Certificate of conformity (COC) Midiana, pills, 21pcs

Midiana, pills, 21pcs

$79.0

Active ingredient:	Drospirenone, Ethinylestradiol
Dosage form:	Pills
Indications for use:	Contraception

Add to wishlist

Categories: Contraceptive, Medication, Obstetrics, gynecology

Description
Reviews (0)

Composition

Active ingredients:

ethinyl estradiol 30 mcg,

drospirenone 3 mg,

Auxiliary substances:

lactose monohydrate,

corn starch, pregelatinized corn starch,

povidone K 25,

magnesium stearate,

Shell:

Opadray II white 85G18490 (polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, soy lecithin).

Pharmacological action

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

Midiana® is a combined oral contraceptive containing ethinyl estradiol and drospirenone. In a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid properties. It lacks any estrogenic, glucocorticoid, or anti-glucocorticoid activity. This provides drospirenone with a pharmacological profile similar to natural progesterone.

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

Pharmacokinetics

Drospirenone

Suction. When taken orally, drospirenone is rapidly and almost completely absorbed. C_max active substance in serum — 37 ng / ml, T_max-1-2 hours after a single dose. During the first cycle of use, the maximum C_ss of drospirenone in serum is about 60 ng / ml and is reached in 7-14 hours. Bioavailability ranges from 76 to 85%. Food intake does not affect the bioavailability of drospirenone.

Distribution. After oral use, a two-phase decrease in serum drospirenone concentration is observed, which is characterized by T_1/2 (1.6±0.7) and (27±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 ingredient is a free hormone. Ethinylestradiol-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.

Biotransformation. After oral use, drospirenone undergoes significant metabolism. Most of the metabolites in plasma are acidic 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 involvement of cytochrome P450.

Elimination. The rate of metabolic clearance of drospirenone in serum is (1.5±0.2) ml / min / kg. Drospirenone is only excreted in trace amounts in unchanged form. Drospirenone metabolites are excreted by the kidneys and through the intestines in a ratio of approximately 1.2: 1.4. T_1/2 during excretion of metabolites by the kidneys and through the intestines is approximately 40 hours.

C_ss. During the first treatment cycle, the maximum C_ss (approximately 60 ng / ml) of drospirenone in serum is reached after 7-14 hours. There is a 2-3-fold increase in the concentration of drospirenone. A further increase in the serum concentration of drospirenone is observed after 1-6 cycles of use, after which an increase in the concentration is not observed.

Ethinyl Estradiol

Suction. Ethinyl estradiol is rapidly and completely absorbed after oral use. _Cmax after a single dose of 30 mcg — about 100 pg / ml, Tmax-1-2 hours. For ethinyl estradiol, a significant first-pass effect is expressed with high individual variability. Absolute bioavailability varies and is approximately 45%.

Distribution. The apparent Vd is about 5 l / kg, and the binding to plasma proteins is about 98%. Ethinyl estradiol induces the synthesis of SHBG and transcortin in the liver. With a daily intake of 30 micrograms of ethinyl estradiol, the plasma concentration of SHBG increases from 70 to about 350 nmol/l. Ethinyl estradiol passes into breast milk in small amounts (approximately 0.02% of the dose).

Biotransformation. Ethinyl Estradiol is completely metabolized. The metabolic clearance rate is 5 ml/min/kg.

Elimination. Ethinyl estradiol is practically not excreted unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4: 6. T_1/2 for the excretion of metabolites is approximately 1 day. The elimination T_1/2 is 20 hours.

C_ss. The C_ss condition is reached during the 2nd half of the treatment cycle.

Certain categories of the population

Effect on kidney function. The C_ss of drospirenone in serum in women with mild renal insufficiency (creatinine clearance 50-80 ml / min) was comparable to that in women with normal renal function (creatinine clearance >80 ml/min). The average serum drospirenone concentration was 37% higher in women with moderate renal insufficiency (creatinine clearance 30-50 ml / min) than in women with normal renal function. Drospirenone therapy was well tolerated in women with mild to moderate renal insufficiency.

