Drospirenone preparations containing. Drospirenone: what is this hormone, main characteristics and purpose of the hormone

Chemical properties

Drospirenone - what is it? This substance belongs to the group of oral contraceptives. Most often it is used in combination with other hormones. The drug may have a therapeutic effect on androgen-dependent diseases .

Drospirenone - what is this hormone? Drospirenone is a synthetic hormone that is close to natural in its properties. progesterone , derivative spironolactone . Molecular weight of a chemical compound = 366.5 grams per mole. The density of the substance \u003d 1.26 grams per cm3, the melting point is approximately 200 degrees Celsius.

Drospirenone on Wikipedia is mentioned in articles about hormonal contraception and the effect medicines on human sexual function.

pharmachologic effect

Gestagennoe , antigonadotropic , antimineralocorticoid , antiandrogenic .

Pharmacodynamics and pharmacokinetics

Due to the fact that this substance has pronounced antiandrogenic properties, it has a positive effect on the flow androgen-dependent diseases , such as acne , alopecia and seborrhea . Drospirenone stimulates excretion sodium ions and other fluids from the body, as a result of which it normalizes arterial pressure, swelling and soreness in the mammary glands subsides, body weight decreases.

Clinical studies have shown that after 4 months of using the drug, systolic pressure decreases by an average of 2-4 mm Hg, and diastolic pressure by 1-3 mm Hg. Art., weight is reduced by 1-2 kg. In women during menopause, the likelihood of developing colon cancer , hyperplasia and endometrial cancer .

Synthetic hormone does not have estrogenic , androgenic and glucocorticosteroid activity , does not change insulin resistance and body response to glucose . During treatment with the drug, the patient's level decreases. cholesterol in blood and LDL , slightly increasing the concentration triglycerides .

After taking tablets containing Drospirenone, the active substance is quickly and almost completely absorbed by the body. The bioavailability of the substance is about 75-85%. Parallel eating does not affect pharmacokinetics of the drug . The concentration of the drug in the blood plasma decreases in two phases, the half-life is 35-40 hours. With a systematic, daily intake, the equilibrium concentration of the drug is observed after 10 days.

The agent has a high degree of binding to plasma proteins (serum albumen ) - about 95-97%. The main metabolites of the hormone are formed without affecting cytochrome P450 system . The drug is excreted in the form of metabolites with feces and urine, a small part is excreted unchanged.

Indications for use

• as part of complex therapy for the prevention of postmenopausal osteoporosis ;
• if hormonal contraception is needed in women with a deficiency folate or fluid retention in the body;
• as a hormone replacement treatment for menopausal disorders to eliminate tides , sweating and other vasomotor symptoms;
• with involutional changes in the genitourinary tract in women with an unremoved uterus;
• in combination with other synthetic hormones for contraception;
• for contraception in severe PMS ;
• in severe and moderate form acne for contraception.

Contraindications

• patients with allergies on Drospirenone;
• at porphyria ;
• persons with a penchant for education blood clots ;
• with severe liver failure;
• during lactation;
• at thromboembolism or thrombophlebitis in severe form;
• if the patient has vaginal bleeding of unknown origin;
• at breast cancer or other genital organs;
• pregnant women.

Side effects

During treatment with the drug may develop:

• allergic reactions of varying severity, dizziness;
• thromboembolism pulmonary artery or vessels of the brain;
• thrombophlebitis , blood clots in the veins of the retina;
• arterial hypertension , swelling, headaches;
• calculous cholecystitis ;
• drowsiness ,apathy , depressive states ;
• decreased visual acuity, vomiting, weight gain or loss;
• galactorrhea , nausea, hirsutism ;
• alopecia , pain and swelling of the mammary glands;
• bloody or unusual vaginal discharge;
• decreased sex drive, chloasma ;
• insomnia , lowering the seizure threshold, varicose veins .

Drospirenone, instructions for use (Method and dosage)

Depending on the combination in which this hormone is in the tablet, it is prescribed according to various treatment regimens. According to the instructions for Drospirenone tablets, it is taken once a day, at the same time.

Therapy begins after the abolition of the previous hormonal agent, in accordance with the doctor's recommendations. The duration of treatment is also set on an individual basis and often depends on the effectiveness of the therapy.

Overdose

In case of overdose, nausea, vaginal bleeding, and vomiting may occur. Due to the fact that the drug has no specific antidote the treatment is symptomatic.

Interaction

With long-term treatment with drugs that induce liver enzymes ( barbiturates , carbamazepine , oscarbazepine , hydantoin derivatives , primidone , rifampicin , topiramate , griseofulvin , felbamate ) increases the clearance of a given substance and reduces their effectiveness. As a rule, this effect appears 2-3 weeks after the start of therapy and persists for a month after stopping the drugs.

The drug reduces the effectiveness of drugs that stimulate the smooth muscles of the uterus and anabolic steroids .

Terms of sale

special instructions

In a number of uncontrolled randomized trials, an increased risk of developing venous thromboembolism during drug treatment. It is necessary to prescribe the drug with extreme caution to women who have a predisposition to the occurrence of venous thromboembolism (heredity, obesity , age). It is necessary to carefully correlate the risk-benefit indicators.

Rarely, on the background of treatment, benign ones occurred, and even more rarely - malignant tumors of the liver . If the patient has any symptoms this disease, pain in the area under the ribs, an increase in the organ and intra-abdominal bleeding, then treatment must be interrupted.

In patients with moderate to mild renal insufficiency, taking this synthetic hormone may affect the concentration potassium ions in blood serum. There is a small risk of developing hyperkalemia especially if the patient is additionally taking potassium-sparing drugs .

Before starting treatment with the drug, it is recommended to undergo a gynecological and general medical examination, it is recommended to pay special attention to cytological examination of church mucus and mammary glands, blood coagulation system, exclude pregnancy. During therapy, these studies should be repeated periodically.

With antibiotics

It is likely that some antibiotics may interfere with drug metabolism.

Instructions from tablets Listel.Ru

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Description of the active substance Drospirenone / Drospirenone.

Formula: C24H30O3, chemical name: (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3',4',6,6a,7,8,9,10,11,12 ,13,14,15,15a,16-hexadecahydro-10,13-dimethylspiro-cyclopenta[a]phenanthrine-17,2'(5H)-furan]-3,5'(2H)-dione).
Pharmacological group: hormones and their antagonists / estrogens, gestagens; their homologues and antagonists.
Pharmachologic effect: gestagenic, antiandrogenic, antigonadotropic, antimineralocorticoid.

Pharmacological properties

Drospirenone is a derivative of spironolactone. Drospirenone has a therapeutic effect on androgen-dependent diseases: seborrhea, acne, androgenetic alopecia. Drospirenone increases the excretion of water and sodium ions, which can prevent weight gain, blood pressure, breast tenderness, swelling, and other symptoms associated with fluid retention. Drospirenone does not have androgenic, estrogenic, antiglucocorticosteroid, glucocorticosteroid activity, does not affect insulin resistance and glucose tolerance, which, together with antiandrogenic and antimineralocorticoid effects, provides it with a pharmacological and biochemical profile that is similar to natural progesterone. Drospirenone reduces the rise in triglyceride levels, which is caused by estradiol. The mechanism of action of drospirenone is still unclear. When administered orally, drospirenone is completely and rapidly absorbed. The bioavailability of drospirenone is 76 - 85%. Food intake does not affect bioavailability. The maximum concentration is reached after 1 hour and is 22 ng / ml with multiple and single doses of 2 mg of drospirenone. This is followed by a biphasic decrease in plasma levels of drospirenone with a terminal elimination half-life of approximately 35 to 39 hours. Approximately 10 days later daily intake drospirenone reaches equilibrium concentration. Due to the long half-life of drospirenone, the steady-state concentration is 2 to 3 times the concentration at a single dose. Drospirenone binds to plasma albumin and does not bind to corticoid-binding globulin and globulin, which binds sex hormones. Approximately 3 - 5% of drospirenone does not bind to proteins. The main metabolites of drospirenone are 4,5-dihydrodrospirenone-3-sulfate and the acidic form of drospirenone, which are formed without the participation of the cytochrome P450 system. The clearance of drospirenone is 1.2 - 1.5 ml / min / kg. Drospirenone is excreted mainly in the form of metabolites with feces and urine in a ratio of 1.4: 1.2, with a half-life of approximately 40 hours; an insignificant part of drospirenone is excreted unchanged.

