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

Pharmacokinetics

Drospirenone

Suction

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

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

Distribution

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

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

Metabolism

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

breeding

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

Ethinylestradiol

Suction

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

Distribution

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

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

Metabolism

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

breeding

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

Pharmacokinetics in special clinical situations

In case of impaired renal function

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

In violation of liver function

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

Release form

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

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

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

placebo pills

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

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

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

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

Dosage

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

How to start taking Dimia ®

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

Switching from other combined contraceptives (combined per oral contraceptives tablet, vaginal ring, or transdermal patch)

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

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

A woman can switch from taking a mini-pill to taking Dimia ® on any day (from the implant or from the IUD on the day they are removed, from injectable forms of drugs on the day the next injection was due), but in all cases it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

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

After childbirth or abortion in the second trimester of pregnancy.

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

Taking missed pills

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

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

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

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

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

Accordingly, women can be given the following recommendations:

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

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

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

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

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

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

The use of the drug in gastrointestinal upset

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

Postponement of menstrual bleeding "withdrawal"

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

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

Overdose

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

Treatment: no antidotes. Treatment should be symptomatic.

Interaction

Influence of others medicines for Dimia ®

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

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

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

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

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

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

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

Effect of Dimia ® on other medicinal products

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

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

Other interactions

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

Laboratory tests

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

Side effects

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

Organ system class	Frequent (≥1/100 to< 1/10)	Less frequent (≥1/1000 to< 1/100)	Rare (≥ 1/10,000 to< 1/1000)
Infections and infestations			candidiasis, incl. oral cavity
From the blood and lymphatic system			anemia, thrombocytopenia
From the side of the immune system			allergic reactions
From the side of metabolism and nutrition		increase body weight	increased appetite, anorexia, hyperkalemia, hyponatremia, weight loss
From the side of the psyche	emotional lability	depression, decreased libido, nervousness, drowsiness	anorgasmia, insomnia
From the side of the nervous system	headache	dizziness, paresthesia	vertigo, tremor
From the organ of vision			conjunctivitis, dryness of the mucous membrane of the eye, visual impairment
From the side of the cardiovascular system		migraine, phlebeurysm, increase in blood pressure	tachycardia, phlebitis, vascular damage, nose bleed, fainting
From the digestive system	nausea, abdominal pain	vomit, diarrhea
From the side of the liver and biliary tract			pain in the gallbladder cholecystitis
From the skin and subcutaneous tissue		rash (including acne), itching	chloasma, eczema, alopecia, acne dermatitis, dry skin, erythema nodosum, hypertrichosis, skin lesions, skin striae, contact dermatitis, photodermatitis, skin nodules
From the musculoskeletal system		backache, limb pain, muscle cramps
From the reproductive system and mammary glands	chest pain, no withdrawal bleeding	vaginal candidiasis, pelvic pain, breast enlargement, fibrocystic breast, vaginal discharge, flushes of blood vaginitis, acyclic spotting, painful menstrual bleeding profuse bleeding "withdrawal", scanty menstrual bleeding, dryness of the vaginal mucosa, change in the cytological picture in a Pap smear	painful intercourse, vulvovaginitis, postcoital bleeding, breast cyst, breast hyperplasia, mammary cancer, cervical polyps, endometrial atrophy, ovarian cyst, uterine enlargement
Are common disorders		asthenia, increased sweating, edema (generalized edema, peripheral edema, facial edema)	feeling of discomfort

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

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

Indications

• oral contraception.

Contraindications

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

• thrombosis (arterial and venous) and thromboembolism at present or in history (including thrombosis, deep vein thrombophlebitis; pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders);
• conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history;
• multiple or pronounced risk factors for venous or arterial thrombosis, incl. complicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of the cerebral vessels or coronary arteries; uncontrolled arterial hypertension, major surgery with prolonged immobilization, smoking over the age of 35, obesity with a BMI >30 kg/m 2 ;
• hereditary or acquired predisposition to venous or arterial thrombosis, for example, resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antibodies against phospholipids (presence of antibodies to phospholipids - antibodies to cardiolipin, lupus anticoagulant);
• pancreatitis with severe hypertriglyceridemia at present or in history;
• severe chronic or acute renal failure;
• a liver tumor (benign or malignant) at present or in history;
• hormone-dependent malignant neoplasms of the genital organs or the mammary gland at present or in history;
• bleeding from the vagina of unknown origin;
• migraine with a history of focal neurological symptoms;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption, lapp lactase deficiency (lactase deficiency in some peoples of the North);
• pregnancy and suspicion of it;
• lactation period;
• hypersensitivity to the drug or any of the components of the drug.

Carefully

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

Application features

Use during pregnancy and lactation

The drug Dimia ® is contraindicated in pregnancy.

If pregnancy occurs during the use of the drug Dimia ® , it should be stopped immediately. Extended epidemiological studies have found neither an increased risk of birth defects in children born to women who took COCs before pregnancy, nor a teratogenic effect of COCs when they were inadvertently taken during pregnancy.

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

The drug Dimia ® can affect lactation: reduce the amount of milk and change its composition. Small amounts of contraceptive steroids and/or their metabolites may be excreted in milk during COC use. These amounts may affect the child. The use of Dimia ® during breastfeeding contraindicated.

Application for violations of liver function

Contraindicated:

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

Application for violations of kidney function

Contraindicated:

• severe chronic or acute renal failure

Use in children

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

special instructions

If there are any of the conditions/risk factors mentioned below, the benefits of taking COCs should be assessed individually for each woman and discussed with her before starting use. If an adverse event worsens or if any of these conditions or risk factors appear, the woman should contact her doctor. The doctor must decide whether to stop taking the COC.

Circulatory disorders

Taking any combined oral contraceptive increases the risk of venous thromboembolism (VTE). The increased risk of VTE is most pronounced in the first year of a woman's use of a combined oral contraceptive.

Epidemiological studies have shown that the incidence of VTE in women with no risk factors who took low doses of estrogen (<0.05 мг этинилэстрадиола) в составе комбинированного перорального контрацептива, составляет примерно 20 случаев на 100 000 женщин-лет (для левоноргестрелсодержащих КПК "второго поколения") или 40 случаев на 100 000 женщин-лет (для дезогестрел/гестоденсодержащих КПК "третьего поколения"). У женщин, не пользующихся КПК, случается 5-10 ВТЭ и 60 беременностей на 100 000 женщин-лет. ВТЭ фатальна в 1-2% случаев.

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

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

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

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

• unusual unilateral pain and / or swelling of the lower extremities;
• sudden severe chest pain, whether or not it radiates left hand or not;
• sudden shortness of breath;
• sudden onset of cough;
• any unusual severe prolonged headache;
• sudden partial or complete loss of vision;
• diplopia;
• impaired speech or aphasia;
• vertigo;
• collapse with or without partial epileptic seizures;
• weakness or very noticeable numbness that suddenly affects one side or one part of the body;
• movement disorders;
• symptom complex "acute" abdomen.

