Compound

One tablet contains

active substances: crystalline drospirenone 100% 3 mg and micronized ethinyl estradiol 100% 0.02 mg,

excipients: lactose monohydrate, corn starch, pregelatinized starch, macrogol and polyvinyl alcohol copolymer, magnesium stearate,

film coating composition: Opadry II white 85G18490: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, lecithin (soy),

placebo composition: microcrystalline cellulose, type 12, anhydrous lactose, pregelatinized starch, magnesium stearate, anhydrous colloidal silicon dioxide,

composition of the film coating (placebo): Opadry II green 85F21389: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, indigo carmine (E 132), quinoline yellow (E 104), iron oxide black (E 172), yellow sun sunset (E 110).

Description

Tablets, round, biconvex surface, film-coated white or almost white color, engraved on one side with "G73"

Tablets, film-coated green, round, with a biconvex surface (placebo).

pharmachologic effect

Pearl Index: 0.31 (upper 95% confidence interval: 0.85).

The contraceptive effect of the drug is based on the interaction various factors, the most important of which are inhibition of ovulation and changes in the endometrium.

DIMIA® 24+4 is a combined oral contraceptive (COC) with a combination of ethinyl estradiol and the progestin drospirenone. At a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid effects. It does not have estrogenic, glucocorticoid and antiglucocorticoid activity. Thus, drospirenone has a pharmacological profile similar to the natural hormone progesterone.

In clinical studies, it was found that the antimineralocorticoid properties of the drug DIMIA® lead to a weak antimineralocorticoid effect.

It has antiandrogenic activity, which leads to a decrease in the formation of acne and a decrease in the production of sebaceous glands, does not affect the increase in the formation of globulin that binds sex hormones (inactivation of endogenous androgens) caused by ethinylestradiol.

Pharmacokinetics

Drospirenone

Suction

When taken orally, drospirenone is rapidly and almost completely absorbed. The maximum concentration of drospirenone in serum, equal to 37 ng / ml, is reached 1-2 hours after a single oral administration. Bioavailability ranges from 76 to 85%. Eating does not affect the bioavailability of drospirenone.

Distribution

Following oral administration, serum levels of drospirenone decrease with a terminal elimination half-life of 31 hours. There is an association of drospirenone with serum albumin, but the drug does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG). Only 3-5% of the total active substance concentrations in serum are presented as free steroid. The increase in SHBG induced by ethinylestradiol does not affect the binding of drospirenone to serum proteins. The mean apparent volume of distribution of drospirenone is 3.7±1.2 l/kg.

Metabolism

Drospirenone is extensively metabolized after oral administration. The main metabolites in blood plasma are the acid form of drospirenone, formed during the opening of the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, both are formed without the participation of the P450 system. Drospirenone is metabolized to a small extent by cytochrome P450 3A4, and is able to inhibit this enzyme, as well as cytochrome P450 1A1, cytochrome P450 2C9 and cytochrome P450 2C19 in vitro.

Elimination

The rate of metabolic clearance of drospirenone in serum is 1.5±0.2 ml/min/kg. Drospirenone is excreted only in trace amounts unchanged. Drospirenone metabolites are excreted in faeces and urine in a ratio of approximately 1.2:1.4. The elimination half-life for excretion of metabolites in urine and faeces is approximately 40 hours.

Equilibrium concentration

During one cycle of treatment, the maximum equilibrium concentration of drospirenone in serum (approximately 70 ng / ml) is reached after 8 days of treatment. Serum concentrations of drospirenone increase by about 3 orders of magnitude, due to the ratio of the terminal half-life and dosing interval.

Ethinylestradiol

Suction

Ethinylestradiol, after oral administration, is rapidly and completely absorbed. The maximum concentration in blood serum after a single dose of 33 pg / ml is reached after 1-2 hours. After first pass conjugation and first pass metabolism in the small intestine and liver, the absolute bioavailability is 60%. Concomitant food intake reduces the bioavailability of ethinylestradiol in approximately 25% of the people examined, while no such changes were found in other people.

Distribution

Serum levels of ethinylestradiol decrease in two phases, with a terminal pharmacokinetic phase characterized by a half-life of about 24 hours. Ethinylestradiol binds to albumin about 98.5% and induces an increase in the concentration of SHBG and CSH in serum. The apparent volume of distribution is approximately 5 l/kg.

Metabolism

Ethinylestradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation, with the formation of a variety of hydroxylated and methylated metabolites, presented both in the form of free metabolites and in the form of conjugates with glucuronic and sulfuric acids.

Ethinylestradiol is completely metabolized. The rate of metabolic clearance of ethinylestradiol is 5 ml/min/kg.

Elimination

Ethinylestradiol is practically not excreted unchanged. Metabolites of ethinylestradiol are excreted in the urine and bile in a ratio of 4:6. The half-life of metabolites is approximately 1 day. The elimination half-life is 20 hours.

Equilibrium concentration

The state of equilibrium concentration is reached during the second half of the treatment cycle, and the serum level of ethinylestradiol increases by a factor of about 2.0-2.3.

Effect on kidney function

Steady-state serum drospirenone levels in women with mild renal impairment (creatinine clearance CLcr = 50-80 ml/minute) were comparable to those in women with normal function kidneys (CLcr> 80 ml/minute). Serum levels of drospirenone were on average 37% higher in women with moderate renal insufficiency t (CLcr = 30-50 ml/minute) compared with those in women with normal renal function. Drospirenone therapy was well tolerated by women with both mild and moderate renal impairment.

Treatment with drospirenone did not have a clinically significant effect on serum potassium concentration.

Effect on liver function

In a single dose study, total clearance (CL/f) in volunteers with moderate hepatic insufficiency was approximately 50% reduced compared with people with normal liver function.

The observed decrease in drospirenone clearance in volunteers with moderate hepatic insufficiency does not lead to any significant differences in serum potassium concentration.

Even with diabetes and concomitant treatment with spironolactone (two factors that can provoke hyperkalemia in a patient), there was no increase in serum potassium concentration above the upper limit of normal.

It can be concluded that the drospirenone/ethinylestradiol combination is well tolerated by patients with moderate hepatic impairment (Child-Pugh class B).

ethnic groups

There were no clinically relevant differences in the pharmacokinetics of drospirenone or ethinylestradiol in Japanese women and Caucasian women.

Contraindications

Pregnancy and lactation

Current or history of venous thrombosis (eg, deep vein thrombosis, pulmonary embolism)

Current or history of arterial thrombosis (eg, myocardial infarction) or prior conditions (eg, angina pectoris and transient ischemic attack)

Current or past cerebrovascular disease

Presence of severe or multiple risk factors for arterial thrombosis

Diabetes mellitus with vascular complications

Severe arterial hypertension

Severe dyslipoproteinemia

Hereditary or acquired predisposition to venous or arterial thrombosis, such as resistance to APC (activated protein C, activated protein C), antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (cardiolipin antibodies, lupus anticoagulant)

Pancreatitis with severe hypertriglyceridemia, including history

Current or history of severe liver disease (before normalization of liver tests)

Severe chronic renal failure or acute renal failure

Liver tumors (benign or malignant), current or history

Hormone-dependent malignant diseases of the reproductive system (genital organs, mammary glands) or suspicion of them

Unexplained vaginal bleeding

Migraine with a history of local neurological symptoms

Hypersensitivity to the active substance or any of the excipients

Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome

Drug Interactions

Metabolism in the liver

Some drugs, due to the induction of microsomal enzymes, are able to increase the clearance of sex hormones (hydantoin, phenytoin, barbiturates, primidone, carbamazepine and rifampicin; the same effect of oxycarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal remedy based on St. John's wort (Hypericum perforatum) is also possible. induction of microsomal liver enzymes usually does not appear within 2-3 weeks, but may then persist for at least 4 weeks after discontinuation of drug therapy.

Possible effects of HIV protease inhibitors (eg ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg nevirapine) and their combinations on hepatic metabolism have been reported.

enterohepatic recirculation

Co-administration with certain antibiotics, such as penicillins and tetracyclines, reduces the enterohepatic recirculation of estrogen, which can lead to a decrease in the concentration of ethinyl estradiol.

Women receiving any of the above classes medicines or individual active substances, must use a barrier method of contraception in addition to DIMIA®, or switch to any other method of contraception. Women receiving permanent treatment with drugs containing active substances that affect liver enzymes must additionally use a non-hormonal method of contraception within 28 days after their withdrawal.

Women receiving rifampicin therapy should use a barrier method of contraception in addition to taking COCs and continue to use it for 28 days after stopping treatment with rifampicin. If concomitant medication lasts longer than the expiration date of the active tablets in the package, the placebo tablets should be discarded and the active tablets from the next package should be started immediately.

The basic metabolism of drospirenone in human plasma is generated without the involvement of the cytochrome P450 system. Inhibitors of this enzyme system, therefore, do not affect the metabolism of drospirenone.

Effect of DIMIA® on other medicinal products

Oral contraceptives may interfere with the metabolism of certain other active compounds. In addition, their concentrations in plasma and tissues can change - both increase (for example, cyclosporine) and decrease (for example, lamotrigine).

In female volunteers taking omeprazole, simvastatin and midazolam as indicator substrates, the effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.

Pregnancy and lactation

If pregnancy occurs while taking DIMIA®, the drug should be discontinued immediately. Conducted epidemiological studies did not reveal any increased risk during childbirth for children in women who took COCs before pregnancy, nitrateogenic effect when COCs were inadvertently taken during pregnancy. Such studies with the drug were not conducted.

COCs can affect lactation because they can reduce the amount and composition of breast milk. Thus, the use of COCs cannot be recommended until a breastfeeding woman has completely stopped breastfeeding. Small amounts of contraceptive hormones or their metabolites may be excreted in milk during COC use. These amounts may have an effect on the child.

Features of influence medicinal product on the ability to manage vehicle and potentially dangerous mechanisms

Studies studying the effect of the drug on the ability to drive a car and work with mechanisms with an increased risk of injury have not been conducted.

Dosage and administration

Tablets should be taken every day at about the same time, if necessary, with a small amount of liquid, in the sequence indicated on the package. It is necessary to take one tablet a day for 28 days in a row. Each next pack should begin after taking the last tablet from the previous pack. Withdrawal bleeding usually starts 2-3 days after taking the placebo pills (last row) and may not be over by the time the next pack is started.

If earlier hormonal contraceptives not used (last month)

DIMIA® is started on the first day of a woman's natural menstrual cycle (that is, on the first day of her menstrual bleeding).

If you change another COC, vaginal ring or transdermal patch

It is preferable for a woman to start taking DIMIA® the day after the usual hormone-free interval in the regimen of the previous combined contraceptive. When replacing the vaginal ring or transdermal patch, it is advisable to start taking DIMIA® on the day of their removal of the previous agent; in such cases, DIMIA® should be started no later than the day of the scheduled replacement procedure.

When replacing a progestin-only method (mini-pills, injectables, implants) or an intrauterine system (IUS) with progestin release

A woman can switch from the minipill any day (from the implant or IUS on the day it was removed, from the injectable from the day the next injection was due). However, in all these cases, it is desirable to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester

A woman can start taking immediately. Under this condition, there is no need for additional contraceptive measures.

After childbirth or termination of pregnancy in the second trimester

It is desirable for a woman to start taking the drug DIMIA® on the 21-28th day after childbirth or termination of pregnancy in the second trimester. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. If there is sexual intercourse before taking the drug, pregnancy should be excluded or it is necessary to wait for the first menstruation.

Taking missed pills

Skipping a placebo tablet from the last (4th) row of the blister can be ignored. However, they should be discarded to avoid inadvertently prolonging the placebo phase. The instructions below apply only to missed active tablets:

If the delay in taking the pill was less than 12 hours, contraceptive protection is not reduced. The woman should take the missed pill as soon as possible and take the next pill at the usual time.

