Midian - instructions for use, dose, side effects, contraindications

atExcipients: lactose monohydrate 48.17 mg, corn starch 16.8 mg, corn pregelatinized corn starch 9.6 mg, povidone-K25 1.6 mg, magnesium stearate 0.8 mg;

Pcasing (Opadry II white** 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.

** Code Colorcon 85G18490

Description:

Round, biconvex tablets covered with a film membrane, white or almost white; on one side engraving "G63", the other side without engraving. The cross-sectional view is white or almost white.

Pharmacotherapeutic group:Contraceptive agent combined (estrogen + progestogen)

ATX: & nbsp

G.03.A.A.12 Drospirenone and ethinylestradiol

Pharmacodynamics:

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

Medication MIDIANA® is a combined oral contraceptive containing ethinyl estradiol and drospirenone. In a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid properties. It is devoid of any estrogenic, glucocorticoid and antiglucocorticoid activity. This provides drospirenone pharmacological profile, similar to natural progesterone.

There is evidence of a reduced risk of developing endometrial and ovarian cancer when combined oral contraceptives are used.

Pharmacokinetics:

Drospirenone (3 mg)

Suction

When administered orally, drospirenone quickly and almost completely absorbed. The maximum concentration of active substance in the serum, equal to 37 ng / ml, is achieved 1-2 hours after a single dose. During one treatment cycle, the maximum equilibrium concentration of drospirenone in the serum is about 60 ng / ml and is achieved after 7-14 hours. Bioavailability ranges from 76% to 85%. Eating does not affect the bioavailability of drospirenone.

Distribution

After oral administration, there is a two-phase decrease in serum drospirenone concentration, which is characterized by a half-life 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) and corticosteroid-binding globulin (transcortin). Only 3-5% of the total serum concentration of the active substance is a free hormone. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone with serum proteins. The average apparent volume of distribution is 3.7 ± 1.2 l / kg.

Biotransformation

After oral administration, drospirenone undergoes significant metabolism. Most metabolites in the plasma are represented by acid forms of drospirenone, obtained by opening the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, which are formed without involvement of the cytochrome P450 system. According to research in vitro Drospirenone is metabolized with a negligible cytochrome P450.

Elimination

The metabolic clearance rate of drospirenone in the serum is 1.5 ± 0.2 ml / min / kg. Drospirenone is excreted only in trace amounts in unmodified form. Metabolites of drospirenone are excreted by the kidneys and through the intestine in a ratio of approximately 1.2: 1.4. The elimination half-life for excretion of metabolites by the kidneys and through the intestine is approximately 40 hours.

The equilibrium concentration

During one treatment cycle, the maximum equilibrium concentration of drospirenone in the serum (approximately 60 ng / ml) is achieved after 7-14 hours. There is a 2-3-fold increase in the concentration of drospirenone. Further increase in serum concentration of drospirenone is observed after 1-6 cycles of admission, after which no increase in concentration is observed.

Ethinylestradiol (30 μg)

Suction

Ethinyl estradiol after oral administration quickly and completely absorbed. The maximum serum concentration after a single dose of 30 mcg is achieved after 1-2 hours and is about 100 pg / ml. For ethinyl estradiol but a significant effect of the "first passage" with high individual variability is expressed. Absolute bioavailability varies and is approximately 45%.

Distribution

The apparent volume of distribution is about 5 l / kg, the connection with plasma proteins is about 98%. Ethinylestradiol induces the synthesis of SHBG and transcortin in the liver. With daily intake of 30 μg ethinyl estradiol, the plasma concentration of SHBG increases from 70 nmol / L to about 350 nmol / l. Ethinylestradiol in small amounts falls into breast milk (approximately 0.02% of the dose).

Biotransformation

Ethinyl estradiol is completely metabolized. (The metabolic clearance rate is 5 ml / min / kg).

Elimination

Ethinyl estradiol is practically not excreted unchanged. Metabolites of ethinyl estradiol excreted by the kidneys and through the intestine in a ratio of 4: 6. The half-life for excretion of metabolites is approximately 1 day. Elimination half-life is 20 hours.

The equilibrium concentration

The state of equilibrium concentration is reached during the second half of the treatment cycle.