Drospirenone treatment did not have a clinically significant effect on serum potassium concentrations.

Effect on liver function. In women with moderate hepatic insufficiency (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. At the end of the distribution phase, the reduction in drospirenone concentration was approximately 1.8 times higher in subjects with moderate hepatic impairment compared to people with normal liver function.

After a single dose, the total clearance of volunteers with moderate hepatic insufficiency was reduced by about 50% compared to people with normal liver function.

The observed decrease in drospirenone clearance in volunteers with moderate hepatic insufficiency does not lead to any significant differences in serum potassium concentrations. Even with diabetes mellitus and concomitant treatment with spironolactone (two factors that can provoke hyperkalemia in a patient), there was no increase in serum potassium concentrations above the ULN.

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

Indications

Pregnancy prevention.

Use during pregnancy and lactation

During pregnancy and lactation, the use of Midiana is contraindicated. If pregnancy occurs against the background of hormonal contraception, immediate withdrawal of the drug is necessary.

The few available data on unintentional use of combined oral contraceptives indicate that there is no teratogenic effect and an increased risk for children and women during childbirth.

Combined oral contraceptives affect lactation, can reduce the amount and change the composition of breast milk. Small amounts of hormonal contraceptives or their metabolites are found in milk during hormonal contraception and can affect the baby.

The use of combined oral contraceptives is possible after complete cessation of breastfeeding.

Contraindications

Midiana®Preparation it should not be assigned 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 withdrawal is required.

hypersensitivity to the drug or any component;
the presence of venous thrombosis in the present or history (deep venous thrombosis, pulmonary embolism);
the presence of thrombosis of the arteries in the present or in history (e. g. myocardial infarction);
the harbingers of thrombosis (including transient ischemic attack, angina), including in the anamnesis;
complicated lesions of valvular apparatus of the heart, atrial fibrillation, uncontrolled hypertension;
major surgery with prolonged immobilization;
the Smoking age 35 years;
liver failure;
cerebrovascular disease currently or in history;
the presence of a severe or multiple risk factors for arterial thrombosis (diabetes with vascular complications, severe hypertension, severe dislipoproteinemia);
hereditary or acquired predisposition for venous or arterial thrombosis, such as resistance to activated protein C, antithrombin III deficiency, deficiency of protein C, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant);
pancreatitis, including history, if pronounced hypertriglyceridemia;
severe liver disease at present or in history (up to the normalization of liver tests);
severe chronic renal insufficiency or acute renal failure;
liver tumors (benign or malignant) at present or in the anamnesis;
hormone-dependent malignant diseases of the reproductive system (genitals, mammary glands) or suspected of them;
vaginal bleeding of unknown origin;
migraine with a history of focal neurological symptoms;
pregnancy or suspected of it;
lactation period;
hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption.

With caution: risk factors for thrombosis and thromboembolism — smoking under 35 years of age, obesity, dyslipoproteinemia, controlled arterial hypertension, migraines without focal neurological symptoms, uncomplicated heart valve defects, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebral circulation disorders at a young age in one of the closest relatives); diseases in which peripheral circulatory disorders may occur-diabetes mellitus diabetes, systemic lupus erythematosus (SLE), hemolytic — uremic syndrome, Crohn’s disease, ulcerative colitis, sickle cell anemia, superficial venous phlebitis; hereditary angioedema; hypertriglyceridemia; liver diseases; diseases that first occurred or worsened during pregnancy or against the background of previous use of sex hormones (including jaundice and/or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in the anamnesis, small chorea-Sydenham’s disease); chloasma; postpartum period.

Side effects

When taking combined oral contraceptives, irregular bleeding (spotting spotting or breakthrough bleeding) may occur, especially during the first months of use.