A woman should consult with a specialist before taking COCs.

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

• increase in age;
• hereditary predisposition (venous thromboembolism has ever happened to siblings or parents at a relatively early age);
• prolonged immobilization, advanced surgery, any surgery on the lower extremities or major trauma. In such situations, it is recommended to stop taking the drug (in the case of a planned surgical intervention, at least four weeks in advance) and not resume until two weeks after the full restoration of mobility. If the drug has not been discontinued in advance, anticoagulant treatment should be considered;
• there is no consensus on the possible role of varicose veins and superficial thrombophlebitis in the appearance or exacerbation of venous thrombosis.

The risk of arterial thromboembolic complications or acute cerebrovascular accident when taking COCs increases with:

• increase in age;
• smoking (women over 35 are strongly advised to stop smoking if they want to take COCs);
• dyslipoproteinemia;
• arterial hypertension;
• migraine without focal neurological symptoms;
• obesity (BMI over 30 kg/m2);
• hereditary predisposition (arterial thromboembolism ever in siblings or parents at a relatively early age). If a hereditary predisposition is possible, a woman should consult a specialist before taking COCs;
• damage to the heart valves;
• atrial fibrillation.

The presence of one major risk factor for venous disease or multiple risk factors for arterial disease may also be a contraindication. Anticoagulant therapy should also be considered. Women taking COCs should be properly instructed to inform their physician if symptoms of thrombosis are suspected. If thrombosis is suspected or confirmed, COC use should be discontinued. It is necessary to start adequate alternative contraception due to the teratogenicity of anticoagulant therapy (indirect anticoagulants - coumarin derivatives).

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

Other medical conditions associated with adverse vascular events include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia.

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

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

A meta-analysis of 54 epidemiological studies found a slight increase in the relative risk (RR = 1.24) of breast cancer in women who currently take COCs. The risk gradually decreases over 10 years after stopping COCs. Because breast cancer rarely develops in women under 40 years of age, an increase in the number of diagnosed cases of breast cancer in COC users has little effect on the overall likelihood of breast cancer. These studies did not find sufficient evidence of a causal relationship. The increased risk may be due to earlier diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both. Diagnosed breast cancer in women who have ever taken COCs was clinically less severe, due to the early diagnosis of the disease.

Rarely, benign liver tumors and, even more rarely, malignant liver tumors have occurred in women taking COCs. In some cases, these tumors were life-threatening due to intra-abdominal bleeding. This should be taken into account when making a differential diagnosis in case of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.

Other states

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

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

Although a slight increase in blood pressure has been observed in many women taking COCs, a clinically significant increase was rare. Only in these rare cases is immediate discontinuation of COCs warranted. If, when taking COCs in patients with concomitant arterial hypertension, blood pressure constantly increases or significantly elevated blood pressure cannot be corrected with antihypertensive drugs, COCs should be discontinued. After normalization of blood pressure with antihypertensive drugs, COCs can be resumed.

The following diseases appeared or worsened during both pregnancy and COC use, but evidence of their relationship with COC use is inconclusive: jaundice and / or itching associated with cholestasis, stones in gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; rheumatic chorea (Sydenham's chorea); herpes during pregnancy; otosclerosis with hearing loss.

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of edema.

Acute or chronic liver disease may be an indication to discontinue COC use until liver function tests return to normal. Recurrence of cholestatic jaundice and/or cholestasis-associated pruritus, which developed during a previous pregnancy or with earlier use of sex hormones, is an indication for discontinuation of COCs.

Although COCs may affect peripheral insulin resistance and glucose tolerance, changing the treatment regimen in patients with diabetes mellitus while taking low-hormone COCs (containing< 0.05 мг этинилэстрадиола) не показано. Однако следует внимательно наблюдать женщин с сахарным диабетом, особенно на ранних стадиях приема КПК.

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

Chloasma may occur from time to time, especially in women who have a history of chloasma of pregnancy. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet light while taking COCs.

Drospirenone + ethinyl estradiol coated tablets contain 48.53 mg lactose monohydrate, placebo tablets contain 37.26 mg anhydrous lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should not take this medicine.

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

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

Medical examinations

Before you start taking or re-using Dimia ®, you should collect a complete medical history (including family history) and exclude pregnancy. It is necessary to measure blood pressure, conduct a medical examination, guided by contraindications and precautions. A woman needs to be reminded of the need to carefully read the instructions for use and adhere to the recommendations indicated in it. The frequency and content of the survey should be based on existing practice guidelines. The frequency of medical examinations is individual for each woman, but should be carried out at least once every 6 months.

Women need to be reminded that oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of the COC may decrease, for example, if you skip taking drospirenone + ethinylestradiol tablets, gastrointestinal disorders during the period of taking drospirenone + ethinylestradiol tablets, or while taking other medicines.

Insufficient cycle control

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

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

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

Influence on the ability to drive vehicles and control mechanisms

Content

The use of hormonal pills is considered the most effective method of contraception. Today, various pharmaceutical companies produce a huge number of products that help women avoid unwanted pregnancies. One of the most popular is Dimia. Many experts advise it to their patients due to the good tolerance of the main components and the rare occurrence of side effects.

Pharmacological action

The combination drug Dimia is a monophasic oral agent. This medicine contains ethinyl estradiol and drospirenone (an analogue of natural progesterone). The active substances that make up the drug do not have estrogenic, antiglucocorticoid, glucocorticoid abilities. The drug achieves its effectiveness by changing the endometrium, inhibiting ovulation and increasing the viscosity of the secretion of the cervix, which prevents the penetration of spermatozoa into its cavity.

After taking the drug inside, the active substances are completely absorbed into the bloodstream from the small intestine. They are distributed evenly throughout all tissues of the body. The maximum concentration of the drug is reached two hours after ingestion. The decay products of ethinylestradiol and drospirenone are excreted from the body mainly in the urine.

Release form and composition

The drug Dimia (dimia) is produced in the form of round, biconvex white film-coated tablets with a special marking G73 on one side. Also, the composition of the medicine additionally includes green placebo tablets that do not contain active active ingredients. One package of the drug includes 28 tablets, packaged in one or three blisters. The composition of the product is presented in the table:

How to take Dimia

Dimia hormonal tablets should be taken daily, at the same time, with water, in the order indicated on the blister pack. The medicine should be taken continuously for 28 days, one piece per day. Taking tablets from the next package should be started after the remedy from the previous box is over. Only a doctor can tell you how to take Dimia correctly, without health consequences. As a rule, the beginning of the use of the tool is different:

• When switching from other OCs (oral contraceptives), it is necessary to start drinking Dimia the next day after taking the last tablet of another drug (28 pieces) or a week after using the drug containing 21 capsules. When using a transdermal patch or vaginal ring, take dimia only after they have been removed.
• Before starting taking the pills, if a woman has not used other OCs for a month, it is necessary to start drinking dimia from the first day of the menstrual cycle. You can take the remedy from the 3rd day of the onset of menstruation, but you should use condoms for a week.
• After removal of the intrauterine device, the use of tablets begins on the day of the procedure.
• If a woman took non-combined progesterone-based drugs, then the contraceptive can be started on any day.
• When a pregnancy is terminated in the first trimester, a woman, as prescribed by a doctor, can drink pills on the same day.
• After an abortion or childbirth, experts advise starting taking pills on the 28th day.