Some categories of the population

Effect on kidney function

The equilibrium serum concentration of drospirenone in women with a low degree of renal insufficiency (creatinine clearance (CK) = 50-80 ml / minute) was comparable to that in women with normal renal function (CC> 80 ml / minute). The concentration of drospirenone in the serum was on average 37% higher in women with an average degree of renal failure (CK = 30-50 ml / minute) compared with that in women with normal renal function. Drospirenone therapy was well tolerated in women with mild to moderate renal impairment.

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

Effects on liver function

In women with moderate hepatic insufficiency (class B according to the Child-Pugh classification), the average plasma concentration curve did not match that of women with normal liver function. The values of the maximum concentration (C_max) observed in the absorption and distribution phase were the same.At the end of the distribution phase, a decrease in the concentration of drospirenone was approximately 1.8 times higher in volunteers with moderate hepatic impairment compared to people with normal liver function.

After a single reception, the total clearance (Cl/ F) in volunteers with moderate hepatic insufficiency was approximately 50% lower in comparison with people with normal liver function.

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

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

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

Indications:Contraception.

Contraindications:

Preparation MIDNANA® should not be assigned in the presence of any of the conditions listed below.If any of these conditions develop for the first time against the background of taking the drug, its immediate cancellation is required:

- presence of vein thrombosis at present or in anamnesis (deep vein thrombosis, pulmonary embolism);

- presence of thrombosis of arteries now or in the anamnesis (for example, myocardial infarction) or previous conditions (for example, angina and transient ischemic attack);

- complicated heart valve disease, atrial fibrillation, uncontrolled hypertension;

- Serious surgical intervention with prolonged immobilization;

- smoking over the age of 35;

- liver failure;

- cerebrovascular diseases at present or in the anamnesis;

- 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 APS (activated protein C), insufficiency of antithrombin III, deficiency of protein C, protein deficiency S, hyperhomocysteinemia and the presence of antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant);

- pancreatitis, including in history, if marked hypertriglyceridemia was noted;

- severe liver disease (prior to normalization of liver samples) at present or in the anamnesis;

- severe chronic renal failure or acute renal failure;

- liver tumors (benign or malignant), currently or in history;

- hormone-dependent malignant diseases of the reproductive system (genitals, mammary glands) or suspicion of them;

- bleeding from the vagina of unknown origin;

- migraine with focal neurological symptoms in history;

- pregnancy or suspected of it;

- lactation period;

- hypersensitivity to the drug or any of its components;

- hereditary intolerance to galactose, lactase deficiency, glucose-galactose malabsorption /

Carefully:

Risk factors for thrombosis and thromboembolism: smoking before the age of 35, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurologic symptoms,uncomplicated heart valve defects, hereditary predisposition to thrombosis (thrombosis, myocardial infarction, or cerebral circulation impairment at a young age in one of the next of kin); diseases in which there may be violations of peripheral blood circulation: diabetes, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of superficial veins; hereditary angioedema, hypertriglyceridemia, liver disease; diseases that first appeared or worsened during pregnancy or on the background of previous reception of sex hormones (including jaundice and / or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in the anamnesis, small chorea (Sydenham's disease), chloasma, postpartum period.

Pregnancy and lactation:

During pregnancy and lactation, the use of MIDIAA® is contraindicated. If pregnancy occurred against the background of hormonal contraception, immediate withdrawal of the drug is necessary.The scarce data on the inadvertent, by negligence, intake of combined oral contraceptives indicate a teratogenic effect and an increased risk to children and women during childbirth.

Combined oral contraceptives affect lactation, can reduce the amount and change the composition of breast milk. Small amounts of hormonal contraceptives or their metabolites are found in milk during hormonal contraception and can affect the baby. The use of combined oral contraceptives is possible after complete cessation of breastfeeding.

Dosing 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 blister pack. It is necessary to take one tablet a day for 21 consecutive days. The taking of tablets from each subsequent package should begin after a 7-day interval in the intake of tablets, during which menstrual bleeding usually occurs.It usually begins 2-3 days after the last pill is taken and may not end by the time the next package begins.

How to take MIDIANA®

If previously hormonal contraceptives were not applied (in the last month):

Reception of combined oral contraceptives begins on the first day of the woman's natural menstrual cycle (that is, on the first day of menstrual bleeding).

If another combined oral contraceptive, vaginal ring or transdermal patch:

For a woman, it is preferable to start taking MIDIANA® the day after receiving the last active tablet of the previous combined oral contraceptive; In such cases, the medication MIDIANA® should not begin later than the next day after a normal break in taking the tablets or taking inactive tablets of its previous combined oral contraceptive. When replacing the vaginal ring or transdermal patch, taking an oral contraceptive MIDNIt is advisable to start ANA® on the day of removal of the previous remedy; in such cases, the reception of MIDIANA® should begin no later than the day of the planned replacement procedure.

