In this article you can read the instructions for using the contraceptive drug Midiana. Feedback from site visitors - consumers - is presented of this medicine, as well as the opinions of specialist doctors on the use of Midiana in their practice. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Midiana in the presence of existing structural analogues. Use for contraception and pregnancy prevention in women. Composition of the drug.
Midiana- combined oral contraceptive drug, containing ethinyl estradiol and drospirenone. The contraceptive effect is based on the interaction various factors, the most important of which are inhibition of ovulation and changes in the endometrium.
At a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid properties. Does not have 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 when using combined oral contraceptives.
Compound
Ethinyl estradiol + Drospirenone + excipients.
Pharmacokinetics
Drospirenone
When taken orally, drospirenone is rapidly and almost completely absorbed. Bioavailability ranges from 76% to 85%. Food intake does not affect the bioavailability of drospirenone. 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 ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to serum proteins. 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, drospirenone is metabolized with little participation of cytochrome P450. 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.
Drospirenone treatment did not have a clinically significant effect on serum potassium concentrations.
Ethinyl estradiol
Ethinyl estradiol is rapidly and completely absorbed after oral administration. Ethinyl estradiol exhibits a significant first-pass effect with high individual variability. Absolute bioavailability varies and is approximately 45%. A state of equilibrium concentration is achieved during the second half of the treatment cycle. Ethinyl estradiol induces the synthesis of SHBG and transcortin in the liver. Ethinyl estradiol enters in small quantities into breast milk(approximately 0.02% of the dose). Ethinyl estradiol is completely metabolized. It is practically not displayed unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4:6.
Indications
- contraception.
Release forms
Film-coated tablets.
Instructions for use and dosage regimen
The tablets must be taken every day at approximately the same time, if necessary, with a small amount of liquid, in the sequence indicated on the blister pack. You must take 1 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.
If hormonal contraceptives have not been used previously (in the last month), taking combined oral contraceptives begins on the 1st day of natural menstrual cycle women (that is, on the 1st day of menstrual bleeding).
If changing from another combined oral contraceptive, vaginal ring or transdermal patch, it is preferable to start taking Midiana the day after taking the last active tablet of the previous combined oral contraceptive; in such cases, taking Midiana should not be started later than the next day after the usual pill break or inactive pills of her previous combined oral contraceptive. When replacing a vaginal ring or transdermal patch, it is advisable to start taking the oral contraceptive Midiana on the day the previous drug is removed; in such cases, taking Midiana should begin no later than the day of the planned replacement procedure.
In the case of changing a method using only progestins (mini-pills, injectable forms, implants) or progestin-releasing intrauterine contraceptives: a woman can switch from the mini-pill on any day (from an implant or intrauterine contraceptive - on the day of its removal, from injection form- from the day when the next injection was due). 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 1st trimester, a 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 2nd trimester, it is advisable for a woman to start taking Midiana on the 21-28th day after childbirth or termination of pregnancy in the 2nd 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 following pills are taken at usual time.
If the delay in taking the pills is more than 12 hours, contraceptive protection may be reduced. Tactics when skipping a drug dose are based on the following two rules:
1.Taking pills should not be stopped for more than 7 days.
2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous pill use are necessary.
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 contraception. However, if she has missed more than 1 tablet, it is necessary to use additional measures contraception 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 pills from new packaging should be started as soon as the current pack is finished, that is, without a break between two packs. Most likely, there will be no withdrawal bleeding until the end of the second package, but spotting may occur. bloody issues 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.
Gastrointestinal disorders
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 specified in the section “Taking missed tablets.”
If the patient does not want to change the normal regimen of taking the drug, she must take an additional tablet (or several tablets) from a different package.
How to Delay Withdrawal Bleeding
To delay the onset of withdrawal bleeding, you must continue taking 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 Midiana from a new pack after the usual 7-day break. To move the day of the onset 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).
Side effect
- headache;
- emotional lability;
- depression;
- decreased libido;
- increased libido;
- menstrual irregularities;
- intermenstrual bleeding;
- pain in the mammary glands;
- discharge from the mammary glands;
- hearing loss;
- poor tolerance contact lenses;
- nausea, vomiting;
- abdominal pain;
- diarrhea;
- acne (blackheads or pimples);
- eczema;
- skin rash;
- hives;
- erythema nodosum;
- erythema multiforme;
- chloasma, especially if there is a history of chloasma during pregnancy;
- thrombosis (venous and arterial);
- thromboembolism;
- weight gain;
- fluid retention;
- weight loss;
- bronchospasm;
- acyclic vaginal bleeding (spotting or breakthrough uterine bleeding);
- engorgement;
- soreness;
- enlargement of the mammary glands;
- vaginal candidiasis;
- vaginitis;
- discharge from the mammary glands;
- increased vaginal discharge.
Contraindications
- the presence of venous thrombosis currently or in history (deep vein thrombosis, pulmonary embolism);
- 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;
- major surgery with prolonged immobilization;
- smoking over the age of 35;
- 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 3 deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
- pancreatitis, incl. history, if severe hypertriglyceridemia was noted;
- severe liver disease (before normalization of liver tests) currently or in history;
- 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 (genital organs, mammary glands) or suspicion of them;
- bleeding from the vagina of unknown origin;
- migraine with a history of focal neurological symptoms;
- hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- pregnancy or suspicion of it;
- lactation period;
- hypersensitivity to the drug or any of its components.
Carefully:
- risk factors for the development of thrombosis and thromboembolism (smoking under 35 years of age, obesity);
- dyslipoproteinemia;
- controlled arterial hypertension;
- migraine without focal neurological symptoms;
- uncomplicated heart valve defects;
- 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, hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of superficial veins);
- hereditary angioedema;
- hypertriglyceridemia;
- liver diseases;
- 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 disease), chloasma, postpartum period).
Use during pregnancy and breastfeeding
During pregnancy and lactation, the use of Midiana is contraindicated. If pregnancy occurs while taking hormonal contraception, immediate discontinuation of the drug is necessary.
The limited available data on unintentional use of combined oral contraceptives suggests no teratogenic effect and an increased risk for children and women during childbirth.
Combined oral contraceptives affect lactation and can reduce the amount and change the composition of breast milk. Small quantities hormonal contraceptives or their metabolites are found in milk during hormonal contraception and may affect the child. The use of combined oral contraceptives is possible after complete cessation breastfeeding.
special instructions
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 it is necessary to discontinue the combined oral contraceptive.
Circulatory system disorders
Incidence of venous thromboembolism (VTE) when using low-dose estrogen combined oral contraceptives (< 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).
An additional risk of VTE is observed during the first year of combined oral contraceptive use. VTE leads to fatal outcome in 1-2% of cases.
Epidemiological studies have also found an association between combined oral contraceptive use 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, in those taking 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 pain in the chest, with or without radiation to the left arm;
- sudden shortness of breath;
- sudden attack 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 very significant loss of sensation that suddenly appeared 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;
- in the presence of 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, serious surgical intervention, any leg surgery or major injury. In these situations, it is recommended to stop taking the drug (in case elective surgery at least four weeks before) and do not 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 a 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;
- with arterial hypertension;
- for migraines;
- for diseases of the heart valves;
- with atrial fibrillation.
The presence of one serious risk factor or multiple risk factors for arterial or venous disease, respectively, may be a contraindication.
Women using combined oral contraceptives should contact their doctor immediately 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.