Indications

As part of combined treatment: prevention of postmenopausal osteoporosis; substitution hormonal treatment with menopausal disorders in the post-menopausal period, including vasomotor symptoms (increased sweating, hot flashes), depression, sleep disturbance, irritability, involutional changes in the genitourinary tract and skin in women with an unremoved uterus; contraception; contraception and treatment of severe premenstrual syndrome; contraception and treatment of moderate acne); contraception in women with folate deficiency; contraception for women with symptoms of hormone-dependent fluid retention in the body.

Dosing and Administration of Drospirenone

The method of administration and doses are set individually by the doctor, depending on the indications and the dosage form used.

Contraindications for use

Hypersensitivity, porphyria, tendency to thrombosis, pronounced violations of the functional state of the liver, acute forms of thromboembolic diseases or phlebitis, vaginal bleeding of unknown origin, cancer of the breast and genital organs, pregnancy, breast-feeding.

Application restrictions

Pathology of the circulatory system, including arterial hypertension, severe violations of the functional state of the kidneys, bronchial asthma, diabetes mellitus, pathology of the central nervous system including depression, epilepsy, migraine.

Use during pregnancy and lactation

Drospirenone is contraindicated in pregnancy and lactation.

Side effects of drospirenone

Allergic reactions, thromboembolism (including cerebral and pulmonary arteries), retinal vein thrombosis, thrombophlebitis, dizziness, increased blood pressure, calculous cholecystitis, edema, cholestatic hepatitis, headache, drowsiness, depression, dysphoria, apathy, blurred vision, nausea, decreased appetite, vomiting, galactorrhea, changes in body weight, alopecia, hirsutism, enlargement, tension and pain and mammary glands, disorders menstrual cycle(intermittent bleeding, contraction), decreased libido, spotting bloody issues, breakthrough uterine bleeding, change in the nature of vaginal discharge, a condition similar to premenstrual syndrome, an increase in the size of fibromyomas, benign formations of the mammary glands, skin itching, skin rash, chloasma, erythema multiforme, erythema nodosum, migraine, anxiety, fatigue, insomnia, palpitations, edema, varicose veins, muscle cramps, intolerance contact lenses.

Interaction of drospirenone with other substances

Long-term therapy with drugs that induce liver enzymes (including barbiturates, hydantoin derivatives, primidone, rifampicin, carbamazepine, oxcarbazepine, felbamate, topiramate, griseofulvin) may increase the clearance of sex hormones and reduce their effectiveness. Drospirenone may reduce the effectiveness of anabolic steroids and drugs that stimulate uterine smooth muscle.

Overdose

With an overdose of drospirenone, nausea, vomiting, vaginal bleeding are possible. Necessary symptomatic treatment there is no antidote.

Trade names of drugs with the active substance drospirenone

Used in combined preparations:
Drospirenone + Estradiol: Angeliq®;
Drospirenone + Ethinylestradiol: Dailla®, Jess®, Midiana®, Yarina®;
Drospirenone + Ethinylestradiol + [Calcium levometholinate]: Jess® Plus, Yarina® Plus;
Ethinylestradiol + Drospirenone: Dimia®, Yarina®.

Farmgroup:

Reviews and comments

Good evening! I read that

Inna Sun, 21/09/2014 — 23:12

Good evening! I read that the drug JES is effectively used to treat acne in adolescence. I would like to know the dosage and contraindications. For a 14-year-old girl, the menstrual cycle has not been established, the rashes are very plentiful, is it possible to use the drug?

It's too early for Jess girl

It's too early for the girl Jess, it is advisable to wait for a regular cycle.

Drospirenone is a hormone that belongs to the group of oral contraceptives. On its basis, a large number of contraceptive drugs are manufactured, as well as medicines that have a therapeutic effect on androgen-dependent diseases. You can buy the substance in any city, but only by prescription. The low cost allows you to use the hormone even in the absence of financial opportunities.

General information

Before you start using various oral contraceptives, you need to understand in detail what kind of hormone Drospirenone is. Its properties allow the use of the substance in combination with other hormones, which maximizes the therapeutic effect.

Substance Information

Drospirenone is a synthetic hormone and is a derivative of Spironolactone, a potassium-sparing diuretic, competitive antagonist of aldosterone and other mineralocorticoids. By their own pharmacological properties it is very similar to natural Progesterone - an endogenous steroid and progestogenic sex hormone that affects the menstrual cycle, pregnancy and embryonic development in humans.

Main chemical and physical parameters:

• molecular weight - 366.5 µg/mol;
• melting point - 200 degrees Celsius;
• density - 1.26 g / cubic centimeter.

The hormone is able to influence the sexual function of a person, as well as have antigonadotropic, gestagenic, antiandrogenic and antimineralocorticoid effects.

To find out which contraceptives contain Drospirenone, you need to consult with your doctor. Only he can accurately determine the most effective option that will perform its functions efficiently and not have a negative impact on health.

Drospirenone is often used in various combination birth control pills(COC) as an active ingredient. V pure form The hormone is found in only two drugs:

1. Yarina. This medication is available in the form of film-coated tablets. It is used only to prevent unwanted pregnancy. The drug has many contraindications, so it should be taken with extreme caution. It is important to follow all the prescriptions of doctors and limit the number of tablets taken.
2. Angelique. This medicine is also available as film-coated tablets, which may vary in color. It is used for the prevention of postmenopausal osteoporosis, as well as for menopausal disorders in women with an unremoved uterus. The drug has practically no negative effect on the body, but has several features of use. If you follow all of them, then you can avoid any side effects.

In all other contraceptives, Drospirenone is used as one of the components. In the right proportions, it complements other chemical compounds and allows you to achieve the desired therapeutic effect.

In all these preparations and their analogues, Ethinylestradiol, Estradiol, Dienogest, Chlormadinone, Cyproterone acetate act as an additional active substance.

Indications for use

Most drugs based on Drospirenone have the same indications, so they are often considered together. Doctors recommend using the hormone only as directed. Otherwise, you can harm your health.

• prevention of postmenopausal osteoporosis (as part of complex therapy);
• hormonal contraception in women with fluid retention or folate deficiency (essential vitamins);
• hot flashes, sweating and other vasomotor symptoms in menopausal disorders;
• involutional changes in the genitourinary tract (only in patients with an unremoved uterus);
• prevention of pregnancy (in combination with other synthetic hormonal agents);
• contraception for severe premenstrual syndrome.

Main contraindications

Drospirenone has several contraindications. They must be taken into account before buying medicines and starting to use them. Otherwise, you can form various problems that develop into a full-fledged disease.

It is forbidden to use drugs with the hormone Drospirenone in such situations:

• porphyrin disease (a hereditary disorder of pigment metabolism with an increased content of porphyrins in the blood and tissues, as well as their increased release);
• tendency to thrombosis;
• severe form of thrombophlebitis and thromboembolism;
• acute liver failure;
• the presence of vaginal bleeding of unknown etiology;
• all trimesters of pregnancy;
• period breastfeeding baby;
• individual intolerance to the hormone.