If a woman missed taking another pill, the following recommendations should be followed in relation to the resumption of their use:

• skipping a placebo tablet can be ignored and then you need to continue taking the next day according to the scheme indicated in the instructions;
• if less than 12 hours have passed since the missed dose, the patient should take the pill as soon as possible;
• if more than 12 hours have passed since the last use of the drug, then the woman should take a pill when she remembers it, even if it coincides with the next one (you can take 2 pills at once).

Indications and contraindications for taking pills

Dimia contraceptives are indicated for women of reproductive age to prevent unwanted pregnancy. In addition, the use of the drug is possible in the treatment of such diseases:

• fibroids;
• endometriosis;
• dysfunction of the menstrual cycle;
• iron deficiency anemia;
• polycystic ovary syndrome;
• premenstrual syndrome.

The use of tablets is contraindicated in the following situations:

• thrombophlebitis, thromboembolism (movement of blood clots through arterial vessels) or thrombosis (the appearance of blood clots in the lumen of venous or arterial vessels);
• malignant hormone-dependent neoplasms of the mammary glands or organs of the reproductive system;
• hereditary or acquired predisposition to thrombosis (lack of protein, hyperhomocysteinemia);
• individual intolerance to the main or auxiliary components of the drug;
• pancreatitis (inflammation of the pancreas);
• pathological processes that preceded the appearance of severe thrombosis (transient ischemic attack, myocardial infarction, angina pectoris);
• transferred surgical intervention with further immobilization of the body;
• acute or chronic severe insufficiency of kidney activity;
• the presence in the female body of processes that can lead to cardiovascular diseases (damage to the heart valves, disruption of the rhythm of contractions, pathology of the coronary vessels);
• smoking over the age of 35;
• lactation period;
• hypertension;
• liver disease;
• acquired or congenital lactase deficiency;
• the presence of pathological bleeding from the vagina;
• confirmed pregnancy.

Care should be taken to take the drug in the postpartum period and with concomitant pathologies leading to impaired peripheral circulation:

• Crohn's disease;
• diabetes mellitus;
• sickle cell anemia;
• systemic lupus erythematosus;
• hereditary angioedema,
• phlebitis of superficial veins;
• hypertriglyceridemia (increased levels of triglycerides in the blood).

Side effects

Before starting to use a medicinal contraceptive, a woman should consult a doctor, because. there is a risk of thromboembolic complications. In addition, the use of the drug can lead to the development of such side effects:

• emotional instability;
• nausea, vomiting;
• dizziness;
• migraine;
• stomach ache;
• inflammation of the gallbladder (cholecystitis);
• headache;
• depression;
• drowsiness;
• tremor (trembling) of the hands;
• muscle cramps;
• increased blood pressure;
• tachycardia (increased heart rate);
• thrombocytopenia (decrease in the number of platelets);
• phlebitis (inflammation of the veins);
• anemia (anemia);
• development of vaginal candidiasis;
• weight gain;
• back pain;
• dyspareunia (painful intercourse);
• breast enlargement;
• acne (acne);
• dryness of the vaginal mucosa;
• alopecia (hair loss);
• allergic reactions.

If side effects or complications develop (coughing up blood, double vision, sudden or partial loss of vision), you should immediately seek medical help. The risk of negative symptoms and vascular thrombosis increases with arterial hypertension, alcohol abuse, increased body weight, and age over 40 years. The use of the drug does not exclude the possibility of infection with infectious diseases, sexually transmitted.

Interaction of Dimia with other drugs

The effectiveness of a contraceptive can be weakened by the combined use of a drug with barbiturates (a group of drugs derived from barbituric acid) and drugs that affect liver enzymes: Griseofulvin, Oxcarbazepine, Topiramate, Phenytoin, Primidone, Felbamate, Rifampicin. In addition, the instructions indicate that drugs that contain St. John's wort in their chemical composition, when used simultaneously with dimia, induce (stimulate) microsomal liver enzymes, which also negatively affects the female body.

A decrease in the circulation of estrogen and at the same time the effectiveness of a contraceptive occurs while using Ampicillin and Tetracycline with antibiotics. HIV protease inhibitors and their combinations have a negative effect on the hepatic metabolism of the drug. Women with short-term treatment with any of the above means should temporarily use barrier methods of contraception (condom).

Analogues

The manufacturer of the drug Dimia is the Hungarian company Gedeon Richter. Absolute structural analogues of the agent, similar in the mechanism of action and chemical composition, are:

• Midian;
• Angelique;
• Yarina;
• Jess;
• Vidor;
• Dailla;
• Belara;
• Simicia;
• Yarina plus;
• Annabella;
• Delcia;
• Modell trend.

Price for Dimia tablets

You can buy dimia at any pharmacy, but you will need to get a prescription from your doctor. You can not start taking pills on your own or on the recommendation of friends, before you start using it, you should definitely visit a specialist. The cost of the drug depends on the region of distribution and the number of tablets in the package, the average price for 28 pieces is 700 rubles. The approximate cost of a contraceptive in Moscow is presented in the table.

Tradename

Description

For drospirenone + ethinyl estradiol tablets:
white or almost white, round, biconvex film-coated tablets, about 6 mm in diameter; one side of the tablet is engraved with “G73”.
For placebo tablets:
Green, round, biconvex film-coated tablets, diameter 6 mm.

Pharmacotherapeutic group

Combined contraceptive (estrogen + gestagen)

ATC Code:

Release form, composition and packaging

Active ingredient	1 film-coated tablet
Drospirenone	3 mg
Ethinylestradiol	0.02 mg
Excipients
Core: lactose monohydrate, corn starch, pregelatinized corn starch, macrogol and polyvinyl alcohol copolymer, magnesium stearate; Film shell: Opadry II white 85G18490 (polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, soy lecithin).
Excipients (tablet placebo)
Core: microcrystalline cellulose, anhydrous lactose, pregelatinized corn starch, magnesium stearate, colloidal silicon dioxide, anhydrous. Film coat: Opadry II 85F21389 green (polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, indigo carmine aluminum lacquer (E132), quinoline yellow aluminum lacquer (E104), iron dioxide black (E172), sunset yellow FCF aluminum lacquer (E110)).
Release form: 24 tablets of the drug and 4 tablets of placebo in a blister pack made of PVC / PE / PVDC film and aluminum foil. 1 or 3 blister packs in a cardboard case, enclosed together with instructions for medical use in a cardboard box.