Meta-analysis 54 epidemiological studies demonstrated that there was 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 last years In women who have taken or are taking combined oral contraceptives, the risk of 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 increase in risk may be due to more early diagnosis breast cancer in women using combined oral contraceptives, the biological effect of combined oral contraceptives or a combination of both. Breast tumors in women who had ever taken combined oral contraceptives were 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. At differential diagnosis Liver tumors should be considered when a woman taking combined oral contraceptives experiences severe upper abdominal pain, 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 for ULN, as well as during concomitant use of drugs that retain potassium in the body.
In women with hypertriglyceridemia or a family history of hypertriglyceridemia, an increased risk of pancreatitis cannot be excluded when taking combined oral contraceptives. Although slight increase Blood pressure has been reported in many women taking combined oral contraceptives, but clinically significant increases have rarely been observed. 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, combined oral contraceptives should be discontinued. If necessary, combined oral contraceptives can be continued if antihypertensive therapy has achieved normal values HELL.
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 stones in gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham's chorea; history of herpes during pregnancy; hearing loss associated with otosclerosis.
In women with hereditary angioedema exogenous estrogens may cause or worsen symptoms 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, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (containing< 50 мкг этинилэстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться врачом, особенно в начале приема комбинированных пероральных контрацептивов.
Increased endogenous depression, epilepsy, Crohn's disease and ulcerative colitis when using combined oral contraceptives. Chloasma can sometimes develop, especially in women with a history of chloasma during pregnancy. Women prone to chloasma should avoid prolonged exposure to the sun and ultraviolet radiation while taking combined oral contraceptives.
1 tablet contains 48.17 mg of lactose. 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
Before starting to use hormonal contraceptives, you must consult with your gynecologist and undergo appropriate medical examination. Further observation and frequency medical examinations carried out on an individual basis, but at least once every 6 months.
STDs and HIV infection
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 disorders occur, or if 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 3 cycles.
If irregular bleeding recurs or develops after previous regular cycles, then non-hormonal causes should be considered and adequate interventions implemented. diagnostic measures to exclude malignant neoplasms or pregnancy. These may include diagnostic curettage.
Some women may not develop withdrawal bleeding during a break from 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 previously been taken regularly or if there are no consecutive withdrawal bleeds, pregnancy should be ruled out before continuing to take combined oral contraceptives.
Impact on the ability to drive vehicles and operate machinery
There have been no studies examining the effect of the drug on driving ability.
Drug interactions
Interaction between oral contraceptives and other medicines may lead to breakthrough uterine bleeding and/or decreased contraceptive reliability. The following types of interaction are described in the literature.
Effect on liver metabolism
Some drugs (phenytoin, barbiturates, primidone, carbamazepine and rifampicin) due to the induction of microsomal enzymes can increase the clearance of sex hormones. Possibly the same effect of oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal remedy based on St. John's wort.
Reported possible action HIV protease inhibitors (for example, ritonavir) and non-nucleoside reverse transcriptase inhibitors (for example, nevirapine) and their combinations on metabolism in the liver.
Effect on enterohepatic recirculation
Clinical observations show that concomitant use with certain antibiotics, such as penicillins and tetracyclines, reduces the enterohepatic recirculation of estrogens, which may lead to a decrease in ethinyl estradiol concentrations.
Women taking any of the above drugs should use a barrier method of contraception in addition to Midiana or switch to any other method of contraception. Women receiving permanent treatment drugs containing active substances that affect microsomal liver enzymes, an additional non-hormonal method of contraception must be used for 28 days after their discontinuation. Women taking antibiotics (other than rifampicin 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 taking 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.
The effect of Midiana on 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, cyclosporine) and decrease (for example, lamotrigine).
Based on the results of inhibition studies and interaction studies in female volunteers taking omeprazole, simvastatin and midazolam as tracer substrates, the effect of drospirenone 3 mg on the metabolism of other active substances 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: ACE inhibitors, angiotensin 2 receptor antagonists, some NSAIDs (for example, indomethacin), potassium-sparing diuretics and aldosterone antagonists. However, in a study assessing the interaction ACE inhibitor with the combination of drospirenone + ethinyl estradiol in women with moderate arterial hypertension, there was no significant difference between serum potassium concentrations in women receiving enalapril and placebo.
Taking hormonal contraceptives may affect the results of certain laboratory tests, including biochemical indicators of liver function, thyroid gland, adrenal glands and kidneys, 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.
Analogues of the drug Midiana
Structural analogues of the active substance:
- Dailla;
- Jess;
- Jess Plus;
- Dimia;
- Simicia;
- Yarina;
- Yarina Plus.
Analogues pharmacological group(estrogens and gestagens):
- Anteovin;
- Artisia;
- Belara;
- Gynodian Depot;
- Gynoflor E;
- Desmoulins;
- Jess;
- Diana is 35;
- Divina;
- Divitren;
- Diecyclen;
- Eura;
- Janine;
- Individual;
- Claira;
- Klymen;
- Climodien;
- Klimonorm;
- Cliogest;
- Lindinet;
- Logest;
- Marvelon;
- Mercilon;
- Microgynon;
- NuvaRing;
- Novinet;
- Non Ovlon;
- Ovidon;
- Oralcon;
- Pauzogest;
- Revmelid;
- Regulon;
- Rigevidon;
- Silest;
- Silhouette;
- Three Mercy;
- Three regol;
- Triquilar;
- Trisequence;
- Femaflor;
- Femoden;
- Femoston;
- Cyclo Proginova;
- Eviana;
- Egestrenol;
- Yarina;
- Yarina Plus.
If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.
Contraception (prevention of unwanted pregnancy).
Release form of the drug Midiana
film-coated tablets 3 mg + 30 mcg; contour packaging 21 with a pocket for carrying a blister, cardboard pack 1;
film-coated tablets 3 mg + 30 mcg; contour packaging 21 with a pocket for carrying a blister, cardboard pack 3;
Pharmacodynamics of the drug Midiana
Low-dose monophasic oral combined estrogen-progestogen contraceptive drug.
The contraceptive effect is mainly achieved by suppressing ovulation and increasing the viscosity of cervical mucus.
In women taking combined oral contraceptives, the menstrual cycle becomes more regular and symptoms are less frequent. painful menstruation, the intensity and duration of bleeding decreases, resulting in a reduced risk iron deficiency anemia. There is also evidence of a reduced risk of endometrial and ovarian cancer.
Drospirenone contained in the drug has an antimineralocorticoid effect and is able to prevent weight gain and the appearance of other symptoms (for example, edema) associated with estrogen-dependent fluid retention. Drospirenone also has antiandrogenic activity and helps reduce acne (blackheads), oily skin and hair. This effect of drospirenone is similar to the effect of natural progesterone produced female body. This should be taken into account when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne(acne) and seborrhea. When used correctly, the Pearl index (an indicator reflecting the number of pregnancies in 100 women using contraception during the year) is less than 1. If you miss pills or misuse The Pearl index may increase.
Pharmacokinetics of the drug Midiana
Drospirenone
When taken orally, drospirenone is rapidly and almost completely absorbed. After a single oral dose, the serum Cmax of drospirenone, equal to 37 ng/ml, is achieved within 1–2 hours. Bioavailability ranges from 76 to 85%. Food intake does not affect the bioavailability of drospirenone.
Drospirenone binds to serum albumin (0.5–0.7%) and does not bind to sex steroid binding globulin (SGBS) or corticosteroid binding globulin (CBG). Only 3–5% of the total concentration in the blood serum is found in free form. The increase in SHPS induced by ethinyl estradiol does not affect the binding of drospirenone to serum proteins.
