How to move from the median. Median birth control pills - reviews, recommendations, indications, advantages

Midiana is a contraceptive drug.

Release form and composition

The dosage form of Midiana is coated tablets. film-coated: round, biconvex, white, with “G63” engraved on one side (21 tablets per blister, in cardboard box 1 or 3 blisters).

Composition of 1 tablet:

• active ingredients: drospirenone – 3 mg, ethinyl estradiol – 0.03 mg;
• excipients: magnesium stearate, lactose monohydrate, corn starch, pregelatinized corn starch, povidone K-25;
• film shell: white opadry Colorcon 85G18490 [polyvinyl alcohol, soy lecithin, talc, titanium dioxide (E171), macrogol 3350].

Pharmacological properties

Pharmacodynamics

Midiana – combination drug, its contraceptive effect is due primarily to inhibition of ovulation, as well as structural and functional changes in the endometrium.

In addition to the contraceptive effect, drospirenone in therapeutic doses has antiandrogenic and weak antimineralocorticoid effects, while it does not have estrogenic, glucocorticoid, or antiglucocorticoid activity, which makes it similar to natural progesterone in its pharmacological profile.

In addition, there is evidence that when taking combined oral contraceptives, the risk of developing ovarian and endometrial cancer is reduced.

Pharmacokinetics

Drospirenone

Absorption of drospirenone is not complete; its bioavailability is 76–85% and does not depend on food intake. The maximum serum concentration is 37 ng/ml and is achieved within several hours. During the first cycle, a steady-state concentration of 60 ng/ml is achieved after 7–14 hours. The decrease in serum concentration occurs in two phases by binding to serum albumin.

Metabolites of drospirenone are represented by acidic forms formed during the opening of the lactone ring. The average apparent volume of distribution is 3.7 l/kg. The rate of metabolic clearance is 1.5 ml/min/kg. The elimination process occurs exclusively in trace amounts in unchanged form; metabolic products are excreted by the kidneys and intestines. The half-life is 40 hours.

Ethinyl estradiol

When taken orally, ethinyl estradiol short term completely absorbed. Its absolute bioavailability is 45%. The maximum concentration after taking the first dose is 0.03 mg and is achieved within several hours. Plasma protein binding is 98%, apparent volume of distribution is 5 l/kg. Ethinyl estradiol can induce the synthesis of SHBG (sex hormone binding globulin) and transcortin in the liver. The substance is completely metabolized. The rate of metabolic clearance is 5 ml/min/kg. Ethinyl estradiol is excreted in the form of metabolic products by the kidneys and intestines. 0.02% of its dose is found in breast milk.

Indications for use

According to the instructions, Midiana is indicated for contraception.

Contraindications

Absolute:

• complicated lesions of the heart valve apparatus, uncontrolled arterial hypertension, atrial fibrillation;
• long-term immobilization during major surgical operations;
• venous thrombosis, including a history (deep vein thrombosis, thromboembolism pulmonary artery);
• arterial thrombosis or conditions preceding their onset, including a history (for example, myocardial infarction, angina, transient ischemic attack);
• the presence of risk factors for arterial thrombosis, such as diabetes mellitus, severe dyslipoproteinemia, severe arterial hypertension;
• predisposition to arterial or venous thrombosis(eg, activated protein C resistance, protein C deficiency, protein S deficiency, antithrombin III deficiency, hyperhomocysteinemia, and the presence of antiphospholipid antibodies such as anticardiolipin antibodies, lupus anticoagulant);
• cerebrovascular diseases, including a history;
• pancreatitis (including a history of severe hypertriglyceridemia);
• liver failure;
• liver tumors, including those with a history (benign or malignant);
• severe liver diseases, including a history (before normalization of liver tests);
• renal failure(acute or severe chronic);
• hormone dependent malignant diseases reproductive system or suspicion of them;
• vaginal bleeding unknown origin;
• migraine with a history of focal neurological symptoms;
• smoking over the age of 35;
• pregnancy or suspicion of it, lactation period;
• glucose-galactose malabsorption, hereditary galactose intolerance, lactase deficiency;
• increased sensitivity to any of the components of Midiana.