In the case of replacement of the method using only progestins (mini-pili, injection forms, implants) or intrauterine contraceptives with the release of progestins:

A woman can switch from a mini-drunk on any day (with an implant or an intrauterine device contraceptive - on the day of removal, from the injection form - from the day when the next injection was to be made). However, in all these cases it is desirable to use an additional barrier method of contraception during the first 7 days of taking the tablets.

After termination of pregnancy in the first trimester:

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

After childbirth or interruption of pregnancy in the second trimester:

It is advisable for a woman to begin taking the medication MIDIANA® on the 21-28th day after the delivery or the 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. In the event of sexual intercourse, pregnancy should be excluded before the start of the drug or it is necessary to wait for the first menstruation.

Acceptance of missed tablets

If the delay in taking the pill was less than 12 hours, Contraceptive protection is not reduced. A woman needs to take a pill as soon as possible, the following tablets are taken at the usual time.

If the delay in taking the tablets was more than 12 hours, contraceptive protection can be reduced. Tactics when skipping the drug is based on the following two simple rules:

1. The taking of tablets can not be stopped for more than 7 days;

2. In order to achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous administration of tablets are necessary.

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

Week 1

It is necessary to 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, the barrier method of contraception should be used for the next 7 days. If the sexual intercourse took place within 7 days before passing the pill, it is necessary to take into account the probability of pregnancy. The more pills are missed and the closer this pass to the 7-day break in taking the drug, the higher the risk of pregnancy.

Week 2

It is necessary to 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 contraception. However, if she missed more than 1 tablet, additional contraceptive measures should be taken in the next 7 days.

Week 3

The probability of reducing the contraceptive effect is significant because of the upcoming 7-day break in taking the tablets. However, adjusting the schedule of taking tablets, it is possible to prevent a decrease in contraceptive protection.

If you follow any of the two following tips, additional methods of contraception will not be needed if during the previous 7 days before skipping the pill the woman took all the pills correctly. If this is not the case, she should follow the first of the two methods and also use additional contraceptive measures during the next 7 days.

1. It is necessary to 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.Receiving tablets from a new package should be started as soon as the current packaging is finished, that is, without interruption between receiving two packages. Most likely, bleeding "cancellation" will not be until the end of the second package, but there may be spotting spotting or breakthrough uterine bleeding on the days of taking the tablets.

2. A woman can be recommended to stop taking tablets from this package. Then you need to stop taking the pills for 7 days, including the days when she forgot to take the pills, and then start taking the pills from the new package.

In the case of missing tablets and the absence of an interval of bleeding "cancellation" in the first drug-free interval, pregnancy should be excluded.

Councils in the case of disorders of the gastrointestinal tract

In case of severe reactions from the gastrointestinal tract (such as vomiting or diarrhea), absorption may be incomplete, and additional contraceptive measures should be taken.

In case of vomiting within 3-4 hours after taking the pill, it is necessary to take a new, replacement tablet as soon as possible. A new tablet should be taken within 12 hours after the usual intake time, if possible.If more than 12 hours are missed, the rules for taking the drug should be observed, if possible,

Acceptance of missed tablets

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 the bleeding of "cancellation"

To delay the day of the beginning of the bleeding "cancellation" it is necessary to continue taking the drug MIDIANA® from the new package without interruption in admission. Delay is possible until the end of the tablets in the second package.

During the lengthening of the cycle, spotting spotting from the vagina or breakthrough uterine bleeding can occur. To resume reception of the drug MIDIANA® from a new pack follows after an ordinary 7-day break.

To transfer the day of the beginning of the bleeding "cancellation" for another day of the week of the usual schedule, you should shorten the nearest break in taking the tablets for as many days as necessary. The shorter the interval, the higher the risk that there will be no "bleeding" of bleeding, and spotting spotting and breakthrough uterine bleeding (as in the case of a delay in the onset of bleeding "cancellation") will be noted during the taking of tablets from the second package.