After oral administration, drospirenone is completely metabolized.
Most metabolites in plasma are represented by acidic forms of drospirenone, which are formed without the involvement of the cytochrome P450 system.
The level of drospirenone in the blood serum decreases in 2 phases. Drospirenone is not excreted unchanged. Drospirenone metabolites are excreted in feces and urine in a ratio of approximately 1.2–1.4. T1/2 for excretion of metabolites in urine and feces is approximately 40 hours.
During cyclic treatment, the maximum steady-state serum concentration of drospirenone is achieved in the second half of the cycle.
A further increase in the serum concentration of drosperinone is observed after 1–6 cycles of administration, after which no increase in concentration is observed.
Ethinyl estradiol
After oral administration, ethinyl estradiol is rapidly and completely absorbed. Serum Cmax of approximately 54–100 pg/ml is achieved in 1–2 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, resulting in its oral bioavailability, on average, about 45%.
Ethinyl estradiol is almost completely (approximately 98%), although nonspecifically, bound by albumin. Ethinyl estradiol induces the synthesis of GSPC.
Ethinyl estradiol undergoes presystemic conjugation, as in the mucosa small intestine, and in the liver. The main route of metabolism is aromatic hydroxylation.
The decrease in the concentration of ethinyl estradiol in the blood serum is biphasic. It is not excreted from the body unchanged. Metabolites of ethinyl estradiol are excreted in urine and bile in a ratio of 4:6 with T1/2 for about 24 hours.
Equilibrium concentration is achieved during the second half of the cycle.
Using Midiana during pregnancy
The drug is not prescribed during pregnancy and breastfeeding. If pregnancy is detected while taking the drug, it should be discontinued immediately. However, extensive epidemiological studies have not revealed increased risk developmental defects in children, born by women who received sex hormones before pregnancy or teratogenic effects in cases of taking sex hormones through negligence in the early stages of pregnancy. At the same time, data on the results of taking the drug during pregnancy are limited, which does not allow us to draw any conclusions about negative impact drug for pregnancy, newborn and fetal health. Currently, no significant epidemiological data are available.
Taking combined oral contraceptives may reduce the amount of breast milk and change its composition, so their use is not recommended until you stop breastfeeding. Small amounts of sex steroids and/or their metabolites may be excreted in milk.
Contraindications to the use of the drug Midiana
COCs should not be used if you have one of the following conditions or diseases. If any of these conditions or diseases occurs for the first time while using the COC, the drug should be stopped immediately:
Presence or history of venous thromboembolic diseases (for example, deep vein thrombosis, pulmonary embolism);
- presence or history of arterial thromboembolic diseases (myocardial infarction) or prodromal symptoms of thrombosis (for example, transient cerebrovascular accident, angina pectoris);
-presence or history of cerebrovascular diseases;
- the presence of severe or multiple risk factors for venous or arterial thrombosis: diabetes mellitus with vascular damage, severe hypertension, severe dyslipoproteinemia;
- hereditary or acquired predisposition to venous or arterial thrombosis, such as resistance to argon plasma coagulation (APC), antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
- pancreatitis, including in history, if severe hypertriglyceridemia was noted;
-presence or history of severe liver disease until liver function tests return to normal values;
- severe renal failure or acute renal failure;
-presence or history of liver tumors (benign or malignant);
-known or suspected malignant tumors(for example, genitals or mammary glands), which are dependent on sex hormones;
-vaginal bleeding of unknown etiology;
-diagnosed pregnancy or suspected pregnancy;
-migraine with local neurological symptoms in the anamnesis;
-increased sensitivity to the active substances or any of the components of the drug.
Side effects of the drug Midiana
When taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use.
Others have been observed in women taking combined oral contraceptives: unwanted effects, the connection of which with taking drugs has not been confirmed, but also not refuted.
From the digestive system: often - nausea, abdominal pain; infrequently - vomiting, diarrhea.
From the central nervous system: often - asthenic syndrome, headache, decreased mood, mood swings, nervousness; infrequently - migraine, decreased libido; rarely - increased libido.
On the part of the organ of vision: rarely - intolerance to contact lenses ( discomfort when wearing them).
From the reproductive system: often - pain in the mammary glands, engorgement of the mammary glands, menstrual irregularities, vaginal candidiasis, uterine bleeding; infrequently - hypertrophy of the mammary glands; rarely - vaginal discharge, discharge from the mammary glands.
From the skin and its appendages: often - acne; uncommon - rash, urticaria; rarely - erythema nodosum, erythema multiforme.
Other: often - weight gain; infrequently - fluid retention; rarely - weight loss, hypersensitivity reactions.
As with other combined oral contraceptives, in rare cases the development of thrombosis and thromboembolism is possible.
In women with hereditary angioedema, estrogen may cause or worsen symptoms.
Method of administration and dosage of the drug Midiana
The tablets must be taken every day at approximately the same time, if necessary, with a small amount of liquid, in the sequence indicated on the blister pack. You should take 1 tablet per day for 21 days in a row. Each subsequent package should begin after a 7-day interval in taking the pills, during which menstrual-like bleeding usually occurs. It usually starts 2-3 days after taking the last tablet and may not end until you start the next pack.
If hormonal contraceptives were not used in the previous period (last month), taking the pills should begin on the 1st day of the woman’s natural cycle (that is, on the first day of menstrual bleeding).
Switching from another combined hormonal contraceptive (pill, vaginal ring or transdermal patch). It is advisable that a woman starts taking Midiana tablets the day after taking the last active tablet of the previous COC; in such cases, taking Midiana should not begin later than the next day after the usual break in taking pills or taking inactive pills of a preliminary contraceptive. When switching from a vaginal ring or transdermal patch, it is advisable to start taking Midiana on the day the previous product is removed; in such cases, taking Midiana should begin no later than the planned transition procedure.
Switching from a progestogen-only method (mini-pill, injection, implant) or a progestogen-containing intrauterine system. A woman can start taking Midiana any day after stopping taking the “mini-pill” (in the case of an implant or intrauterine system - on the day of their removal, in the case of an injection - instead of the next injection). However, in all cases it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the drug.
After an abortion in the first trimester of pregnancy. The use of the drug should be started immediately on the same day after surgery. In this case, there is no need to use additional contraception.
After childbirth or abortion in the second trimester of pregnancy
If breastfeeding, see Pregnancy and lactation period. Women should be advised to start taking Midiana from the 21st to 28th day after childbirth or abortion in the second trimester of pregnancy. If a woman starts taking the pill later, it should be recommended to additionally use a barrier method of contraception during the first 7 days of taking the pill. However, if sexual intercourse has already taken place, then before starting to use the PDA, you should exclude pregnancy or wait until your first menstruation.
Skipping a pill. If the delay in taking the pill does not exceed 12 hours, the contraceptive effect of the drug is not reduced. The missed pill should be taken as soon as it is discovered. The next tablet in this pack should be taken at the usual time. If the delay in taking a forgotten pill exceeds 12 hours, contraceptive protection may decrease. In this case, you can follow two basic rules:
1. A break in taking pills can never be more than 7 days.
2. Adequate suppression of the hypothalamus-pituitary-ovarian system is achieved by continuous use of tablets for 7 days.
In accordance with this, in Everyday life The following recommendations should be followed.
1st week
A woman should take the last missed tablet as soon as possible, even if she has to take 2 tablets at the same time. After this, she continues to take the pills at the usual time. In addition, you should use a barrier method of contraception, such as a condom, for the next 7 days. If sexual intercourse took place in the previous 7 days, the possibility of pregnancy should be taken into account. The more tablets are missed and the closer the break in taking the drug, the higher the risk of pregnancy.