If the delay in taking the tablets was more than 12 hours, contraceptive protection may be reduced. Correction of missed tablets should be guided by the following two simple rules:

Tablets should not be stopped for more than 7 days;

To achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous tablet intake are necessary.

Accordingly, in daily practice, the following advice can be given:

You should take the last missed tablet as soon as possible, even if it means taking two tablets at the same time. The next tablet is taken at the usual time. In addition, a barrier method of contraception must be used for the next 7 days. If sexual intercourse took place within 7 days before missing the tablet, the possibility of pregnancy must be considered. The more pills missed and the closer this pass is to the 7-day break in taking the drug, the higher the risk of pregnancy.

You should take the last missed tablet as soon as possible, even if it means taking two tablets at the same time. The next tablet is taken at the usual time. If a woman has taken the pills correctly during the previous 7 days, there is no need to use additional contraceptives. However, if she missed more than 1 tablet, extra precautions should be taken for the next 7 days.

The likelihood of a decrease in the contraceptive effect is significant due to the approach of the placebo pill phase. However, by adjusting the pill schedule, a decrease in contraceptive protection can be prevented.

If you follow any of the following two tips, no additional methods of contraception will be needed if the woman has taken all the pills correctly in the previous 7 days before missing the pill. If this is not the case, she should follow the first of the two methods and also use additional precautions for the next 7 days.

1. Take the last missed tablet as soon as possible, even if it means taking two tablets at the same time. The next tablets are taken at the usual time until the active tablets run out. 4 placebo tablets from the last row should not be taken, you must immediately start taking the tablets from the next package. Most likely, there will be no "withdrawal" bleeding until the end of the second pack, but there may be spotting or breakthrough bleeding. uterine bleeding on the days of taking the tablets.

2. A woman can be advised to stop taking active tablets from the started package. Instead, she should take the placebo pills from the last row for 4 days, including the days she skipped the pills, and then start taking the pills from the next pack.

In the event of missed pills and no "withdrawal" bleeding in the placebo pill phase, pregnancy should be ruled out.

Tips for gastrointestinal disorders

In case of severe gastrointestinal reactions (such as vomiting or diarrhoea), absorption may not be complete and additional contraceptive measures should be used.

In case of vomiting within 3-4 hours after taking the active tablet, a new replacement tablet should be taken as soon as possible. The next tablet, if possible, should be taken within 12 hours after the usual time of taking. If more than 12 hours are missed, if possible, it is necessary to follow the rules for taking the drug indicated in the section "Accepting the missed pills". If the patient does not want to change the normal mode of taking the drug, she must take an additional tablet (or several tablets) from another package.

How to Delay "Withdrawal" Bleeding

To delay the day of the onset of menstruation, it is necessary to skip taking the placebo tablets from the started package and start taking active DIMIA® 24+4 tablets from the new package without interrupting the intake. A delay is possible until the end of the tablets in the second package.

During the lengthening of the cycle, there may be spotting from the vagina or uterine breakthrough bleeding. Regular taking DIMIA® 24+4 ends after the placebo phase.

To move the day of the start of menstruation to another day of the week of the usual schedule, shorten the upcoming phase of placebo tablets by as many days as necessary. The shorter the interval, the higher the risk that there will be no “withdrawal” bleeding, and spotting spotting and breakthrough bleeding will be noted during the reception of the second package (as in the case of a delay in the onset of menstruation).

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Side effect

Often (>1/100 to<1/10)

Headache

Emotional lability, depression

Nausea

Menstrual disorders (metrorrhagia, amenorrhea), intermenstrual bleeding

Chest pain

Uncommon (>1/1000 to<1/100)

Dizziness, migraine

Nervousness, drowsiness, decreased mood, paresthesia

Hypertension

Phlebeurysm

Soreness and tension of the mammary glands, fibrocystic changes in the mammary gland

Nausea, vomiting, gastritis, abdominal pain, dyspepsia, flatulence, diarrhea

Acne, pruritus, dry skin

Back pain, limb pain, muscle cramps

Decreased libido

Vaginal discharge, vaginal candidiasis, vaginal dryness, vaginitis

Menstrual irregularities (dysmenorrhea, hypomenorrhea, menorrhagia)

Asthenia, increased sweating, fluid retention in the body

Weight gain

Rare (>1/10,000 to<1/1 000)

Weight loss

Increased appetite, anorexia

Hives

Anemia, thrombocytopenia

Hyperkalemia, hyponatremia

Anorgasmia, insomnia

Vertigo, tremor

Nosebleeds, fainting

Thromboembolism, venous thrombosis/thromboembolism, arterial thrombosis/thromboembolism

Conjunctivitis, dry eyes, poor contact lens tolerance

Tachycardia, arterial hypertension

Tumors of the liver

Crohn's disease, ulcerative colitis

Epilepsy

Endometriosis, uterine fibroids

porfiria

Systemic lupus erythematosus

Herpes pregnant

Chorea

Hemolytic uremic syndrome

cholestatic jaundice

Chloasma, dry skin, acne or contact dermatitis

Angioedema

Eczema, hypertrichosis, photodermatitis, erythema nodosum, erythema multiforme

Breast cyst, breast hyperplasia

Painful intercourse, postcoital bleeding, withdrawal bleeding, cervical polyps, endometrial atrophy, ovarian cyst, uterine enlargement

Increased libido

Overdose

Symptoms: nausea, vomiting, slight vaginal bleeding in young girls.

Treatment: symptomatic.

Interaction with other drugs

In patients with renal insufficiency, the simultaneous administration of drospirenone and ACE inhibitors or NSAIDs (non-steroidal anti-inflammatory drugs) does not significantly affect the level of potassium in the blood serum. However, the concomitant use of DIMIA® and aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, it is necessary to study the level of potassium in the serum during the first cycle of taking the drug.

Note: Co-administration of drugs should be discussed to identify possible drug interactions.

Laboratory research

Hormone use for contraception may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, as well as levels 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 norms.

Due to its small antimineralocorticoid activity, drospirenone increases the activity of renin and plasma aldosterone.

Application features

Precautionary measures

If any of the conditions/risk factors listed below are currently present, then the potential risk and expected benefit of COC use should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, worsen, or appear for the first time, the woman should consult her doctor, who can decide whether to discontinue COCs.

Circulatory system disorders

Epidemiological studies have shown that the incidence of VTE (venous thromboembolism) in women without risk factors for VTE taking low-dose estrogen combined oral contraceptives (<50 мкг этинилэстрадиола) составляет примерно от 20 случаев на 100 000 женщин в год (для левоноргестрел-содержащих КОК «второго поколения» или до 40 случаев на 100 000 женщин в год (для дезогестрел/гестоден-содержащих КОК «третьего поколения»). Это сравнимо с цифрами от 5 до 10 случаев на 100 000 женщин, не использующих контрацептивы, и 60 случаев на 100 000 беременностей.

The use of any combined oral contraceptive is associated with an increased risk of venous thromboembolism comparable to that without use. The additional risk is highest during the first year of using a combined oral contraceptive. Venous thromboembolism is fatal in 1-2% of cases.

Epidemiological studies have also associated COC use with an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic attacks).

In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, for example, hepatic, mesenteric, renal arteries and veins, the central retinal vein and its branches, have been described.

Symptoms of venous or arterial thrombosis/thromboembolism or cerebrovascular disease may include:

unusual unilateral pain and/or swelling of a limb

sudden severe chest pain, with or without radiating to the left arm

sudden shortness of breath

sudden bout of coughing

any unusual, severe, prolonged headache

sudden partial or complete loss of vision

diplopia

slurred speech or aphasia

dizziness

loss of consciousness with or without a seizure

weakness or severe loss of sensation that suddenly appears on one side or in one part of the body

movement disorders

symptom of "acute abdomen".

The risk of complications associated with venous thromboembolism when taking COCs increases:

with age

if there is a family history (venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); if a hereditary predisposition is suspected, a woman needs to consult a specialist before prescribing COCs

after prolonged immobilization, major surgery, any operation on the legs or major trauma. In these situations, it is recommended to stop taking the drug (in the case of a planned operation, at least four weeks before it) and not resume taking it within two weeks after the end of immobilization. Additionally, it is possible to prescribe antithrombotic therapy if the pills were not stopped at the recommended time

obesity (body mass index over 30 mg/m2)

there is no consensus on the possible role of varicose veins and thrombophlebitis of superficial veins in the onset or progression of venous thrombosis.

The risk of arterial thromboembolic complications of thrombosis or cerebrovascular disease in women taking COCs is increased:

with age

in smokers (women over 35 are strictly advised not to smoke if they want to use COCs)

with dyslipoproteinemia

with hypertension

with migraine

in valvular heart disease

with atrial fibrillation.

The presence of one of the major risk factors or multiple risk factors for arterial or venous disease, respectively, may be a contraindication. Women using COCs should immediately consult a doctor if symptoms of a possible thrombosis occur. In cases of suspected thrombosis or confirmed thrombosis, COC use should be discontinued. An adequate method of contraception must be selected due to the teratogenicity of anticoagulant therapy (coumarins).

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

Other diseases that are associated with severe vascular disease include 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) may be grounds for immediate discontinuation of these drugs.

An increased risk of cervical cancer with long-term use of combined oral contraceptives has been reported in some epidemiological studies. Its association with combined oral contraceptives has not been proven. Controversy remains as to the extent to which these results relate to sexual behavior and other factors, such as human papillomavirus (HPV) ( HPV).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk (RR=1.24) of developing breast cancer diagnosed in women who used combined oral contraceptives at the time of the study. Its association with taking combined oral contraceptives has not been proven. Observed increased risk may be due to earlier diagnosis of breast cancer in women using combined oral contraceptives. Breast cancers in women who have ever used combined oral contraceptives were clinically less pronounced than in women who have never used such drugs.

In rare cases, against the background of the use of combined oral contraceptives, the development of benign liver tumors was observed, and in extremely rare cases, the development of malignant liver tumors. In some cases, these tumors lead to life-threatening intra-abdominal bleeding. In the case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding during the differential diagnosis in a woman taking COCs, the likelihood of developing a liver tumor should be considered.

Other states

The progestin component in DIMIA® is an aldosterone antagonist with potassium-sparing properties. In most cases, an increase in potassium levels is not expected. But in a clinical study in some patients with mild to moderate renal impairment, concomitant use of potassium-sparing drugs slightly increased serum potassium levels when taking drospirenone. Therefore, it is recommended to check the serum potassium level during the first cycle of treatment in patients with renal insufficiency, whose serum potassium level before treatment was at the upper limit of normal, and who are additionally using potassium-sparing drugs.

In women with hypertriglyceridemia, or a family history of this disease, an increased risk of developing pancreatitis while taking combined oral contraceptives cannot be ruled out.

Although a slight increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically significant increases have been rare. Only in rare cases is immediate withdrawal of COCs justified. If, while taking COCs, existing arterial hypertension, persistently or significantly elevated blood pressure does not adequately respond to antihypertensive treatment, it is worth stopping taking COCs.

The following conditions have been reported to develop or worsen both during pregnancy and when taking combined oral contraceptives, but their relationship with the use of combined oral contraceptives has not been proven: jaundice and / or pruritus associated with cholestasis, formation of gallstones, porphyria, systemic lupus erythematosus , hemolytic uremic syndrome, Sydenham's chorea, herpes of pregnancy, hearing loss associated with otosclerosis. In women with a tendency to Quincke's edema, exogenous estrogens may induce or exacerbate the symptoms of angioedema.

Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice and / or itching associated with cholestasis, which developed for the first time during pregnancy or previous sex hormone use, requires discontinuation of COC use.