Side effects:

During the simultaneous administration of drospirenone and ethinyl estradiol, the following adverse reactions were reported:

Class of organ systems	Frequency
	Often ≥1 / 100 to <1/10	Infrequently ≥1 / 1,000 to <1/100	Rarely ≥1 / 10000 to <1/1000
Disturbances from the nervous system	headache, emotional lability, depression	decreased libido	increased libido
Disorders from the endocrine system	disorders of the menstrual cycle, intermenstrual bleeding, pain in the mammary gland		discharge from the mammary glands
Impaired sensory organs			hearing loss, poor tolerance of contact lenses
Infringements from digestive system	nausea, abdominal pain	vomiting, diarrhea
Disturbances from the skin and subcutaneous tissue		acne, eczema, skin rash, urticaria, erythema nodosum, erythema multiforme, itching; Chlamydia, especially if there is a history of chloasma in pregnant women;
Disorders from the vascular system	migraine	increase or decrease in blood pressure	thromboses (venous and arterial), thromboembolism
Systemic disorders and complications at the site of administration	weight gain	fluid retention	weight loss
Immune system disorders			bronchospasm
Disorders from the reproductive system and breast	acyclic vaginal bleeding (spotting bloody discharge or breakthrough uterine bleeding), roughness, tenderness, enlargement of the mammary glands, candidiasis of the vagina	vaginitis	discharge from the mammary glands, increased discharge from the vagina

Overdose:

Information on overdose of drospirenone and ethinylestradiol-containing drugs is not available. However, there may be nausea, vomiting, and bloody discharge / bleeding from the vagina.

There is no specific antidote. Symptomatic treatment should be given.

Interaction:

The interaction between oral contraceptives and other medications can lead to breakthrough uterine bleeding and / or a decrease in contraceptive reliability. The following types of interactions are described in the literature:

Influence on metabolism in the liver

Some drugs due to the induction of microsomal enzymes can increase the clearance of sex hormones (phenytoin, barbiturates, primidon, carbamazepine and rifampicin; possibly the same effects of oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, and herbal remedies based on St. John's wortHypericum perforatum).

The possible effect of HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and their combinations on liver metabolism has been reported.

Effect on intestinal hepatic recirculation

Clinical observations show that simultaneous application of some antibioticssuch as penicillins and tetracyclines, reduces intestinal hepatic recycling of estrogens, which can lead to a decrease in the concentration of ethinylestradiol.

Women taking any of the aforementioned classes of drugs should use the barrier method of contraception in addition to the MIDIANA preparation or switch to any other method of contraception. Women who receive constant treatment with drugs containing active substances that affect microsomal liver enzymes should additionally use a non-hormonal contraceptive method within 28 days after their withdrawal.Women taking antibiotics (other than rifampicin or griseofulvin) should temporarily use the barrier method of contraception in addition to the combined oral contraceptive, both during the administration of the drug, and within 7 days after its withdrawal. If the concomitant use of the drug is initiated at the end of the reception of the MIDIANA® package, the next package should be started without an interruption in admission.

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

Effect of MIDIANA® on other medications

Oral contraceptives can affect the metabolism of other medicines. In addition, their concentrations in plasma and tissues can vary - how to increase (for example, ciclosporin), and decrease (for example, lamotrigine). Based on the results of inhibition studies in vitro and interaction studies in vivo among women volunteers omeprazole, simvastatin and midazolam as indicators-substrates, the effect of drospirenone in a dose of 3 mg on the metabolism of other active substances is unlikely.

Other interactions

There is a theoretical possibility of increasing serum potassium concentration in women receiving oral contraceptives concomitantly with other drugs that increase serum potassium concentration: angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, some non-steroidal anti-inflammatory drugs (for example, indomethacin), potassium-sparing diuretics and aldosterone antagonists. However, in a study evaluating the interaction of an ACE inhibitor with a combination drospirenone + ethinylestradiol in women with moderate arterial hypertension, there was no significant difference between serum potassium concentrations in women who received enalapril and placebo.

Laboratory research

The intake of hormonal contraceptives can affect the results of individual laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function,as well as the concentration of plasma transport proteins, such as corticosteroid-binding globulin and lipid / lipoprotein fractions, carbohydrate metabolism, blood coagulation and fibrinolysis. Changes usually occur within laboratory norms.

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

Special instructions:

Precautionary measures

If any of the conditions / risk factors listed below are currently available, the potential risk and expected benefit of using a combined oral contraceptive in each individual case should be weighed carefully and discussed with the woman before she decides to start taking the drug. In case of weighting, strengthening or the first manifestation of any of these conditions or risk factors, a woman should consult with her doctor who can decide whether to cancel the combined oral contraceptive.

