Dimiya - instructions for use, doses, side effects, contraindications

Excipients: Lactose monohydrate 48.530 mg 16.600 mg corn starch, pregelatinized corn starch 9.600 mg of macrogol and polyvinyl alcohol copolymer 1.450 mg magnesium stearate 0.800 mg.

Film sheath (Opadraj II white * 2,000 mg): polyvinyl alcohol 0,880 mg, titanium dioxide 0,403 mg, macrogol-3350 0,247 mg, talc 0,400 mg, lecithin soybean 0,070 mg.

*code 85G18490

Placebo tablets

Composition per 1 tablet:

cellulose microcrystalline 42.39 mg, lactose 37.26 mg, corn starch pregelatinized starch 9.00 mg, magnesium stearate 0.90 mg, silicon dioxide colloid 0.45 mg.

Film sheath (Opadrai II green ** 3.0000 mg): polyvinyl alcohol 1.2000 mg, titanium dioxide 0.7086 mg, macrogol-3350 0.6060 mg, talc 0.4440 mg, indigocarmine 0.0177 mg, quinoline yellow dye 0.0177 mg, ferric oxide black oxide 0.0030 mg; dye sunset sunset yellow 0.0030 mg.

** code 85F21389

Description:

For tablets, drospirenone + ethinyl estradiol: round, biconvex tablets, covered with a film coating of white or almost white color, marked "G73" on one side of an embossed tablet. On the cross section, the nucleus is white or almost white in color.

For placebo tablets: torifle, biconvex tablets, covered with a film membrane of green color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:contraceptive combination (estrogen + progestogen)

ATX: & nbsp

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

Pharmacodynamics:

The drug Dimia® is a combined monophasic oral contraceptive (COC) containing drospirenone and ethinyl estradiol. According to its pharmacological profile, drospirenone is close to natural progesterone: it does not possess estrogenic, glucocorticoid and antiglucocorticoid activity and is characterized by pronounced antiandrogenic and moderate antimineralocorticoid action. 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 of the cervix and changes in the endometrium. Perl index, an indicator that reflects the frequency of pregnancy in 100 women of reproductive age during the year of contraceptive use, is less than 1.

Pharmacokinetics:

Drospirenone

Suction

When administered orally, drospirenone is rapidly and almost completely absorbed in the gastrointestinal tract. The maximum concentration of drospirenone in the serum - about 38 ng / ml - is achieved approximately 1-2 hours after a single dose.

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

Distribution

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

Metabolism

Drospirenone is actively metabolized after ingestion. The main metabolites in the blood plasma are the acid forms of drospirenone formed when the lactone ring is opened, and 4,5-dihydro-drospirenone-3-sulfate, both formed without the participation of the P450 system. Drospirenone is to a small extent metabolized by cytochrome P450 3A4 and is able to inhibit this enzyme, as well as cytochrome P450 1A1, cytochrome P450 2C9 and cytochrome P450 2S19 in vitro.

Excretion

The renal clearance of metabolites of drospirenone in the blood serum is 1.5 ± 0.2 ml / min / kg.Drospirenone is excreted only in trace amounts in unmodified form. Metabolites of drospirenone are excreted by the kidneys and through the intestine with an excretion ratio of about 1.2: 1.4. The half-life of metabolites by the kidneys and through the intestine is about 40 h.

The equilibrium concentration

During the treatment cycle, the maximum equilibrium concentration of drospirenone in the blood plasma is about 70 ng / ml, it is achieved after 8 days of treatment. Serum concentrations of drospirenone increase about 3-fold due to the ratio of the final half-life and the dosing interval.

Ethinylestradiol

Suction

When taken orally ethinyl estradiol absorbed quickly and completely. The maximum concentration in the blood serum - about 33 pkg / ml - is achieved within 1-2 hours after a single oral intake. Absolute bioavailability as a result of presystemic conjugation and presystemic metabolism is approximately 60%. Simultaneous food intake reduced the bioavailability of ethinyl estradiol in approximately 25% of the patients examined; there were no other changes.

Distribution

Serum concentrations of ethinyl estradiol decreased biphasic, in the phase of the final distribution, the elimination half-life is approximately 24 hours. Ethinylestradiol is well, but non-specifically associated with serum albumin (approximately 98.5%) and induces an increase in serum levels of SHBG. The apparent volume of distribution is about 5 l / kg.