Although combined oral contraceptives may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using combined oral contraceptives (containing
< 0.05 мг этинилэстрадиола). Тем не менее, женщины с сахарным диабетомдолжны тщательно наблюдаться, особенно на ранней стадии приема КОК.

Cases of Crohn's disease and ulcerative colitis have also been described with the use of combined oral contraceptives, however, the relationship with the use of drugs has not been proven.

Worsening of endogenous depression, epilepsy, Crohn's disease, and ulcerative colitis has been reported with COCs.

In rare cases, chloasma may develop, especially in women with skin pigmentation during pregnancy. Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

This medicinal product contains 48.53 mg lactose per tablet, inactive tablets contain 37.26 mg anhydrous lactose per tablet. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should be aware of this. Women allergic to soy lecithin may experience mild allergic reactions.

Medical examinations/consultations

Before starting the use or resuming the use of the drug DIMIA®, a woman is recommended to undergo a thorough general medical examination (including anamnesis), to exclude pregnancy. Blood pressure should be measured and a physical examination performed. The doctor should be guided by the contraindications for taking COCs and warnings. The woman should be instructed to read the abstract carefully and follow the advice given. The frequency and nature of examinations should be based on certain practical guidelines and adapted to the characteristics of each woman.

Women 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 by skipping pills, gastrointestinal disorders, or concomitant medication.

Reduced cycle control

Irregular bleeding (spotting or withdrawal bleeding) may occur with all combined oral contraceptives, especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy. They may include scraping.

In some women, withdrawal bleeding may not develop during the pill break. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. However, if combined oral contraceptives have been taken irregularly before, or if there are no consecutive withdrawal bleedings, pregnancy should be excluded before continuing to take combined oral contraceptives.

Release form

24 tablets of the drug and 4 tablets of placebo in a blister pack made of PVC / PE / PVDC film and aluminum foil.

1 or 3 blister packs in a cardboard case, enclosed together with instructions for medical use in the state Russian language in a cardboard box.

Storage conditions

Store in the original packaging, protected from light, at a temperature of 15°C to 25°C.

Keep out of the reach of children!

In addition, as auxiliary compounds in the composition of the drug there are such substances as: corn starch (16.6 mg.), including pregelatinized (9.6 mg.), magnesium stearate (0.8 mg.) and polyvinyl alcohol copolymer (1.45 mg.).

The drug shell contains a complex of compounds Opadry II 85G18490, which in turn includes substances such as talc, titanium dioxide, and soy and macrogol.

As part of the second tablet (so-called placebo ), coated with a green shell contains 37.26 mg. lactose , 42.39 mg. MCC, 0.9 mg. magnesium stearate , 0.45 mg. colloidal silicon dioxide , as well as 9 mg. pregelatinized cornstarch .

film sheath placebo pills contains a complex of compounds under the name Opadry II 85F21389 , whose chemical composition is macrogol ,polyvinyl alcohol , talc, quinoline yellow dye , indigo carmine , as well as the Sunset dye.

Release form

Dimia tablets containing active substances drospirenone And ethinylestradione have a round biconvex shape. On one side of the tableted medicinal product, the marking “G73” is embossed.

The same round and biconvex shape placebo pills are distinguished by the green color of the shell. One package of the drug contains 28 tablets, which can be packaged in 1 or 3 blisters.

pharmachologic effect

Dimia is a combined drug, which is monophasic contraceptive .

Pharmacodynamics and pharmacokinetics

This medicinal product contains ethinylestradiol , and drospirenone (substance close to natural origin). The active substances that make up this contraceptive do not have antiglucocorticoid, estrogenic, glucocorticoid abilities , as well as a pronounced moderate antimineralocorticoid And antiandrogenic action .

Its effectiveness contraceptive Dimia achieves through several factors, for example, due to inhibition of ovulation , changes endometrium and raising secretion viscosity located in cervix .

When taken orally drospirenone almost completely and fairly quickly absorbed in the stomach. The maximum concentration of the substance in the blood (Cmax) is reached a maximum of two hours after ingestion contraceptive . After the stage of distribution and metabolism drospirenone be excreted from the body kidneys , a small part of the drug is excreted with the help of intestines .

Active ingredient ethinylestradiol, included in contraceptive, as well as drospirenone is rapidly absorbed and reaches its maximum concentration in the blood after two hours. The compound is excreted from the body intestines and kidneys .

Indications for use

Dimia is used as a contraceptive.

Contraindications

This contraceptive is contraindicated in such conditions as:

• hypersensitivity to any of the active components of the drug;
• venous or arterial ;
• heart attack ;
• cerebrovascular disorders ;
• some diseases of cardio-vascular system e.g. damage heart valve or atrial fibrillation ;
• stroke ;
• cerebrovascular disease ;
• hypertension ;
• smoking, provided that the woman has reached the age of 35 years or more;
• , including suspicions of her;
• period lactation ;
• kidney failure ;
• , including benign ones;
• causeless vaginal bleeding ;
• lactase deficiency ;
• Lapp's insufficiency .

Dimia contraceptives should be used with caution when , otorosclerosis, porphyria, chorea minor, thromboembolism, cholelithiasis, as well as in diseases that are accompanied by disorders blood circulation , For example, Crohn's disease , phlebitis , and others.

Side effects of Dimia

Side effects of Dimia can be expressed in the following ailments from the side genitourinary, nervous, digestive and cardiovascular systems :

• vaginal bleeding spotting or breakthrough acyclic character ;
• engorgement of the mammary glands;
• rare but can develop hypertrophy mammary glands, as well as the composition of secretions vagina ;
• increase or decrease libido ;
• migraine ;
• mood changes;
• extremely rare, but may occur arterial , and ;
• nausea ;
• hyperkalemia ;
• vomit .

In addition, while taking the drug, there may be allergic reactions and expressed in , skin rashes, and . It should be remembered that when using contraceptive , including the drug Dimia, body weight may increase, as well as intolerance to contact lenses, develops chloasma (hyperpigmentation) .

Dimia tablets, instructions for use (Method and dosage)

You can read about how to take the drug correctly in the instructions for Dimia. These contraceptives should be taken every day without skipping. Doctors recommend doing this at the same time, always in the order that is usually indicated on the blister. TOcontraceptives Dimia, as well as other similar drugs, should be used continuously for 28 days.

new packaging birth control pills Dimia should be opened only after the end of the previous one. Approximately from the third day from the start of taking the last row of tablets in a blister (placebo period), mild bleeding . If the packaging contraceptive did not end by the end of the month, then they start taking the pills again on the first day menses .

During sexual intercourse during the first seven days of using the drug, additional methods must be used. contraception (barrier). When switching to the use of Dimia after other complex contraceptives , For example, transdermal patch , tablets ,vaginal rings and so on, you should start taking this drug immediately the next day after using the previous method contraception .

When switching to Dimia after using contraceptive , which contain exclusively ( injections, implants, ) or after you can take this drug on any convenient day. However, before using the tablets, you should apply barrier methods of contraception.

As prescribed by the doctor, a woman can start taking these pills on the day after the interruption. pregnancy (, vacuum) . After childbirth it is recommended to wait 28 days and only then resume taking the drug. It is important to note that a missed appointment placebo pills (from the 4th row of the blister) is an insignificant factor.

However, this rule does not apply to tablets containing active substances in their composition. ethinylestradiol and drospirenone . If 12 hours have not passed since the last pill, then the level of contraceptive protection does not decrease. The missed tablet should be taken as soon as possible and the next one at the usual time.

You should not take a break in taking pills for more than 7 days, since this is the amount of time needed to suppress hypothalamic-pituitary ovarian system . For correct use contraceptive you should adhere to the following recommendations:

• if you miss taking a pill during the first week of using the drug, a woman should resume use as soon as possible contraceptive , and also in order to avoid the risk of becoming pregnant, be sure to resort to additional methods barrier contraception over the next seven days;
• if you miss taking the drug from 8 to 14 days of its use, you should also resume using Dimia as soon as possible, and then return to the usual schedule, while there is no need for additional contraception if the woman did not forget to take birth control pills in the previous seven days;
• efficiency and reliability of this method contraception is significantly reduced if the missed dose of the drug fell on the period from 15 to 24 days of its use, since at this time the woman needs to switch to placebo pills .

To avoid unwanted pregnancy if the last of the described situations of skipping the drug occurs, the woman should take the pill as soon as possible to replace the missed one. Next, you should stick to your usual schedule of taking the drug until the active pills run out. As a result of mixing the intake schedule contraceptive , designed for 28 days, will remain in the blister placebo pills which do not need to be accepted.

Most likely, with this variant of normal withdrawal bleeding there will be no contraceptive until the end of the next package, however, I may appear spotting . If you miss taking the drug between 15 and 24 days of the start of its use, the woman may not return to the usual schedule of use contraceptives and take 4 days (including missed days) placebo pills and then proceed with a new package.

If with this option did not come "withdrawal" bleeding then the possibility of pregnancy should be considered. In the presence of gastrointestinal disorder the effectiveness of the drug is reduced, since the active compounds will not be completely absorbed by the stomach. If, after 4 hours after taking the contraceptive pill, the woman vomited, it is worth immediately taking the second one, i.e. replacement tablet.

If not monthly when taking Dimia, this may signal the onset of pregnancy . It is worth noting that spotting "cancellation" a woman can correct, for example, delay it on her own by changing the schedule for taking the drug.

For this you can skip placebo pills and immediately start taking tablets containing the active compound from the new package. It is noteworthy that when postponing or shifting withdrawal bleeding may appear acyclic spotting or profuse bleeding .

Overdose

At the moment, there is no information about cases of overdose of Dimia. However, based on experience with complex contraceptives similar to this drug in case of overdose, symptoms such as nausea, vaginal bleeding, and vomit . If these symptoms occur, stop using the drug and consult a doctor for advice.

Interaction

To avoid weakening the effectiveness of contraceptives, you should not use Dimia in conjunction with drugs that affect liver enzymes , For example, , Primidone, Phenytoin, Oxcarbazepine, Felbamate, barbiturates and others, as well as medicines containing St. John's wort in their chemical composition.

On hepatic metabolism drugs can have a negative effect HIV protease inhibitors and non-nucleoside , as well as their combinations. downgrade estrogen circulation , and consequently, the effectiveness of Dimia occurs while taking And .

For 28 and 7 days (respectively) after taking drugs that affect induction of liver enzymes, and antibiotics you should stop using this drug. Contraceptives can affect the effect of some drugs, so before using Dimia, you should carefully read the instructions.

Terms of sale

Available by prescription only.

Storage conditions

Contraceptives are stored out of the reach of children, at a temperature not exceeding 25 C.

Best before date

special instructions

Constant use contraceptives may increase the risk of development. Moreover, this risk is highest in the first year of using a contraceptive. If the following symptoms occur while taking Dimia, you should immediately stop using the drug:

• swelling of the lower extremities And strong pain ;
• suddenvision loss ;
• cough ;
• causeless severe headache;
• diplopia ;
• vertigo ;
• speech disorder ;
• acute abdomen ;
• collapse ;
• numbness ;
• weakness ;
• movement disorders .

During the use of Dimia, the risk of dangerous thromboembolic disorders occurs significantly when:

• hereditary disposition;
• after the age of 30;
• immobilization and after emergency surgery;
• smoking;
• hypertension ;
• dyslipoproteinemia ;
• diseases heart valves.

When using a contraceptive, be sure to take into account the risk of thromboembolism especially after childbirth , as well as the development of other adverse effects when diabetes mellitus, Crohn's disease, colitis, anemia and so on. Women should not start taking the drug without the advice of a doctor, as well as a preliminary medical examination.

It is important to exclude pregnancy . During use of the contraceptive, "withdrawal" bleeding may occur, so the assessment of the normality of such secretions can be carried out after three months (adaptation period) since the start of the use of birth control pills.

Instructions for use:

Composition and form of release Dimia

Dimia tablets are produced, film-coated.