In some cases, Drospirenone is considered relatively banned. In such a situation, it is allowed to use it with extreme caution. During the period of treatment, it is important not only to comply with the prescribed dosages, but also to limit the duration of the course of taking the drugs. If the slightest negative changes in the state of health are detected, the therapy should be stopped immediately and seek help from the nearest medical facility.

With caution, Drospirenone is taken in such cases:

• diabetes.

• arterial hypertension (long-term increase in blood pressure);
• cholestatic jaundice (a pathological process in the patient's body, in which bile does not enter the duodenum through the liver, but accumulates in the blood);
• cholestatic itching that appears during pregnancy;
• Gilbert's syndrome (a hereditary disease characterized by episodes of jaundice, which develops as a result of an increase in indirect bilirubin in the blood serum);
• Rotor's syndrome (hereditary pigmentary hepatosis);
• Dubin-Johnson syndrome (pigmented hepatosis, characterized by impaired excretion of conjugated bilirubin from hepatocytes into the bile capillaries);
• endometriosis (a disease characterized by the growth of endometrial cells);
• diabetes.

Instructions for use

In order for Drospirenone to have the most effective effect, it is necessary to take it correctly. To do this, accurately calculate the dosage and determine the allowable duration of use. Only in this case it is possible to achieve the desired therapeutic effect and avoid any negative consequences.

Dosages and rules

Dosages and rules

All preparations containing Drospirenone are available in the form of tablets intended for oral administration. They must be swallowed whole and washed down with plenty of clean water without gas (at least 200 ml). In this case, the liquid must be heated to room temperature. It is forbidden to crush the tablets in any way, as this may lead to a loss of their effectiveness.

1. It is forbidden to use more than 1 tablet per day, as this may adversely affect the female body.
2. You can take Drospirenone at any time of the day. It is important to take the tablets every day at the same time (for example, before going to bed or after waking up).
3. If you miss a dose, it is forbidden to compensate for forgetfulness and drink 2 tablets at once.
4. If a long-term suspension of the course is necessary, the therapy regimen should be adjusted. This work should be entrusted to a highly qualified doctor who will take into account all the nuances of the current situation and find the best solution.

Side effects

If it is wrong to take contraceptives containing the hormone Drospirenone, then you may encounter side effects. As a result, their health may deteriorate.

1. Circulatory system. In rare cases, patients may experience thrombocytosis and anemia.
2. The immune system. The drug can cause various allergic reactions. There are negative consequences from the increased sensitivity of the body to the hormone.
3. Metabolism. Women taking Drospirenone may develop hyponatremia and hyperkalemia.
4. Nervous system. Patients often complain of severe headaches and dizziness. Migraine develops, nervousness, drowsiness and depression appear. With large overdoses, tremor, vertigo and anorgasmia may occur.
5. organs of vision. Drospirenone can affect visual acuity, as well as cause dry eye syndrome and conjunctivitis.
6. The cardiovascular system. With errors in taking pills, tachycardia and arterial hypertension may develop. Rarely, arterial and venous thromboembolism, varicose veins, epistaxis, and phlebitis are formed.
7. Digestive system. Women suffer from pain in the abdomen, exacerbation of gastritis, severe diarrhea, bouts of nausea and vomiting. Gastrointestinal disorders, candidiasis are much less common oral cavity and a feeling of fullness in the abdomen.
8. Skin covers. A common side effect is a rash on the surface of the skin, accompanied by severe itching. In addition, acne dermatitis, eczema, erythema, hypertrichosis and dry skin occur.
9. Musculoskeletal system. The hormone can cause pain in the back, limbs and muscles.
10. reproductive system. In women, there are pains in the mammary glands, amenorrhea and metrorrhagia. With excessive dosages, vaginal and uterine bleeding, menstrual irregularities, hypomenorrhea and dysmenorrhea may occur.
11. General disorders. Patients may experience increased sweating, weight gain, weakness, asthenia.

special instructions

During clinical trials, some features of Drospirenone were discovered. Thanks to them, errors in application can be avoided and dosages can be accurately calculated.

1. Studies have found that the use of the hormone increases the risk of developing venous thromboembolism. Because of this, changes in the health status of women predisposed to this disease should be closely monitored.
2. Patients with mild to moderate renal insufficiency should regularly monitor the concentration of potassium ions in the blood.
3. It is possible to use contraceptives containing Drospirenone only after passing a full examination and passing all the tests.
4. Women suffering from chronic liver diseases should periodically monitor the performance of this organ.
5. With moderate hypertriglyceridemia, it is necessary to monitor the amount of triglycerides in the blood.
6. Patients with diabetes varying degrees of severity can use Drospirenone only under medical supervision.
7. The hormone does not combine well with alcohol, therefore, for the period of therapy, you should refrain from drinking alcohol.
8. Drospirenone causes drowsiness and reduces the reaction rate. Because of this feature, it is forbidden to drive a car or any other vehicle. It is not recommended to perform work that requires special care and increased concentration.

Pharmacological interaction

Before taking drugs containing Drospirenone, it is necessary to take into account not only their characteristics, but also the interaction with other drugs. Some combinations may cause the development side effects and reduce the therapeutic effect.

The main combinations and their consequences for the body:

1. When taken simultaneously with drugs that induce liver enzymes (Carbamazepine, Primidone, Topiramate), their effectiveness decreases.
2. Drospirenone reduces the therapeutic effect of taking anabolic steroids and drugs that stimulate the smooth muscles of the uterus.
3. The concentration of the hormone in the blood is significantly reduced due to interaction with antibiotics of the tetracycline and penicillin groups.
4. Combination with paracetamol may result in increased bioavailability.
5. Some non-steroidal anti-inflammatory drugs may affect the concentration of potassium in the blood serum.
6. Drospirenone increases the activity of Aldosterone and Renin.

Cost and comparison with other hormones

All medicines containing Drospirenone are included in the register of medicines (RLS), so they can be sold throughout Russia. You can buy them not only in large settlements, but also in smaller ones. The cost of drugs in Moscow can vary from 1 to 5 thousand rubles. In other cities and regions of the country, the price is slightly lower than the capital, and in neighboring states it is higher.

To determine which is better, Drospirenone, Desogestrel or any similar hormone, it is necessary to study in detail all the available information. Thanks to her, you can find out the main differences and choose the best option that will not have a negative impact on the patient.

Drospirenone or Gestodene is best taken only after consulting a doctor and undergoing various tests. Otherwise, each of these hormones can cause deterioration and the development of side effects.

Drospirenone is one of the most popular hormones in oral contraceptives. With its correct application and compliance with all the recommendations of doctors, you can achieve the desired result and avoid any complications.

A substance called drospirenone is a chemical compound related to progestogens used to create hormonal contraceptives. This chemical compound can only be used in combination with estrogens, and cannot be prescribed in its pure form for contraceptive purposes.

In addition to contraceptive activity, drospirenone in contraceptives has a therapeutic effect in diseases such as seborrhea and acne.

Properties and difference from other hormones

The distinctive properties of the hormone drospirenone are that this chemical compound has a therapeutic effect in the so-called androgen-dependent diseases. These diseases include oily seborrhea and acne. In addition, this substance helps to remove excess interstitial fluid from the body, thereby eliminating edema, normalizing blood pressure, reducing body weight and stopping pain in the mammary glands.

Women with severe premenstrual syndrome know firsthand about each of these symptoms. Also, throughout the replacement hormone therapy, tablets with drospirenone reduce the level of low-density lipoproteins in the female body and increase the content of triglycerides.