Relative:

• risk factors for the development of thrombosis and thromboembolism;
• smoking before the age of 35;
• dyslipoproteinemia;
• controlled arterial hypertension;
• migraine without focal neurological symptoms;
• heart valve defects (uncomplicated);
• hereditary predisposition to thrombosis;
• diseases that can lead to peripheral circulatory disorders (diabetes mellitus, Crohn's disease, systemic lupus erythematosus, hemolytic-uremic syndrome, ulcerative colitis, sickle cell anemia, phlebitis of superficial veins);
• hypertriglyceridemia;
• hereditary angioedema;
• liver diseases;
• diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (porphyria, herpes, jaundice, itching, cholelithiasis, otosclerosis with hearing impairment, chloasma, chorea minor);
• postpartum period.

Instructions for use of Midiana: method and dosage

Midiana tablets should be taken for 21 days, every day at the same time, in the sequence indicated on the blister pack. This should be followed by a break in taking the drug (7 days), during which, as a rule, menstrual bleeding occurs (usually 2-3 days after stopping use), sometimes continuing until the start of the next package.

If during the previous month hormonal contraceptives have not been used, the first tablet should be taken on the first day menstrual cycle(that is, on the first day menstrual bleeding).

To replace another oral combined contraceptive, transdermal patch or vaginal ring taking Midiana should be started the day after taking the last one active tablet or on the day of removal of any previously used product.

You can switch from the mini-pill any day, from injection form– on the day when the next injection was planned, from an implant or intrauterine contraceptive – on the day of its removal. In all these cases, an additional method of contraception is recommended in the first 7 days after the transition.

After termination of pregnancy in the first trimester, taking pills can be started immediately, and there is no need for additional methods contraception.

If pregnancy is terminated in the second trimester or after childbirth, taking Midiana should begin on days 21–28. If you start taking the pills later, an additional method of contraception is recommended in the first 7 days of using the drug. If you had sexual intercourse before taking Midiana, you should rule out pregnancy or wait until your menstruation begins.

Taking missed pills

If there is a delay in taking Midiana for no more than 12 hours, the contraceptive effect does not decrease. In this case, you need to take the pill as soon as possible and then take them at the usual time.

If you are more than 12 hours late in taking your pill, you should remember 2 rules:

• Do not interrupt taking the drug for more than 7 days;
• Continuous use of the drug is required for 7 days to adequately suppress the hypothalamic-pituitary system of ovarian functioning.

• first week: take the missed dose as soon as possible, up to simultaneous administration 2 tablets. Then the drug is taken at the usual time, and additional barrier methods of contraception are used for 7 days. The likelihood of pregnancy depends on the number of pills missed and the proximity to the 7-day break;
• second week: take the missed dose as quickly as possible, up to taking 2 tablets at the same time. Then the drug is taken at the usual time. If no pills have been missed in the previous 7 days, there is no need for additional methods of contraception. If you miss at least 1 pill, an additional method of contraception is required for the next 7 days;
• third week: if no pills have been missed in the previous 7 days, there is no need for additional methods of contraception; otherwise, it is necessary, or you should take the drug as soon as possible and then continue taking it as usual, and then start a new package without a break, or stop taking the tablets for 7 days (including missed days) and then continue taking them from a new package.

To delay withdrawal bleeding, you should not take a break from taking Midiana, but start taking the next package immediately after the previous one. The delay can last until the end of taking tablets from 2 packs. In this case, spotting is possible, as well as the risk of breakthrough uterine bleeding. After a 7-day break, the drug is continued from a new package. To delay the onset of withdrawal bleeding, the next break in taking the drug should be shortened by the required number of days. However, the shorter this break, the higher the risk of absence of withdrawal bleeding and the appearance of spotting and breakthrough uterine bleeding while taking tablets from the second package.

If severe reactions from the gastrointestinal tract occur, incomplete absorption of the drug is possible, and therefore, in this case, additional contraceptive measures are necessary. If vomiting occurs within 3-4 hours after taking the tablet, you should take a new tablet as quickly as possible.

If you plan to continue your usual regimen of taking Midiana, an additional tablet(s) should be taken from a different package.