1 tablet of Dimia contains the following active ingredients: 20 μg of ethinylestradiol and 3 mg of drospirenone. The preparation also contains such additional substances: magnesium stearate, pregelatinized corn starch, lactose monohydrate, copolymer of polyvinyl alcohol and macrogol.

The drug is produced in blisters of 28 tablets.

Pharmacological action of Dimia

Dimia contains ethinyl estradiol and drospirenone. Drospirenone in its pharmacological action can be compared with natural progesterone. It does not have antiglucocorticoid, glucocorticoid and estrogenic activity and has a pronounced antiandrogenic and moderate antimineralocorticoid effect.

The contraceptive effect of the drug Dimia is based on its ability to inhibit the onset of ovulation, change the endometrium and increase the viscosity of the secretory fluid of the cervix.

According to reviews, Dimia is a very effective contraceptive.

Indications for use Dimia

The instructions for Dimia indicate that the tablets are indicated for women of childbearing age for oral contraception.

Method of application Dimia and dosing regimen

Dimia tablets should be taken every day at approximately the same time. Tablets are taken in the order indicated on the blister pack, and washed down with a small amount of water. Duration of admission is 28 days, 1 tablet per day. Taking Dimia tablets from the next package should be started the next day after taking the last tablet from the previous package. As a rule, bleeding begins 2-3 days after the start of taking the placebo tablets (last row) and does not necessarily end before the start of taking the tablets from the next package.

Contraindications

According to the instructions, Dimia, like other combined contraceptive drugs, is contraindicated in the following cases:

• any conditions preceding thrombosis (including angina pectoris, transient ischemic attacks);
• venous and arterial thrombosis and thromboembolism (including stroke, myocardial infarction, deep vein thrombophlebitis, cerebrovascular disorders, pulmonary embolism);
• hereditary or acquired tendency to develop arterial or venous thrombosis;
• various risk factors that contribute to the development of arterial or venous thrombosis (arterial hypertension, cerebrovascular disease, damage to the valvular apparatus of the heart, smoking after the age of 35, obesity, etc.);
• acute or severe chronic renal failure;
• pancreatitis with severe hypertriglyceridemia;
• bleeding from the vagina of an unexplained nature;
• benign or malignant liver tumor;
• the presence of any severe liver disease;
• the period of breastfeeding (negatively affects the amount and composition of milk);
• hormone-dependent malignant tumors of the breast or genital organs;
• hypersensitivity to one or more components of the drug;
• the presence of pregnancy or suspicion of it;
• lactose intolerance, lack of lactase;
• migraine with focal neurological symptoms.

According to reviews, Dimia should be prescribed with great care in the following cases:

• hereditary angioedema;
• postpartum period;
• diseases that contribute to impaired peripheral circulation (systemic lupus erythematosus, diabetes mellitus, ulcerative colitis, Crohn's disease, phlebitis of superficial veins, hemolytic-uremic syndrome, sickle cell anemia);
• hypertriglyceridemia;
• diseases that have developed during pregnancy or against the background of a previous intake of sex hormones (jaundice, chorea, atherosclerosis with hearing impairment, herpes, porphyria, chloasma).

Side effects

According to reviews, Dimia can cause the following unwanted side effects:

• Lymphatic and hematopoietic system: thrombocytopenia, anemia.
• Metabolism: anorexia, decrease or increase in body weight, increased appetite, hyponatremia, hyperkalemia.
• Infections: candidiasis.
• Immune system: development of various allergic reactions.
• Nervous system: dizziness, headache, paresthesia, tremor, vertigo, depression, insomnia, anorgasmia, drowsiness, decreased libido.
• Cardiovascular system: varicose veins, migraine, epistaxis, tachycardia, fainting, increased blood pressure.
• Digestive system: diarrhea, vomiting, nausea, abdominal pain.
• Musculoskeletal system: pain in the limbs and back, muscle cramps.
• From the skin and subcutaneous tissue: itching, rash, eczema, dry skin, skin stretch marks, contact dermatitis.
• Biliary tract and liver: cholecystitis, gallbladder tenderness.
• Reproductive system: chest pain, no bleeding, breast enlargement, pelvic pain, vaginitis, vaginal discharge, heavy or scanty bleeding, dryness of the vaginal mucosa, cervical polyps, cyst or breast hyperplasia.

Overdose

To date, there have been no reports of Dimia regarding an overdose. According to the general experience with oral contraceptives, Dimia tablets can cause overdose symptoms such as nausea, vomiting, minor bleeding from the vagina.

The use of Dimia tablets during pregnancy and lactation

According to the instructions, Dimia is contraindicated during pregnancy and breastfeeding.

If pregnancy occurs while taking Dimia tablets, then their further intake should be stopped immediately. According to epidemiological studies, taking Dimia, according to the instructions, does not have any negative consequences on the development of the fetus, however, undesirable effects that have a negative impact on the course of pregnancy cannot be ruled out.

According to reviews, Dimia negatively affects lactation, reduces the amount of breast milk and changes its composition, which has a negative effect on the child. Therefore, it is advisable to stop breastfeeding while taking the drug.

special instructions

It is necessary to start taking Dimia tablets only after examination and consultation with a doctor. In the event of any undesirable effects while taking Dimia, a woman should immediately consult a doctor.

Storage conditions

Dimia is a prescription drug with a recommended shelf life of no more than 24 months.

Catad_pgroup Combined oral contraceptives

The most physiological contraceptive that preserves the quality of sexual life. For the treatment of heavy and / or prolonged menstrual bleeding without organic pathology.
INFORMATION IS PROVIDED STRICTLY
FOR HEALTHCARE PROFESSIONALS

Dimia - official instructions for use

Registration number:

Trade name of the drug:

International non-proprietary name:

Dosage form:

Compound:

for 1 tablet:
Drospirenone + ethinyl estradiol tablets
active substance: drospirenone 3.000 mg, ethinylestradiol 0.020 mg;
Excipients: lactose monohydrate, corn starch, pregelatinized corn starch, macrogol and polyvinyl alcohol copolymer, magnesium stearate.
Film casing (Opadray II white*): polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, soy lecithin.
*code 85G18490
placebo pills
microcrystalline cellulose, lactose, pregelatinized corn starch, magnesium stearate, colloidal silicon dioxide.
Film casing (Opadry II green**): polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, indigo carmine, quinoline yellow dye, iron oxide black dye; dye sunny sunset yellow.
** code 85F21389

Description:

For drospirenone + ethinyl estradiol tablets:
Round, biconvex, white or off-white film-coated tablets, marked "G73" on one side of the tablet, embossed. In cross section, the nucleus is white or almost white.
For placebo pills:
Round, biconvex, green film-coated tablets. In cross section, the nucleus is white or almost white.

Pharmacotherapeutic group:

ATX code:

Pharmacological properties

Pharmacodynamics
Dimia® is a combined hormonal contraceptive with antimineralocorticoid and antiandrogenic effects. The contraceptive effect of combined oral contraceptives (COCs) is based on the interaction of various factors, the most important of which include the suppression of ovulation and changes in the properties of the secretion of the cervix, as a result of which it becomes less permeable to spermatozoa.
When used correctly, the Pearl Index (the number of pregnancies per 100 women per year) is less than 1. If pills are missed or used incorrectly, the Pearl Index may increase.
In women taking COCs, the menstrual cycle becomes more regular, painful periods are less common, the intensity of bleeding decreases, which reduces the risk of anemia. In addition, according to epidemiological studies, the use of COCs reduces the risk of developing endometrial cancer and ovarian cancer.
Drospirenone contained in Dimia® has an antimineralocorticoid effect. Prevents weight gain and the appearance of edema associated with fluid retention caused by estrogens, which ensures good tolerability of the drug. Drospirenone has a positive effect on premenstrual syndrome (PMS). The combination of drospirenone/ethinyl estradiol has been shown to be clinically effective in relieving symptoms of severe PMS, such as severe psychoemotional disturbances, breast engorgement, headache, muscle and joint pain, weight gain, and other symptoms associated with the menstrual cycle. Drospirenone also has antiandrogenic activity and helps to reduce the symptoms of acne (blackheads), oily skin and hair. This action of drospirenone is similar to the action of natural progesterone produced by the body.
Drospirenone does not have androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. All this, combined with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone.
In combination with ethinylestradiol, drospirenone shows a favorable effect on the lipid profile, characterized by an increase in high density lipoproteins.

Pharmacokinetics
Drospirenone
Suction
When taken orally, drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum plasma concentration after a single oral administration is reached after about 1-2 hours and is about 38 ng / ml. Bioavailability 76-85%. Simultaneous administration with food does not affect the bioavailability of drospirenone.
Distribution
After oral administration, a two-phase decrease in the concentration of drospirenone in blood plasma is observed, with half-lives of 1.6 ± 0.7 hours and 27.0 ± 7.5 hours, respectively. Drospirenone binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG ), or with corticosteroid-binding globulin. Only 3-5% of the total plasma concentration of drospirenone is present as free steroids. The increase in SHBG induced by ethinylestradiol does not affect the binding of drospirenone to plasma proteins. The mean apparent volume of distribution of drospirenone is 3.7±1.2 l/kg.
Metabolism
Drospirenone is extensively metabolized after oral administration. Most metabolites in plasma are represented by acidic forms of drospirenone. Drospirenone is also a substrate for oxidative metabolism catalyzed by the cytochrome P450 isoenzyme CYP3A4.
breeding
The rate of metabolic clearance of drospirenone in plasma is 1.5±0.2 ml/min/kg. In unchanged form, drospirenone is excreted only in trace amounts. Drospirenone metabolites are excreted through the intestines and by the kidneys in a ratio of approximately 1.2:1.4. The half-life of metabolites by the kidneys and through the intestines is about 40 hours.
Equilibrium concentration
During cyclic administration, the maximum equilibrium concentration of drospirenone in the blood plasma is reached between the 7th and 14th day of taking the drug and is approximately 70 ng / ml. Plasma concentrations of drospirenone increase by about 2-3 times (due to cumulation), due to the ratio of the terminal half-life and dosing interval. A further increase in the concentration of drospirenone in the blood plasma is observed between 1 and 6 cycles of administration, after which no increase in concentration is observed.
Special populations of patients
Patients with renal insufficiency
Steady-state plasma concentrations of drospirenone in women with mild renal insufficiency (creatinine clearance (CC) 50–80 ml/min) were comparable to those in women with normal renal function (CC>80 ml/min). In women with moderate renal insufficiency (CC 30-50 ml / min), the plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Treatment with drospirenone was well tolerated in all groups. Drospirenone did not have a clinically significant effect on the concentration of potassium in the blood plasma. The pharmacokinetics of drospirenone in severe renal insufficiency has not been studied.
Patients with liver failure
Drospirenone is well tolerated by patients with mild to moderate hepatic impairment (Child-Pugh class B). Pharmacokinetics in severe hepatic impairment has not been studied.
Ethinylestradiol
Suction
When taken orally, ethinylestradiol is rapidly and completely absorbed. The maximum plasma concentration after a single oral administration is reached after 1-2 hours and is about 88-100 pg / ml. Absolute bioavailability as a result of first pass conjugation and first pass metabolism is approximately 60%. Simultaneous food intake reduced the bioavailability of ethinylestradiol in approximately 25% of the examined patients, while no such changes were observed in other patients.
Distribution
The concentration of ethinylestradiol in the blood plasma decreases biphasically, the terminal phase is characterized by an elimination half-life of approximately 24 hours.
Ethinylestradiol is significantly, but non-specifically, bound to serum albumin (approximately 98.5%) and induces an increase in plasma concentrations of SHBG. The apparent volume of distribution is about 5 l/kg.
Metabolism
Ethinylestradiol undergoes significant primary metabolism in the intestine and liver. Ethinylestradiol and its oxidized metabolites are primarily conjugated to glucuronides or sulfate. The rate of metabolic clearance of ethinyl estradiol is about 5 ml / min / kg.
breeding
Ethinylestradiol is practically not excreted unchanged. Metabolites of ethinylestradiol are excreted by the kidneys and through the intestines in a ratio of 4:6. The half-life of metabolites is about 24 hours.
Equilibrium concentration
The state of equilibrium concentration is reached during the second half of the cycle of taking the drug, and the concentration of ethinylestradiol in the blood plasma increases by about 1.5-2.3 times.
Preclinical safety data
Preclinical data from standard studies of repeated dose toxicity, as well as genotoxicity, carcinogenic potential and reproductive toxicity, do not indicate a particular risk to humans. However, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.