Important! Oral contraceptives based on drospirenone, during menopause, significantly reduce the likelihood of developing cancer and endometrial hyperplasia, as well as colon cancer in women.

Drospirenone or gestodene

Both chemical compounds are synthetic hormones. latest generation. Gestodene and drospirenone have a high level of effectiveness and a minimal risk of adverse reactions. If we talk about the differences between the hormone drospirenone and the hormone gestodene, then drugs based on gestodene are more often prescribed to patients with severe signs of dysmenorrhea in order to restore the regularity of the menstrual cycle. Preparations based on drospirenone are advisable to prescribe in order to protect against the onset of unwanted pregnancy, as well as to reduce the severity of premenstrual syndrome. It is important to remember that drospirenone therapy can cause hyperkalemia and thromboembolic complications.

Drospirenone or dienogest

These biologically active compounds belong to the category of progestins that are part of combined oral contraceptives. The key difference between the hormone drospirenone and dienogest is that dienogest combines not only the action of progesterone, but also the effect of testosterone. Also, dienogest is the only progesterone analogue that can suppress the effect of 17-beta-estradiol at the peripheral level, without significantly affecting the level of follicle-stimulating and luteinizing hormones.

Drospirenone or desogestrel

Both biologically active compounds are new generation hormonal contraceptives. By analogy with gestodene, desogestrel is used to eliminate clinical signs dysmenorrhea.

It is impossible to say unequivocally that drospirenone or the hormone desogestrel is better, since both substances differ in contraceptive and therapeutic efficacy.

The only difference is that compared to drospirenone, desogestrel does not increase the risk of gaining extra pounds.

Dosage and rules for taking the hormone

Contraceptive contraceptives with drospirenone can be prescribed for various regimens, which are selected by the attending physician on an individual basis. As a rule, the standard scheme for taking such drugs requires the use of a contraceptive 1 tablet, 1 time per day, at a strictly designated time. Regardless of the name, drugs based on drospirenone are dispensed in pharmacies only on medical prescriptions.

drug interaction

Contraceptives based on drospirenone significantly inhibit the effects of uterotonics and anabolic steroids.

Also, drospirenone negatively affects the level of effectiveness of such medicines like Primidone, Oscarbazepine, Carbamazepine, barbiturate derivatives, Rifampicin, Felbamate.

Contraceptives with drospirenone

All contraceptive preparations with drospirenone are combined in general list including the following names:

Each of the above drugs contains a combination of drospirenone and ethinyl estradiol. Jess Plus and Yarina Plus preparations, in addition to these components, include calcium levomefolikat.

Indications

Given the antimineralocorticoid, antigonadotropic, antiandrogenic and progestogenic properties of drospirenone, this type of contraception can be prescribed if there are such indications:

1. Folate deficiency.
2. Oily seborrhea and acne.
3. As part of the complex therapy of postmenopausal osteoporosis.
4. Severe manifestations of premenstrual syndrome.
5. Chronic stagnation of fluid in the body.
6. Severe manifestations of menopause.
7. To protect against unwanted pregnancy.

Contraindications

Hormonal contraceptives containing drospirenone cannot be used if there are such contraindications:

Side effects of contraceptives with drospirenone

Taking a contraceptive consisting of drospirenone and estradiol, you may encounter a list of such adverse reactions from the body:

1. Headache and dizziness.
2. Skin and systemic allergic reactions.
3. Bloody discharge from the genital tract in the intermenstrual period.
4. Chloasma.
5. Alopecia.
6. Varicose veins.
7. Increase or decrease in body weight.
8. Insomnia, drowsiness, depressive disorders and apathy.
9. Formation of stones in gallbladder.
10. Nausea and vomiting.
11. Decreased visual acuity.
12. Galactorrhea.

If the contraceptive dosing regimen is violated, complications such as uterine bleeding, vomiting and nausea may occur.

Important Notes

Before starting a course of therapy with contraceptive pills containing drospirenone, you need to pay attention to the following recommendations:

In addition, the pharmacological effect of biphasic hormonal COCs based on drospirenone is significantly reduced when interacting with antibacterial drugs penicillin and tetracycline series.

In order to avoid the development of serious complications, the choice of names of contraceptives and their dosages should be performed by the attending gynecologist on an individual basis.

Russian name

Drospirenone + Estradiol

Latin name of substances Drospirenone + Estradiol

Drospirenonum + Oestradiolum ( genus. Drospirenoni + Oestradioli)

Pharmacological group of substances Drospirenone + Estradiol

Model clinical and pharmacological article 1

Pharma action. Combined estrogen-gestagenic drug. Estradiol in the human body turns into natural 17 beta-estradiol. Drospirenone is a derivative of spironolactone with progestogenic, antigonadotropic and antiandrogenic, as well as antimineralocorticoid effects. Estradiol compensates for the deficiency of estrogen in the body after menopause and provides effective treatment of psycho-emotional and vegetative menopausal symptoms (such as "hot flashes", increased sweating, sleep disturbance, increased nervous irritability, irritability, palpitations, cardialgia, dizziness, headache, decreased libido, myalgia , arthralgia); involution of the skin and mucous membranes, especially the mucous membranes of the genitourinary system (urinary incontinence, dryness and irritation of the vaginal mucosa, dyspareunia). Prevents bone loss caused by estrogen deficiency, which is mainly associated with the suppression of osteoclast function and a shift in the process of bone remodeling towards bone formation. It has been proven that long-term use of HRT can reduce the risk of peripheral bone fractures in postmenopausal women. With the abolition of HRT, the rate of decrease in bone mass is comparable to that characteristic of the period immediately after menopause. It has not been proven that, using HRT, it is possible to restore bone mass to pre-menopausal levels. HRT also has a positive effect on the content of collagen in the skin, skin density, and slows down the formation of wrinkles. Due to the antiandrogenic properties of drospirenone, the drug has a therapeutic effect on androgen-dependent diseases such as acne, seborrhea, androgenetic alopecia. Drospirenone has antimineralocorticoid activity, increases the excretion of Na + and water, which can prevent an increase in blood pressure, body weight, edema, breast tenderness, and other symptoms associated with fluid retention. After 12 weeks of using the drug, there is a slight decrease in blood pressure (systolic - an average of 2-4 mm Hg, diastolic - 1-3 mm Hg). The effect on blood pressure is more pronounced in women with borderline arterial hypertension. After 12 months of using the drug, the average body weight remains unchanged or decreases by 1.1-1.2 kg. Drospirenone is devoid of androgenic, estrogenic, glucocorticosteroid and antiglucocorticosteroid activity, does not affect glucose tolerance and insulin resistance, which, in combination with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone. Taking the drug leads to a decrease in the concentration of total cholesterol and LDL, as well as a slight increase in the concentration of triglycerides. Drospirenone reduces the rise in triglycerides caused by estradiol. The addition of drospirenone prevents the development of hyperplasia and endometrial cancer. Observational studies suggest that among postmenopausal women, the use of HRT reduces the incidence of colon cancer. The mechanism of action is still unclear.