Structural formula, gross formula and chemical name

Pharmacological properties

Combined oral contraceptive (CPC) containing ethinyl estradiol and drospirenone progestogen. At a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid effects. It does not have estrogenic, glucocorticoid and antiglucocorticoid activity. Thus, drospirenone has a pharmacological profile similar to the natural hormone progesterone.
In clinical studies, it was found that the antimineralocorticoid properties of Dimia® lead to a weak antimineralocorticoid effect.
It has antiandrogenic activity, which leads to a decrease in the formation of acne and a decrease in the production of sebaceous glands, does not affect the increase in the formation of globulin that binds sex hormones (inactivation of endogenous androgens) caused by ethinylestradiol.
: 0.31 (upper 95% confidence interval: 0.85). The contraceptive effect of the drug is based on the interaction of various factors, the most important of which are the inhibition of ovulation and changes in the endometrium.

Pharmacokinetics

Drospirenone

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

Distribution
After oral administration, serum levels of drospirenone decrease with a terminal half-life of 31 hours. Drospirenone is associated with serum albumin, but the drug does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG). Only 3-5% of the total active substance concentrations in serum is presented as a free steroid. The increase in SHBG induced by ethinylestradiol does not affect the binding of drospirenone to serum proteins. The average apparent V d of Drospirenone is 3.7 ± 1.2 l / kg.
During one cycle of treatment, the maximum C ss of drospirenone in serum (approximately 70 ng / ml) is reached after 8 days of treatment. Serum concentrations of drospirenone increase by about 3 orders of magnitude, due to the ratio of the final T 1/2 and the dosing interval.

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

breeding
The rate of metabolic clearance of drospirenone in serum is 1.5±0.2 ml/min/kg. Drospirenone is excreted only in trace amounts in unchanged form. Drospirenone metabolites are excreted in faeces and urine in a ratio of approximately 1.2:1.4. T 1/2 for excretion of metabolites with urine and faeces is approximately 40 hours.

Ethinylestradiol

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

Distribution
Serum ethinylestradiol levels decrease in two phases, the final pharmacokinetic phase is characterized by T 1/2 about 24 hours. Ethinylestradiol binds to albumin about 98.5% and induces an increase in the concentration of SHBG and CSH in serum. The apparent V d is approximately 5 l/kg.
State C ss is achieved during the second half of the treatment cycle, and the serum level of ethinylestradiol increases by a factor of about 2.0-2.3.

Metabolism
Ethinylestradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation, with the formation of a variety of hydroxylated and methylated metabolites, presented both in the form of free metabolites and in the form of conjugates with glucuronic and sulfuric acids. Ethinylestradiol is completely metabolized. The rate of metabolic clearance of ethinylestradiol is 5 ml/min/kg.

breeding
Ethinylestradiol is practically not excreted unchanged. Metabolites of ethinylestradiol are excreted in the urine and bile in a ratio of 4:6. T 1/2 metabolites is approximately 1 day. Elimination T 1/2 is 20 hours.

Pharmacokinetics in special groups of patients

Patients with impaired renal function. Serum C ss of drospirenone in women with mild renal insufficiency: (CC 50-80 ml / min) was comparable to that in women with normal renal function (CC> 80 ml / min). Serum levels of drospirenone were on average 37% higher in women with moderate renal insufficiency (CC = 30-50 ml / min) compared with women with normal renal function. Drospirenone therapy was well tolerated by women with both mild and moderate renal impairment.
Drospirenone treatment had no clinically significant effect on serum potassium contraception.

Patients with impaired liver function.
In a single dose study, total clearance in volunteers with moderate hepatic impairment was approximately 50% reduced compared with that in subjects with normal hepatic function.
The observed decrease in drospirenone clearance in volunteers with moderate hepatic insufficiency does not lead to any significant differences in serum potassium concentration. Even with diabetes and concomitant treatment with spironolactone (two factors that can provoke hyperkalemia in a patient), there was no increase in serum potassium concentration above ULN. It can be concluded that the drospirenone/ethinylestradiol combination is well tolerated by patients with moderate hepatic impairment (Child-Pugh class B).

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

Indications for use

• Oral contraception.

The drug has a positive effect on the symptoms associated with fluid retention in the body, as well as on acne and seborrhea, due to its antimineralocorticoid and antiandrogenic action.

Dosage and administration

Tablets should be taken every day at about the same time, if necessary, with a small amount of liquid, in the sequence indicated on the package. It is necessary to take 1 tablet / day for 28 days in a row. Each next pack should begin after taking the last tablet from the previous pack. Withdrawal bleeding usually begins on day 23 after taking the placebo tablets (last row) and may not have ended by the time the next pack is started.

If you have not used hormonal contraceptives before (in the last month)
Dimia® is started on the first day of a woman's natural menstrual cycle (i.e., on the first day of her menstrual bleeding).

When replacing another PDA, vaginal ring, or transdermal patch
For a woman, it is preferable to start taking Dimia the day after the usual hormone-free interval in the previous combined contraceptive regimen. When replacing the vaginal ring or transdermal patch, it is advisable to start taking Dimia ® on the day the previous remedy is removed; in such cases, taking Dimia® should begin no later than the day of the scheduled replacement procedure.

In case of replacement of the method with the use of only gestagens (mini-pills, injectable forms, implants) or intrauterine system (IUD) with the release of gestagens

A woman can switch from the mini-pill any day (from the implant or IUD on the day it was removed, from the injectable from the day the next injection was due). However, in all these cases, it is desirable to use additionally during the first 7 days of taking the tablets.

After termination of pregnancy in the first trimester

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

After childbirth or termination of pregnancy in the second trimester

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

Taking missed pills

Skipping a placebo tablet from the last (4th) row of the blister can be ignored. However, they should be discarded to avoid inadvertently prolonging the placebo phase. The instructions below apply only to missed active tablets:
If the delay in taking the pill was less than 12 hours, contraceptive protection is not reduced. The woman should take the missed pill as soon as possible and take the next pill at the usual time. If the delay in taking the tablets was more than 12 hours, contraceptive protection may be reduced. Correction of missed tablets should be guided by the following two simple rules:

1. 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 intake are required.

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

Week 1
You should take the last missed tablet as soon as possible, even if it means taking two tablets at the same time. The next tablet is taken at the usual time. In addition, a barrier method of contraception must be used for the next 7 days. If sexual intercourse took place within 7 days before missing the tablet, the possibility of pregnancy must be considered. The more pills missed and the closer this pass is to the 7-day break in taking the drug, the higher the risk of pregnancy.

Week 2
You should take the last missed tablet as soon as possible, even if it means taking two tablets at the same time. The next tablet is taken at the usual time. If a woman has taken the pills correctly during the previous 7 days, there is no need to use additional contraceptives. However, if she missed more than 1 tablet, extra precautions should be taken for the next 7 days.

Week 3
The likelihood of a decrease in the contraceptive effect is significant due to the approach of the placebo pill phase. However, by adjusting the pill schedule, a decrease in contraceptive protection can be prevented. If you follow any of the following two tips, no additional methods of contraception will be needed if the woman has taken all the pills correctly in the previous 7 days before missing the pill. If this is not the case, she should follow the first of the two methods and also use additional precautions for the next 7 days.