Side effects

• nervous system: depression, emotional lability, headache, decreased or increased libido;
• endocrine system: disruption of the menstrual cycle, pain in the mammary glands, intermenstrual bleeding, discharge from the mammary glands;
• sense organs: hearing loss, poor tolerance of contact lenses;
• digestive system: abdominal pain, nausea, diarrhea, vomiting;
• skin and subcutaneous tissue: eczema, acne, skin rash, urticaria, erythema nodosum and multiforme, itching, chloasma;
• vascular system: migraine, increased or decreased blood pressure, thrombosis (arterial and venous), thromboembolism;
• systemic and local reactions: weight gain, fluid retention, weight loss;
• immune system: bronchospasm;
• reproductive system and mammary gland: vaginal candidiasis, acyclic vaginal bleeding (spotting or breakthrough uterine bleeding), pain, engorgement, enlarged mammary glands, vaginitis, discharge from the mammary glands, increased vaginal discharge.

Overdose

There is no evidence of overdose of drospirenone and ethinyl estradiol. However, nausea, vomiting, and spotting or bleeding from the vagina may occur. In such cases, symptomatic therapy is recommended.

Special instructions

It is necessary to weigh the benefit/risk ratio if the patient has the risk factors described below. If one of these conditions intensifies or appears for the first time, it is recommended to consult a doctor:

• circulatory system disorders: the risk of venous thromboembolism (VTE) in patients taking Midiana is slightly higher than in women who do not use hormonal contraceptives, but lower than in pregnant women. The risk of VTE is especially increased during the first year of using Midiana. VTE in 1–2% of cases leads to fatal outcome. There is also a small risk of arterial thromboembolism and other blood vessels. However, the cause-and-effect relationship between the occurrence of data side effects with the use of combined oral contraceptives has not been proven. Symptoms of thrombosis or thromboembolism of veins and arteries: unilateral pain or swelling of the limb, sudden severe pain in the chest, shortness of breath, coughing fit, unusually prolonged headache, sudden loss vision (partial or complete), diplopia, aphasia, slurred speech, dizziness, loss of consciousness with seizure or without it, weakness, loss of sensation in one part of the body (very significant), movement disorders, signs acute abdomen. The risk of thrombosis and thromboembolism is increased in the presence of the following risk factors: age, presence of thromboembolism in relatives, prolonged immobilization, obesity, smoking (especially over the age of 35 years), dyslipoproteinemia, arterial hypertension, migraine, heart valve disease, atrial fibrillation. The presence of one or more of these factors may be a contraindication to taking Midiana;
• tumors: some studies suggest increased risk development of cervical cancer with long-term use combined oral contraceptives. A meta-analysis of 54 epidemiological studies showed that their use slightly increased the relative risk of developing breast cancer. This risk decreases within 10 years after their discontinuation. Clinical manifestations breast cancer in patients who had ever taken combined oral contraceptives was less pronounced than in women who had never taken them. Rarely, the development of benign tumors liver, and even more rarely – malignant. Sometimes life-threatening intra-abdominal bleeding occurred. Symptoms this complication: severe pain in the upper abdomen, enlarged liver or signs of intra-abdominal bleeding;
• other conditions: Midiana is capable of slightly retaining potassium due to the progesterone component, which is an aldosterone antagonist, especially in patients with mild or moderate renal failure and the simultaneous prescription of potassium-retaining drugs. In this group of patients, in the first cycle of taking the drug, it is recommended to control the level of potassium in the blood serum. Women with hypertriglyceridemia (including a family history) are at risk of developing pancreatitis while taking Midiana. IN in rare cases possibly significant, long-term, not treatable antihypertensive drugs increased blood pressure requiring discontinuation of the drug. In the presence of hereditary angioedema, there is a risk of increasing its symptoms. With diabetes, patients need careful medical supervision, especially when starting to take Midiana. There are reports of increased endogenous depression, epilepsy, ulcerative colitis and Crohn's disease while taking combined oral contraceptives.

Before taking Midiana you should undergo medical examination. Follow-up and frequency medical examinations are installed on an individual basis, but at least once every 6 months. The drug does not protect against sexually transmitted diseases, including HIV infection.

Taking Midiana can cause cycle irregularity; therefore, assessment of the regularity of bleeding can only be objective after three cycles of taking the drug.

The absence of withdrawal bleeding two times in a row is a reason to conduct research to exclude/confirm pregnancy.