Metabolism

Ethinyl estradiol is a substrate of presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinylestradiol is first metabolized by aromatic hydroxylation, with a wide range of hydroxylated and methylated metabolites that are present in both the free form and conjugates with glucuronic acid. The renal clearance of metabolites of ethinyl estradiol is approximately 5 ml / min / kg.

Excretion

Unchanged ethinyl estradiol practically not excreted from the body. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestine in a ratio of 4: 6. The half-life of the metabolite is about 24 hours.

The equilibrium concentration

Equilibrium concentration occurs in the second half of the treatment cycle,and the serum concentration of ethinyl estradiol is increased by 2.0-2.3 times.

Pharmacokinetics the special patient groups

In case of impaired renal function

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

When a violation of liver function

Drospirenone is well tolerated by patients with mild to moderate degree hepatic insufficiency (class B by Child-Pugh). Pharmacokinetics for severe liver failure was not studied.

Indications:

Oral contraception.

Contraindications:

The drug Dimia®, like other combined oral contraceptives (COCs), is contraindicated in any of the conditions listed below:

- thrombosis (arterial and venous) and thromboembolism at present or in the anamnesis (including thrombosis, deep vein thrombophlebitis, pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders). Conditions preceding thrombosis (including, transient ischemic attacks, angina pectoris) are currently or in history;

- multiple or severe risk factors for venous or arterial thrombosis, including complicated heart valve disease, atrial fibrillation, cerebrovascular or coronary artery disease; uncontrolled arterial hypertension, voluminous surgery with prolonged immobilization, smoking over the age of 35, obesity with a body mass index> 30 kg / m²;

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

- pregnancy and suspicion of it;

- lactation period;

- Pancreatitis with severe hypertriglyceridemia at present or in the anamnesis;

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

- severe chronic or acute renal failure;

- at present, or in an anamnesis, a liver tumor (benign or malignant);

- hormone-dependent malignant neoplasms of genital organs or breast cancer at the present time or in the anamnesis;

- bleeding from the vagina of unknown origin;

- Migraine with focal neurologic symptoms in history;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption, lactase deficiency of Lappa;

- 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 heart valve defects, hereditary predisposition to thrombosis (thrombosis,myocardial infarction or impaired cerebral circulation at a young age in someone of the next of kin); diseases in which can be marked disturbance of peripheral blood circulation: diabetes without vascular complications, systemic lupus erythematosus (SLE), hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis superficial veins; hereditary angioedema, hypertriglyceridemia, severe liver disease (before normalization of functional liver samples); diseases that first appeared or worsened during pregnancy or on the background of previous reception of sex hormones (including jaundice and / or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in the anamnesis, small chorea (Sydenham's disease), chloasma, postpartum period.

Pregnancy and lactation:

The drug Dimia® is contraindicated during pregnancy.

If the pregnancy occurred during the use of the drug Dimia®, its reception should be stopped immediately. Expanded epidemiological studies have not revealed an increase in the risk of birth defects in children born from women taking COCs before pregnancy,nor teratogenic effects of COCs during their unintentional admission during pregnancy.

According to preclinical research, it is impossible to exclude unwanted effects that affect the course of pregnancy and fetal development due to the hormonal action of the active components.

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

Dosing and Administration:

Mode of application: for oral administration.

How to take the drug Dimia®

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. The taking of tablets from the next package begins after the last tablet from the previous package is received. The "cancellation" bleeding usually begins 2-3 days after the start of taking the placebo tablets (last row) and does not necessarily end at the beginning of the next package.

How to start taking Dimia®

Hormonal contraceptives were not used in the last month

Reception of the drug Dimia® begins on the first day of the menstrual cycle (ie on the first day of menstrual bleeding). The onset of admission is possible on the 2nd-5th day of the menstrual cycle, in which case an additional use of the barrier method of contraception is necessary during the first 7 days of taking the tablets from the first package.

Transition from other combined contraceptives (combined oral contraceptives in the form of tablets, vaginal ring or transdermal patch)

Dimia® begin receiving the drug should be on the next day after the last inactive tablet (for products containing 28 tablets) or the next day after taking the last active tablet of the previous package (and possibly the next day after the usual 7-day break) - for preparations containing 21 tablets in a package. In the case of the woman vaginal ring or transdermal patch the drug Dimia® preferably started on the day of removal, or - at the latest on the day when the planned introduction of a new ring or replacement of plaster.