1. You should take the last missed tablet as soon as possible, even if it means taking two tablets at the same time. The next tablets are taken at the usual time until the active tablets run out. 4 placebo tablets from the last row should not be taken, you must immediately start taking the tablets from the next package. Most likely, there will be no “withdrawal” bleeding until the end of the second pack, but there may be spotting or breakthrough bleeding on the days of taking the pills.
2. A woman can be advised to stop taking active tablets from the started package. Instead, she should take the placebo pills from the last row for 4 days, including the days she skipped the pills, and then start taking the pills from the next pack.
   In the event of missed pills and no withdrawal bleeding in the placebo pill phase, pregnancy should be ruled out.

Gastrointestinal disorders
In the event of severe gastrointestinal reactions (such as vomiting or diarrhea), absorption may not be complete and additional contraceptive measures should be used.
In case of vomiting within 3-4 hours after taking the active tablet, a new replacement tablet should be taken as soon as possible. The next tablet, if possible, should be taken within 12 hours after the usual time of admission. If more than 12 hours are missed, if possible, it is necessary to follow the rules for taking the drug indicated in the section “Acceptance of missed pills”. If the patient does not want to change the normal mode of taking the drug, she must take an additional tablet (or several tablets) from another package.

How to Delay “Withdrawal” Bleeding
To delay the day of the onset of menstruation, it is necessary to skip taking the placebo tablets from the started package and start taking active Dimia ® tablets from the new package without interrupting the intake. A delay is possible until the end of the tablets in the second package.
During the lengthening of the cycle, there may be spotting from the vagina or uterine breakthrough bleeding. Regular intake of Dimia ® ends after the placebo phase.
To move the day of the start of menstruation to another day of the week of the usual schedule, shorten the upcoming phase of placebo tablets by as many days as necessary. The shorter the interval, the higher the risk that there will be no “withdrawal” bleeding, and spotting spotting and breakthrough bleeding will be noted during the reception of the second package (as in the case of a delay in the onset of menstruation).

Side effect

Undesirable effects of Dimia

Common (≥ 1/100 to 1/10)	Uncommon (≥ 1/1000 to 1/100)	Rare (≥ 1/10,000 to 1/1,000)
- headache, - emotional lability; - depression; - nausea; - menstrual irregularities (metrorrhagia, amenorrhea); - intermenstrual bleeding; - chest pain.	- dizziness; - migraine; - nervousness; - drowsiness; - decreased mood; - paresthesia; - hypertension; - phlebeurysm; - soreness and tension of the mammary glands; - fibrocystic changes in the mammary gland; - nausea; - vomit; - gastritis; - abdominal pain; - dyspepsia; - flatulence; - diarrhea; - acne; - skin itching; - dry skin; - back pain; - pain in the limbs; - muscle cramps; - decreased libido; - vaginal discharge; - canlidosis of the vagina; - dryness in the vagina; - vaginitis; - menstrual disorders (dysmenorrhea, hypomenorrhea, menorrhagia); - asthenia; - increased sweating; - fluid retention in the body; - increase in body weight.	- weight loss, - increased appetite, - anorexia, - urticaria – anemia, - thrombocytopenia, - hyperkalemia, - hyponatremia, - anorgasmia, - insomnia, - vertigo, - tremor - nose bleed, - fainting - thromboembolism, - venous thrombosis / thromboembolism, - arterial thrombosis / thromboembolism, - conjunctivitis, - dry eyes - poor tolerance to contact lenses, - tachycardia, - arterial hypertension, - Liver tumors - Crohn's disease, - nonspecific ulcerative colitis, - epilepsy, – endometriosis, - uterine fibroids - porphyria, - systemic lupus erythematosus, - pregnancy herpes - Sydenham's chorea - hemolytic uremic syndrome, - cholestatic jaundice, - chloasma, - dry skin, – acne or contact dermatitis, - angioedema, - eczema, - hypertrichosis, - photodermatitis, - erythema nodosum - erythema multiforme, - breast cyst - breast hyperplasia, - painful intercourse - postcoital bleeding - withdrawal bleeding - polyps of the cervix, - atrophy of the endometrium, - ovarian cyst, - uterine enlargement - increased libido.

Contraindications

• pregnancy;
• breastfeeding period;
• the presence of vein thrombosis at present or in history (for example, deep vein thrombosis, pulmonary embolism);
• the presence of arterial thrombosis at present or in history (for example, myocardial infarction) or previous conditions (for example, angina and transient ischemic attack);
• cerebrovascular disease at present 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 APC (activated protein C), antithrombin 3 deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (cardiolipin antibodies, lupus anticoagulant);
• pancreatitis with severe hypertriglyceridemia, incl. in history;
• severe liver disease (before normalization of liver tests) at present 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;
• vaginal bleeding of unknown origin;
• migraine with a history of local neurological symptoms;
• galactose intolerance, lactase deficiency or malabsorption syndrome of glucose and galactose;
• hypersensitivity to the active substance or any of the excipients.

Pregnancy and lactation

If pregnancy occurs while taking Dimia ® ‚ the drug must be immediately discontinued. Conducted epidemiological studies have not revealed any increased risk during childbirth for children in women who took COCs before pregnancy, nor a teratogenic effect when COCs were inadvertently taken during pregnancy. Such studies with the drug have not been conducted.
COCs can affect lactation because they can reduce the amount and composition of breast milk. Thus, the use of COCs cannot be recommended until a breastfeeding woman has completely stopped breastfeeding. Small amounts of contraceptive hormones or their metabolites may be excreted in milk during COC use. These quantities may have an effect on the child.

special instructions

If any of the conditions/risk factors listed below are currently present, then the potential risk and expected benefit of COC use should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, worsen, or appear for the first time, the woman should consult her physician, who may decide whether or not to discontinue COCs.

Circulatory system disorders
Epidemiological studies have shown that the incidence of VTE (venous thromboembolism) in women without risk factors for VTE taking low-dose estrogen COCs (< 50 мкг этинилэстрадиола) составляет примерно от 20 случаев на 100 000 женщин в год (для левоноргестрел-содержащих КПК второго поколения) или до 40 случаев на 100 000 женщин в год (для дезогестрел/гестоден- содержащих КОК третьего поколения). Это сравнимо с цифрами от 5 до 10 случаев на 100 000 женщин, не использующих контрацептивы, и 60 случаев на 100 000 беременностей.
The use of any combined oral contraceptive is associated with an increased risk of venous thromboembolism comparable to that without use. The additional risk is highest during the first year of using a combined oral contraceptive. Thromboembolism of the veins leads to lethal outcome in 1-2% of cases.
Epidemiological studies have also linked COC use to an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic attacks).
In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as hepatic, mesenteric, renal arteries and veins, the central retinal vein and its branches, have been described.