Impact on the ability to drive vehicles and complex mechanisms

There have been no studies of the influence of Midiana on the ability to drive vehicles and other complex mechanisms, requiring speed of psychomotor reactions.

Use during pregnancy and lactation

The use of Midiana tablets is contraindicated during pregnancy and breastfeeding. If pregnancy occurs while taking the drug, you should immediately stop using it.

For liver dysfunction

Acute or chronic liver dysfunction requires discontinuation of Midiana until the parameters normalize.

Drug interactions

• phenytoin, barbiturates, carbamazepine, primidone, rifampicin, oxcarbazepine, topiramate, ritonavir, felbamate, griseofulvin, St. John's wort: possible increased clearance of sex hormones due to the induction of microsomal enzymes;
• ritonavir and other HIV protease inhibitors, non-nucleoside inhibitors reverse transcriptase(for example, nevirapine): affect hepatic metabolism;
• antibiotics tetracycline and penicillin series: may cause a decrease in ethinyl estradiol concentrations by reducing enterohepatic recirculation of estrogens.

When using Midiana with the above drugs, it is recommended to use an additional barrier method of contraception, or switch to the use of other contraceptives. When using drugs containing active substances that affect microsomal liver enzymes (and within 28 days after their discontinuation), as well as antibiotics (and within 7 days after their discontinuation), a non-hormonal method of contraception should be additionally used (with the exception of griseofulvin and rifampicin) .

Taking the drug may affect the metabolism of drugs taken simultaneously:

• cyclosporine: plasma concentration of Midiana increases;
• lamotrigine: plasma concentration of Midiana decreases;
• renin: its activity increases.

Analogs

Analogues of Midiana are: Yarina, Simitsia, Anabella, Vidora, Jess, Dimia, Leia, Modell Trend, Yamera.

Terms and conditions of storage

Store away from light, at a temperature not exceeding 25 °C. Keep away from children.

Shelf life – 2 years.

For 1 tablet:

d active substances: drospirenone 3 mg, ethinyl estradiol 0.03 mg;

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

n tape(OpadrayII 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 85G1 8490

Round, biconvex, film-coated tablets, white or almost white; On one side there is an engraving "G63", the other side without engraving. The cross-sectional appearance is white or almost white.

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

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

There is evidence of a reduced risk of developing endometrial and ovarian cancer with the use of combined oral contraceptives.

Drospirenone (3 mg)

Suction

When taken orally, drospirenone is rapidly and almost completely absorbed. Maximum concentration active substance in serum, equal to 37 ng/ml, is achieved 1-2 hours after a single dose. During one dosing cycle, the maximum steady-state serum concentration of drospirenone is approximately 60 ng/ml and is achieved within 7-14 hours. Bioavailability ranges from 76% to 85%. Food intake does not affect the bioavailability of drospirenone.

Distribution

After oral administration There is a biphasic decrease in the concentration of drospirenone in the serum, 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 free hormone. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to serum proteins. The average apparent volume of distribution is 3.7 ± 1.2 l/kg.

Biotransformation

Following oral administration, drospirenone undergoes significant metabolism. Most metabolites in 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 the involvement of the cytochrome P450 system. According to research invitro Drospirenone is metabolized with little participation of cytochrome P450.

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 by the kidneys and intestines in a ratio of approximately 1.2:1.4. The half-life for excretion of metabolites by the kidneys and intestines is approximately 40 hours.

Equilibrium concentration

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

Ethinyl estradiol (30 mcg)

Suction

Ethinyl estradiol is rapidly and completely absorbed after oral administration. The maximum serum concentration after a single dose of 30 mcg is reached after 1-2 hours and is about 100 pg/ml. For a, there is a significant first-pass effect with high individual variability. Absolute bioavailability varies and is approximately 45%.

Distribution

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

Biotransformation

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

Elimination

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

Equilibrium concentration

A state of equilibrium concentration is achieved during the second half of the treatment cycle.