2nd week
A woman should take the last missed tablet as soon as possible, even if she has to take 2 tablets at the same time. After this, she continues to take the pills at the usual time. Provided the woman has taken the pills correctly for 7 days before the missed pill, there is no need to use additional contraception. Otherwise, or if you miss more than one pill, it is recommended to additionally use a barrier method of contraception for 7 days.
3rd week
The likelihood of a decrease in the contraceptive effect is significant due to the upcoming break in taking pills for 7 days. However, if you follow the pill regimen, you can avoid a decrease in contraceptive protection. If you adhere to one of the following options, there will be no need to use additional contraceptives, provided correct intake tablets for 7 days before missing. Otherwise, it is recommended to stick with the first of the following options and use additional methods over the next 7 days.
1. A woman should take the last missed pill as soon as possible, even if she has to take 2 pills at the same time. After this, she continues to take the pills at the usual time. Tablets from a new package should be taken immediately after finishing the previous one, that is, there should be no break between packages. It is unlikely that menstrual bleeding will begin before the end of taking the tablets from the second pack, although spotting or breakthrough bleeding may occur while taking the tablets.
2. The woman may also be advised to stop taking the pills in the current pack. In the second case, the break in taking the drug should be 7 days, including days of missing pills; You should start taking the pills with the next pack.
If a woman misses a pill and does not have menstrual bleeding during the first regular dosage break, the possibility of pregnancy should be considered.
Recommendations in case of gastrointestinal disorders
In case of severe gastrointestinal disorders (vomiting, diarrhea), incomplete absorption of the drug may occur; in this case, additional contraception should be used.
If vomiting occurs within 3-4 hours after taking the tablet, you must take a new replacement tablet as quickly as possible. The new tablet must be taken within 12 hours after the usual dosing time. If more than 12 hours have passed, you must follow the rules for taking the drug indicated in the section Skipping a pill. If a woman does not want to change her usual dosing schedule, she will need to take additional tablet(s) from a different package.
How to change the timing of withdrawal bleeding. To delay the day of the onset of menstruation, a woman should continue to take Midiana tablets from a new package and not take a break from taking the drug. If desired, the period of administration can be continued until the end of the second package. In this case, breakthrough bleeding or spotting may be noted. The usual use of the drug Midiana is restored after a 7-day break from taking tablets.
To shift the onset of menstruation to another day of the week, it is recommended to shorten the break in taking pills by as many days as desired. It should be noted that the shorter the break, the more often there will be no menstrual-like and breakthrough bleeding or spotting while taking tablets from the second package (as in the case of a delay in the onset of menstruation).
Overdose with Midiana
To date, there is no data on a combined overdose of drospirenone and ethinyl estradiol.
Based on general data on the use of COCs, symptoms that may occur during an overdose are identified: nausea, vomiting, and in young girls - minor bleeding from the vagina. There is no specific antidote; treatment should be symptomatic.
Interactions of the drug Midiana with other drugs
Interactions between oral contraceptives and other drugs may result in breakthrough bleeding and/or loss of contraceptive effectiveness.
Hepatic metabolism: interactions may occur with drugs that induce microsomal enzymes (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and drugs containing St. John's wort Hypericum perforatum), which may cause an increase in the clearance of sex hormones.
Enterohepatic circulation: It is possible that the enterohepatic circulation of estrogens may be decreased by certain antibiotics that may decrease ethinyl estradiol concentrations (e.g. penicillin and tetracycline antibiotics).
When treated with any of the above drugs, a woman should temporarily use a barrier method in addition to taking COCs or choose another method of contraception. When treating with drugs that induce microsomal enzymes, the barrier method should be used throughout the entire period of treatment with the corresponding drug and for another 28 days after stopping its use. When treating with an antibiotic (with the exception of rifampicin and griseofulvin), the barrier method should be used for another 7 days after its discontinuation. If the barrier method is still being used and the tablets in the CCP package have already run out, taking the tablets from the next package should be started without the usual break.
The main metabolites of drospirenone in blood plasma are formed without the participation of the cytochrome P450 system. Therefore, it is unlikely that inhibitors of this enzyme system affect the metabolism of drospirenone.
The influence of Midiana on other drugs. Oral contraceptives may affect the metabolism of other drugs. Taking this into account, they can change the concentration active ingredients in plasma and tissues - both increase (for example, cyclosporine) and decrease (for example, lamotrigine).
Based on in vitro inhibition and in vivo interaction in female volunteers taking omeprazole, simvastatin and midazolam as tracer substrates, an effect of drospirenone 3 mg on the metabolism of other drugs is unlikely.
Other interactions. In patients with renal failure, simultaneous administration of drospirenone and ACE inhibitors or NSAIDs does not have a significant effect on serum potassium levels. However, the simultaneous use of Midiana 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 blood serum during the first cycle of taking the drug. See also SPECIAL INSTRUCTIONS.
Note: To determine the potential for interaction with drugs that are simultaneously prescribed with COCs, it is recommended that you read the instructions for medical use these drugs.
Laboratory research. Taking contraceptives may affect the results of certain laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, as well as levels of transport proteins in the blood plasma, such as corticosteroid binding globulin and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis. Changes usually occur within laboratory limits.
Due to its slight antimineralocorticoid activity, drospirenone increases the activity of plasma renin and aldosterone.
Special instructions when taking Midiana
If any of the following conditions/risk factors are present, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of the following conditions or risk factors worsen, or occur for the first time, a woman is advised to consult a doctor, who may decide whether to discontinue the drug.
Circulatory system disorders
The incidence of venous and arterial thrombotic and thromboembolic diseases in women without risk factors who took COCs with a low dose of estrogen (<50 мкг этинилэстрадиола), такие как Мидиана, составляет примерно 20–40 случаев на 100 тыс. женщин в год. Это сравнимо с цифрами от 5 до 10 случаев на 100 тыс. женщин, не применяющих контрацептивы, и 60 случаев на 100 тыс. беременностей.
The use of any COC is associated with an increased risk of venous thromboembolism. The additional risk of venous thromboembolism is greatest during the first year of combined contraceptive use. Venous thromboembolism is fatal in 1–2% of cases.
An association has been identified between the use of COCs and an increased risk of arterial thromboembolism.
Extremely rare cases of thrombosis of other blood vessels, for example, arteries and veins of the liver, kidneys, mesenteric vessels, cerebral vessels or retina, have been described in women using combined contraceptives. The connection with the use of COCs has not been proven.
Symptoms of venous or arterial thrombotic/thromboembolic or cerebrovascular events may include:
Unilateral pain or swelling in the lower extremities;
-sudden severe chest pain with or without radiation to the left arm;
-sudden shortness of breath;
-sudden onset cough;
- any unusual, severe, prolonged headache;
-sudden partial or complete loss of vision;
-diplopia;
-speech impairment or aphasia;
-dizziness;
-loss of consciousness with or without partial epileptic seizure;
-weakness or very pronounced sudden numbness of one side or one part of the body;
-motility disorder;
acute stomach
Factors that increase the risk of venous or arterial thrombotic/thromboembolic events:
Age;
-family history (venous or arterial thromboembolism of close relatives at a relatively early age). If a hereditary predisposition is suspected, the woman needs to consult a specialist before prescribing a PDA;
-prolonged immobilization, radical surgical interventions, any surgical operations on the lower extremities or significant injuries. In these cases, it is recommended to stop using the drug (for planned operations at least 4 weeks before the operation) and not to resume taking it earlier than 2 weeks after the end of immobilization.
