Levonorgestrel and drospirenone which is better. What contraceptives contain drospirenone? Substance information

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 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 of the small intestine and in the liver. It is primarily metabolized by aromatic hydroxylation, resulting in a wide range of hydroxylated and methylated metabolites, which are present both in free form and in the form of 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 plasma in women with mild renal insufficiency (creatinine clearance - 50-80 ml / min) was comparable to the corresponding indicators in women with normal renal function (creatinine clearance > 80 ml / min). In women with moderate renal insufficiency (creatinine clearance from 30 ml / min to 50 ml / min), the plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Drospirenone was well tolerated in all groups. Drospirenone did not have a clinically significant effect on the content of potassium in the blood serum. Pharmacokinetics in severe renal 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 advice 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 severe risk factors for venous or arterial thrombosis, including complicated lesions of the valvular apparatus of the heart, atrial fibrillation, cerebrovascular or coronary artery disease; uncontrolled arterial hypertension, major 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 of) severe liver disease, provided that liver function is not currently normal;

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 cerebrovascular accident 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 (disease 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 affecting 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 continuously for 28 days, 1 tablet per day. Taking pills from the next pack begins after taking the last pill from the previous pack. Withdrawal bleeding usually begins 2-3 days after the start of placebo tablets (last row) and does not necessarily end by the start of the next pack.

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). It is also possible to start taking it on the 2nd-5th day of the menstrual cycle, in which case additional use of a barrier method of contraception is necessary during the first 7 days of taking the tablets from the first package.

Switching from other combined contraceptives (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 the implant or 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, an additional method of contraception (barrier, such as a condom) is needed for 7 days.

Days 15-24. The reliability of the method inevitably declines as the placebo pill phase approaches. However, correcting the pill regimen can still help prevent pregnancy. If one of the two schemes described below is followed, and if the woman has observed the drug regimen in the previous 7 days before skipping the pill, there will be no need to use additional contraceptive measures. If this is not the case, she must complete the first of the two regimens and use additional precautions for the next 7 days.

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

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

Listed below 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. The maximum induction of microsomal liver enzymes is not achieved within 2-3 weeks, but after that it persists for at least 4 weeks after discontinuation of drug therapy.

Contraceptive failure has also been reported with antibiotics such as ampicillin and tetracycline. The mechanism of this phenomenon is 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 administration 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 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;

Sharp belly.

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 the lower extremities or major trauma. In such situations, it is recommended to stop taking the drug (in the case of a planned surgical intervention, at least 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 bowel disease (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 making a differential diagnosis in case of severe abdominal pain, 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 a clinical study in some patients with mild to moderate kidney disease who were taking potassium-sparing drugs, serum potassium increased slightly while taking drospirenone. Therefore, it is recommended to monitor serum potassium levels during the first cycle of treatment in patients with renal insufficiency in whom serum potassium levels were at the upper limit of normal before treatment, and especially when taking potassium-sparing drugs at the same time. 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, blood pressure constantly increases or significantly elevated blood pressure cannot be corrected with antihypertensive drugs, taking 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 liver disease may be an indication to stop taking combined oral contraceptives until normalization of liver function tests. Recurrence of 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.

Although 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 ранних стадиях приема 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

Marina Pozdeeva about modern possibilities and forms of combined hormonal contraception

More than 55 years have passed since the appearance of the first hormonal contraceptive - Enovida. Today, drugs have become more low-dose, safer and more diverse in form.

Combined oral contraceptives (COCs)

Most drugs use the estrogen ethinyl estradiol at a dosage of 20 micrograms. As a gestagen is used:

  • norethindrone;
  • norgestrel;
  • norethindrone acetate;
  • norgestimate;
  • desogestrel;
  • Drospirenone is the most modern progestin.

A new trend in the production of COCs is the release of drugs that increase the level of folate in the blood. These COCs contain drospirenone, ethinyl estradiol and calcium levomefolate (a folic acid metabolite) and are indicated for women planning pregnancy in the near future.

Monophasic COCs have a constant dose of estrogen and progestin. Two-phase COCs contain two, three-phase - three, and four-phase - four combinations of estrogen and progestogen. Multiphasic drugs do not have advantages over monophasic combined oral contraceptives in terms of efficacy and side effects.

About three dozen COCs are available on the pharmaceutical market, the vast majority of which are monophasic. They are available in the form of 21+7:21 hormonally active tablet and 7 placebo tablets. This facilitates consistent daily monitoring of regular COC use.