Disorders of the circulatory system

The frequency of venous thromboembolism (VTE) when combined orally(<50 μg ethinylestradiol, such as MIDIANA®) is approximately 20 to 40 cases per 100,000 women per year, which is slightly higher than in women who do not use hormonal contraceptives (5 to 10 of cases per 100,000 women), but lower than women during pregnancy (60 cases per 100,000 pregnancies). An additional risk of VTE is noted during the first year of combined oral contraceptive use. VTE leads to a lethal outcome in 1-2% of cases.

Epidemiological studies also revealed a link between combined oral contraceptive and an increased risk of arterial thromboembolism. Very rare cases of thrombosis of other blood vessels, for example, liver, mesenteric, renal, brain vessels and retina, both arteries and veins, have been described. oral hormonal contraceptives. The causal relationship between the occurrence of these side effects and the use of combined oral contraceptives has not been proven.

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

- unusual unilateral pain and / or swelling of the limb;

- sudden severe pain in the chest, with or without irradiation in the left arm;

- sudden shortness of breath;

- a sudden attack of coughing;

- any unusual, strong, prolonged headache;

- sudden partial or complete loss of vision;

- Diplomacy;

- slurred speech or aphasia;

- dizziness;

- loss of consciousness with or without convulsive seizure;

- weakness or very significant loss of sensitivity, suddenly appeared from one half or in one part of the body;

- motor disorders;

- symptom of an "acute abdomen."

The risk of complications associated with VTE when taking a combined oral contraceptive increases:

- with age;

- if there is a family history (venous or arterial thromboembolism in close relatives or parents at a relatively young age); if hereditary predisposition is assumed, a woman needs specialist advice before prescribing a combined oral contraceptive;

- after prolonged immobilization, serious surgical intervention, any foot surgery or extensive 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 to resume the appointment within two weeks after the end of the immobilization. Additionally, antiplatelet therapy may be prescribed if oral hormonal contraceptive use has not been discontinued at the recommended time;

- with obesity (body mass index more than 30 mg / m²);

The risk of arterial thrombosis and thromboembolism when taking a combined oral contraceptive increases:

- with age;

- smokers (women older than 35 years are strictly not recommended to smoke if they want to use combined oral contraceptives);

- with dyslipoproteinemia;

- with arterial hypertension;

- with migraine;

- with diseases of the valvular heart;

- 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 who use combiOral contraceptives should be consulted immediately if symptoms of possible thrombosis occur. In cases of suspected thrombosis or confirmed thrombosis, the use of a combined oral contraceptive should be discontinued.It is necessary to choose an adequate method of contraception due to teratogenicity of anticoagulant therapy (coumarins).

You should consider the increased risk of thromboembolism in the postpartum period. Other diseases that are associated with severe vascular pathology include diabetes mellitus, systemic lupus erythematosus, haemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia.

The increase in frequency and severity of migraine during use of combined oral contraceptives (which may be preceded by cerebrovascular disorders) can be grounds for immediate discontinuation of these drugs.

Tumors

The most significant risk factor for developing cervical cancer is infection with the human papillomavirus. Some epidemiological studies have reported an increased risk of developing cervical cancer with long-term use of combined oral contraceptives, but there are conflicting views as to the extent to which these findings are related to, for example, research on cervical cancer or the use of barrier methods of contraception.

A meta-analysis of 54 epidemiological studies has demonstrated that there is a slightly increased relative risk (RR = 1.24) in the development of breast cancer diagnosed in women who at the time of the study used combined oral contraceptives. Excess risk gradually decreases within 10 years after discontinuation of combined oral contraceptives. Since breast cancer is rare in women younger than 40 years, an increase in the number diagnosed in recent years in women who have been taking or taking combined oralcontraceptives, breast cancer is small in relation to the overall risk of developing breast cancer. These studies do not support the causal relationship between the use of combined oral contraceptives and breast cancer. The observed increase in risk may be the result of an earlier diagnosis of breast cancer in women using combined oral contraceptives, the biological effect of combined oral contraceptives, or a combination of both.Cancerous breast tumors in women who have ever taken combined oral contraceptives were clinically less pronounced than in women who never took them.