Additionally, it is possible to prescribe antithrombotic therapy if the pills were not stopped within the recommended time frame;
Obesity (body mass index >30 kg/m2);
-there is no consensus regarding possible role varicose veins And superficial thrombophlebitis in the development of venous thromboembolism;
- smoking (in combination with heavy smoking and increasing age, the risk increases, especially in women over 35 years old);
-dyslipoproteinemia;
-AG;
-migraine;
- heart valve diseases;
-atrial fibrillation.
The presence of one of the serious or multiple risk factors for arterial or venous disease may be a contraindication. Women using COCs should consult a doctor immediately if symptoms of possible thrombosis occur. If thrombosis is suspected or thrombosis is confirmed, COC use 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 during the postpartum period must be taken into account. Other diseases that may be associated with serious circulatory disorders 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 or its exacerbation during the use of COCs (which may be a prodromal symptom of cerebrovascular accident) may require urgent cessation of COC use.
Tumors
The most significant risk factor for developing cervical cancer is infection with the human papillomavirus. Some epidemiological studies suggest an additional increase in the risk of cervical cancer with long-term use of COCs, but this is still controversial because the extent to which the study results account for associated risk factors such as cervical smear findings and sexual behavior, including use of barrier methods of contraception.
Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women who are current or recent users of COCs is small relative to the overall risk of developing breast cancer. The research results do not provide a proven cause-and-effect relationship. The increased risk may be due to both more early diagnosis breast cancer in women using COCs, and the biological effect of COCs or a combination of two factors. There is a tendency that breast cancer detected in women who have ever taken COCs is clinically less severe than in women who have never used COCs.
In rare cases, benign, and even less often, malignant liver tumors were detected in women using COCs. In some cases, these tumors caused life-threatening intra-abdominal bleeding. In case of complaints of severe pain in the epigastric region, liver enlargement or signs of intra-abdominal bleeding, the differential diagnosis should take into account the possibility of a liver tumor in women taking COCs.
Other states
In patients with renal failure, the ability to excrete potassium may be reduced. It was found that taking drospirenone does not affect serum potassium concentrations in patients with mild to moderate renal failure. The risk of developing hyperkalemia is theoretically possible only in those patients with renal failure whose serum potassium concentration before treatment was in the upper limits of the control range and who are additionally taking potassium-sparing drugs.
Women with hypertriglyceridemia or a family history of this pathology are at risk of developing pancreatitis when using COCs.
Although slight increases in blood pressure have been described in many women taking COCs, clinical significant increase AD is an isolated phenomenon. Only in rare cases is it necessary to immediately stop taking COCs. If, during the use of a COC with pre-existing hypertension, blood pressure values are constantly elevated or a significant increase in blood pressure does not adequately respond to antihypertensive therapy, the use of the COC should be discontinued. If necessary, taking COCs can be continued if normal blood pressure values are achieved with antihypertensive therapy. The occurrence or exacerbation of the following diseases has been reported during pregnancy and with the use of COCs, but their relationship with the use of COCs has not been conclusively established: jaundice and/or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; 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 disorders liver function, it may be necessary to discontinue use of COCs until liver function tests return to normal. If cholestatic jaundice relapses, which first occurred during pregnancy or previous use of sex hormones, taking COCs should be discontinued.
Although COCs may influence peripheral insulin resistance and glucose tolerance, there are no data regarding the need to change the therapeutic regimen in women with diabetes mellitus taking low-dose COCs (containing<0,05 мг этинилэстрадиола). Однако женщины с сахарным диабетом должны быть под тщательным наблюдением врача в течение приема КПК.
Crohn's disease and ulcerative colitis may be associated with COC use.
Chloasma can sometimes occur, especially in women with a history of chloasma during pregnancy. Patients prone to chloasma should avoid exposure to direct sunlight or ultraviolet radiation while taking COCs.
This medicinal product contains 48.17 mg of lactose per tablet. Patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should take this into account.
Medical examination
Before starting to use the COC, it is necessary to carefully study the patient's medical history, including family history, and conduct a medical examination, taking into account contraindications (see CONTRAINDICATIONS) and adverse reactions (see ADVERSE REACTIONS). It is necessary that the patient carefully read the instructions for medical use and follow the recommendations indicated therein. The frequency and nature of examinations should be based on current standards of medical practice, taking into account individual circumstances.
The patient should be warned that oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced efficiency
The effectiveness of COCs may be reduced if pills are missed, gastrointestinal disorders occur, or if other medications are taken at the same time.
Cycle control
When taking COCs, you may experience intermenstrual bleeding (spotting or breakthrough bleeding), especially during the first months of using the drug. Given this, examinations for any irregular bleeding should be carried out only after a period of adaptation of the body to the drug, which is approximately 3 cycles.
If irregular bleeding continues or occurs after several normal regular cycles, non-hormonal causes should be considered and appropriate diagnostic work-up undertaken to rule out malignancy or pregnancy. These may include curettage. Some women may not experience menstrual bleeding while not taking COCs. If the COC was taken according to the instructions described in the APPLICATION section, then pregnancy is unlikely. However, if the use of the contraceptive was irregular or if there is no menstrual bleeding for 2 cycles, pregnancy must be ruled out before continuing to use the COC.
During pregnancy and breastfeeding. The drug is contraindicated for use during pregnancy. If pregnancy occurs while taking Midiana, the drug should be discontinued. However, the results of epidemiological studies do not indicate an increased risk of birth defects in children whose mothers took oral contraceptives before pregnancy, nor do they indicate the existence of a teratogenic effect when unintentionally taking oral contraceptives in early pregnancy. Such studies have not been conducted with Midiana.
Hormonal contraceptives can reduce milk production and composition, and also pass into breast milk in small amounts, so taking these drugs during breastfeeding is contraindicated.
Children. The drug is not intended for use in children.
Content
According to accepted terminology, Midiana is a contraceptive drug that prevents unwanted pregnancy. Drospirenone and ethinyl estradiol are responsible for the contraceptive, antiandrogenic and antimineralocorticosteroid properties of the drug. The medicine is produced by the Hungarian company Gedeon Richter.
Composition of Midiana
The drug Midiana is available in tablet form. Their composition:
Pharmacodynamics and pharmacokinetics
The effect of the drug is based on inhibition of ovulation and structural and functional changes in the endometrium. Midiana belongs to the combined oral contraceptives. Drospirenone has weak antimineralocorticoid and antiandrogenic effects, but does not have estrogenic, antiglucorticoid, or glucocorticoid activity.
The component is similar in action to natural progesterone. Drospirenone is not completely absorbed when taken orally, has 76% bioavailability, and binds to serum albumin. Its metabolites are represented by acidic forms, their half-life is 40 hours. Ethinyl estradiol is rapidly and completely absorbed and has 45% bioavailability.
The substance reaches its highest concentration after a few hours and is 98% bound to plasma proteins. It induces the synthesis of globulin and transcortin. Metabolic products are excreted by the kidneys and intestines in a ratio of 4:6. The half-life of excretion of ethinyl estradiol is one day, the elimination half-life is 20 hours.
Indications for use
The only indication for the use of Midiana tablets is contraception - protection against unwanted pregnancy by increasing the viscosity of cervical mucus, preventing the fertilized egg from attaching to the uterine cavity, and suppressing ovulation. The instructions list additional benefits of the drug as the elimination of edema, hormone-dependent fluid retention, weight loss, elimination of seborrhea, and acne.