While taking combined oral contraceptives in women, other undesirable effects were observed, the relationship of which with the use of drugs is not confirmed, but it is 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. From the side of the visual organ: rarely – intolerance to contact lenses (unpleasant sensations when wearing them). From the side of the reproductive system: often-breast pain, breast engorgement, menstrual irregularities, vaginal candidiasis, uterine bleeding; infrequently-hypertrophy of the mammary glands; rarely-vaginal discharge, discharge from the mammary glands. From the side of the skin and its appendages: often – acne; infrequently-rash, urticaria; rarely-erythema nodosum, erythema multiforme. Other services: often-weight gain; infrequently-fluid retention; rarely-weight loss, hypersensitivity reactions.

As with other combined oral contraceptives, thrombosis and thromboembolism may occur in rare cases. In women with hereditary angioedema, taking oestrogens may cause or worsen its symptoms.

Interaction

Interactions between oral contraceptives and other medications may lead to breakthrough uterine bleeding and / or reduced contraceptive reliability. The following types of interaction are described in the literature.

Effect on liver metabolism

Some drugs (phenytoin, barbiturates, primidone, carbamazepine, and rifampicin) can increase the clearance of sex hormones due to the induction of microsomal enzymes. The same effect of oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and a herbal remedy based on St. John’s wort is possible.

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

Effect on intestinal-hepatic recirculation

Clinical observations show that concomitant use with certain antibiotics, such as penicillins and tetracyclines, reduces the intestinal-hepatic recycling of estrogens, which can lead to a decrease in the concentration of ethinyl estradiol.

Women taking any of the above-mentioned medications 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 should additionally use a non-hormonal method of contraception within 28 days after their withdrawal. 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 its withdrawal. If concomitant use of the drug is initiated at the end of taking a package of Midian, the next package should be started without the usual break in reception. The main metabolism of drospirenone in human plasma is carried out without the involvement of the cytochrome P450 system. Inhibitors of this enzyme system, therefore, do not affect the metabolism of drospirenone.

Effect of Midian on other medicinal products

Oral contraceptives can affect the metabolism of other medications. 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 indicator substrates, the effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.

Other interactions

There is a theoretical possibility of increasing the concentration of serum potassium in women receiving oral contraceptives simultaneously with other drugs that increase the concentration of potassium in the blood serum: ACE inhibitors, angiotensin II receptor antagonists, some NSAIDs (for example, Indometacin), potassium-sparing diuretics and aldosterone antagonists. However, in a study evaluating the interaction of an ACE inhibitor with a combination of drospirenone+ethinyl estradiol in women with moderate arterial hypertension, there was no significant difference between serum potassium concentrations in women treated with enalapril and placebo.

Laboratory tests

The use of hormonal contraceptives can affect the results of individual laboratory tests, including biochemical parameters 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 clotting and fibrinolysis. Changes usually occur within the limits of laboratory standards.

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

How to take, course of use and dosage

Tablets should 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 consecutive days. Taking tablets from each subsequent package should begin after a 7-day interval in taking tablets, during which menstrual-like bleeding usually occurs. It usually begins 2-3 days after taking the last pill and may not end by the time the next package starts.

If hormonal contraceptives have not been used before (in the last month), combined oral contraceptives are taken on the 1st day of a woman’s natural menstrual cycle (i. e., on the 1st day of menstrual bleeding).

In case of replacement of 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, Midiana should not start later than the next day after the usual break in taking tablets or taking inactive tablets of her previous combined oral contraceptive. When replacing a vaginal ring or transdermal patch, it is advisable to start taking the Midian oral contraceptive on the day of removal of the previous drug; in such cases, the Midian drug should start no later than the day of the intended replacement procedure.

If the method is replaced with only progestins (mini-pills, injectable forms, implants) or intrauterine contraceptives with the release of progestins: a woman can switch from mini-pills on any day (from the implant or intrauterine contraceptive-on the day of its removal, from the injectable form-from the day when the next injection was supposed to be made). 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 medication immediately. If this condition is met, there is no need for additional contraceptive measures.