In rare cases, against the background of the use of combined oral contraceptives, the development of benign liver tumors, and even more rare - malignant. In some cases, these tumors caused life-threatening abdominal bleeding. In the differential diagnosis of liver tumors, it is necessary to take into account when a woman receiving combined oral contraceptives has severe pain in the upper abdomen, augmentation of the liver or signs of intra-abdominal bleeding.

Other states

Progesterone component in the preparation MIDIANA® is an aldosterone antagonist, with the property of retaining potassium. In most cases, there is no increase in potassium concentration. However, in a clinical study in some patients with mild or moderate renal failure and simultaneous administration of potassium-retarding drugs, the concentration of potassium in serum is insignificant but increased with drospirenone.Thus, it is recommended to check the serum potassium concentration in the first cycle of the drug in patients with renal insufficiency and potassium concentration before treatment at the upper limit of the norm, and also with the simultaneous use of drugs that retard potassium in the body.

In women with gipertriglyceridemia or a family history of hypertriglyceridemia, the risk of developing pancreatitis during combined oral contraceptives can not be ruled out.

Although a small increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically relevant increases have been rare. Only in rare cases is it necessary to immediately stop taking combined oral contraceptives. If during the reception of combined oral contraceptives in patients with hypertension, the blood pressure values are constantly raised or not reduced with the use of antihypertensive drugs, the use of combined oral contraceptives should be discontinued.If necessary, the use of combined oral contraceptives can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions develop or worsen, both during pregnancy and when taking combined oral contraceptives, but their association with combined oral contraceptives has not been proven: jaundice and / or pruritus associated with cholestasis; formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy in anamnesis; hearing loss associated with otosclerosis.

In women with hereditary angioedema, exogenous estrogens can cause or exacerbate symptoms of angioedema.

In acute or chronic liver function disorders, it may be necessary to stop using combined oral contraceptives until the liver function returns to normal. Recurrent cholestatic jaundice and / or cholestasis-induced pruritus that develops for the first time during pregnancy or previous reception of sex hormones requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may affect peripheral insulin resistance and glucose tolerance, there is no need to change therapeuticsin patients with diabetes mellitus, who use low-dose combined oral contraceptives (containing <0.05 mg of ethinylestradiol). Nevertheless, women with diabetes should be carefully observed by a doctor, especially at the beginning of taking combined oral contraceptives.

Also reported was an increase in endogenous depression, epilepsy, Crohn's disease and ulcerative colitis with combined oral contraceptives. Sometimes chloasma can develop, especially in women with chloasma during pregnancy in the anamnesis. Women with a tendency to chloasma when taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Medication MIDIANA® contains 48.17 mg of lactose in one tablet. Patients with hereditary intolerance to galactose, lactase deficiency, or glucose / galactose absorption disorders on a lactose-free diet should not take the drug.

Medical examination / consultation

Before starting the use of hormonal contraceptives it is necessary to consult with the treating gynecologist and undergo the appropriate medical examination. Further monitoring and frequency of medical examinations are carried out on an individual basis, but at least once every 6 months. The drug MIDIANA®, like other combined oral contraceptives, does not protect against HIV infection and other sexually transmitted diseases.

Decreased efficiency

The effectiveness of combined oral contraceptives can be reduced in case of missing tablets, disorders of the gastrointestinal tract, or with the simultaneous administration of other medications.

Reduced cycle control

On the background of taking combined oral contraceptives, there may be irregular bleeding (spotting spotting or breakthrough uterine bleeding), especially during the first months of use. Therefore, the evaluation of any irregular bleeding is significant only after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles,then nonhormonal causes should be considered and adequate diagnostic measures taken to exclude malignant neoplasms or pregnancy. These can include diagnostic scraping.

In some women, bleeding "cancellation" may not develop during a break in taking combined oral contraceptives. If combined oral contraceptives are taken according to the rules for taking the drug specified in the instructions, pregnancy is unlikely. However, if previously combined oral contraceptives were taken irregularly or if there were no consecutive "bleeding" bleedings, pregnancy should be ruled out before continuing with combined oral contraceptives.

Effect on the ability to drive transp. cf. and fur:

Studies that study the effect of the drug on the ability to drive a car, was not conducted.

Form release / dosage:Tablets, film-coated, 3 mg + 0.03 mg.

Packaging:

For 21 tablets in a blister of PVC / PVDC - aluminum foil.

For 1 or 3 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008855/10

Date of registration:30.08.2010 / 17.05.2017

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp24.04.2018

Illustrated instructions

Instructions

Midian® (Midiana®)