Indications for use

• Contraception.
• Contraception and treatment of moderate acne (acne vulgaris).
• Contraception and treatment of severe premenstrual syndrome (PMS).

Contraindications

Dimia® is contraindicated in the presence of any of the conditions, diseases/risk factors listed below. If any of these conditions, diseases / risk factors develop for the first time while taking the drug, the drug should be immediately canceled:

• thrombosis (venous and arterial) and thromboembolism at present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders;
• conditions preceding thrombosis (including transient ischemic attacks, angina pectoris), currently or in history;
• identified acquired or hereditary predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);
• the presence of a high risk of venous or arterial thrombosis (see section "Special Instructions");
• migraine with focal neurological symptoms at present or in history;
• diabetes mellitus with vascular complications;
• liver failure and severe liver disease (before normalization of liver function tests);
• liver tumors (benign or malignant) at present or in history;
• severe renal failure, acute renal failure;
• adrenal insufficiency;
• identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them;
• bleeding from the vagina of unknown origin;
• pregnancy or suspicion of it;
• breastfeeding period;
• hypersensitivity to any of the components of the drug Dimia®;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the preparation contains lactose monohydrate);
• hypersensitivity to peanuts or soy.

If any of the conditions, diseases/risk factors listed below are currently present, then the potential risk and expected benefit of COC use should be carefully weighed in each individual case:

• risk factors for the development of thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident under the age of 50 in any of the next of kin; overweight (body mass index (BMI) less than 30 kg / m 2); dyslipoproteinemia; controlled arterial hypertension; migraine; uncomplicated heart valve disease; violation of the heart rhythm;
• other diseases in which peripheral circulatory disorders may occur: diabetes mellitus; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; as well as phlebitis of superficial veins;
• hereditary angioedema;
• hypertriglyceridemia;
• liver disease;
• diseases that first arose or worsened during pregnancy or against the background of a previous intake of sex hormones (for example, jaundice, cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes pregnant, Sydenham's chorea);
• postpartum period.

Use during pregnancy and during breastfeeding

Pregnancy
Dimia® is contraindicated during pregnancy. If the patient is planning a pregnancy, she may stop taking Dimia® at any time. If pregnancy is detected during the use of Dimia®, it should be discontinued immediately. However, extensive epidemiological studies have not found any increased risk of malformations in children born to women who received sex hormones (including COCs) before pregnancy, or teratogenicity when sex hormones were taken inadvertently in early pregnancy.
Existing data on the results of taking Dimia® during pregnancy are limited, which does not allow drawing any conclusions about the effect of the drug on the course of pregnancy, the health of the newborn and the fetus. There are currently no significant epidemiological data on Dimia®.
breastfeeding period
The use of the drug Dimia® during breastfeeding is contraindicated. Taking COCs can reduce the amount of breast milk and change its composition, so their use is not recommended until breastfeeding is stopped. A small amount of sex hormones and / or their metabolites can pass into breast milk and affect the body of the newborn.

Dosage and administration

Method of application: for oral administration.
How to take Dimia®
The tablets should be taken daily, at about the same time, with a small amount of water, in the order indicated on the blister pack. Tablets are taken continuously for 28 days, 1 tablet per day. Taking tablets from each subsequent package should be started the next day after taking the last tablet from the previous package. "Withdrawal" bleeding usually begins 2-3 days after the start of the green placebo tablets (last row) and may not end before the start of the next pack of tablets. Pills from a new pack should always be started on the same day of the week, and "withdrawal" bleeding will occur on about the same days each month.
How to start taking Dimia®

• In the absence of taking any hormonal contraceptive drugs in the previous month
  Dimia® should be started on the first day of the menstrual cycle (i.e. on the first day of menstrual bleeding), in which case additional contraceptive measures are not required. It is allowed to start taking on the 2nd-5th day 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 other combined contraceptive products (COC, vaginal ring or transdermal patch)
  It is preferable to start taking Dimia the day after taking the last inactive tablet (for preparations containing 28 tablets per package) or the day after taking the last active tablet from the previous package, but in no case later than the day after the usual 7- day break (for preparations containing 21 tablets). Dimia® should be started on the day the vaginal ring or patch is removed, but no later than the day a new ring or patch is to be inserted.
• When switching from contraceptive preparations containing only gestagens ("mini-pill", injectable forms, implant), or from a progestogen-releasing intrauterine contraceptive
  A woman can switch from a mini-drink to Dimia® any day (without a break); from an implant or intrauterine contraceptive with a progestogen - on the day of its removal, from an injectable contraceptive - on the day when the next injection should be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.
• After an abortion in the first trimester of pregnancy
  A woman can start taking the drug immediately after a spontaneous or medical abortion in the first trimester of pregnancy. If this condition is met, the woman does not need additional contraceptive measures.
• After an abortion in the second trimester of pregnancy or childbirth
  The drug can be started on the 21-28th day after a spontaneous or medical abortion or after childbirth, in the absence of breastfeeding. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if sexual intercourse has already taken place, pregnancy should be excluded before taking Dimia®, or it is necessary to wait for the first menstruation.

Stopping Dimia®
You can stop taking the drug at any time. If a woman is not planning a pregnancy or pregnancy is contraindicated because she is taking medications that are potentially harmful to the fetus, other methods of contraception should be discussed with her doctor.
If a woman is planning a pregnancy, it is recommended to stop taking the drug and wait for natural menstrual bleeding, and only then try to get pregnant. This will help to more accurately calculate the gestational age and time of birth.
Taking missed pills
Missing a placebo tablet from the last (4th) row of the blister can be ignored.
However, they should be discarded to avoid inadvertently prolonging the placebo phase. The following recommendations apply only to missing active tablets. If the delay in taking the drug was less than 24 hours, contraceptive protection is not reduced. The woman should take the missed pill as soon as possible and take the next pill at the usual time.
If the delay in taking the tablets was more than 24 hours, contraceptive protection may be reduced. The more pills missed, and the closer the missed pills are to the inactive green placebo pill phase, the higher the chance of pregnancy.
In this case, you can be guided by the following two basic rules:

1. The drug should never be interrupted for more than 7 days;
2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous tablet intake are required.

Accordingly, the woman can be given the following recommendations:

• When skipping tablets in the period from 1 to 7 days of admission:
  The woman should take the last missed tablet as soon as she remembers, even if it means taking two tablets at the same time. She continues to take the next pills at the usual time. In addition, over the next 7 days, you must additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before skipping the pill, the possibility of pregnancy should be considered.
• When skipping tablets in the period from 8 to 14 days of admission:
  The woman should take the last missed tablet as soon as she remembers, even if it means taking two tablets at the same time. She continues to take the next pills at the usual time. If during the 7 days preceding the first missed pill, the woman took the pills correctly, there is no need for additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.
• When skipping tablets in the period from 15 to 24 days of admission:
  The risk of reduced reliability is inevitable due to the approaching period of inactive green placebo pills. You must strictly adhere to one of the two following options. In this case, if during the 7 days preceding the first missed tablet, all the tablets were taken correctly, there is no need to use additional contraceptive methods. Otherwise, the woman must use the first of the following regimens and additionally use a barrier method of contraception (eg, a condom) for 7 days.

1. The woman should take the last missed tablet as soon as she remembers, even if it means taking two tablets at the same time. The next pills are taken at the usual time until the active pills in the pack are finished, the 4 green placebo pills from the last row should be discarded and the pills from the next pack should be started immediately.
   "Withdrawal" bleeding is unlikely until the pills in the second pack are finished, but "spotting" discharge and/or "breakthrough" bleeding may occur while taking the pills.
2. The woman may also stop taking active tablets from the current pack. She should then take the green placebo pills from the last row for 4 days, including the days she skipped pills, and then start taking the pills from the new pack.
   If a woman misses taking the active pills and does not experience withdrawal bleeding while taking the inactive green placebo pills, pregnancy should be ruled out.

Recommendations for gastrointestinal disorders
In case of severe gastrointestinal disturbances, absorption may be incomplete, so additional contraceptive measures should be taken. If within 3-4 hours after taking the active tablet there was vomiting or diarrhea, you should be guided by the recommendations when skipping tablets. If a woman does not want to change her usual regimen and postpone the start of her period to another day of the week, an additional active tablet should be taken.
How to change/delay the timing of withdrawal bleeding
To delay the onset of withdrawal bleeding, the woman should continue taking the tablets from the next pack of Dimia®, skipping the inactive green pills from the current pack. Thus, the cycle can be extended as desired for any period until the active tablets from the second package run out, that is, about 3 weeks later than usual.
If you plan to start the next cycle earlier, at any time you need to stop taking the active tablets from the second package, discard the remaining active tablets and start taking the inactive green tablets (within a maximum of 4 days), and then start taking the tablets from the new package. In this case, approximately 2-3 days after taking the last active tablet from the previous package, "withdrawal" bleeding should begin. While taking the drug from the second package, a woman may experience "spotting" discharge and / or "breakthrough" uterine bleeding. Regular intake of Dimia® is then resumed after the end of the period of taking the inactive green tablets.
To reschedule the onset of "withdrawal" bleeding to another day of the week, the woman should shorten her next inactive green pill period by the desired number of days. The shorter the interval, the higher the risk that she will not have "withdrawal" bleeding and will have "spotting" discharge and/or "breakthrough" bleeding in the future while taking the pills from the second pack.
Use in special categories of patients
Children and teenagers
The drug Dimia® is indicated only after the onset of menarche. Available data do not suggest dose adjustment in this group of patients.
Elderly patients
Dimia® is not indicated after menopause.
Patients with impaired liver function
Dimia® is contraindicated in women with severe liver disease until liver function tests return to normal (see also sections "Contraindications" and "Pharmacological properties").
Patients with impaired renal function
Dimia® is contraindicated in women with severe renal insufficiency or with acute renal failure (see also sections "Contraindications" and "Pharmacological properties").

Side effect

The following adverse drug reactions (ADRs) have been reported during the use of the drospirenone/ethinylestradiol combination.
Adverse drug reactions are presented by system organ class according to the MedDRA classification and with the frequency of occurrence: often (> 1/100 and<1/10), нечасто (>1/1000 and<1/100) и редко (>1/10 000 and<1/1000). В пределах каждой группы, выделенной в зависимости от частоты возникновения, НЛР представлены в порядке уменьшения их тяжести. Для дополнительных нежелательных реакций, выявленных только в процессе пострегистрационных наблюдений, и для которых оценку частоты возникновения провести не представлялось возможным, указано «частота неизвестна».

* The frequency of irregular bleeding decreases as the duration of taking Dimia® increases.

Additional Information
Listed below are adverse reactions with a very rare frequency of occurrence or with delayed symptoms, which are believed to be associated with taking drugs from the COC group (see also sections "Contraindications" and "Special Instructions").
Tumors

• The frequency of diagnosing breast cancer in women taking COCs is slightly increased. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women taking COCs is insignificant in relation to the overall risk of this disease.
• Tumors of the liver (benign and malignant).