How to take Midiana
Instructions for use of Midiana contain important rules for taking tablets. In conventional therapy, they are taken orally, washed down with water. You need to use the drug every day, starting from the first day of the menstrual cycle. Reception lasts three weeks, after which a week-long break is taken for the onset of menstrual-like bleeding. Other admission rules:
- When replacing the drug after using another oral contraceptive, vaginal ring or transdermal patch, you should start taking the tablets the next day after taking the previous dose or on the day you remove the used products.
- You can switch to Midiana from the mini-pill any day, on the day of removal of the implant, intrauterine contraceptive, or next injection. During the first week, additional contraception using condoms is recommended.
- After an abortion in the first trimester of pregnancy, taking the pills begins without interruption; the necessary protective measures are not required. If pregnancy is terminated in the second trimester or after the birth of a child, admission begins after 3-4 weeks. If the interval is longer, weekly protection with barrier contraceptives is required.
- If you miss a pill for up to 12 hours, contraceptive protection is reduced, so you need to take the missed dose as early as possible and continue taking it according to the regimen. If you miss it for 12 hours or more, follow the rules: discontinuation of use does not last more than a week; to achieve adequate suppression of ovarian function, regulated by the pituitary gland and hypothalamus, seven days of continuous use of the drug are required.
- In the first week of the cycle, if a dose is missed, take it as soon as possible, you can even take 2 at the same time. Then the medicine is taken according to the standard regimen, but the woman must take additional protection during the week. In the second week of the cycle, the missed dose is taken as soon as possible. If more than one tablet is missed, sexual intercourse should be accompanied by the use of a condom. In the third week of the cycle, missing a dose threatens to reduce contraceptive protection to a greater extent than in the first or second. To circumvent this risk, you need to take a dose as soon as possible and, after finishing the package, start a new one without stopping for menstruation. During this, breakthrough or spotting bleeding may occur. The second option: stop taking the pills, wait for bleeding, then continue taking a new package.
- To delay bleeding, you do not need to take breaks in taking the drug. The delay lasts until the end of the second package, after which it is necessary to take a “rest”. Bleeding may occur while taking the second pack. To postpone the start of menstruation to another day, you need to shorten the break by the required number of days.
- If taking Midiana is accompanied by vomiting or diarrhea, then the active substances may not be completely absorbed. If a woman vomits 3-4 hours after taking the pills, then she needs to take a new one as soon as possible, and the next one within 12 hours after the prescribed time. In case of vomiting that occurred more than 12 hours ago from the moment of taking the tablet, follow the rules of standard use. If there are no changes, take an additional one or more doses from the next pack.
special instructions
It is useful to study the special instructions section in the instructions for use. It says:
- When treating with active substances that affect microsomal liver enzymes, non-hormonal contraceptives are used for a month after their discontinuation.
- If the concomitant drug is taken at the end of taking the Midiana package, the next pack of tablets is taken without a week's break.
- When combining the drug with antibiotics (except Grzeofulvin, Rifampicin), it is necessary to temporarily resort to additional protective measures for a week after their discontinuation.
During pregnancy
The instructions prohibit the use of Midiana tablets during pregnancy and lactation. If conception occurs while using contraceptives, immediate discontinuation of the drug is recommended. It is known that there is no teratogenic effect on the fetus and the woman during pregnancy and while taking the drug, but there is a risk. Penetrating into breast milk, the active components of the medication can adversely affect the baby.
In childhood
The drug is prohibited for use by persons under puberty and adulthood. This limitation is associated with unstable hormonal levels in patients under 18 years of age, and the risk of impaired development of the body and reproductive system. It is prohibited to treat acne in adolescents under 18 years of age with contraceptive pills. Only a gynecologist can prescribe the drug based on blood tests and medical history.
Midiana and alcohol
Drinking alcohol while taking Midiana does not affect the functioning of hormones, but ethanol acts on the liver, where their metabolism occurs. Alcoholic drinks speed up the liver and affect the production of enzymes and hormones. Under the influence of ethyl alcohol, the duration of the tablet is reduced and the contraceptive function is reduced. It is safe to drink no more than a glass of wine, a glass of whiskey, vodka, or a bottle of beer no more than twice a week.
Drug interactions
The instructions for use of Midiana talk about drug interactions with other drugs. Some combinations are undesirable:
- Barbiturates, Phenytoin, Ritonavir, Carbamazepine, Rifampicin, Griseofulvin, St. John's wort preparations, and HIV protease inhibitors can reduce the effect of the tablets.
- Nevirapine, when combined with Midiana, negatively affects the metabolism of the liver and thyroid gland.
- Penicillins, tetracyclines, and iron supplements can reduce the concentration of ethinyl estradiol.
- Cyclosporine increases the plasma level of Midiana, while Lamotrigine decreases it.
- The combination of tablets with Renin leads to an increase in the activity of the latter and an increase in the concentration of the mineralocorticosteroid hormone aldosterone.
- Taking the drug may affect the readings of laboratory tests, biochemical parameters of the adrenal glands, liver, kidneys, the concentration of transport plasma proteins, lipid and lipoprotein fractions.
Side effects of Midiana
Midiana is well tolerated. side effects may develop in the first days of treatment. According to the instructions, possible reactions are highlighted:
- headache, mood lability, depression, decreased or increased libido;
- menstrual irregularities, galactorrhea, intermenstrual bleeding;
- hearing loss, dry eyes;
- nausea, vomiting, abdominal pain, diarrhea;
- acne, chloasma, urticaria, eczema, erythema;
- weight loss;
- bronchospasm;
- acyclic vaginal bleeding, vaginitis, galactosemia, vaginal candidiasis.
Overdose
To date, there have been no cases of overdose with Midiana. Possible symptoms of overdose include nausea, spotting, vomiting, and vaginal bleeding. When they develop, the doctor prescribes symptomatic treatment. There is no specific antidote for exceeding the dose of the drug.
Contraindications
Midiana is prescribed with caution for obesity, controlled arterial hypertension, dyslipoproteinemia, chloasma, and the postpartum period. Contraindications, according to the instructions, are:
- hypersensitivity to the components of the composition;
- myocardial infarction, angina pectoris;
- thrombosis of veins, arteries, predisposition to their development, thromboembolism, embolism;
- atrial fibrillation, uncontrolled hypertension, ischemic attack;
- complications of heart valves;
- prolonged immobilization after surgery;
- smoking after 35 years;
- liver tumors, kidney, liver failure;
- pancreatitis, hypertriglyceridemia;
- antithrombin deficiency;
- hormone-dependent malignant tumors;
- bleeding of unknown origin;
- migraine;
- diabetes;
- pregnancy;
- lactase deficiency.
Terms of sale and storage
Midiana is a prescription drug. Stored at temperatures up to 25 degrees for two years.
Analogs
You can find an analogue of Midiana among oral contraceptive pills with the same or similar active composition. These include:
- Yarina - tablets based on drospirenone and ethinyl estradiol;
- Simitsia - contraceptive tablet contraceptives containing ethinyl estradiol, drospirenone;
- Dailla is a medicine to prevent unwanted pregnancy based on ethinyl estradiol and drospirenone.
Midian price
The cost of the drug depends on the number of tablets in the pack, the trade markup of the pharmacy or website. Approximate prices for Midiana and its analogues in Moscow.
When taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use.
While taking combined oral contraceptives, women experienced other undesirable effects, the connection of which with taking the drugs has not been confirmed, but has not been refuted.