Transition from contraceptives containing only progestogens (mini-pili, injections, implants), or from the intrauterine system (IUD) that secretes progestogens

A woman can switch from taking a mini-drink to taking Dimia® any day (from the implant or the IUD on the day of their removal, from the injectable form of the drugs - the day the next injection was to be made), but in all cases it is necessary to use additionally barrier method of contraception during the first 7 days of taking the tablets.

After abortion in the first trimester of pregnancy

Reception of the drug Dimia® can be started as prescribed by the doctor on the day of termination of pregnancy. In this case, the woman does not need to take additional measures of contraception.

After childbirth or abortion in the second trimester of pregnancy

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

Acceptance of missed tablets

Passing the placebo tablet from the last (4th) row of the blister can be ignored. However, they should be discarded to avoid unintended prolongation of the placebo phase. The notes below apply only to missed tablets containing active ingredients.

If the delay in taking the pill was less than 12 hours, Contraceptive protection is not reduced. A 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 is exceeds 12 hours, contraceptive protection can be reduced. In doing so, you can follow two basic rules:

1. The intake of tablets should never be interrupted for more than 7 days;

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

In accordance with these women, the following recommendations can be made:

- Days 1-7

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

- Days 8-14

A woman should take the missed pill as soon as she remembers it, even if it means taking two tablets at the same time. Then she should take the pill at the usual time. If within 7 days preceding the first missed tablet, a woman took the pill 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.

- Days 15-24

The reliability of the method inevitably decreases, as the phase of the placebo tablets approaches. However, correction of the pill regimen can still help in preventing pregnancy. When one of the two following schemes, unless the previous 7 days before passing woman tablets complied dosing regimen, the need for additional contraceptive measures would not arise.If this is not the case, she must perform the first of the two schemes and use additional precautions for the next 7 days.

1. A woman should take the last missed tablet as soon as she remembers it, even if it means taking two tablets at the same time. Then she should take the pill at the usual time, until the active tablets are over. 4 placebo tablets from the last row should not be taken, you just need to start taking the tablets from the next blister pack. Most likely, bleeding "cancellation" will not be until the end of the second package, but there may be "smearing" spotting or bleeding "cancellation" on the days of taking the drug from the second package.

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

If a woman missed taking the pills and subsequently had no bleeding of "withdrawal" in the phase of the placebo tablets, the possibility of pregnancy should be considered.

Use of the drug in case of gastrointestinal upset

In the case of severe gastrointestinal disorders (eg, vomiting or diarrhea), 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 pill, it is necessary to take a new (replacement) pill as soon as possible. If possible, the next tablet should be taken within 12 hours of the usual time of taking the tablets. If more than 12 hours have passed, it is recommended that you follow the directions for missing tablets. If a woman does not want to change the usual scheme for taking tablets, she should take an additional pill from another package.

Postponement of menstrual bleeding "cancellation"

To delay bleeding, a woman should miss taking placebo tablets from the started package and begin taking the tablets drospirenone + ethinylestradiol from the new packaging. The delay can be prolonged until the active tablets in the second package run out. During the delay, the woman may have acyclic copious or "smearing" spotting from the vagina.Regular reception of the drug Dimia® resumes after the placebo phase.

To shift the bleeding for another day of the week, it is recommended to shorten the forthcoming phase of taking tablets for the desired number of days. With the shortening of the cycle, it is more likely that the woman will not have a menstrual bleeding of "cancellation", but there will be acyclic copious or "spotting" bloody discharge from the vagina with the next package (the same as with the lengthening cycle).