Other states

• women with hypertriglyceridemia have an increased risk of pancreatitis while taking COCs;
• increase in blood pressure;
• conditions that develop or worsen while taking COCs, but their relationship has not been proven: jaundice and / or itching associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis;
• in women with hereditary angioedema, estrogens may cause or exacerbate its symptoms;
• liver dysfunction;
• changes in glucose tolerance or effects on insulin resistance;
• Crohn's disease, ulcerative colitis;
• chloasma;
• hypersensitivity (including symptoms such as rash, urticaria).

Interaction
The interaction of COCs with other drugs (enzyme inducers) can lead to "breakthrough" bleeding and / or a decrease in contraceptive efficacy (see section "Interaction with other drugs").
If any of the side effects listed in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Serious violations in case of overdose have not been reported. In preclinical studies, there were also no serious adverse effects resulting from overdose.
Symptoms that may occur in overdose: nausea, vomiting, spotting vaginal discharge or metrorrhagia.
Treatment. There is no specific antidote, symptomatic treatment should be carried out.

Interaction with other drugs

Effects of other medicinal products on Dimia®
Interaction with drugs that induce microsomal enzymes is possible, as a result of which the clearance of sex hormones may increase, which, in turn, may lead to "breakthrough" uterine bleeding and / or a decrease in the contraceptive effect. Women who receive treatment with such drugs in addition to Dimia® are recommended to use a barrier method of contraception or choose another non-hormonal method of contraception (if long-term use of inducer drugs is necessary).
The barrier method of contraception should be used during the entire period of taking concomitant drugs, as well as within 28 days after their withdrawal. If the use of microsomal liver enzyme inducers continues after the end of the active tablets in the Dimia® package, you should start taking the Dimia® tablets from the new package without taking the green placebo tablets from the old package.

• Substances that increase the clearance of Dimia®(weakening efficacy by enzyme induction): phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, and preparations containing St. John's wort.
• Substances with different effects on the clearance of Dimia®
  When co-administered with Dimia, many inhibitors of HIV or hepatitis C proteases and non-nucleoside reverse transcriptase inhibitors can either increase or decrease plasma concentrations of estrogens or progestogens. In some cases, this effect may be clinically significant.
• Substances that reduce the clearance of COCs (enzyme inhibitors)
  Strong and moderate inhibitors of CYP3A4, such as azole antimycotics (eg, itraconazole, voriconazole, fluconazole), verapamil, macrolides (eg, clarithromycin, erythromycin), diltiazem, and grapefruit juice may increase plasma concentrations of estrogen or progestogen, or both. It was shown that etoricoxib at doses of 60 and 120 mg / day, when taken together with COCs containing 0.035 mg of ethinylestradiol, increases the concentration of ethinylestradiol in blood plasma by 1.4 and 1.6 times, respectively.

Effect of Dimia® on other medicinal products
COCs can interfere with the metabolism of other drugs, resulting in an increase (eg, cyclosporine) or a decrease (eg, lamotrigine) in plasma and tissue concentrations.
In vitro, drospirenone is able to weakly or moderately inhibit cytochrome P450 isoenzymes CYP1A1, CYP2C9, CYP2C19 and CYP3A4.
Based on in vivo interaction studies in female volunteers treated with omeprazole, simvastatin or midazolam as marker substrates, it can be concluded that a clinically significant effect of drospirenone 3 mg on drug metabolism mediated by enzymes of the cytochrome P450 system is unlikely.
In vitro, ethinyl estradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 isoenzymes, as well as an irreversible inhibitor of CYP3A4 / 5, CYP2C8 and CYP2J2 isoenzymes. In clinical studies, the administration of a hormonal contraceptive containing ethinyl estradiol did not lead to any increase or only a slight increase in plasma concentrations of substrates of the CYP3A4 isoenzyme (for example, midazolam), while the concentrations of substrates of the CYP1A2 isoenzyme in the blood plasma may slightly increase (eg, theophylline) or moderately (eg, melatonin and tizanidine).
Other forms of interaction
In patients with preserved renal function, the combined use of drospirenone and angiotensin-converting enzyme inhibitors or non-steroidal anti-inflammatory drugs does not significantly affect the concentration of potassium in the blood plasma. However, the concomitant use of Dimia® with aldosterone antagonists or potassium-sparing diuretics has not been studied. In such cases, the concentration of potassium in the blood plasma must be monitored during the first cycle of taking the drug (see section "Special Instructions").

special instructions

If any of the conditions, diseases/risk factors listed below are currently present, then the potential risk and expected benefit of COC use in each individual case should be carefully weighed and discussed with the woman before she decides to start taking the drug. In case of worsening, worsening or first manifestation of any of these conditions, diseases or risk factors, a woman should consult her doctor, who can decide on the need to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of COCs and an increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders). These diseases are rare.
The risk of developing venous thromboembolism (VTE) is highest in the first year of using these drugs. An increased risk is present after the initial use of COCs or the resumption of use of the same or different COCs (after a break between doses of 4 weeks or more). Data from a prospective study involving 3 groups of patients show that this increased risk is present mainly during the first 3 months of the drug. The overall risk of VTE in patients taking low-dose COCs (<0,05 мг этинилэстрадиола) в 2-3 раза выше, чем у небеременных пациенток, которые не принимают КОК, тем не менее, этот риск остается более низким по сравнению с риском ВТЭ при беременности и родах. ВТЭ может угрожать жизни или привести к летальному исходу (в 1-2% случаев).
VTE manifesting as deep vein thrombosis or pulmonary embolism can occur with any COC.
Very rarely, when using COCs, thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or vessels of the retina. There is no consensus regarding the relationship between the occurrence of these diseases and the use of COCs.
Symptoms of deep vein thrombosis (DVT) include the following: unilateral swelling of the lower extremity or along a vein in the lower extremity, pain or discomfort in the lower extremity only when standing or walking, localized temperature increase in the affected lower extremity, redness or discoloration of the skin on the lower limb.
Symptoms of pulmonary embolism (PE) are as follows: difficulty or rapid breathing; sudden cough, including hemoptysis; sharp pain in the chest, which may worsen with a deep breath; sense of 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 or less severe conditions/diseases (eg, respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction.
Symptoms of a stroke are as follows: sudden weakness or loss of sensation in the face, limbs, especially on one side of the body, sudden confusion, problems with speech and understanding; sudden unilateral or bilateral loss of vision; sudden disturbance of gait, dizziness, loss of balance or coordination of movements; sudden, severe or prolonged headache with no apparent cause; loss of consciousness or fainting with or without an epileptic seizure.
Other signs of vascular occlusion: sudden pain, swelling and slight blueness of the extremities, an "acute" abdomen.
Symptoms of myocardial infarction include: pain, discomfort, feeling of pressure, heaviness, squeezing or fullness in the chest, in the arm or behind the breastbone; discomfort with irradiation to the back, cheekbone, larynx, arm, stomach; cold sweats, nausea, vomiting or dizziness, severe weakness, feeling anxious or short of breath; fast or irregular heartbeat.
Arterial thromboembolism can be life threatening or fatal. In women with a combination of several risk factors or a 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;
• in 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 (BMI over 30 kg/m2);
• family history (for example, venous or arterial thromboembolism ever 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;
• prolonged immobilization, major surgery, any lower limb surgery, or major trauma. In these cases, the use of Dimia® should be discontinued. In the case of a planned operation, the drug should be stopped at least 4 weeks before it and not resumed for two weeks after the full restoration of motor activity. Temporary immobilization (eg, air travel longer than 4 hours) may also be a risk factor for venous thromboembolism, especially if other risk factors are present;
• dyslipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve disease;
• atrial fibrillation.

The use of any combined hormonal contraceptive increases the risk of VTE. The use of drugs containing levonorgestrel, norgestimate or norethisterone is associated with the lowest risk of VTE. The use of other drugs, such as Dimia®, can lead to a two-fold increase in risk. The decision to use another drug other than the one with the lowest risk of developing VTE should only be made after discussion with the woman to ensure that she understands that the use of Dimia® is accompanied by the likelihood of developing VTE, understands how her risk factors affect the likelihood of developing VTE, and also understands that in every first year of using the drug, the risk of developing VTE for her is greatest.
The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.
An increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders can 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 disorders) is the basis for the immediate discontinuation of these drugs.
Biochemical indicators that indicate 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 (cardiolipin antibodies, lupus anticoagulant).
When evaluating the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition can reduce the risk of thrombosis associated with it. It should also be borne in mind that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose COCs (<0,05 мг этинилэстрадиола).
Tumors
The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs, but the relationship with the use of COCs has not been proven. Controversy remains as to the extent to which these findings are related to screening for cervical pathology or sexual behavior (lower use of barrier methods of contraception).
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 these drugs. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women who are currently taking COCs or have recently taken them is insignificant in relation to the overall risk of this disease. The observed increase in risk may be due to earlier diagnosis of breast cancer in women using COCs, their biological effects, or a combination of both factors. In women who used COCs, earlier stages of breast cancer are detected than in women who have never used them.
In rare cases, against the background of 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. These conditions should be taken into account when conducting a differential diagnosis in case of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.
Tumors can be life threatening or fatal.
Other states
Clinical studies have shown no effect of drospirenone on the concentration of potassium in the blood plasma in patients with mild to moderate renal insufficiency. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial concentration of potassium at the upper limit of normal, while taking drugs that lead to potassium retention in the body. In women with an increased risk of developing hyperkalemia, it is recommended to determine the concentration of potassium in the blood plasma during the first cycle of taking Dimia®.
In women with hypertriglyceridemia (or a family history of this condition), there may be an increased risk of developing pancreatitis while taking COCs.
Although a slight increase in blood pressure has been described in many women taking COCs, clinically significant increases have been rare. 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. Taking COCs 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 when taking COCs, but their relationship with COC use has not been proven: jaundice and / or itching associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. There are also described cases of worsening of the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis against the background of the use of COCs.
In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen the symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COCs.
Although COCs may affect 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 мг этинил-эстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться во время приема КОК.
Occasionally, chloasma may develop, especially in women with a history of chloasma of pregnancy. Women with a tendency to chloasma while taking COCs should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.
Laboratory tests
Taking COCs may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein concentrations, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the boundaries of normal values. Drospirenone increases the activity of plasma renin and aldosterone, which is associated with its antimineralocorticoid action.
Medical examinations
Before starting or resuming the use of Dimia®, it is necessary to familiarize yourself with the history of life, the woman's family history, conduct a thorough medical (including measurement of blood pressure, heart rate, BMI) and gynecological examination (including examination of the mammary glands and cytological examination of a scraping from the cervix), exclude pregnancy. The volume of additional studies and the frequency of follow-up examinations is determined individually. Usually control examinations should be carried out at least 1 time in 6 months.
Women should be warned that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced efficiency
The effectiveness of COCs can be reduced in the following cases: when active tablets are missed, with vomiting and diarrhea, or as a result of drug interactions.
Insufficient control of the menstrual cycle
While taking COCs, irregular bleeding (“spotting” spotting and / or “breakthrough” bleeding) may occur, especially during the first months of use. Therefore, evaluation of any irregular bleeding should be done only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough diagnostic examination should be performed to rule out malignancy or pregnancy.
Some women may not experience "withdrawal" bleeding while taking the green inactive placebo pills. If the drug was taken as directed, it is unlikely that the woman is pregnant. However, if the drug has been taken irregularly before, or if there are no two withdrawal bleedings in a row, pregnancy should be excluded before continuing to take the drug.
Lactose
Dimia®, film-coated tablets, contains lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency and malabsorption of glucose and galactose should not take this medicine.
Soya
Dimia® film-coated tablets contain soy lecithin. Patients with peanut and soy allergy should not take this drug.

Influence on the ability to drive vehicles and mechanisms

Not found.