From the digestive system: often - nausea, abdominal pain; infrequently - vomiting, diarrhea.
From the side of the central nervous system: often - asthenic syndrome, headache, decreased mood, mood swings, nervousness; infrequently - migraine, decreased libido; rarely - increased libido.
On the part of the organ of vision: rarely - intolerance to contact lenses (unpleasant sensations when wearing them).
From the reproductive system: often - pain in the mammary glands, engorgement of the mammary glands, menstrual irregularities, vaginal candidiasis, uterine bleeding; infrequently - hypertrophy of the mammary glands; rarely - vaginal discharge, discharge from the mammary glands.
From the skin and its appendages: often - acne; uncommon - rash, urticaria; rarely - erythema nodosum, erythema multiforme.
Other: often - weight gain; infrequently - fluid retention; rarely - weight loss, hypersensitivity reactions.
As with other combined oral contraceptives, in rare cases the development of thrombosis and thromboembolism is possible.
In women with hereditary angioedema, estrogen may cause or worsen symptoms.
They didn't suit me either. But there is nowhere to go. Still alive. I've been drinking for a year
So. The 4th month of my eating midian has begun. From +, I get my periods every month (they didn’t happen at all. Moreover, the ultrasound is excellent, hormones are normal, well, that’s how special I am), from -, I have gained weight, especially my sides. There is nervousness. What jumped up somewhere, it seems to me that I am dying. My hair is falling out. And every time I sneeze, I get sick. There is no immunity. And it seems like nothing. Drink for another 3 months. I'm tired, honestly. The stomach and intestines don’t say thank you.
Is not a fact. I’m also all hairy, but my testosterone is normal. So there you go.
No, it won't help. I know for sure. I've been taking these pills for a year now.
I used to take other OCs, and they started giving me problems with my skin and excess weight. On the doctor’s advice, I started taking Midiana tablets and took a course of Lavita vitamins to remove the effect of the previous OCs. I’ve been drinking for two months and I’m already seeing improvements, I’ve finally managed to lose weight and have a pimple-free face.
I've been drinking Median for 1.5 years now. Everything is just super, my period lasts 3 days, but it was 5-6, but this is just normal, my periods become less heavy when I take OK. The breasts have increased. The desire for sex has not disappeared at all, as happens to many. I also take Lavita vitamins; my gynecologist advised me to take them while taking OK. The package lasts for a month. I drink it in the morning, after breakfast, and in the afternoon I take a Median tablet. Facial skin and hair have become much better!!!
I took Midiana for 5 months - everything was fine, they helped me well. During the first cycle, only my lower abdomen ached a little - the doctor said that everything was fine. Face and hair have become better. When the time came to give them up, it was a pity - I started seeing pimples on my face again)
I was very worried that taking OK would make me gain weight, but now I can say that I’m not fat anyway and taking OK doesn’t affect my weight in any way. I have Midiana, I found out about the pills not so long ago, but I started taking them because the doctor said they would also help with the skin. And indeed, the face is now much cleaner, and the protection is normal, there is no unplanned pregnancy. And most importantly, my husband is not nervous about having to think about how to protect himself.
The gynecologist prescribed me Midiana to regulate my cycle. I took these pills for half a year and then took a break. The cycle returned to normal and the pain in the lower abdomen during menstruation went away. As a contraceptive, median is very effective, and the price is right for me, not expensive. Cheaper than Yarina.
A combined oral contraceptive drug containing ethinyl estradiol and drospirenone. The contraceptive effect is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in the endometrium.
At a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid properties. Does not have 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 when using combined oral contraceptives.
Pharmacokinetics
Drospirenone
Suction
When taken orally, drospirenone is rapidly and almost completely absorbed. Cmax of the active substance in serum, equal to 37 ng/ml, is achieved 1-2 hours after a single dose. Bioavailability ranges from 76% to 85%. Food intake does not affect the bioavailability of drospirenone.
Distribution
During one cycle of administration, the C ss max of drospirenone in the serum is about 60 ng/ml and is achieved after 7-14 hours. A 2-3-fold increase in the concentration of drospirenone is noted. 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.
After oral administration, a biphasic decrease in the concentration of drospirenone in the serum is observed, which is characterized by T 1/2 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 ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to serum proteins.
The average apparent Vd is 3.7±1.2 l/kg.
Metabolism
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 in vitro studies, drospirenone is metabolized with little participation of cytochrome P450.
Removal
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. T1/2 for excretion of metabolites by the kidneys and through the intestines is approximately 40 hours.
Pharmacokinetics in special clinical situations
C ss of drospirenone in serum in women with mild renal failure(CrCl 50-80 ml/min) was comparable to that in women with normal function kidneys (creatinine clearance > 80 ml/min). Serum drospirenone concentrations were on average 37% higher in women with moderate renal impairment (creatinine clearance 30-50 ml/min) compared with those in women with normal renal function. Drospirenone therapy was well tolerated by women with mild to moderate renal impairment.
Drospirenone treatment did not have a clinically significant effect on serum potassium concentrations.
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 Cmax values 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 (Cl/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 simultaneous treatment spironolactone (two factors that can precipitate hyperkalemia in the patient), there was no increase in serum potassium concentration above the ULN. It can be concluded that the combination of drospirenone/ethinyl estradiol is well tolerated in patients with moderate hepatic impairment (Child-Pugh class B).
Ethinyl estradiol
Suction
Ethinyl estradiol is rapidly and completely absorbed after oral administration. Cmax after a single dose of 30 mcg is achieved after 1-2 hours and is about 100 pg/ml. Ethinyl estradiol exhibits a significant first-pass effect with high individual variability. Absolute bioavailability varies and is approximately 45%.
Distribution
A state of equilibrium concentration is achieved during the second half of the treatment cycle.
The apparent V d is about 5 l/kg, the connection with blood plasma proteins is about 98%.
Ethinyl estradiol 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.
Ethinyl estradiol passes into breast milk in small quantities (approximately 0.02% of the dose).
Metabolism
Ethinyl estradiol is completely metabolized. The rate of metabolic clearance is 5 ml/min/kg.
Removal
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. T1/2 of metabolites is approximately 1 day. Elimination T1/2 is 20 hours.
Release form
White or almost white film-coated tablets white, round, biconvex, with "G63" engraving on one side; on a cross section, white or almost white.
Excipients: 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.
Film shell composition: 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).
21 pcs. - blisters (1) - cardboard packs.
21 pcs. - blisters (3) - cardboard packs.
Dosage
The tablets must be taken every day at approximately the same time, if necessary, with a small amount of liquid, in the sequence indicated on the blister pack. It is necessary to take 1 tablet/day for 21 days in a row. 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.
If hormonal contraceptives have not been used previously (in the last month), taking combined oral contraceptives begins on the 1st day of a woman’s natural menstrual cycle (that is, on the 1st day of menstrual bleeding).
If replacing another combined oral contraceptive, vaginal ring or transdermal patch, it is preferable to start taking Midiana ® the day after taking the last active tablet of the previous combined oral contraceptive; in such cases, taking Midiana ® should not be started later than the next day after the usual tablet-free interval or inactive tablets of the previous combined oral contraceptive. When replacing a vaginal ring or transdermal patch, it is advisable to start taking the oral contraceptive Midiana ® on the day the previous drug is removed; in such cases, taking Midiana ® should begin no later than the day of the planned replacement procedure.