Individual categories population

Effect on kidney function

Steady-state serum concentrations of drospirenone in women with weak degree renal failure (creatinine clearance (CC) = 50-80 ml/minute) was comparable to that in women with normal function kidneys (creatinine clearance > 80 ml/minute). Serum drospirenone concentrations were on average 37% higher in women with average degree renal failure (CC = 30-50 ml/minute) compared with that in women with normal renal function. Drospirenone therapy was well tolerated by women with mild to moderate renal impairment.

Treatment with drospirenone had no clinical effect significant impact on serum potassium concentration.

Effect on liver function

In women with moderate hepatic impairment (Child-Pugh class B), the mean plasma concentration curve did not correspond to that in women with normal liver function. The maximum concentration values ​​(Cmax) observed in the absorption and distribution phases were the same. During the end of the distribution phase, the decrease in drospirenone concentrations was approximately 1.8 times greater in volunteers with moderate hepatic impairment compared with those with normal liver function.

After a single dose, total clearance (C l /F) in volunteers with moderate hepatic impairment was reduced by approximately 50% compared to people with normal liver function.

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

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

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

Preparation M IDI ANA® should not be prescribed if any of the conditions listed below are present. If any of these conditions develop for the first time while taking the drug, its immediate discontinuation is required:

The presence of venous thrombosis currently or in history (deep vein thrombosis, pulmonary embolism);

The presence of current or history of arterial thrombosis (eg, myocardial infarction) or previous conditions (eg, angina and transient ischemic attack);

Complicated lesions of the heart valve apparatus, atrial fibrillation, uncontrolled arterial hypertension;

- serious surgery with long-term immobilization;

Smoking over 35 years of age;

Liver failure;

Cerebrovascular diseases currently or in history;

The 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), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);

Pancreatitis, including a history of severe hypertriglyceridemia;

Serious illnesses liver (before normalization of liver tests) currently or in history;

Severe chronic renal failure or acute renal failure;

Liver tumors (benign or malignant), current or in history;

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

Bleeding from the vagina of unknown origin;

History of migraine with focal neurological symptoms;

Pregnancy or suspicion of it;

Lactation period;

Hypersensitivity to the drug or any of its components;

Hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption/

Risk factors for the development of thrombosis and thromboembolism: smoking under the age of 35 years, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated valvular heart disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or disorder cerebral circulation V at a young age from any of the immediate relatives); diseases in which peripheral circulatory disorders may occur: diabetes mellitus, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of the superficial veins; hereditary angioedema, hypertriglyceridemia, liver disease; diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (including jaundice and/or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, history of herpes during pregnancy, minor chorea (Sydenham's disease), chloasma, postpartum period.

During pregnancy and lactation, the use of MIDIANA® is contraindicated. If pregnancy occurs against the background hormonal contraception, immediate discontinuation of the drug is necessary. The limited available data on unintentional, careless use of combined oral contraceptives indicate a lack of teratogenic effect and an increased risk for children and women during childbirth.

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

The tablets must be taken every day at approximately the same time, washed down if necessary. a small amount liquids in the order indicated on the blister pack. You must take one tablet per day for 21 consecutive days. Taking tablets from each subsequent package should begin after a 7-day tablet-taking interval, during which menstrual-like bleeding usually occurs. It usually starts 2-3 days after taking the last tablet and may not end by the time you start the next pack.

How to take MIDIANA®

If hormonal contraceptives have not been used previously (in last month):

Combined oral contraceptives begin on the first day of a woman's natural menstrual cycle (that is, the first day of menstrual bleeding).

In case of replacement of another combined oral contraceptive, vaginal ring or transdermal patch:

It is preferable for a woman to start taking MIDIANA® the day after taking the last active tablet of the previous combined oral contraceptive; in such cases, reception medicine MIDIAN® should not start later next day after a normal pill break or taking inactive pills from her previous combined oral contraceptive. When replacing a vaginal ring or transdermal patch, taking oral contraceptive M IDI It is advisable to start ANA® on the day of removal of the previous product; in such cases, taking MIDIANA® should start immediately later in the day planned replacement procedure.

If changing to a progestin-only method (mini-pills, injectables, implants) or progestin-releasing intrauterine devices:

A woman can switch from the mini-pill any day (from an implant or intrauterine contraceptive- on the day of its removal, from the injection form - from the day when the next injection should have been given). However, in all these cases, it is advisable to use an additional barrier method of contraception during the first 7 days of taking the pills.