Pharmacokinetics. Estradiol: after oral administration, it is rapidly and completely absorbed. During absorption and "primary passage" through the liver, estradiol is largely metabolized (including estrone, estriol and estrone sulfate). Bioavailability - about 5%. Eating does not affect the bioavailability of estradiol. C max - 22 pg / ml, TC max - 6-8 hours. C ss of estradiol after repeated administration is approximately 2 times higher than after a single dose. On average, the concentration of estradiol in the blood serum is in the range of 20-43 pg / ml. After stopping the drug, the concentrations of estradiol and estrone return to their original values ​​within 5 days. Estradiol binds to albumin and sex hormone-binding globulin (SHBG). The free fraction of estradiol in serum is approximately 1-12%, and the fraction of the substance associated with SHBG is 40-45%. The apparent volume of distribution is about 1 l / kg. It is metabolized mainly in the liver, and also partially in the intestines, kidneys, skeletal muscles and target organs with the formation of estrone, estriol, catechol estrogens, as well as sulfate and glucuronide conjugates of these compounds, which have significantly less estrogenic activity or are pharmacologically inactive. The clearance of estradiol is about 30 ml / min / kg. Estradiol metabolites are excreted in the urine and bile with T 1/2 - 24 hours. Drospirenone: after oral administration, it is rapidly and completely absorbed. Bioavailability - 76-85%. Eating does not affect bioavailability. Cmax - 22 ng / ml, TC max - 1 hour after single and multiple doses of 2 mg of drospirenone. After that, a two-phase decrease in serum concentration is observed with a final T 1/2 of about 35-39 hours. C ss is achieved after about 10 days of daily administration of the drug. Due to the long T 1/2 of drospirenone, C ss is 2-3 times higher than the concentration after a single dose. Drospirenone binds to serum albumin and does not bind to SHBG and corticoid-binding globulin. About 3-5% of drospirenone does not bind to proteins. The main metabolites are the acidic form of drospirenone and 4,5-dihydrodrospirenone-3-sulfate, which are formed without the participation of the cytochrome P450 system. Drospirenone clearance - 1.2-1.5 ml / min / kg. It is excreted mainly in the form of metabolites with urine and feces in a ratio of 1.2:1.4, with a T 1/2 of about 40 hours; a small part is displayed unchanged.

Indications. HRT for menopausal disorders in the post-menopausal period in women with an unremoved uterus. Prevention of postmenopausal osteoporosis.

Contraindications. Hypersensitivity, vaginal bleeding of unknown origin, established or suspected breast cancer, established or suspected hormone-dependent precancerous diseases or hormone-dependent malignant tumors, benign or malignant liver tumors (including history), severe liver disease, severe kidney disease, incl. .h. in history (before normalization of renal function), acute arterial thrombosis or thromboembolism (including myocardial infarction, stroke), deep vein thrombosis in art. exacerbations, venous thromboembolism (including history), severe hypertriglyceridemia, pregnancy, lactation.

Carefully. Arterial hypertension, congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndrome), cholestatic jaundice or cholestatic itching during pregnancy, endometriosis, uterine fibroids, diabetes mellitus.

Dosing. Inside, 1 tablet daily. The tablet is swallowed whole with a small amount of liquid. If a woman is not taking estrogen or is switching from another combination hormonal drug for continuous use, she can start treatment at any time. Patients who transition from combination drug for cyclic HRT, should start taking the drug after the end of the "withdrawal" bleeding.

After finishing taking 28 tablets from the current package, the next day start a new package, taking the first tablet on the same day of the week as the first tablet from the previous package.

The time of day when a woman takes the drug does not matter, however, if she started taking the pills at any particular time, she should stick to this time and beyond. The forgotten tablet should be taken as soon as possible. If more than 24 hours have passed since the usual time of administration, an additional tablet should not be taken. If several tablets are missed, vaginal bleeding may develop.

Side effect. On the part of the reproductive system: "breakthrough" uterine bleeding and spotting (usually stop during therapy), a change in the nature of vaginal discharge, an increase in the size of fibroids, a condition similar to premenstrual syndrome; soreness, tension and / or enlargement of the mammary glands, benign formations of the mammary glands.

From the side digestive system: dyspepsia, bloating, nausea, vomiting, abdominal pain, recurrence of cholestatic jaundice.

From the side skin: skin rash, pruritus, chloasma, erythema nodosum, erythema multiforme.

From the side of the central nervous system: headache, migraine, dizziness, emotional lability, anxiety, increased nervous excitability, increased fatigue, insomnia.

Others: rarely - palpitations, edema, increased blood pressure, varicose veins, superficial thrombophlebitis, venous thrombosis and thromboembolism, muscle cramps, changes in body weight, changes in libido, visual impairment, intolerance to contact lenses, allergic reactions.

Overdose. Acute toxicity studies have not revealed the risk of developing acute side effects in case of accidental administration of the drug in an amount many times higher than the daily therapeutic dose.

Symptoms (presumed): nausea, vomiting, vaginal bleeding.

Treatment: symptomatic, there is no specific antidote.

Interaction. Long term treatment Drugs that induce liver enzymes (including hydantoin derivatives, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, griseofulvin) can increase the clearance of sex hormones and reduce their clinical effectiveness. The maximum induction of enzymes is usually observed 2-3 weeks after the start of treatment and may persist for 4 weeks after discontinuation of the drug.

In rare cases, against the background of the concomitant use of certain antibiotics (including penicillin and tetracycline groups), a decrease in the concentration of estradiol was observed.

Drugs that are heavily conjugated (including paracetamol) can increase the bioavailability of estradiol due to competitive inhibition of the conjugation system during absorption.

Ethanol can increase the concentration of circulating estradiol.

Special instructions. Not used for contraception. If contraception is necessary, non-hormonal methods should be used (with the exception of calendar and temperature methods). If pregnancy is suspected, the drug should be discontinued until pregnancy has been ruled out.

A number of controlled, randomized, as well as epidemiological studies have revealed an increased relative risk of developing venous thromboembolism (including deep vein thrombosis or PE) against the background of HRT. Therefore, when prescribing HRT to women with risk factors for venous thromboembolism, the risks and benefits should be weighed and discussed with the patient.

Risk factors for the development of venous thromboembolism include individual and family history (the presence of venous thromboembolism in close relatives at a relatively young age may indicate a genetic predisposition) and severe obesity. The risk of venous thromboembolism also increases with age. Question about a possible role varicose veins veins in the development of venous thromboembolism remains controversial.

The risk of venous thromboembolism may temporarily increase with prolonged immobilization, extensive elective, traumatological operations, or massive trauma. Depending on the cause or duration of immobilization, the question of the advisability of temporarily stopping HRT should be decided.

Treatment should be stopped immediately if symptoms of thrombotic disorders appear or if they are suspected.

In the course of randomized controlled trials with long-term use of combined conjugated estrogens and medroxyprogesterone, there was no evidence of a positive effect on the cardiovascular system. An increased risk of stroke has also been found. To date, there have been no long-term randomized controlled trials with other drugs for HRT in order to identify a positive effect on morbidity and mortality rates related to CVS. Therefore, it is not known whether the increased risk extends to HRT preparations containing other types of estrogens and progestogens.

With prolonged estrogen monotherapy, the risk of developing endometrial hyperplasia or carcinoma increases. Studies have confirmed that the combination with gestagens reduces the risk of hyperplasia and endometrial cancer. According to clinical studies and observational studies, an increased risk of developing breast cancer was found in women using HRT for several years. This may be due to earlier diagnosis, the biological effects of HRT, or a combination of both. The relative risk increases with the duration of treatment (by 2.3% for 1 year of use). This is comparable to an increase in the risk of breast cancer in women with each year of delay in the onset of natural menopause (by 2.8% for 1 year of delay). The increased risk gradually decreases to normal levels during the first 5 years after stopping HRT. Breast cancer found in women taking HRT is usually more localized than in women not taking it.

HRT increases mammographic density of the mammary glands, which in some cases can have a negative impact on the radiological detection of breast cancer.