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

• unusual unilateral pain and/or swelling of a limb;
• sudden severe chest pain, with or without radiating to the left arm; sudden shortness of breath;
• sudden 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 a seizure;
• weakness or severe 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 venous thromboembolism when taking COCs increases:

• with age;
• if there is a family history (venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); if a hereditary predisposition is expected, a woman needs to consult a specialist before prescribing a PDA;
• after prolonged immobilization, major surgery, any operation on the legs or major trauma. In these situations, it is recommended to stop taking the drug (in case of planned operation, at least four weeks before it) and do not resume reception within two 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 over 30 mg/m2);
• there is no consensus on the possible role of varicose veins and superficial vein thrombophlebitis in the onset or progression of venous thrombosis.

The risk of arterial thrombotic complications of thrombosis of a cerebrovascular disorder in women taking COCs increases:

• with age;
• in smokers (women over 35 years of age are strictly advised not to smoke if they want to use PDAs);
• with dyslipoproteinemia;
• with hypertension;
• with migraine;
• with diseases of the heart valves;
• with atrial fibrillation.

The presence of one of the major risk factors or multiple risk factors for arterial or venous disease, respectively, may be a contraindication. Women using COCs should immediately consult a doctor if symptoms of a possible thrombosis occur. In cases of suspected thrombosis or confirmed thrombosis, COCs 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 thromboembolism in the postpartum period should be taken into account.

Other diseases

Other diseases that are associated with severe vascular disease include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia.
An increase in the frequency and severity of migraine during COC use (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs.
An increased risk of developing cervical cancer with long-term use of combined oral contraceptives has been reported in some epidemiological studies. Its association with COC use has not been proven. Controversy remains as to the extent to which these results relate to sexual behavior and other factors such as human papillomavirus (HPV).

Mammary cancer

A meta-analysis of 54 epidemiological studies demonstrated that there is a slightly increased relative risk (RR=1.24) of breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. Its association with COC use has not been proven. The observed increase in risk may be due to earlier diagnosis of breast cancer in women using combined oral. Breast cancer in women who have ever used combined oral contraceptives were clinically less pronounced than in women who have never used such drugs. In rare cases, against the background of the use of COCs, the development of benign liver tumors was observed, and in extremely rare cases, the development of malignant liver tumors. In some cases, these tumors lead to life-threatening intra-abdominal bleeding. In the case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding during the differential diagnosis in a woman taking COCs, the likelihood of developing a liver tumor should be considered.

Other states

The progestin component in Dimia® is an aldosterone antagonist with potassium-sparing properties. In most cases, potassium levels are not expected to increase. But in a clinical study in some patients with mild to moderate renal impairment, concomitant use of potassium-sparing drugs slightly increased serum potassium levels when taking drospirenone. Therefore, it is recommended to check the serum potassium level during the first cycle of treatment in patients with renal insufficiency, whose serum potassium level was at the upper limit of normal before treatment, and who are additionally using potassium-sparing drugs.
In women with hypertriglyceridemia‚ or a family history of this disease, an increased risk of developing pancreatitis during COC use cannot be excluded. Although a slight increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically significant increases have been rare. Only in rare cases is the immediate abolition of the CCP justified. If, while taking COCs with existing arterial hypertension, persistently or significantly elevated blood pressure does not adequately respond to antihypertensive treatment, it is worth stopping taking COCs.
The following conditions have been reported to develop or worsen during both pregnancy and COC use, but have not been shown to be associated with COC use: jaundice and/or itching associated with cholestasis, gallstone formation, porphyria, systemic erythematosus lupus, hemolytic uremic syndrome, Sydenham's chorea, herpes of pregnancy, hearing loss associated with otosclerosis. In women with a tendency to angioedema, exogenous estrogens may induce or exacerbate the symptoms of angioedema.
Acute or chronic liver dysfunction may require the discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice and / or pruritus associated with cholestasis, which developed for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COCs. Although COC may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using combined oral contraceptives (containing< 0.05 мг этинилэстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться, особенно на early stage taking PDA.
Cases of Crohn's disease and ulcerative colitis have also been described with the use of COCs, however, the relationship with the use of drugs has not been proven.
Worsening of endogenous depression, epilepsy, Crohn's disease, and ulcerative colitis has been reported with COCs.
In rare cases, chloasma may develop, especially in women with skin pigmentation during pregnancy. Women with a tendency to chloasma should avoid prolonged exposure to the sun and ultraviolet radiation while taking COCs. The drug contains 48.53 mg of lactose per tablet and 37.26 mg of anhydrous lactose per inactive tablet. Patients with rare hereditary galactose intolerance, lactase deficiency or malabsorption of glucose-galactose who are on a lactose-free diet should be aware of this.
Women who are allergic to soy lecithin may experience mild allergic reactions.

Medical examinations/consultations

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

COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of COCs may be reduced by skipping pills, gastrointestinal disorders, or concomitant medication.

Reduced cycle control

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

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

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

Influence on the ability to drive vehicles and control mechanisms

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

Overdose

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

Interaction with other drugs

Some drugs, due to the induction of microsomal enzymes, are able to increase the clearance of sex hormones (hydantoin, phenytoin, barbiturates, primidone, carbamazepine and rifampicin; the same effect of oxycarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal remedy based on St. John's wort (Hypericum perforatum) is also possible). Maximal induction of microsomal liver enzymes usually does not occur within 2-3 weeks, but may then persist for at least 4 weeks after drug therapy has been discontinued. 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.
Co-administration with certain antibiotics, such as penicillins and tetracyclines, reduces the enterohepatic recirculation of estrogen, which can lead to a decrease in the concentration of ethinyl estradiol.
Women receiving any of the above classes of drugs or individual active substances should use a barrier method of contraception in addition to Dimia ® or switch to any other method of contraception. Women receiving permanent treatment with drugs containing active substances that affect liver enzymes must additionally use a non-hormonal method of contraception within 28 days after their withdrawal.
Women receiving rifampicin therapy should use a barrier method of contraception in addition to taking COCs and continue to use it for 28 days after stopping treatment with rifampicin. If concomitant medication lasts longer than the expiration date of the active tablets in the package, the placebo tablets should be discarded and the active tablets from the next package should be started immediately.
The basic metabolism of drospirenone in human plasma is generated without the involvement of the CYP system. Inhibitors of this enzyme system, therefore, do not affect the metabolism of drospirenone.
Oral contraceptives may interfere with the metabolism of certain other active compounds. In addition, their concentrations in plasma and tissues can change, both increase (eg, cyclosporine) and decrease (eg, lamotrigine).
In female volunteers taking omeprazole, simvastatin and midazolam as indicator substrates, the effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.
In patients with renal insufficiency, the simultaneous administration of drospirenone and ACE inhibitors or NSAIDs does not significantly affect the level of potassium in the blood serum. However, the simultaneous use of the drug Dimia ® and aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, it is necessary to study the level of potassium in the serum during the first cycle of taking the drug.
Co-administration of drugs should be discussed to identify possible drug interactions.
Hormone use for contraception may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, as well as levels of plasma transport proteins such as corticosteroid-binding globulin and lipid / lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis. Changes usually occur within laboratory norms.
Due to its small antimineralocorticoid activity, drospirenone increases the activity of renin and plasma aldosterone.