After termination of pregnancy in the first trimester:

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

After childbirth or termination of pregnancy in the second trimester:

It is advisable for a woman to start taking MIDIANA® on days 21-28 after childbirth or termination of pregnancy in the second trimester. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. If you have sexual intercourse, pregnancy should be excluded before starting to take the drug or you must wait until your first menstruation.

Taking missed pills

If the delay in taking the pill is less than 12 hours, contraceptive protection is not reduced. The woman needs to take the pill as soon as possible, the next pills are taken at the usual time.

If you are late in taking your pills more than 12 hours, contraceptive protection may be reduced. The tactics for skipping a drug dose are based on the following two simple rules:

1. Taking pills should not be stopped for more than 7 days;

2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian axis, 7 days of continuous pill use are necessary.

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

Week 1

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

Week 2

You should take the last missed tablet as soon as possible, even if this 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 over the previous 7 days, there is no need to use additional funds contraception. However, if she has missed more than 1 tablet, additional contraceptive measures must be used for the next 7 days.

Week 3

The likelihood of a decrease in the contraceptive effect is significant due to the upcoming 7-day break in taking pills. However, by adjusting the schedule for taking pills, you can prevent a decrease in contraceptive protection.

If you follow any of the following two tips, additional ways Contraception will not be needed if the woman has taken all her pills correctly in the previous 7 days before missing a pill. If this is not the case, she should follow the first of the two methods and also use additional contraception for the next 7 days.

1. You should take the last missed pill as soon as possible, even if this means taking two pills at the same time. The next tablet is taken at the usual time. Taking tablets from a new package should be started as soon as the current package ends, that is, without a break between taking two packages. Most likely, withdrawal bleeding will not occur until the end of the second package, but spotting may be observed. spotting or breakthrough uterine bleeding on days of taking the pills.

2. A woman may be advised to stop taking tablets from this package. She should then stop taking the pills for 7 days, including days when she forgot to take the pills, and then start taking the pills from a new pack.

If you miss taking pills and there is no “withdrawal” bleeding during the first drug-free interval, pregnancy must be ruled out.

Advice in case of frustration gastrointestinal tract

In case of severe gastrointestinal reactions (such as vomiting or diarrhea), absorption may be incomplete and additional contraceptive measures must be used.

If you vomit within 3-4 hours after taking the tablet, you should take a new replacement tablet as soon as possible. New pill If possible, should be taken within 12 hours of the usual dosing time. If more than 12 hours are missed, if possible, you must follow the rules for taking the drug,

Taking missed pills

If the patient does not want to change the normal regimen of taking the drug, she should take an additional tablet (or several tablets) from a different package.

How to delay withdrawal bleeding

To delay the day of the onset of withdrawal bleeding, it is necessary to continue taking the drug MIDIANA® from the new package without interruption. A delay is possible until the end of the tablets in the second package.

During the lengthening of the cycle, spotting bloody discharge from the vagina or breakthrough uterine bleeding may occur. You should resume taking MIDIAN® from a new pack after the usual 7-day break.

To move the day of the start of withdrawal bleeding to another day of the week of the usual schedule, you should shorten the next break in taking pills by as many days as necessary. The shorter the interval, the higher the risk that there will be no “withdrawal” bleeding, and while taking tablets from the second package, spotting and breakthrough uterine bleeding will be observed (as well as in the case of a delay in the onset of “withdrawal” bleeding).

The following have been reported during concomitant use of drospirenone and ethinyl estradiol: adverse reactions:

There is no information about an overdose of drospirenone and ethinyl estradiol-containing drugs. However, nausea, vomiting and spotting/bleeding from the vagina may occur.

There is no specific antidote. Symptomatic treatment should be carried out.

Interactions between oral contraceptives and other drugs may result in breakthrough uterine bleeding and/or decreased contraceptive reliability. The following types of interactions are described in the literature:

Effect on liver metabolism

Some drugs, due to the induction of microsomal enzymes, are able to increase the clearance of sex hormones (, barbiturates, and; perhaps the same effect of oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal remedy based on St. John's wort (St. John's wort) Hypericum perforatum).

The 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.