Side effects:

During the reception of the drug Dimia®, the following undesirable effects were recorded:

Class of organ system	Frequent (> 1/100 to <1/10)	Less frequent (> 1/1000 to <1/100)	Rare (> 1/10000 to <1/1000)
Infections and invasions			Candidiasis, including oral cavity
Violations of the blood and lymphatic system			Anemia, thrombocytopenia
Disorders from the immune system systems			Allergic reaction
Disorders from the metabolism and nutrition		Weight gain	Increased appetite, anorexia, hyperkalemia, hyponatremia, weight loss
Violations psyche	Emotional lability	Depression, decreased libido, nervousness, drowsiness	Anorgasmia, insomnia
Disturbances from the nervous system	Headache	Dizziness, paresthesia	Vertigo, tremor
Disturbances on the part of the organ of sight			Conjunctivitis, dryness of the mucous membrane of the eye, visual impairment
Heart Disease			Tachycardia
Vascular disorders		Migraine, varicose veins, increased blood pressure	Phlebitis, vascular injury, epistaxis, fainting
Disorders from the gastrointestinal tract	Nausea, abdominal pain	Vomiting, diarrhea
Disturbances from the liver and bile ducts			Morbidity of the gallbladder, cholecystitis
Disturbances from the skin and subcutaneous cellulose		Rash (including acne), itching	Chloasma, eczema, alopecia, acne dermatitis, dry skin, erythema nodosum, hypertrichosis, skin lesions, skin striae, contact dermatitis, photodermatitis, cutaneous nodules
Disturbances of the musculoskeletal and connective tissue		Back pain, pain in the limbs, muscle cramps
Disorders from the reproductive system and breast	Pain in the chest, absence of bleeding "cancellation"	Vaginal candidiasis, pelvic pain, enlargement of the mammary glands, fibrocystic breast, vaginal discharge, blood flushes, vaginitis, acyclic spotting, painful menstrual bleeding, profuse bleeding "cancellations", meager menstrual bleeding, dryness of the vaginal mucosa, alteration of the cytological pictures in the Pap smear	Painful sexual intercourse, vulvovaginitis, postcoital bleeding, breast cyst, mammary gland hyperplasia, breast cancer, cervical polyps, endometrial atrophy, ovarian cyst, uterine enlargement
Are common disorders and disorders at the site of administration		Asthenia, increased sweating, edema (generalized edema, peripheral edema, edema of the face)	Feeling discomfort

Women using COC had the following serious adverse events:

venous thromboembolic diseases;

- arterial thromboembolic diseases;

- Liver tumors;

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

- Chloasma;

- acute or chronic liver disease may cause the need to stop taking COCs before normalizing the parameters of functional liver samples;

- In women with hereditary angioedema, exogenous estrogens can induce or enhance symptoms of angioedema.

Overdose:

There have not been any cases of an overdose of Dimia®. Based on the combined experience of combined oral contraceptives Potential symptoms of an overdose may be: nausea, vomiting, slightly pronounced bleeding from the vagina.

There are no antidotes. Further treatment should be symptomatic.

Interaction:

Note: Before taking concomitant medications, you should read the instructions for using the drug to identify potential interactions.

The effect of other drugs on the preparation Dimia®

Interactions between oral contraceptives and other medicines may entailacyclic bleeding and / or ineffectiveness of contraception. The interactions described below are reflected in the scientific literature. The mechanism of interaction with hydantoin, barbiturates, primidon, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations of St. John's wort perfumed (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 this is maintained for a minimum of 4 weeks after discontinuation of drug therapy.

Inefficiency of contraception was also noted when taking antibiotics, for example, ampicillin and tetracycline. The mechanism of this phenomenon is not clear.

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

Women receiving rifampicin therapy, in addition to taking COC,should use the barrier method of contraception and continue its use within 28 days after cessation of treatment with rifampicin. If the taking of concomitant drugs lasts longer than the end of the active tablets in the package, the intake of inactive tablets should be discontinued and immediately begin taking the tablets drospirenone + ethinylestradiol from the following packaging.

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

The major metabolites of drospirenone in human plasma are formed without the involvement of the cytochrome P450 system. Inhibitors of cytochrome P450, therefore, are unlikely to affect the metabolism of drospirenone.

The effect of Dimia® on other drugs

Oral contraceptives can affect the metabolism of some other active substances. Accordingly, the concentrations of these substances in the blood plasma or tissues can either increase (for example, cyclosporine) or decrease (for example, lamotrigine).

Based on inhibition studies in vitro and interactions in vivo women volunteers who took omeprazole, simvastatin and midazolam as a substrate, the effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.

Other interactions

In patients without renal failure, concomitant administration of drospirenone and angiotensin-converting enzyme (ACE) inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) does not significantly affect the serum potassium content. But nevertheless, the simultaneous use of the preparation of Dimia® with aldosterone antagonists or potassium-sparing diuretics has not been investigated. In this case, during the first cycle of treatment, the concentration of serum potassium should be monitored.