Against the background of the use of sex hormones, in rare cases, benign, and even more rarely, malignant tumors of the liver were observed, in some cases with life-threatening intra-abdominal bleeding. With the appearance of pain in the upper abdomen, enlargement of the liver or signs of intra-abdominal bleeding with differential diagnosis consideration should be given to the possibility of a liver tumor.

It has been established that estrogens increase the lithogenicity of bile, which increases the risk of developing cholelithiasis in predisposed patients.

Treatment should be stopped immediately when migraine-like or frequent and unusually severe headaches appear for the first time, as well as when other symptoms appear - possible precursors of cerebral thrombotic stroke.

The relationship between HRT and the development of clinically significant arterial hypertension has not been established. In women taking HRT, a slight increase in blood pressure has been described, a clinically significant increase is rare. However, in some cases, with the development of persistent clinically significant arterial hypertension while taking HRT, it is necessary to consider the issue of canceling HRT.

In renal insufficiency, the ability to excrete K + may decrease. Drospirenone does not affect the serum K + concentration in patients with mild to moderate renal insufficiency. The risk of developing hyperkalemia cannot theoretically be excluded in the group of patients in whom the concentration of K + in serum before treatment was determined at the upper limit of the norm, and who additionally take potassium-sparing drugs.

With mild violations of liver function, incl. various forms of hyperbilirubinemia (Dubin-Johnson syndrome, Rotor), medical supervision is necessary, as well as periodic studies of liver function. If liver function tests deteriorate, HRT should be discontinued.

In case of recurrence of cholestatic jaundice or cholestatic pruritus, observed for the first time during pregnancy or previous treatment with sex hormones, HRT should be stopped immediately.

Special monitoring is required for women with moderate hypertriglyceridemia. In such cases, the use of HRT can cause a further increase in the concentration of triglycerides in the blood, which increases the risk of developing acute pancreatitis.

Although HRT may affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the treatment regimen for diabetic patients during HRT. However, diabetic women should be supervised during HRT.

Some patients under the influence of HRT may develop undesirable manifestations of estrogen stimulation, incl. pathological uterine bleeding. Frequent or persistent abnormal uterine bleeding during treatment is an indication for endometrial examination.

If the treatment of irregular menstrual cycles does not work, an examination should be carried out to rule out an organic disease.

Under the influence of estrogens, uterine fibroids can increase in size. In this case, treatment should be discontinued.

If a prolactinoma is suspected, this disease should be excluded before starting treatment.

In some cases, chloasma may occur, especially in women with a history of chloasma of pregnancy. During HRT, women with a tendency to develop chloasma should avoid prolonged exposure to the sun or UV radiation.

The following conditions may occur or worsen on the background of HRT (the relationship with HRT has not been proven): epilepsy, benign tumors mammary glands, bronchial asthma, migraine, porphyria, otosclerosis, systemic lupus erythematosus, chorea.

Before starting or resuming HRT, a woman is recommended to undergo a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination cervical mucus), exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. Control examinations should be carried out periodically.

Reception of sex hormones can affect the biochemical parameters of liver function, thyroid gland, adrenal glands and kidneys, on the content of transport proteins in plasma, such as SHBG and lipid / lipoprotein fractions, indicators carbohydrate metabolism, coagulation and fibrinolysis. The drug does not adversely affect glucose tolerance.

HRT is not prescribed during pregnancy or breastfeeding. Large-scale epidemiological studies of sex hormones used for contraception or HRT have not found an increased risk of birth defects in children born to women who took such hormones before pregnancy

State register of medicines. Official publication: in 2 volumes - M .: Medical Council, 2009. - V.2, part 1 - 568 p.; part 2 - 560 p.

Pharmacological group: oral contraceptives
Systematic (IUPAC) name: (6R, 7R, 8R, 9S, 10R, 13S, 14S, 15S, 16S, 17S) - 1.3", 4", 6.6a, 7,8,9,10,11 ,12,13,14,15,15, 16 - hexadecahydro - 10,13 - dimethylspiro - cyclopenta [a] phenanthrene -17, 2 "(5H) - furan] -3.5 "(2H) - dione)
Application: oral
Bioavailability 76%
Protein binding 97%
Metabolism: liver, negligible (CYP3A4-mediated)
Half-life: 30 hours
Excretion: renal and fecal
Formula: C 24 H 30 O 3
Mol. mass: 366.493 g/mol

Drospirenone (INN, USAN), also known as 1,2-dihydrospirorenone, is a synthetic hormone used in birth control pills. Drospirenone is marketed under the brand names Yasmin, Yasminelle, Yaz, Beyaz, Ocella, Zarah, and Angeliq, all of which are combination products of Drospirenone with an estrogen such as ethinyl estradiol.

Medical use

Drospirenone is part of some birth control pills and is used in hormone replacement therapy. In combination with ethinyl estradiol, it is used as a contraceptive. The drug is also approved by the US FDA for women to prevent unwanted pregnancy and for the treatment of moderate acne and premenstrual dysphoric disorder.

Side effects

Women taking birth control pills containing drospirenone face a six to seven times risk of developing thromboembolism (dangerous blood clots) compared to women who do not take any birth control pill, and a twofold risk (or three times the risk, as some epidemiological studies show, in according to the FDA) compared with women who take birth control pills containing levonorgestrel, although the actual risk is low, it affects 9-27 women out of 10,000 when taking oral contraceptives during the year (up to 9 cases for levonorgestrel and up to 27 cases - for drospirenone, or about 0.09% versus 0.3% per year). Drospirenone can increase potassium levels to dangerous levels (hyperkalemia). This effect can be dangerous or, in some cases, even fatal for some women taking other drugs that also increase potassium levels, such as ACE inhibitors, agonists angiotensin-II receptors, potassium-sparing diuretics, potassium supplements, heparin, aldosterone antagonists and NSAIDs. Yasmin was the first oral contraceptive to use drospirenone. Yaz, the top selling oral contraceptive in the US, also contains drospirenone. On the labels of all contraceptives containing drospirenone, there is a warning that the drugs should not be used by women with liver dysfunction, kidney failure or adrenal insufficiency. Like all oral contraceptives, these birth control pills should also not be used by women who smoke or have a history of DVT (deep vein thrombosis), stroke, or other blood clots. Although all oral contraceptives may increase the risk of venous thromboembolism, including fatal clots, several studies have shown that women taking contraceptives containing drospirenone are at an increased risk. One study showed that users of these contraceptives have over a 600 percent risk of developing these blood clots compared to those who do not take such contraceptives. The risk increases by 360 percent in women who take birth control pills containing levonorgestrel, another type of progesterone found in many birth control pills. (however, the "actual" risks are quite small - from 1 in 10,000 cases to 27 per 10,000 cases per year). The US FDA has funded research based on the medical records of more than 800,000 women taking oral contraceptives. It was found that the risk of developing venous thromboembolic complications, including dangerous and potentially fatal blood clots, was 93% higher in women taking oral contraceptives with drospirenone for 3 months or less, and 290% higher in women taking oral contraceptives. contraceptives with drospirenone for 7-12 months, compared with women taking other types of oral contraceptives. Further research is required to determine the exact risk for women of different ages and in different circumstances. The FDA recently updated packaging requirements for drospirenone-containing contraceptives to include a warning to discontinue use before and after surgery, and a warning that contraceptives containing drospirenone may be associated with a higher risk of dangerous blood clots.

Pharmacology

Pharmacodynamics

Drospirenone differs from other synthetic progestins in that its pharmacological profile in preclinical studies indicates that it is closer to natural progesterone. As such, it has potent antimineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and has mild antiandrogenic activity. The antimineralocorticoid properties of drospirenone promote sodium excretion and prevent water retention.