Effect on enterohepatic recirculation

Clinical observations show that simultaneous use with some antibiotics drugs, such as penicillins and tetracyclines, reduce the enterohepatic recirculation of estrogens, which may lead to a decrease in ethinyl estradiol concentrations.

Women taking any of the above classes of drugs should use a barrier method of contraception in addition to MIDIANA® or switch to any other method of contraception. Women receiving continuous treatment with drugs containing active substances that affect microsomal liver enzymes must additionally use a non-hormonal method of contraception for 28 days after their discontinuation. Women taking antibiotics (other than rifampin or griseofulvin) should temporarily use a barrier method of contraception in addition to the combined oral contraceptive, both while taking the drug and for 7 days after stopping it. If concomitant use of the drug is started at the end of a package of MIDIANA®, the next package should be started without the usual break in administration.

The main metabolism of drospirenone in human plasma occurs without the involvement of the cytochrome P450 system. Inhibitors of this enzyme system therefore do not affect the metabolism of drospirenone.

Effect of the drug MIDIANA ® for other drugs

Oral contraceptives may affect the metabolism of other drugs. In addition, their concentrations in plasma and tissues may change - both increase (for example,), and decrease (for example,). Based on inhibition studies invitro and interaction research invivo in female volunteers taking , and as indicator substrates, the effect of drospirenone at 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 concentrations in women receiving oral contraceptives concomitantly with other drugs that increase serum potassium concentrations: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, certain non-steroidal anti-inflammatory drugs (for example), potassium-sparing diuretics and aldosterone antagonists. However, in a study evaluating the interaction of an ACE inhibitor with a combination in women with moderate hypertension, there was no significant difference between serum potassium concentrations in women receiving and placebo.

Laboratory research

Taking hormonal contraceptives may affect the results of certain 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, indicators of carbohydrate metabolism, blood coagulation and fibrinolysis. Changes usually occur within laboratory limits.

Due to its slight antimineralocorticoid activity, drospirenone increases renin activity and plasma aldosterone concentrations.

Precautions

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of using a combined oral contraceptive should be carefully weighed on an individual basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the combined oral contraceptive.

Circulatory system disorders

The incidence of venous thromboembolism (VTE) when using a combination orally th contraceptive with a low dose of estrogen (< 50 мкг этинилэстрадиола, такие как, препарат МИДИАНА®) составляет примерно от 20 до 40 случаев на 100 000 женщин в год, что несколько выше, чем у женщин, не применяющих гормональные контрацептивы (от 5 до 10 случаев на 100 000 женщин), но ниже, чем у женщин во время беременности (60 случаев на 100 000 беременностей). Дополнительный риск ВТЭ отмечается в течение первого года применения комбинированного перорального контрацептива. ВТЭ приводит к летальному исходу в 1-2% случаев.

Epidemiological studies have also found an association between the use of combined oralcontraceptive and an increased risk of arterial thromboembolism. Extremely rare cases of thrombosis of other blood vessels, for example, hepatic, mesenteric, renal, cerebral and retinal vessels, both arteries and veins, have been described in people who took oral hormonal contraceptives. The cause-and-effect 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 chest pain, with or without radiation to the left arm;

Sudden shortness of breath;

Sudden attack of coughing;

Any unusual, severe, long-lasting headache;

Sudden partial or complete loss of vision;

Diplopia;

Slurred speech or aphasia;

Dizziness;

Loss of consciousness with or without a seizure;

Weakness or very significant 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 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 a hereditary predisposition is suspected, the woman needs to consult a specialist before prescribing a combined oral contraceptive;

After prolonged immobilization, major surgery, any leg surgery or major trauma. In these situations, it is recommended to stop taking the drug (in the case of planned surgery, at least four weeks before it) and not to resume taking it for two weeks after the end of immobilization. Additionally, antithrombotic therapy may be prescribed if oral hormonal contraceptives have not been discontinued within the recommended time frame;

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

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

With age;

In smokers (women over 35 years of age are strictly not recommended to smoke if they want to use combined oral contraceptives);

With dyslipoproteinemia;

For arterial hypertension;

For migraines;

For diseases of the heart valves;

For 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 the combination prescribed oral contraceptives, should immediately consult a doctor if symptoms of possible thrombosis occur. In cases of suspected or confirmed thrombosis, the combined oral contraceptive should be discontinued. It is necessary to select an adequate method of contraception due to the teratogenicity of anticoagulant therapy (coumarins).