Release form

Film-coated tablets [set], 3 mg + 0.02 mg.
24 tablets each of drospirenone + ethinyl estradiol and 4 tablets of placebo in a PVC/PE/PVDC-aluminum foil blister pack.
1 or 3 blisters in a cardboard box along with instructions for use. A cardboard flat case for storing the blister is enclosed in a cardboard bundle.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.
Keep out of the reach of children!

Best before date

2 years.
Do not use after the expiry date stated on the packaging.

Holiday conditions

Released by prescription.

Manufacturer

OJSC "Gedeon Richter"
1103 Budapest, st. Dömröi, 19-21, Hungary

Consumer claims should be sent to:
Moscow Representative Office of JSC "Gedeon Richter"
119049 Moscow, 4th Dobryninsky lane, building 8,

Dimia ® is a combined monophasic oral contraceptive containing drospirenone and ethinyl estradiol. According to its pharmacological profile, drospirenone is close to natural progesterone: it does not have estrogenic, glucocorticoid and antiglucocorticoid activity and is characterized by a pronounced antiandrogenic and moderate antimineralocorticoid effect. The contraceptive effect is based on the interaction of various factors, the most important of which are the inhibition of ovulation, an increase in the viscosity of the cervical secretion and changes in the endometrium. The Pearl Index, an indicator that reflects the frequency of pregnancy in 100 women of reproductive age during the year of using a contraceptive, is less than 1.

Pharmacokinetics

Drospirenone

Suction

When taken orally, drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. C max drospirenone in serum is about 38 ng / ml and is reached approximately 1-2 hours after a single dose.

Bioavailability - 76-85%. Simultaneous administration with food does not affect the bioavailability of drospirenone.

Distribution

After oral administration, plasma concentrations of drospirenone decreased with a final half-life of 31 hours. Drospirenone binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (transcortin). Only 3-5% of the total serum concentration of drospirenone exists as free steroids. The increase in SHBG induced by ethinylestradiol does not affect the binding of drospirenone to serum proteins. The average apparent V d of drospirenone is 3.7 ± 1.2 l / kg.

During the cycle of treatment C ss max drospirenone in plasma is about 70 ng / ml, it is achieved after 8 days of treatment. Serum concentrations of drospirenone increase approximately 3-fold due to the ratio of the final T 1/2 and dosing interval.

Metabolism

Drospirenone is extensively metabolized after oral administration. The main metabolites in blood plasma are the acidic forms of drospirenone, formed during the opening of the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, both are formed without the participation of the P450 system. Drospirenone is metabolized to a small extent by CYP3A4 and is able to inhibit this enzyme, as well as CYP1A1, CYP2C9 and CYP2C19 in vitro.

breeding

Renal clearance of drospirenone metabolites in serum is 1.5±0.2 ml/min/kg. Drospirenone is excreted only in trace amounts unchanged. Drospirenone metabolites are excreted by the kidneys and through the intestines with an excretion ratio of about 1.2:1.4. T1 / 2 metabolites by the kidneys and through the intestines is about 40 hours.

Ethinylestradiol

Suction

When taken orally, ethinylestradiol is absorbed rapidly and completely. C max in serum is about 33 pg / ml and is achieved within 1-2 hours after a single oral administration. Absolute bioavailability as a result of first-pass conjugation and first-pass metabolism is approximately 60%. Simultaneous food intake reduced the bioavailability of ethinylestradiol in approximately 25% of the examined patients; there were no other changes.

Distribution

Serum concentrations of ethinylestradiol decreased biphasically, in the final distribution phase T 1/2 is approximately 24 hours. Ethinylestradiol binds well, but non-specifically, to serum albumin (approximately 98.5%) and induces an increase in SHBG serum concentrations. The apparent V d is about 5 l / kg.

C ss is achieved in the second half of the treatment cycle, and the serum concentration of ethinyl estradiol increases by 2-2.3 times.

Metabolism

Ethinylestradiol is a substrate for presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation, producing a wide range of hydroxylated and methylated metabolites, which are present both in free form and as conjugates with glucuronic acid. The renal clearance of ethinylestradiol metabolites is approximately 5 ml/min/kg.

breeding

Unchanged ethinylestradiol is practically not excreted from the body. Metabolites of ethinylestradiol are excreted by the kidneys and through the intestines in a ratio of 4:6. T 1/2 metabolites is about 24 hours.

Pharmacokinetics in special clinical situations

In case of impaired renal function

C ss drospirenone in plasma in women with mild renal insufficiency (CC 50-80 ml / min) was comparable to the corresponding indicators in women with normal renal function (CC > 80 ml / min). In women with moderate renal insufficiency (CC from 30 ml / min to 50 ml / min), the plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Drospirenone was well tolerated in all groups. Drospirenone did not have a clinically significant effect on the content of potassium in the blood serum. Pharmacokinetics in severe renal failure has not been studied.

In violation of liver function

Drospirenone is well tolerated by patients with mild to moderate hepatic impairment (Child-Pugh class B). Pharmacokinetics in severe hepatic impairment has not been studied.

Release form

Tablets, film-coated, white or almost white, round, biconvex, marked "G73" on one side of the tablet, applied by embossing; on a cross section, the core is white or almost white (24 pieces in a blister).

Excipients: lactose monohydrate - 48.53 mg, corn starch - 16.6 mg, pregelatinized corn starch - 9.6 mg, copolymer of macrogol and polyvinyl alcohol - 1.45 mg, magnesium stearate - 0.8 mg.

The composition of the film shell: Opadry II white 85G18490 - 2 mg (polyvinyl alcohol - 0.88 mg, titanium dioxide - 0.403 mg, macrogol 3350 - 0.247 mg, talc - 0.4 mg, soy lecithin - 0.07 mg).

placebo pills

Tablets, film-coated green, round, biconvex; on a cross section, the core is white or almost white (4 pieces in a blister).

Excipients: microcrystalline cellulose - 42.39 mg, lactose - 37.26 mg, pregelatinized corn starch - 9 mg, magnesium stearate - 0.9 mg, colloidal silicon dioxide - 0.45 mg.

The composition of the film shell: Opadry II green 85F21389 - 3 mg (polyvinyl alcohol - 1.2 mg, titanium dioxide - 0.7086 mg, macrogol 3350 - 0.606 mg, talc - 0.444 mg, indigo carmine - 0.0177 mg, quinoline yellow dye - 0.0177 mg, iron oxide dye black - 0.003 mg, dye sunset yellow - 0.003 mg).

28 pcs. - blisters (1) - packs of cardboard.
28 pcs. - blisters (3) - packs of cardboard.

Dosage

The tablets should be taken daily, at about the same time, with a small amount of water, in the order indicated on the blister pack. Tablets are taken continuously for 28 days, 1 tablet per day. Taking pills from the next pack begins after taking the last pill from the previous pack. "Withdrawal" bleeding usually begins 2-3 days after the start of placebo tablets (last row) and does not necessarily end by the start of the next pack.

How to start taking Dimia ®

If hormonal contraceptives have not been used in the last month, Dimia ® is started on the first day of the menstrual cycle (i.e. on the first day of menstrual bleeding). It is also possible to start taking it on the 2nd-5th day of the menstrual cycle, in which case additional use of a barrier method of contraception is necessary during the first 7 days of taking the tablets from the first package.

Switching from other combined contraceptives (combined oral contraceptive pills, vaginal ring, or transdermal patch)

Dimia® should be started the next day after taking the last inactive tablet (for preparations containing 28 tablets) or the day after taking the last active tablet from the previous package (possibly the next day after the end of the usual 7-day break) - for preparations containing 21 tablets per pack. In the case of a woman using a vaginal ring or transdermal patch, it is preferable to start taking Dimia ® on the day they are removed or, at the latest, on the day when a new ring or patch is planned to be inserted.

Switching from progestogen-only contraceptives (mini-pills, injections, implants) or from an intrauterine system (IUD) that releases progestogens.

A woman can switch from taking a mini-pill to taking Dimia ® on any day (from the implant or from the IUD on the day they are removed, from injectable forms of drugs on the day the next injection was due), but 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

Taking the drug Dimia ® can be started on the doctor's prescription on the day of termination of pregnancy. In this case, the woman does not need to take additional contraceptive measures.

After childbirth or abortion in the second trimester of pregnancy.

A woman is recommended to start taking the drug on the 21-28th day after childbirth (provided that she is not breastfeeding) or abortion in the second trimester of pregnancy. If the reception is started later, the woman should use an additional barrier method of contraception during the first 7 days after starting Dimia ®. With the resumption of sexual activity (before the start of taking the drug Dimia ®), pregnancy should be excluded.

Taking missed pills

Missing a placebo tablet from the last (4th) row of the blister can be ignored. However, they should be discarded to avoid inadvertently prolonging the placebo phase. The indications below apply only to missed tablets containing the active ingredients.

If the delay in taking the pill was less than 12 hours, contraceptive protection is not reduced. The woman should take the missed pill as soon as possible (as soon as she remembers) and the next pill at the usual time.

If the delay exceeds 12 hours, contraceptive protection may be reduced. In this case, you can be guided by two basic rules:

1. Taking pills should never be interrupted for more than 7 days;

2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous tablet intake are required.

Accordingly, women can be given the following recommendations:

A woman should take the missed pill as soon as she remembers, even if it means taking two pills at the same time. Then she should take her tablets at the usual time. Also, a barrier method such as a condom should be used for the next 7 days. If sexual intercourse has occurred in the previous 7 days, the possibility of pregnancy should be considered. The more pills missed and the closer this pass is to the 7-day break in taking the drug, the higher the risk of pregnancy.

The woman should take the missed tablet as soon as she remembers, even if it means taking two tablets at the same time. Then she should take her tablets at the usual time. If during the 7 days preceding the first missed pill, the woman took the pills as expected, there is no need for additional contraceptive measures. However, if she missed more than 1 tablet, an additional method of contraception (barrier - for example, a condom) is needed for 7 days.

The reliability of the method inevitably declines as the placebo pill phase approaches. However, correcting the pill regimen can still help prevent pregnancy. If one of the two schemes described below is followed, and if the woman has observed the drug regimen in the previous 7 days before skipping the pill, there will be no need to use additional contraceptive measures. If this is not the case, she must complete the first of the two regimens and use additional precautions for the next 7 days.

1. A woman should take the last missed tablet as soon as she remembers, even if it means taking two tablets at the same time. Then she should take the tablets at the usual time until the active tablets run out. 4 placebo tablets from the last row should not be taken, you must immediately start taking the tablets from the next blister pack. Most likely, there will be no "withdrawal" bleeding until the end of the second pack, but there may be spotting or "withdrawal" bleeding on the days of taking the drug from the second pack.

2. A woman can also stop taking active tablets from the started package. Instead, she should take the placebo pills from the last row for 4 days, including the days she skipped pills, and then start taking the pills from the next pack.

If a woman misses a pill and does not subsequently experience "withdrawal" bleeding in the placebo pill phase, the possibility of pregnancy should be considered.

The use of the drug in gastrointestinal upset

In case of severe gastrointestinal disturbances (eg, vomiting or diarrhea), the absorption of the drug will be incomplete and additional contraceptive measures will be required. If vomiting occurs within 3-4 hours after taking the active tablet, a new (replacement) tablet should be taken as soon as possible. If possible, the next tablet should be taken within 12 hours of the usual tablet-taking time. If more than 12 hours have passed, it is recommended to proceed according to the instructions for skipping tablets. If a woman does not want to change her usual pill regimen, she should take an additional pill from another pack.

Postponement of menstrual bleeding "withdrawal"

To delay bleeding, the woman should skip taking the placebo tablets from the started package and start taking the drospirenone + ethinyl estradiol tablets from the new package. The delay can be extended until the active tablets in the second pack run out. During the delay, a woman may experience acyclic profuse or spotting bleeding from the vagina. Regular intake of Dimia ® is resumed after the placebo phase.