Storage conditions and expiration dates

The drug should be stored in its original packaging, out of the reach of children, protected from light at a temperature of 15° to 25°C. Shelf life - 2 years.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Analogues

The decision to replace the drug is made by the attending physician, do not take it yourself.

Manufacturer

JSC "Gedeon Richter" 1103, Budapest, st. Demrei, 19-21, Hungary.

white or almost white, round, biconvex, marked "G73" on one side of the tablet, applied by embossing; in cross section, the nucleus is white or almost white.

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

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

placebo pills

Film-coated tablets green, round, biconvex; in cross section, the nucleus is white or almost white.

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

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

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

The description of the drug is based on the official instructions for use and approved by the manufacturer.

pharmachologic effect

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

Pharmacokinetics

Drospirenone

Suction

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

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

Distribution

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

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

Metabolism

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

breeding

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

Ethinylestradiol

Suction

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

Distribution

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

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

Metabolism

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

breeding

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

Pharmacokinetics in special clinical situations

In case of impaired renal function

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

In violation of liver function

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

Indications

- oral contraception.

Dosing regimen

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

How to start taking Dimia ®

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

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

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

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

A woman can switch from taking a mini-pill to taking Dimia ® on any day (from the implant or from the IUD on the day they are removed, from injectable forms of drugs on the day the next injection was due), but in all cases it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

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

After childbirth or abortion in the second trimester of pregnancy.

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

Taking missed pills

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

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

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

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

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

Accordingly, women can be given the following recommendations:

Days 1-7

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

Days 8-14

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

Days 15-24

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

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

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

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

The use of the drug in gastrointestinal upset

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

Postponement of menstrual bleeding "withdrawal"

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

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

Side effect

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

Organ system class	Frequent (≥1/100 to< 1/10)	Less frequent (≥1/1000 to< 1/100)	Rare (≥ 1/10,000 to< 1/1000)
Infections and infestations			candidiasis, incl. oral cavity
From the blood and lymphatic system			anemia, thrombocytopenia
From the side of the immune system			allergic reactions
From the side of metabolism and nutrition		weight gain	increased appetite, anorexia, hyperkalemia, hyponatremia, weight loss
From the side of the psyche	emotional lability	depression, decreased libido, nervousness, drowsiness	anorgasmia, insomnia
From the side of the nervous system	headache	dizziness, paresthesia	vertigo, tremor
From the organ of vision			conjunctivitis, dryness of the mucous membrane of the eye, visual impairment
From the side of the cardiovascular system		migraine, phlebeurysm, increase in blood pressure	tachycardia, phlebitis, vascular damage, nose bleed, fainting
From the digestive system	nausea, abdominal pain	vomit, diarrhea
From the side of the liver and biliary tract			pain in the gallbladder cholecystitis
From the skin and subcutaneous tissue		rash (including acne), itching	chloasma, eczema, alopecia, acne dermatitis, dry skin, erythema nodosum, hypertrichosis, skin lesions, skin striae, contact dermatitis, photodermatitis, skin nodules
From the musculoskeletal system		backache, limb pain, muscle cramps
From the reproductive system and mammary glands	chest pain, no withdrawal bleeding	vaginal candidiasis, pelvic pain, breast enlargement, fibrocystic breast, vaginal discharge, flushes of blood vaginitis, acyclic spotting, painful menstrual bleeding profuse bleeding "withdrawal", scanty menstrual bleeding, dryness of the vaginal mucosa, change in the cytological picture in a Pap smear	painful intercourse, vulvovaginitis, postcoital bleeding, breast cyst, breast hyperplasia, mammary cancer, cervical polyps, endometrial atrophy, ovarian cyst, uterine enlargement
Are common disorders		asthenia, increased sweating, edema (generalized edema, peripheral edema, facial edema)	feeling of discomfort

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

- venous thromboembolic diseases;

- arterial thromboembolic diseases;

- tumors of the liver;

- the occurrence or exacerbation of conditions for which the connection with the use of COCs has not been proven: Crohn's disease, ulcerative colitis, epilepsy, migraine, endometriosis, uterine fibroids, porphyria, systemic lupus erythematosus, herpes during a previous pregnancy, rheumatic chorea, hemolytic uremic syndrome, cholestatic jaundice;

- chloasma;

- acute or chronic liver disease may necessitate discontinuation of COCs until liver function tests return to normal;

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate the symptoms of angioedema.

Contraindications

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

- thrombosis (arterial and venous) and thromboembolism at present or in history (including thrombosis, deep vein thrombophlebitis; pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders);

- conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history;

- multiple or pronounced risk factors for venous or arterial thrombosis, incl. complicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of the cerebral vessels or coronary arteries; uncontrolled arterial hypertension, major surgery with prolonged immobilization, smoking over the age of 35, obesity with a BMI >30 kg/m 2 ;

- hereditary or acquired predisposition to venous or arterial thrombosis, for example, resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antibodies against phospholipids (presence of antibodies to phospholipids - antibodies to cardiolipin, lupus anticoagulant);

- pancreatitis with severe hypertriglyceridemia at present or in history;

- existing severe liver disease (or in history), provided that liver function is not currently normalized;

- severe chronic or acute renal failure;

- a liver tumor (benign or malignant) at the present time or in history;

- hormone-dependent malignant neoplasms of the genital organs or the mammary gland at the present time or in history;

- bleeding from the vagina of unknown origin;

- migraine with a history of focal neurological symptoms;

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption, lapp lactase deficiency (lactase deficiency in some peoples of the North);

- pregnancy and suspicion of it;

- lactation period;

- hypersensitivity to the drug or any of the components of the drug.

WITH caution

- risk factors for the development of thrombosis and thromboembolism: smoking under the age of 35, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated valvular heart disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age one of the next of kin);

- diseases in which peripheral circulatory disorders can occur: diabetes mellitus without vascular complications, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of superficial veins;

- hereditary angioedema;

- hypertriglyceridemia;

- severe liver disease (before normalization of liver function tests);

- diseases that first appeared or worsened during pregnancy or against the background of a previous intake of sex hormones (including jaundice and / or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing loss, porphyria, herpes during pregnancy in history, minor chorea (Sydenham's disease), chloasma;

- postpartum period.

Use during pregnancy and lactation

Dimia ® is contraindicated during pregnancy.

If pregnancy occurs during the use of the drug Dimia ® , it should be stopped immediately. Extended epidemiological studies have found neither an increased risk of birth defects in children born to women who took COCs before pregnancy, nor a teratogenic effect of COCs when they were inadvertently taken during pregnancy.