Pharmacokinetics

At oral intake Drospirenone has approximately 76% bioavailability. It is not bound to sex hormone-binding globulin or corticosteroid-binding globulin, but to other serum proteins. Metabolites are not biologically active, are found in urine and feces and are completely eliminated from the body within 10 days.

Chemistry

The drug is an analogue of spironolactone, with a molecular weight of 366.5 and a molecular formula of C24H30O3.

Lineups

The compound is part of new oral contraceptive formulas:

One tablet of Yasmin contains 3 mg of drospirenone and 30 mcg of ethinyl estradiol. The drug is used for oral contraception. One tablet of Yasminelle contains 3 mg of drospirenone and 20 micrograms of ethinyl estradiol. The drug is used for contraception. Yaz and Beyaz contain drospirenone 3mg and ethinylestradiol 20mcg per tablet and are taken on a 24/4 day schedule with the same indication. Ocella contains 3 mg of drospirenone and 30 mcg of ethinyl estradiol per tablet and is taken daily.

In addition, drospirenone is included in formulas for monitoring menopausal symptoms using DRSP 0.5 mg and estradiol 1 mg per day by mouth (Angelique, introduced to the market in the US in 2007).

Clinico-pharmacological group:  

Included in medications

ATH:

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

Pharmacodynamics:

Combined oral contraceptive containing drospirenone. At a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid properties. It is devoid of any estrogenic, glucocorticoid and antiglucocorticoid activity. This provides drospirenone with a pharmacological profile similar to natural progesterone.

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

Pharmacokinetics:

Drospirenone

Suction. After oral administration, drospirenone is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 76-85% and does not depend on food intake. Eating does not affect the bioavailability of drospirenone.

Distribution. After a single or multiple dose of 2 mg Cmax in serum is reached after 1 hour and is about 22 ng / ml. After that, there is a two-phase decrease in the concentration of drospirenone in serum with a final elimination half-life of about 35-39 hours. Drospirenone binds to albumin and does not bind to sex steroid-binding globulin and corticoid-binding globulin; about 3-5% - free fraction.

Due to the long half-life, C ss is reached after 10 days of daily administration of the drug and exceeds the concentration after a single dose by 2-3 times.

Metabolism. The main metabolites are the acidic form of drospirenone and 4,5-dihydro-drospirenone-3-sulfate, which are formed without the participation of isoenzymes of the cytochrome P450 system.

breeding. Serum clearance of drospirenone is 1.2-1.5 ml/min/kg. Some of the dose received is excreted unchanged. Most of the dose is excreted by the kidneys and through the intestines in the form of metabolites in a ratio of 1.2:1.4; half-life is about 40 hours.

Ethinylestradiol

Suction. When taken orally, it is absorbed quickly and completely. C max in blood serum is about 33 pg / ml, 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 ethinyl estradiol in approximately 25% of the examined patients; there were no other changes.

Distribution. Serum concentrations of ethinylestradiol decrease biphasically, in the terminal distribution phase, the half-life is approximately 24 hours. It binds well, but not specifically to serum albumin (approximately 98.5%) and induces an increase in serum concentrations sex steroid-binding globulin. V d - about 5 l / kg.

Metabolism. Ethinylestradiol is a substrate for presystemic conjugation in the mucosa small intestine and in the liver. It 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.

Withdrawal. Unchanged 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. The half-life of metabolites is about 24 hours.

Css occurs in the second half of the treatment cycle, and the serum concentration of ethinylestradiol increases by 2-2.3 times.

Special patient groups

In violation of kidney function. C ss drospirenone in blood plasma in women with mild renal insufficiency (creatinine clearance - 50-80 ml / min) was comparable with the corresponding indicators in women with normal function kidneys (creatinine clearance > 80 ml/min). In women with kidney failure medium degree severity (creatinine clearance 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. Drospirenone did not have a clinically significant effect on the content of potassium in the blood serum. Pharmacokinetics in severe renal insufficiency 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:

Contraception.

XXI.Z30-Z39.Z30.0 General Tips and advice on contraception

XXI.Z30-Z39.Z30 Surveillance for contraceptive use

Contraindications:

The drug, like other combined oral contraceptives, is contraindicated in any of the following conditions:

Hypersensitivity to the drug or any of the components of the drug;

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), currently or in history;

Multiple or prominent risk factors for venous or arterial thrombosis, including complicated valvular heart disease, atrial fibrillation, cerebrovascular disease, or coronary arteries; uncontrolled arterial hypertension, extensive surgery with prolonged immobilization, smoking over the age of 35, obesity with a body mass index> 30;

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);

Pregnancy and suspicion of it;

lactation period;

Pancreatitis with severe hypertriglyceridemia at present or in history;

Existing (or history) serious disease liver, provided that the function of the liver and is not currently normalized;

Severe chronic or acute renal failure;

Liver tumor (benign or malignant) at present or in history;

Hormone-dependent malignant neoplasms of the genital organs or breast 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.

Carefully:

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 violation cerebral circulation at a young age in one of the next of kin); diseases in which peripheral circulatory disorders can occur (diabetes mellitus without vascular complications, systemic lupus erythematosus, 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.

Pregnancy and lactation:

The drug is contraindicated during pregnancy. If pregnancy occurs during the use of the drug, it should be stopped immediately. Extended epidemiological studies have not revealed an increased risk of birth defects in children born to women who took before pregnancy, nor a teratogenic effect if they were inadvertently taken during pregnancy. According to preclinical studies, undesirable effects that affect the course of pregnancy and fetal development cannot be ruled out due to the hormonal action of the active ingredients.

The drug 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 administration. combined oral contraceptives. These amounts may affect the child. The use of the drug during breastfeeding is contraindicated.

Dosage and administration:

Every day, at about the same time, with a small amount of water, in the order indicated on the blister pack. Tablets are taken in continuous mode 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.

The procedure for taking the drug

Hormonal contraceptives have not been used in the last month. The drug begins on the 1st day of the menstrual cycle (that is, on the 1st day of menstrual bleeding). The start of the reception is possible on the 2-5th day of the menstrual cycle, in this 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 (in the form of tablets, vaginal ring or transdermal patch). It is necessary to start taking the drug the next day after taking the last inactive tablet (for drugs containing 28 tablets) or the next 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 drugs, containing 21 tablets per pack. In the case of a woman using a vaginal ring or transdermal patch, it is preferable to start taking the drug on the day of their removal or, at the latest, on the day when a new ring or patch is planned to be inserted.

Switching from contraceptives containing only progestogens (mini-pills, injections, implants), or from an intrauterine system that releases progestogens. A woman can switch from taking a mini-pill to taking the drug on any day (from an implant or from an intrauterine system 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. The drug 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 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 the drug. With the resumption of sexual activity (before the start of the drug), pregnancy should be excluded.

Taking missed pills

Skipping placebo tablets 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:

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. In addition, for the next 7 days, a barrier method, such as a condom, should be used. 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, additional method contraception (barrier, such as a condom) 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 missed pills and subsequently did not experience withdrawal bleeding during 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.

Delay menstrual-like withdrawal bleeding

To delay bleeding, the woman should skip the placebo pills from the pack she started and start taking the pills from the new pack. 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 the drug 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 copious or spotting vaginal discharge on the next pack (same as with lengthening the cycle).

Side effects:

The most commonly reported adverse reactions to the drug include nausea and pain in the mammary glands. They occurred in more than 6% of women using this drug.

Serious adverse reactions are arterial and venous thromboembolism.

The following are adverse reactions with a very rare frequency of occurrence or with delayed symptoms, which are believed to be associated with the use of drugs from the group of combined oral contraceptives.

The frequency of diagnosing breast cancer in women taking combined oral contraceptives is slightly increased. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women taking combined oral contraceptives is insignificant in relation to the overall risk of this disease.