In the case of changing the method using only progestins (mini-pills, injectable forms, implants) or progestin-releasing intrauterine devices: a woman can switch from the mini-pill on any day (from an implant or intrauterine contraceptive - on the day of its removal, from an injectable form - from the day when the next injection was due). 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, a 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 the 21-28th day 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. In case of sexual intercourse, pregnancy must 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 the delay in taking the pills is more than 12 hours, contraceptive protection may be reduced. Tactics when skipping a drug dose are based on the following two rules:
1) taking pills should not be stopped for more than 7 days;
2) to achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous pill use are necessary.
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.
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 contraception. However, if she has missed more than 1 tablet, additional contraceptive measures must be used for the next 7 days.
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, you will not need additional methods of contraception if you have taken all your 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, there will be no withdrawal bleeding until the end of the second pack, but spotting or breakthrough uterine bleeding may occur on the 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.
Gastrointestinal disorders
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. If possible, the new tablet 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 specified in the section “Taking missed tablets.”
If the patient does not want to change the normal regimen of taking the drug, she must take an additional tablet (or several tablets) from a different package.
How to Delay Withdrawal Bleeding
To delay the onset of withdrawal bleeding, you must continue taking 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 Midiana ® from a new pack after the usual 7-day break. To move the day of the onset 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).
Overdose
There is no information about an overdose of drospirenone and ethinyl estradiol. However, nausea, vomiting and spotting/bleeding from the vagina may occur.
Treatment: there is no specific antidote. Symptomatic treatment should be carried out.
Interaction
Interactions between oral contraceptives and other drugs may result in breakthrough uterine bleeding and/or decreased contraceptive reliability. The following types of interaction are described in the literature.
Effect on liver metabolism
Some drugs (phenytoin, barbiturates, primidone, carbamazepine and rifampicin) due to the induction of microsomal enzymes can increase the clearance of sex hormones. Possibly the same effect of oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal remedy based on St. John's wort.
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 concomitant use with certain antibiotics, such as penicillins and tetracyclines, reduces the enterohepatic recirculation of estrogens, which may lead to a decrease in ethinyl estradiol concentrations.
Women taking any of the above 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 rifampicin 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 taking 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 Midiana ® on 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, cyclosporine) and decrease (for example, lamotrigine).
Based on the results of in vitro inhibition studies and in vivo interaction studies in female volunteers taking omeprazole, simvastatin and midazolam as tracer substrates, an effect of drospirenone 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: ACE inhibitors, angiotensin II receptor antagonists, some NSAIDs (for example, indomethacin), potassium-sparing diuretics and aldosterone antagonists. However, in a study evaluating the interaction of an ACE inhibitor with the combination of drospirenone + ethinyl estradiol in women with moderate hypertension, there was no significant difference between serum potassium concentrations in women receiving enalapril 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.
Side effects
The following adverse reactions have been reported during concomitant use of drospirenone and ethinyl estradiol:
| Organ systems | Frequency | ||
| Often (≥1/100,<1/10) | Uncommon (≥1/1000,<1/100) | Rarely (≥10,000,<1000) | |
| From the nervous system | headache, emotional lability, depression | decreased libido | increased libido |
| From the endocrine system | menstrual irregularities, intermenstrual bleeding, pain in the mammary glands | discharge from the mammary glands | |
| From the senses | hearing loss, poor tolerance to contact lenses |
||
| From the digestive system | nausea, abdominal pain | vomiting, diarrhea | |
| From the skin and subcutaneous tissue | acne, eczema, skin rash, hives, erythema nodosum, erythema multiforme, itching, chloasma, especially if there is a history of pregnancy chloasma | ||
| From the cardiovascular system | migraine | increase or decrease in blood pressure | thrombosis (venous and arterial), thromboembolism |
| Systemic disorders | weight gain | fluid retention | weight loss |
| From the immune system | bronchospasm | ||
| From the reproductive system and mammary glands | acyclic vaginal bleeding (spotting or breakthrough uterine bleeding), engorgement, soreness, enlargement of the mammary glands, vaginal candidiasis | vaginitis | discharge from the mammary glands, increased vaginal discharge |
Indications
- contraception.
Contraindications
Midiana ® 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);
- 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;
- major surgery with prolonged immobilization;
- smoking over the age of 35;
- 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, incl. history, if severe hypertriglyceridemia was noted;
- severe liver disease (before normalization of liver tests) currently or in history;
- 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 (genital organs, mammary glands) or suspicion of them;
- bleeding from the vagina of unknown origin;
- migraine with a history of focal neurological symptoms;
- hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- pregnancy or suspicion of it;
- lactation period;
- hypersensitivity to the drug or any of its components.
Carefully:
- risk factors for the development of thrombosis and thromboembolism (smoking under 35 years of age, obesity);
- dyslipoproteinemia;
- controlled arterial hypertension;
- migraine without focal neurological symptoms;
- uncomplicated heart valve defects;
- hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate family);
- diseases in which peripheral circulatory disorders may occur (diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of the superficial veins);
- hereditary angioedema;
- hypertriglyceridemia;
- liver diseases;
- 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 disease), chloasma, postpartum period).
Features of application
Use during pregnancy and breastfeeding
During pregnancy and lactation, the use of Midiana ® is contraindicated. If pregnancy occurs while taking hormonal contraception, immediate discontinuation of the drug is necessary.
The limited available data on unintentional use of combined oral contraceptives suggests no teratogenic effect and an increased risk for children and women during childbirth.
Combined oral contraceptives affect lactation and 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 may affect the baby. The use of combined oral contraceptives is possible after complete cessation of breastfeeding.
special instructions
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 it is necessary to discontinue the combined oral contraceptive.
Circulatory system disorders
Incidence of venous thromboembolism (VTE) when using low-dose estrogen combined oral contraceptives (< 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).
An additional risk of VTE is observed during the first year of combined oral contraceptive use. VTE is fatal in 1-2% of cases.
Epidemiological studies have also found an association between combined oral contraceptive use 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 patients taking 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, 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 very significant loss of sensation that suddenly appeared on one side or in one part of the body;
- movement disorders;
- symptom complex "acute abdomen".
The risk of complications associated with VTE when taking a combined oral contraceptive increases:
- with age;
- in the presence of 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 (BMI more than 30 mg/m2).
The risk of arterial thrombosis and thromboembolism increases when taking a 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;
- with arterial hypertension;
- for migraines;
- for diseases of the heart valves;
- with atrial fibrillation.
The presence of one serious risk factor or multiple risk factors for arterial or venous disease, respectively, may be a contraindication.
Women using combined oral contraceptives should contact their doctor immediately 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.
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, the increase in breast cancer diagnosed in recent years in women taking or taking combined oral contraceptives 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 tumors in women who had ever taken combined oral contraceptives were 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. In the differential diagnosis of a liver tumor, it should be taken into account when a woman taking combined oral contraceptives experiences 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 for ULN, as well as during concomitant use of drugs that retain potassium in the body.
In women with hypertriglyceridemia or a family history of hypertriglyceridemia, an increased risk of pancreatitis cannot be excluded when taking combined oral contraceptives. Although slight 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 use of combined oral contraceptives should be stopped. 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; Sydenham's 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, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (containing< 50 мкг 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 exposure to the sun and ultraviolet radiation while taking combined oral contraceptives.
1 tablet contains 48.17 mg of lactose. 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
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.
STDs and HIV infection
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 disorders occur, or if 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 3 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 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 previously been taken regularly or if there are no consecutive withdrawal bleeds, pregnancy should be ruled out before continuing to take combined oral contraceptives.
Impact on the ability to drive vehicles and operate machinery
There have been no studies examining the effect of the drug on driving ability.
