrombosis is suspected or confirmed, COC use should be discontinued. It is necessary to start adequate alternative contraception due to the teratogenicity of anticoagulant therapy (indirect anticoagulants - coumarin derivatives).

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

Other medical conditions associated with adverse vascular events include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell disease.

An increase in the frequency or severity of migraine while taking COCs may be an indication for immediate discontinuation of combined oral contraceptives.

Tumors

The most significant risk factor for developing cervical cancer is infection with the human papillomavirus. Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of combined oral contraceptives, but there remains controversy regarding the extent to which these findings are attributable to confounding factors such as testing for cervical cancer or use of barrier methods of contraception.

A meta-analysis of 54 epidemiological studies found a small increase in the relative risk (RR = 1.24) of breast cancer in women who were currently taking COCs. The risk gradually decreases over 10 years after stopping COC use. Because Breast cancer rarely develops in women under 40 years of age, and an increase in the number of diagnosed cases of breast cancer in COC users 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 COC users, the biological effects of COCs, or a combination of both factors. Diagnosed breast cancer in women who had ever taken COCs was clinically less severe, which was due to early diagnosis of the disease.

Rarely, benign liver tumors and, even more rarely, malignant liver tumors have occurred in women taking COCs. In some cases, these tumors were life-threatening due to intra-abdominal bleeding. This should be taken into account when making a differential diagnosis in the event of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.

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 upper limit of normal 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 COCs.

Although slight increases in blood pressure were observed in many women taking COCs, clinically significant increases were rare. Only in these rare cases is it justified to immediately stop taking the COC. If, when taking COCs in patients with concomitant arterial hypertension, blood pressure constantly increases or significantly elevated blood pressure cannot be corrected with antihypertensive drugs, taking COCs should be discontinued. After normalization of blood pressure with the help of antihypertensive drugs, COC use can be resumed.

The following diseases appeared or worsened both during pregnancy and when taking COCs, but the evidence of their relationship with taking COCs is inconclusive: jaundice and/or itching associated with cholestasis, gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; rheumatic chorea (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 stop taking COCs 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 COCs.

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

While taking COCs, 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 with a tendency to chloasma should avoid exposure to the sun or ultraviolet light while taking COCs.

Drospirenone + ethinyl estradiol 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 this drug.

Women who are allergic to soy lecithin may experience allergic reactions.

The effectiveness and safety of Dimia® as a contraceptive have been studied in women of reproductive age. It is assumed that in the postpubertal period up to 18 years of age, the effectiveness and safety of the drug are similar to those in women after 18 years of age. The use of the drug before menarche is not indicated.

Medical examinations

Before starting or re-using Dimia®, obtain a complete medical history (including family history) and exclude pregnancy. It is necessary to measure blood pressure and conduct a medical examination, guided by contraindications and precautions. 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. The frequency of medical examinations is individual for each woman, but should be carried out at least once every 6 months.

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

Reduced efficiency

The effectiveness of the COC may be reduced, for example, if you skip a dose of drospirenone + ethinyl estradiol tablets, have gastrointestinal disorders while taking drospirenone + ethinyl estradiol tablets, or take other medications at the same time.

Insufficient cycle control

As with other COCs, a woman may experience acyclic bleeding (spotting or withdrawal bleeding), or if two bleedings are missed, pregnancy should be ruled out before continuing to take the COC.

Impact on the ability to drive vehicles and operate machinery

Not found.