Tumors of the liver (benign and malignant).

Other states:

erythema nodosum;

Women with hypertriglyceridemia (increased risk of pancreatitis while taking combined oral contraceptives);

Increased blood pressure;

Conditions that develop or worsen while taking combined oral contraceptives, but their relationship with the drug has not been proven (jaundice and / or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea ; herpes of pregnancy; hearing loss associated with otosclerosis);

In women with hereditary angioedema, estrogen use may cause or exacerbate symptoms;

Liver dysfunction;

Impaired glucose tolerance or effect on insulin resistance;

Crohn's disease, ulcerative colitis;

Chloasma;

Hypersensitivity (including symptoms such as rash, urticaria).

Overdose:

Cases of drug overdose have not yet been described.

Based on general experience with combined oral contraceptives Potential overdose symptoms may include: nausea, vomiting, slight bleeding from the vagina.

Treatment: no antidotes. Further treatment should be symptomatic.

Interaction:

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 St. John's wort preparations is based on the ability of these active substances to induce microsomal liver enzymes. Maximum induction of microsomal liver enzymes is not achieved within 2-3 weeks, but thereafter persists for at least 4 weeks after discontinuation drug therapy.

Contraceptive failure has also been reported with antibiotics such as ampicillin and tetracycline. The mechanism of this phenomenon is unclear. 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 combined oral contraceptives, barrier methods of contraception.

Women receiving rifampicin therapy other than combined oral contraceptives 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 tablets from the next package should be started immediately.

If a woman is constantly taking microsomal liver enzyme inducers, 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.

Oral contraceptives may affect the metabolism of some other active substances. Accordingly, the concentrations of these substances in blood plasma or tissues can either increase (for example, ) or decrease (for example, ). Based on inhibition studies in vitro and interactions in vivo in female volunteers who took, and as a substrate, the effect of drospirenone at a dose of 3 mg on the metabolism of other active substances is unlikely.

In patients without renal insufficiency, the simultaneous use of drospirenone and ACE inhibitors or non-steroidal anti-inflammatory drugs does not significantly affect the content of potassium in the blood serum. But still, the simultaneous use of the drug 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.

Special instructions:

If there are any of the conditions/risk factors listed below, benefit from taking combined oral contraceptives should be evaluated individually for each woman and discussed with her before 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 combined oral contraceptives.

Circulatory disorders

Acceptance of any combined oral contraceptive increases the risk of venous thromboembolism. The increased risk of venous thromboembolism is most pronounced in the first year of use by a woman combined oral contraceptives.

Epidemiological studies have shown that the incidence of venous thromboembolism in women with no risk factors who took low doses of estrogen (< 0,05 мг этинилэстрадиола) в составе combined oral contraceptives, is approximately 20 cases per 100,000 woman-years (for levonorgestrel-containing combined oral contraceptives second generation) or 40 cases per 100,000 woman-years (for desogestrel/gestodene-containing combined oral contraceptives third generation). Women who do not use combined oral contraceptives, there are 5-10 venous thromboembolisms and 60 pregnancies per 100,000 woman-years. Venous thromboembolism is fatal in 1-2% of cases.

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

Epidemiological studies have also found an association with combined oral contraceptives with 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 it radiates to the left arm 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, suddenly affecting one side or one part of the body;

Movement disorders;

Acute abdomen.

Before you start taking combined oral contraceptives a woman should consult a specialist. The risk of venous thromboembolic disorders when taking combined oral contraceptives increases:

With increasing age;

hereditary predisposition;

Prolonged immobilization, advanced surgery, any surgical intervention on lower limbs or major injury. In such situations, it is recommended to stop taking the drug (in the case of a planned surgical intervention, at least 4 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;

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

Risk of arterial thromboembolic complications or acute cerebrovascular accident when taking combined oral contraceptives increases with:

Increasing age;

Smoking (Women over 35 are strongly advised to stop smoking if they wish to take combined oral contraceptives);

Dyslipoproteinemia;

arterial hypertension;

Migraines without focal neurological symptoms;

Obesity (body mass index over 30);

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

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 combined oral contraceptives, should be properly instructed to inform the attending physician in case of suspected symptoms of thrombosis. If thrombosis is suspected or confirmed, taking combined oral contraceptives should be stopped. It is necessary to start adequate alternative contraception due to the teratogenicity of anticoagulant therapy with 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 disease intestines (Crohn's disease or ulcerative colitis) and sickle cell anemia.

Increased frequency or severity of migraine while taking combined oral contraceptives may be an indication for their immediate abolition.

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 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 small increase in the relative risk of developing breast cancer in women currently taking combined oral contraceptives. The risk gradually decreases over 10 years after discontinuation combined oral contraceptives. Since breast cancer rarely develops in women under 40 years of age, an increase in the number of diagnosed cases of breast cancer in women using combined oral contraceptives little effect on the overall risk 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 those using combined oral contraceptives, biological action combined oral contraceptives or a combination of both factors. Diagnosed breast cancer in women who have ever taken combined oral contraceptives, clinically was less severe, due to the early diagnosis of the disease.

Rare in women taking combined oral contraceptives, benign liver tumors and, even more rarely, malignant liver tumors have occurred. In some cases, these tumors were life-threatening (due to intra-abdominal bleeding). This should be taken into account when carrying out differential diagnosis in case of occurrence severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding.

Other

The progestogen component of the drug is an aldosterone antagonist that retains potassium in the body. In most cases, an increase in potassium 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 levels during the first cycle of treatment in patients with renal insufficiency, in whom the serum potassium concentration before treatment was at the level upper bound norms 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 combined oral contraceptives. Although a small increase in blood pressure was noted in many women, a clinically significant increase was rare. Only in these rare cases is immediate discontinuation justified. combined oral contraceptives. If upon admission combined oral contraceptives in patients with concomitant arterial hypertension, arterial pressure constantly increases or significantly high blood pressure cannot be corrected with antihypertensive drugs combined oral contraceptives should be stopped. After normalization of blood pressure with the help of antihypertensive drugs, taking combined oral contraceptives can be resumed.

The following diseases appeared or worsened both during pregnancy and when taking combined oral contraceptives: 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. However, evidence for their relationship with intake combined oral contraceptives unconvincing.

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

Acute or chronic diseases liver failure may be an indication for discontinuation combined oral contraceptives until normalization of liver function tests. Recurrent cholestatic jaundice and/or cholestasis-related pruritus that developed during a previous pregnancy or earlier use of sex hormones is an indication for discontinuation combined oral contraceptives.

Though combined oral contraceptives may affect peripheral insulin resistance and glucose tolerance, change in treatment regimen in patients with diabetes mellitus while taking combined oral contraceptives low in hormones (containing< 0,05 мг этинилэстрадиола) не показано. Однако следует внимательно наблюдать женщин с сахарным диабетом, особенно на early stages reception combined oral contraceptives.

During the reception combined oral contraceptives exacerbation of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis was observed.

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 when taking combined oral contraceptives.

Coated tablets contain 48.53 mg lactose monohydrate, placebo tablets contain 37.26 mg anhydrous lactose per tablet. Patients with rare hereditary diseases (such as galactose intolerance, lactase deficiency or malabsorption of glucose-galactose) who are on a lactose-free diet should not take this drug.

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

The efficacy and safety of the drug 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.

Medical examinations

Before starting or re-using the drug, 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.

Reduced efficiency

Efficiency combined oral contraceptives may decrease, for example, when skipping pills, gastrointestinal disorders during the period of taking pills, or concomitantly taking other drugs.

Insufficient cycle control

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

Instructions