Laboratory Tests

Reception of contraceptive steroids may affect the results of some laboratory tests, including the determination of biochemical parameters of the function of the liver, thyroid, adrenals and kidneys, the concentration of plasma proteins (vectors), for example, corticosteroid-binding proteins and lipid / lipoprotein fractions, parameters of carbohydrate metabolism and coagulation parameters and fibrinolysis.In general, the changes remain within the range of normal values. Drospirenone is the cause of increased renin activity in the blood plasma and - due to a slight atimineralocorticoid activity - reduces the concentration of aldosterone in the plasma.

Special instructions:

If there are any conditions / risk factors from among those mentioned below, the benefits of taking COCs should be evaluated individually for each woman and discussed with her before starting the application. In case of an exacerbation of an undesirable phenomenon or in the event of occurrence of any of these conditions or risk factors The woman should contact the attending physician. The doctor must decide whether to interrupt 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 use by a woman of a combined oral contraceptive.

Epidemiological studies have shown that the frequency of VTE in women with no risk factors that took low doses of estrogen (<0.05 mg of ethinylestradiol) in the combined oral contraceptive,is about 20 cases per 100,000 women-years (for levonorgestrel-containing "second generation" COCs) or 40 cases per 100,000 women-years (for desogestrel / gestodensoderzhaschih COC "third generation"). In women who do not use COC, there are 5-10 VTE and 60 pregnancies per 100,000 women-years. VTE is fatal in 1-2% of cases.

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 with or without combination of ethinylestradiol and drospirenone, 0.03 mg + 3 mg, coincides with the frequency of VTE in women using levonorgestrel-containing oral contraceptives and other COCs. The risk of venous thromboembolism with the use of Dimia® is not currently established.

Epidemiological studies have also revealed a linkage of COCs with an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic disorders).

Very rarely, women taking oral contraceptives experienced thrombosis of other blood vessels, for example, veins and arteries of the liver, mesentery, kidneys, brain or retina.There is no consensus on the connection between these phenomena and 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 appearance of cough;

- 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 striking one side or one part of the body;

- movement disorders;

- "sharp" abdomen.

Before starting a COC, a woman should consult a specialist.

The risk of venous thromboembolic disorders when taking combined oral contraceptives (COCs) increases with:

- increase in age;

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

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

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

- the lack of 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 impairment of cerebral circulation when taking combined oral contraceptives (COCs) increases with:

- increase in age;

- Smoking (women over 35 years of age are strongly advised to stop smoking if they want to take COCs);

- dyslipoproteinemia;

- arterial hypertension;

- migraine without focal neurological symptoms;

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

- hereditary predisposition (arterial thromboembolism ever at sibling brothers or parents at a relatively early age). If a hereditary predisposition is possible, a woman should consult a specialist before starting a COC. defeat of the valvular heart; atrial fibrillation.

The presence of one serious risk factor for venous disease or several risk factors for artery disease can also be a contraindication. You should also consider the possibility of anticoagulant therapy. Women taking COC should be properly instructed about the need to inform the doctor in case of suspicion of symptoms of thrombosis. If the thrombosis is suspected or confirmed, the COC should be discontinued. It is necessary to begin adequate alternative contraception due to teratogenicity of anticoagulant therapy (indirect anticoagulants - coumarin derivatives).

An increased risk of thromboembolism in the postpartum period should be considered. Other medical conditions associated with adverse vascular events include diabetes mellitus,systemic lupus erythematosus, haemolytic 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 with COCs may be an indication for the immediate withdrawal 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 developing cervical cancer with long-term use of combined oral contraceptives, but there are conflicting views as to the extent to which these findings are related to, for example, research on cervical cancer or the use of barrier methods of contraception.

A meta-analysis of the results of 54 epidemiological studies revealed a slight increase in relative risk (RR = 1.24) of breast cancer in women who currently take COCs. The risk is gradually reduced within 10 years after discontinuation of COCs.Since breast cancer rarely develops in women under 40 years of age, an increase in the number of diagnosed breast cancers in COCs has little effect on the overall likelihood of breast cancer. In these studies, there was no sufficient evidence of a cause-effect relationship. Increased risk may be due to earlier diagnosis of breast cancer in COCs, the biological effects of COCs, or a combination of both. Diagnosed breast cancer in women who have ever taken COC was clinically less severe, which is due to early diagnosis of the disease.