To shift bleeding to another day of the week, it is recommended to shorten the upcoming phase of taking placebo tablets by the desired number of days. When the cycle is shortened, it is more likely that the woman will not have menstrual-like "withdrawal" bleeding, but will have acyclic profuse or spotting bleeding from the vagina when taking the next pack (same as with lengthening the cycle).

Overdose

There have been no cases of overdose of Dimia ® yet. Based on the general experience with the use of combined oral contraceptives, potential symptoms of overdose may include: nausea, vomiting, slight bleeding from the vagina.

Treatment: no antidotes. Treatment should be symptomatic.

Interaction

Effect of other medicinal products on Dimia ®

Interactions between oral contraceptives and other medicinal products may result in acyclic bleeding and/or contraceptive failure. The interactions described below are reflected in the scientific literature.

The mechanism of interaction with hydantoin, barbiturates, primidone, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations of St. John's wort (Hypericum perforatum) is based on the ability of these active substances to induce microsomal liver enzymes. The maximum induction of microsomal liver enzymes is not achieved within 2-3 weeks, but after that it persists for at least 4 weeks after discontinuation of drug therapy.

Contraceptive failure has also been reported with antibiotics such as ampicillin and tetracycline. The mechanism of this phenomenon is not clear.

Women with short-term treatment (up to one week) with any of the above groups of drugs or single drugs should temporarily use (during the period of simultaneous use of other drugs and for another 7 days after its completion), in addition to PDA, barrier methods of contraception.

Women receiving rifampicin therapy, in addition to taking COCs, should use a barrier method of contraception and continue to use it for 28 days after stopping treatment with rifampicin. If concomitant medications last longer than the expiration date of the active tablets in the package, the inactive tablets should be discontinued and the drospirenone + ethinyl estradiol tablets from the next package should be started immediately.

If a woman is constantly taking drugs - inducers of microsomal liver enzymes, she should use other reliable non-hormonal methods of contraception.

The main metabolites of drospirenone in human plasma are formed without the participation of the cytochrome P450 system. Cytochrome P450 inhibitors are therefore unlikely to interfere with the metabolism of drospirenone.

Effect of Dimia ® on other medicinal products

Oral contraceptives may affect the metabolism of some other active substances. Accordingly, plasma or tissue concentrations of these substances may either increase (eg, cyclosporine) or decrease (eg, lamotrigine).

Based on in vitro inhibition studies and in vivo interaction studies in female volunteers treated with omeprazole, simvastatin and midazolam as a substrate, an effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.

Other interactions

In patients without renal insufficiency, the simultaneous use of drospirenone and ACE inhibitors or NSAIDs does not significantly affect the content of potassium in the blood serum. But still, the simultaneous use of the drug Dimia ® with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, during the first cycle of treatment, it is necessary to control the concentration of serum potassium.

Laboratory tests

The use of contraceptive steroids may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma protein (transporter) concentrations, such as corticosteroid-binding proteins and lipid / lipoprotein fractions, parameters of carbohydrate metabolism and blood coagulation parameters and fibrinolysis. In general, the changes remain within the range of normal values. Drospirenone is the cause of an increase in plasma renin activity and - due to a small antimineralocorticoid activity - reduces the concentration of aldosterone in plasma.

Side effects

The following adverse events have been reported while taking Dimia ®:

Women using combined oral contraceptives (COCs) have experienced the following serious adverse events:

• venous thromboembolic diseases;
• arterial thromboembolic diseases;
• liver tumors;
• the occurrence or exacerbation of conditions for which the relationship with the use of COCs has not been proven: Crohn's disease, ulcerative colitis, epilepsy, migraine, endometriosis, uterine fibroids, porphyria, systemic lupus erythematosus, herpes during a previous pregnancy, rheumatic chorea, hemolytic uremic syndrome, cholestatic jaundice;
• chloasma;
• acute or chronic liver disease may necessitate discontinuation of COCs until liver function tests return to normal;
• in women with hereditary angioedema, exogenous estrogens may induce or exacerbate the symptoms of angioedema.

Indications

• oral contraception.

Contraindications

Dimia ® , like other combined oral contraceptives, is contraindicated in any of the following conditions:

• thrombosis (arterial and venous) and thromboembolism at present or in history (including thrombosis, deep vein thrombophlebitis; pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders);
• conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history;
• multiple or pronounced 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, obesity with a BMI >30 kg/m 2 ;
• hereditary or acquired predisposition to venous or arterial thrombosis, for example, resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antibodies against phospholipids (presence of antibodies to phospholipids - antibodies to cardiolipin, lupus anticoagulant);
• pancreatitis with severe hypertriglyceridemia at present or in history;
• severe chronic or acute renal failure;
• a liver tumor (benign or malignant) at present or in history;
• hormone-dependent malignant neoplasms of the genital organs or the mammary gland at present or in history;
• bleeding from the vagina of unknown origin;
• migraine with a history of focal neurological symptoms;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption, lapp lactase deficiency (lactase deficiency in some peoples of the North);
• pregnancy and suspicion of it;
• lactation period;
• hypersensitivity to the drug or any of the components of the drug.

Carefully

• risk factors for thrombosis and thromboembolism: smoking under the age of 35, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated valvular heart disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the next of kin);
• diseases in which peripheral circulatory disorders can occur: diabetes mellitus without vascular complications, systemic lupus erythematosus (SLE), hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of superficial veins;
• hereditary angioedema;
• hypertriglyceridemia;
• severe liver disease (until normalization of liver function tests);
• diseases that first arose or worsened during pregnancy or against the background of a previous intake of sex hormones (including jaundice and / or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in history, minor chorea (illness Sydenham), chloasma);
• postpartum period.

Application features

Use during pregnancy and lactation

The drug Dimia ® is contraindicated in pregnancy.

If pregnancy occurs during the use of the drug Dimia ® , it should be stopped immediately. Extended 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 when they were inadvertently taken during pregnancy.

According to preclinical studies, undesirable effects that affect the course of pregnancy and fetal development due to the hormonal action of the active components cannot be ruled out.

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 the drug Dimia ® during breastfeeding is contraindicated.

Application for violations of liver function

Contraindicated:

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

Application for violations of kidney function

Contraindicated:

• severe chronic or acute renal failure

Use in children

The use of the drug before the establishment of menarche is not indicated.

special instructions

If there are any of the conditions/risk factors mentioned 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 appear, 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 increased 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 with no risk factors who took low doses of estrogen (<0.05 мг этинилэстрадиола) в составе комбинированного перорального контрацептива, составляет примерно 20 случаев на 100 000 женщин-лет (для левоноргестрелсодержащих КПК "второго поколения") или 40 случаев на 100 000 женщин-лет (для дезогестрел/гестоденсодержащих КПК "третьего поколения"). У женщин, не пользующихся КПК, случается 5-10 ВТЭ и 60 беременностей на 100 000 женщин-лет. ВТЭ фатальна в 1-2% случаев.

Data from a large, prospective, 3-way study showed that the incidence of VTE in women with or without other risk factors for venous thromboembolism, who used the combination of ethinylestradiol and drospirenone, 0.03 mg + 3 mg, coincided with the frequency of VTE in women who used levonorgestrel-containing oral contraceptives and other PDAs. The degree of risk of venous thromboembolism when taking Dimia ® has not yet been established.

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

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

Symptoms of venous or arterial thrombotic / thromboembolic events or acute disorders of cerebral circulation:

• unusual unilateral pain and / or swelling of the lower extremities;
• sudden severe chest pain, whether it radiates to the left arm or not;
• sudden shortness of breath;
• sudden onset of cough;
• any unusual severe prolonged 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 one part of the body;
• movement disorders;
• symptom complex "acute" abdomen.

A woman should consult with a specialist before taking COCs.

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

• increase in age;
• hereditary predisposition (venous thromboembolism has ever happened to siblings or parents at a relatively early age);
• prolonged immobilization, advanced 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 a planned surgical intervention, at least four weeks in advance) and not resume until two weeks after the full restoration of mobility. If the drug has not been discontinued in advance, anticoagulant treatment should be considered;
• there is no 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:

• increase in age;
• smoking (women over 35 are strongly advised to stop smoking if they want to take COCs);
• dyslipoproteinemia;
• arterial hypertension;
• migraine without focal neurological symptoms;
• obesity (BMI over 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 taking COCs;
• damage to the heart valves;
• atrial fibrillation.

The presence of 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).

An 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 anemia.

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

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 conflicting opinions remain as to the extent to which these findings relate to concomitant factors, such as testing for cervical cancer or the use of barrier methods of contraception.

A meta-analysis of 54 epidemiological studies found a slight increase in the relative risk (RR = 1.24) of breast cancer in women who currently take COCs. The risk gradually decreases over 10 years after stopping COCs. Because breast cancer rarely develops in women under 40 years of age, 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 a causal relationship. The increased risk may be due to earlier diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both. Diagnosed breast cancer in women who have ever taken COCs was clinically less severe, due to the 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 case of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.

Other states

The progestogen component of Dimia ® is an aldosterone antagonist that retains potassium in the body. In most cases, an increase in potassium content is not expected. However, in a clinical study in some patients with mild to moderate kidney disease who were taking potassium-sparing drugs, serum potassium increased slightly while taking drospirenone. Therefore, it is recommended to monitor serum potassium during the first cycle of treatment in patients with renal insufficiency, in whom the serum potassium concentration was at the level of the upper limit of normal before treatment and, especially, while taking potassium-sparing drugs.

In women with hypertriglyceridemia or a hereditary predisposition to it, the risk of pancreatitis may be increased when taking COCs.

Although a slight increase in blood pressure has been observed in many women taking COCs, a clinically significant increase was rare. Only in these rare cases is immediate discontinuation of COCs warranted. 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, COCs should be discontinued. After normalization of blood pressure with antihypertensive drugs, COCs can be resumed.

The following diseases appeared or worsened both during pregnancy and when taking COCs, but the evidence for 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 exacerbate symptoms of edema.

Acute or chronic liver disease may be an indication to discontinue COC use until liver function tests return to normal. Recurrence of cholestatic jaundice and/or cholestasis-associated pruritus, 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, changing the treatment regimen in patients with diabetes mellitus while taking low-hormone COCs (containing< 0.05 мг этинилэстрадиола) не показано. Однако следует внимательно наблюдать женщин с сахарным диабетом, особенно на ранних стадиях приема КПК.

Exacerbation of endogenous depression, epilepsy, Crohn's disease, and ulcerative colitis has been observed during COC use.

Chloasma may occur from time to time, especially in women who have a history of chloasma of 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 lactose monohydrate, placebo tablets contain 37.26 mg anhydrous lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should not take this medicine.

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

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

Medical examinations

Before you start taking or re-using Dimia ®, you should collect a complete medical history (including family history) and exclude pregnancy. It is necessary to measure blood pressure, conduct a medical examination, guided by contraindications and precautions. A woman needs to be reminded of the need to carefully read the instructions for use and adhere to the recommendations indicated in it. 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 need to 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 decrease, for example, if you skip taking drospirenone + ethinylestradiol tablets, gastrointestinal disorders during the period of taking drospirenone + ethinylestradiol tablets, or while taking other drugs.

Insufficient cycle control

As with other COCs, a woman may experience acyclic bleeding (spotting or "withdrawal" bleeding), especially in the first months of taking it. Therefore, any irregular bleeding should be assessed after a three-month adjustment period.

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

Some women do not experience "withdrawal" bleeding during the placebo phase. If the COC was taken in accordance with the instructions for use, then it is unlikely that the woman is pregnant. However, if the rules of admission were violated before the first missed menstrual-like "withdrawal" bleeding, or if two bleedings are missed, pregnancy should be excluded before continuing to take COCs.

Influence on the ability to drive vehicles and control mechanisms