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

The drug Dimia ® can affect lactation: reduce the amount of milk and change its composition. Small amounts of contraceptive steroids and/or their metabolites may be excreted in milk during COC use. These amounts may affect the child. The use of the drug Dimia ® during breastfeeding is contraindicated.

special instructions

If there are any of the conditions/risk factors mentioned below, the benefits of taking COCs should be assessed individually for each woman and discussed with her before starting use. If an adverse event worsens or if any of these conditions or risk factors appear, the woman should contact her doctor. The doctor must decide whether to stop taking the COC.

Circulatory disorders

Taking any combined oral contraceptive increases the risk of venous thromboembolism (VTE). The increased risk of VTE is most pronounced in the first year of a woman's use of a combined oral contraceptive.

Epidemiological studies have shown that the incidence of VTE in women with no risk factors who took low doses of estrogen (<0.05 мг этинилэстрадиола) в составе комбинированного перорального контрацептива, составляет примерно 20 случаев на 100 000 женщин-лет (для левоноргестрелсодержащих КПК "второго поколения") или 40 случаев на 100 000 женщин-лет (для дезогестрел/гестоденсодержащих КПК "третьего поколения"). У женщин, не пользующихся КПК, случается 5-10 ВТЭ и 60 беременностей на 100 000 женщин-лет. ВТЭ фатальна в 1-2% случаев.

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

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

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

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

- unusual unilateral pain and / or swelling of the lower extremities;

- sudden severe pain in the chest, regardless of whether it gives to the left arm or not;

- sudden shortness of breath;

- sudden onset of coughing;

any unusual severe prolonged headache;

- sudden partial or complete loss of vision;

- diplopia;

- impaired speech or aphasia;

- vertigo;

- collapse with partial epileptic seizures or without them;

- weakness or very noticeable numbness, suddenly affecting one side or one part of the body;

- movement disorders;

- "acute" abdomen.

A woman should consult with a specialist before taking COCs.

Risk venous thromboembolic disorders

- increase in age;

- hereditary predisposition (venous thromboembolism has ever happened to siblings or parents at a relatively early age);

- prolonged immobilization, advanced surgery, any surgical intervention on the lower extremities or major trauma. In such situations, it is recommended to stop taking the drug (in the case of a planned surgical intervention, at least four weeks in advance) and not resume until two weeks after the full restoration of mobility. If the drug has not been discontinued in advance, anticoagulant treatment should be considered;

- obesity (body mass index more than 30 kg / m 2);

- lack of consensus on the possible role of varicose veins and superficial thrombophlebitis in the appearance or exacerbation of venous thrombosis.

Risk arterial thromboembolic complications or acute cerebrovascular accident when taking COC increases with:

- increase in age;

- smoking (women over 35 are strongly advised to stop smoking if they want to take PDAs);

- dyslipoproteinemia;

- arterial hypertension;

- migraine without focal neurological symptoms;

- obesity (BMI over 30 kg/m2);

- hereditary predisposition (arterial thromboembolism ever in siblings or parents at a relatively early age). If a hereditary predisposition is possible, a woman should consult a specialist before taking COCs;

- damage to the heart valves;

- atrial fibrillation.

The presence of one major risk factor for venous disease or multiple risk factors for arterial disease may also be a contraindication. Anticoagulant therapy should also be considered. Women taking COCs should be properly instructed to inform their physician if symptoms of thrombosis are suspected. If thrombosis is suspected or confirmed, COC use should be discontinued. It is necessary to start adequate alternative contraception due to the teratogenicity of anticoagulant therapy (indirect anticoagulants - coumarin derivatives).

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

Other medical conditions associated with adverse vascular events include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia.

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

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

A meta-analysis of 54 epidemiological studies found a slight increase in the relative risk (RR = 1.24) of breast cancer in women who currently take COCs. The risk gradually decreases over 10 years after stopping COCs. Since breast cancer rarely develops in women under 40 years of age, an increase in the number of diagnosed cases of breast cancer in COC users has little effect on the overall likelihood of developing breast cancer. These studies did not find sufficient evidence of a causal relationship. The increased risk may be due to earlier diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both. Diagnosed breast cancer in women who have ever taken COCs was clinically less severe, due to the early diagnosis of the disease.

Rarely, benign liver tumors and, even more rarely, malignant liver tumors have occurred in women taking COCs. In some cases, these tumors were life-threatening due to intra-abdominal bleeding. This should be taken into account when making a differential diagnosis in case of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.

Other states

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

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

Although a slight increase in blood pressure has been observed in many women taking COCs, a clinically significant increase was rare. Only in these rare cases is immediate discontinuation of COCs warranted. If, when taking COCs in patients with concomitant arterial hypertension, blood pressure constantly increases or significantly elevated blood pressure cannot be corrected with antihypertensive drugs, COCs should be discontinued. After normalization of blood pressure with antihypertensive drugs, COCs can be resumed.

The following diseases appeared or worsened both during pregnancy and when taking COCs, but the evidence for their relationship with taking COCs is inconclusive: jaundice and / or itching associated with cholestasis, gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; rheumatic chorea (Sydenham's chorea); herpes during pregnancy; otosclerosis with hearing loss.

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of edema.

Acute or chronic liver disease may be an indication to discontinue COC use until liver function tests return to normal. Recurrence of cholestatic jaundice and/or cholestasis-associated pruritus, which developed during a previous pregnancy or with earlier use of sex hormones, is an indication for discontinuation of COCs.

Although COCs may affect peripheral insulin resistance and glucose tolerance, changing the treatment regimen in patients with diabetes mellitus while taking low-hormone COCs (containing< 0.05 мг этинилэстрадиола) не показано. Однако следует внимательно наблюдать женщин с сахарным диабетом, особенно на ранних стадиях приема КПК.

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

Chloasma may occur from time to time, especially in women who have a history of chloasma of pregnancy. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet light while taking COCs.

Drospirenone + ethinyl estradiol coated tablets contain 48.53 mg lactose monohydrate, placebo tablets contain 37.26 mg anhydrous lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should not take this medicine.

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

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

Medical examinations

Before you start taking or re-using Dimia ®, you should collect a complete medical history (including family history) and exclude pregnancy. It is necessary to measure blood pressure, conduct a medical examination, guided by contraindications and precautions. A woman needs to be reminded of the need to carefully read the instructions for use and adhere to the recommendations indicated in it. The frequency and content of the survey should be based on existing practice guidelines. The frequency of medical examinations is individual for each woman, but should be carried out at least once every 6 months.

Women need to be reminded that oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of the CCP may decrease, for example, if you skip taking drospirenone + ethinylestradiol tablets, gastrointestinal disorders during the period of taking drospirenone + ethinylestradiol tablets, or while taking other drugs.

Insufficient cycle control

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

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

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

Influence on the ability to drive vehicles and control mechanisms

Not found.

Overdose

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

Treatment: there are no antidotes. Treatment should be symptomatic.

drug interaction

Effect of other medicinal products on Dimia ®

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

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

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

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

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

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

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

Effect of Dimia ® on other medicinal products

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

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

Other interactions

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

Laboratory tests

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

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25°C. Shelf life - 2 years.