After giving birth or terminating pregnancy in the second trimester, it is advisable for a woman to start taking Midiana on the 21st-28th day after giving birth or terminating pregnancy in the second trimester. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.In case of sexual contact before taking the drug, pregnancy should be excluded or it is necessary to wait for the first menstruation.

Taking missed pills

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

If the delay in taking pills is more than 12 hours, the contraceptive protection may be reduced. Tactics for skipping medication are based on the following two rules::

1) the use of tablets should not be stopped for more than 7 days;

2) to achieve adequate suppression of the hypothalamic-pituitary-ovarian system,7 days of continuous tablet use are necessary.

Week 1

Take the last missed pill as soon as possible, even if it means taking two pills at the same time. The next tablet is taken at the usual time. Additionally, a barrier method of contraception should be used for the next 7 days. If sexual contact took place within 7 days before skipping the pill, it is necessary to take into account the probability of pregnancy. The more pills you skip and the closer that skip is to the 7-day break from taking the drug, the higher the risk of pregnancy.

Week 2

Take the last missed pill as soon as possible, even if it means taking two pills at the same time. The next tablet is taken at the usual time. If a woman has taken the pills correctly for the previous 7 days, there is no need to use additional contraceptives. However, if she missed more than 1 pill, additional contraception measures should be used in the next 7 days.

Week 3

The probability of reducing the contraceptive effect is significant due to the upcoming 7-day break in taking pills. However, by adjusting the schedule of 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 the woman took all the pills correctly during the previous 7 days before skipping the pill. If this is not the case, she should follow the first of the two methods and also use additional contraceptive measures for the next 7 days.

1. Take the last missed pill as soon as possible, even if it 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 is finished, that is, without a break between taking two packages. Most likely, withdrawal bleeding will not occur until the end of the second package, but there may be spotting spotting or breakthrough uterine bleeding on the days of taking the pills.

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

If you miss taking pills and there is no withdrawal bleeding during the first free interval from taking the drug, you should exclude pregnancy.

Gastrointestinal disorders

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

In case of vomiting within 3-4 hours after taking the tablet, you should take a new replacement tablet as soon as possible. If possible, a new tablet should be taken within 12 hours after the usual intake time. If you have missed more than 12 hours, if possible, follow the rules for taking the drug specified in the section “Taking missed pills”.

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

How to delay withdrawal bleeding

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

During the lengthening of the cycle, spotting spotting from the vagina or breakthrough uterine bleeding may occur. Resume taking the drug Midiana from a new pack should be after the usual 7-day break. To move the day of the start of withdrawal bleeding to another day of the week of the usual schedule, you should shorten the next break in taking pills for as many days as necessary. The shorter the interval, the higher the risk that withdrawal bleeding will not occur, and while taking tablets from the second package, spotting spotting and breakthrough uterine bleeding will occur (as well as in the case of delaying the onset of withdrawal bleeding).

Overdose

There are no reports of 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 performed.

Special instructions

If any of the conditions / risk factors listed below are currently present, then the potential risk and expected benefit of using a combined oral contraceptive should be carefully weighed on a case-by-case basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors become more severe, worsen, or first appear, a woman should consult with her doctor, who may decide whether to discontinue the combined oral contraceptive.

Circulatory disorders

Frequency of venous thromboembolism (VTE) when using a combined oral contraceptive with a low dose of estrogens (

An additional risk of VTE is noted during the first year of using a combined oral contraceptive. VTE is fatal in 1-2% of cases.

Epidemiological studies have also found an association between the use of a combined oral contraceptive and an increased risk of arterial thromboembolism. Extremely rare cases of thrombosis of other blood vessels, for example, hepatic, mesenteric, renal, brain and retinal vessels, both arteries and veins, have been described in patients taking oral hormonal contraceptives. A causal relationship between the occurrence of these side effects and the use of combined oral contraceptives has not been proven.

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

— unusual unilateral pain and/or swelling of the extremities;

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

sudden breathlessness;

sudden onset 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 convulsive seizure;

— weakness or very significant loss of sensitivity suddenly appeared from one side or in one part of the body;

movement disorders;

— a symptom of “acute abdomen”.