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

An increase in the frequency and severity of migraine during use of combined oral contraceptives (which may precede cerebrovascular events) may 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 cervical cancer with long-term use of combined oral contraceptives, but there remains controversy regarding the extent to which these findings are attributable to confounding factors such as testing for cervical cancer or use of barrier methods of contraception.

A meta-analysis of 54 epidemiological studies demonstrated that there is a slightly increased relative risk (RR = 1.24) of developing breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. The excess risk decreases gradually over 10 years after stopping combined oral contraceptives. Because breast cancer is rare in women under 40 years of age, an increase in the number diagnosed in recent years in women who have taken or are taking combined oral Using contraceptives, breast cancer is small relative to the overall risk of developing breast cancer. These studies do not support a causal relationship between combined oral contraceptives and breast cancer. The observed increased risk may be due to earlier diagnosis of breast cancer in women using combined oral contraceptives, a biological effect of combined oral contraceptives, or a combination of both. Breast cancer in women who had ever taken combined oral contraceptives was clinically less severe than in women who had never taken them.

In rare cases, during the use of combined oral contraceptives, the development of benign liver tumors has been observed, and in even more rare cases, malignant ones. In some cases, these tumors caused life-threatening intra-abdominal bleeding. When differentially diagnosing a liver tumor, it should be taken into account when a woman taking combined oral contraceptives develops severe pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding.

Other states

The progesterone component in 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 to moderate renal impairment and concomitantly prescribed potassium-retaining medications, serum potassium concentrations were slightly increased when taking drospirenone. Therefore, it is recommended to check the serum potassium concentration in the first cycle of dosing in patients with renal failure and pre-treatment potassium concentration values ​​at the upper limit of normal, as well as when concomitantly using drugs that retain potassium in the body.

In women with gi Pertriglyceridemia or a family history of hypertriglyceridemia cannot exclude an increased risk of developing pancreatitis while taking combined oral contraceptives.

Although mild increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. Only in rare cases is it necessary to immediately stop taking combined oral contraceptives. If, while taking combined oral contraceptives in patients with arterial hypertension, blood pressure values ​​are constantly elevated or do not decrease when taking antihypertensive drugs, the combined oral contraceptives should be discontinued. If necessary, combined oral contraceptives can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.

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

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

For acute or chronic liver dysfunction, it may be necessary to discontinue use of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice and/or itching caused by cholestasis, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may have an effect on peripheral insulin resistance and glucose tolerance, no need to change therapists ical regimen in patients with diabetes mellitus using low-dose combined oral contraceptives (containing< 0,05 мг этинилэстрадиола). Тем не менее женщины с сахарным диабетом должны тщательно наблюдаться врачом, особенно в начале приема комбинированных пероральных контрацептивов.

An increase in endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has also been reported with the use of combined oral contraceptives. Chloasma can sometimes develop, especially in women with a history of chloasma during pregnancy. Women prone to chloasma should avoid prolonged sun exposure and ultraviolet radiation while taking combined oral contraceptives.

The drug MIDIANA® contains 48.17 mg of lactose per tablet. Patients with hereditary galactose intolerance, lactase deficiency or glucose/galactose malabsorption who are on a lactose-free diet should not take the drug.

Medical examination/consultation

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

Reduced efficiency

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

Reduced cycle control

While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough uterine bleeding) may occur, especially during the first months of use. Therefore, assessing any irregular bleeding is only meaningful after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures taken to exclude malignancy or pregnancy. These may include diagnostic curettage.

Some women may not develop withdrawal bleeding during a break from taking combined oral contraceptives. If combined oral contraceptives are taken according to the instructions for taking the drug, then pregnancy is unlikely. However, if combined oral contraceptives have not been taken regularly before, or if there are no consecutive withdrawal bleeds, pregnancy should be ruled out before continuing to take combined oral contraceptives.

There have been no studies examining the effect of the drug on driving ability.

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

1 or 3 blisters per cardboard box along with instructions for use.

Store in a place protected from light, at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Do not use after the expiration date stated on the package.