Rarely, women who took COCs had benign liver tumors and, even more rarely, malignant liver tumors. In some cases, these tumors were life-threatening because of intra-abdominal hemorrhage. This should be taken into account when making a differential diagnosis in the event of severe pain in the abdomen, liver enlargement, or signs of intra-abdominal bleeding.

Other

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

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

Although a small increase in blood pressure was noted in many women who took combined oral contraceptives (COCs), clinically significant increases were rare. Only in these rare cases is it justified to immediately stop taking COC. If, when taking COC in patients with concomitant arterial hypertension, the blood pressure (BP) is constantly increased,or significantly increased blood pressure can not be corrected by antihypertensive drugs, the use of COC should be discontinued. After the normalization of blood pressure with the help of antihypertensive drugs, the use of COCs can be resumed.

The following diseases appeared or aggravated in pregnancy and during the administration of COC, however, the evidence of their relationship with the administration of COCs is unconvincing: jaundice and / or pruritus associated with cholestasis, stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; rheumatic chorea (Sydenham's chorea); herpes during pregnancy; otosclerosis with loss of hearing.

In women with hereditary angioedema, exogenous estrogens can induce or enhance symptoms of edema.

Acute or chronic liver disease may be an indication that COC is discontinued before the liver function is normalized. The recurrence of cholestatic jaundice and / or cholestasis-associated pruritus that developed during a previous pregnancy or with earlier use of sex hormones serves as an indication for stopping COCs.

Although COCs may affect peripheral insulin resistance and glucose tolerance, a change in the treatment regimen in patients with diabetes mellitus when taking COCs with a low hormone content (containing <0.05 mg ethinylestradiol) is not indicated. However, women with diabetes mellitus should be closely monitored, especially in the early stages of COC administration.

During the administration of COC, aggravation of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis was observed.

Chloasma may occur from time to time, especially in women who have already had a history of chloasma. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation when taking COC.

Pills drospirenone + ethinylestradiol in the shell contain 48.53 mg of lactose monohydrate, placebo tablets contain 37.26 mg of anhydrous lactose per tablet. Patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency, or glucose-galactose absorption impairment that observe a lactose-free diet, should not take this drug.

Allergic reactions may occur in women who are allergic to soy lecithin.The effectiveness and safety of the drug Dimia® as a contraceptive was studied in women of reproductive age. It is assumed that in the post-pubertal period up to 18 years, the effectiveness and safety of the drug are similar to those in women after 18 years of age. The use of the drug before the menarche is not shown.

Medical examinations

Before starting or re-applying the drug, you should collect a complete medical history (including a 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 mentioned in it. Periodicity and content of the survey should be based on existing practical guidelines. The frequency of medical examinations is individual for each woman, but should be conducted at least once every 6 months.

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

Decreased efficiency

The effectiveness of COCs may be reduced, for example, by skipping tablets drospirenone + ethinylestradiol, gastrointestinal disorders at the time of taking tablets drospirenone + ethinylestradiol or simultaneous administration of other medications.

Insufficient cycle control

As with the use of other COCs, acyclic bleeding ("smearing" or bleeding "withdrawal") can occur in a woman, especially in the first months of admission. Therefore, any irregular bleeding should be assessed after a three-month adaptation period.

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

In some women, bleeding "cancellation" does not occur during the placebo phase. If the COC was taken in accordance with the instructions for use, it is unlikely that the woman is pregnant. However, if the admission rules were violated before the first missed menstrual-like "withdrawal" bleeding, or if two bleedings are missed,Before continuing with COC, pregnancy should be excluded.

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

Not found.

Form release / dosage:

Tablets, film-coated [set], 3 mg + 0.02 mg.

Packaging:

For 24 tablets of drospirenone + ethinyl estradiol and 4 tablets in a blister of PVC / PE / PVDC aluminum foil.

For 1 or 3 blisters in a cardboard box together with instructions for use. In the cardboard box is enclosed a cardboard flat case for storing the blister.

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

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001179

Date of registration:11.11.2011

Date of cancellation:2016-11-11

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

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp22.01.2016

Illustrated instructions

Instructions

Dimia® (Dimia®)