The risk of VTE-related complications increases when taking a combined oral contraceptive. :

— with age;

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

— after prolonged immobilization, serious surgery, any foot surgery or extensive injury. In these situations, it is recommended to stop taking the drug (in the case of elective surgery, at least four weeks before it) and 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—

– if you are obese (BMI more than 30 mg / m%^%2).

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—

– with migraines

— – with heart valve diseases

— – with atrial fibrillation.

The presence of one of the major risk factors or multiple risk factors for arterial or venous disease, respectively, may be a contraindication.

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

An increased risk of postpartum thromboembolism should be considered.

Other diseases that are associated with severe vascular pathology include diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), and sickle cell anemia.

An increase in the frequency and severity of migraines during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be a reason for immediate discontinuation of these drugs.

Tumors

The most significant risk factor for cervical cancer is infection with the human papillomavirus. Some epidemiological studies have reported an increased risk of developing cervical cancer with long-term use of combined oral contraceptives, but conflicting opinions remain about the extent to which these findings relate to concomitant factors, such as testing for cervical cancer or using barrier methods of contraception.

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

In rare cases, against the background of the use of combined oral contraceptives, the development of benign liver tumors was observed, and in even rarer cases, malignant ones. In some cases, these tumors caused life-threatening intra-abdominal bleeding. Differential diagnosis of a liver tumor should be considered if a woman taking combined oral contraceptives has severe upper abdominal pain, enlarged liver, or signs of intra-abdominal bleeding.

Other states

The progesterone component in Midian is an aldosterone antagonist, with the property of delaying potassium. In most cases, there is no increase in the concentration of potassium. However, in a clinical study in some patients with mild or moderate renal insufficiency and concomitant use of potassium-retaining medications, drospirenone showed a slight increase in serum potassium concentrations. Therefore, it is recommended to check the concentration of potassium in the blood serum in the first cycle of taking the drug in patients with renal insufficiency and the values of potassium concentration before treatment for ULN, as well as with the simultaneous use of drugs that retain potassium in the body.

In women with hypertriglyceridemia or a family history of hypertriglyceridemia, an increased risk of developing pancreatitis cannot be excluded while taking combined oral contraceptives. Although a small increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically significant increases have rarely been observed. Only in rare cases is it necessary to immediately stop taking combined oral contraceptives. If blood pressure values are consistently elevated or do not decrease when taking antihypertensive drugs while taking combined oral contraceptives in patients with arterial hypertension, the use of combined oral contraceptives should be discontinued. If necessary, the use of combined oral contraceptives can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions develop or worsen both during pregnancy and with combined oral contraceptives, but their association with combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham’s chorea; a history of herpes during pregnancy; hearing loss associated with otosclerosis.

In women with hereditary angioedema, exogenous estrogens may cause or increase the symptoms of angioedema. In cases of acute or chronic liver function disorders, it may be necessary to stop using combined oral contraceptives until liver function indicators return to normal. Recurrent cholestatic jaundice and / or cholestasis-induced pruritus, 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 However, women with diabetes should be carefully monitored by a doctor, especially at the beginning of taking combined oral contraceptives.

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

One 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 the use of hormonal contraceptives, it is necessary to consult with the attending gynecologist and undergo an appropriate medical examination. Further monitoring and frequency of medical examinations are carried out on an individual basis, but at least once every 6 months.

STDs and HIV infection

The drug 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 in the case of skipping pills, gastrointestinal disorders, or when taking other medications at the same time.

Reduced cycle control

While taking combined oral contraceptives, irregular bleeding (spotting spotting or breakthrough uterine bleeding) may occur, especially during the first months of use. Therefore, the assessment of any irregular bleeding is significant only after an adjustment period of approximately 3 cycles.

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

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

Influence on the ability to drive motor vehicles and manage mechanisms

Studies investigating the effect of the drug on the ability to drive a car have not been conducted.