Combined oral contraceptives (COCs) list: types and names

Mechanism of action

The basic principle of COCs is to inhibit ovulation. Drugs reduce the synthesis of FSH and LH. The combination of estrogen and progestin gives a synergistic effect and increases their antigonadotropic and antiovulatory properties. In addition, COC contraceptives change the consistency of cervical mucus, cause endometrial hypoplasia and reduce the contractility of the fallopian tubes.

Efficiency largely depends on compliance. The frequency of pregnancy during the year ranges from 0.1% with correct use to 5% with violations in the intake regimen.


Advantages

Combined hormonal contraceptives are widely used to treat menstrual disorders, reduce or eliminate ovulatory syndrome. Taking COCs reduces blood loss, so it is advisable to prescribe them for menorrhagia. COCs can be used to correct the menstrual cycle - if necessary, delay the onset of the next menstruation.

COCs reduce the risk of developing benign breast formations, inflammatory diseases of the pelvic organs, and functional cysts. Taking COCs with existing functional cysts contributes to their significant reduction or complete resorption. The use of COCs helps to reduce the risk of malignant ovarian diseases by 40%, endometrial adenocarcinoma - by 50%. The protective effect lasts up to 15 years after drug withdrawal.

Flaws

Side effects: Nausea, breast tenderness, breakthrough bleeding, amenorrhea, headache.

Estrogen, which is part of the COC, is able to activate the blood coagulation mechanism, which can lead to the development of thromboembolism. The risk group for the development of such complications while taking COCs includes women with high levels of LDL and low levels of HDL in the blood, severe diabetes, accompanied by damage to the arteries, uncontrolled arterial hypertension, and obesity. In addition, women who smoke are more likely to develop clotting disorders.

Contraindications for the use of combined oral contraceptives

  • thrombosis, thromboembolism;
  • angina pectoris, transient ischemic attacks;
  • diabetes mellitus with vascular complications;
  • pancreatitis with severe triglyceridemia;
  • liver disease;
  • hormone-dependent malignant diseases;
  • vaginal bleeding of unknown etiology;
  • lactation.

COCs and breast cancer

The most comprehensive analysis of cases of breast cancer development while taking COCs was presented in 1996 by the Collaborative Group on Hormonal Factors in Breast Cancer. The study evaluated epidemiological data from more than 20 countries around the world. The results of the study showed that women who currently take COCs, as well as those who have taken them within the past 1-4 years, have a slightly increased risk of developing breast cancer. The study emphasized that the patients participating in the experiment were much more likely to undergo breast examinations than women who did not take COCs.

Today it is assumed that the use of COCs can act as a cofactor, which only interacts with the main cause of breast cancer and possibly potentiates it.

Transdermal Therapeutic System (TTS)

The transdermal therapeutic system patch is applied for 7 days. The used patch is removed and immediately replaced with a new one on the same day of the week, on the 8th and 15th days of the menstrual cycle.

TTS appeared on the market in 2001 ("Evra"). Each patch contains a week's supply of norelgestromin and ethinylestradiol. TTS is glued to dry, clean skin of the buttocks, abdomen, outer surface of the upper shoulder or torso with minimal hair growth. It is important to monitor the density of TTS attachment every day and not apply cosmetics nearby. The daily release of sex steroids (203 mcg norelgestromin + 33.9 mcg ethinyl estradiol) is comparable to a dose of low-dose COCs. On the 22nd day of the menstrual cycle, the TTC is removed and a new patch is applied after 7 days (on the 29th day).

The mechanism of action, efficacy, disadvantages and advantages are the same as those of COCs.

vaginal ring

Hormonal vaginal ring ("NovaRing") contains etonogestrel and ethinylestradiol (daily release 15 mcg + 120 mcg, respectively). The ring is set for three weeks, after which it is removed and kept for a week break. On the 29th day of the cycle, a new ring is introduced.

The dosage of ethinyl estradiol in the vaginal ring is lower than that of COCs, due to the fact that absorption occurs directly through the vaginal mucosa, bypassing the gastrointestinal tract. Due to the complete suppression of ovulation and regular release, independent of the patient, the effectiveness is higher than that of COCs (0.3-6%). Another advantage of the ring is the low likelihood of dyspeptic side effects. Some patients develop vaginal irritation, discharge. In addition, the ring may accidentally slip out.

The effect of hormonal contraceptives on libido has not been studied enough, research data are contradictory and depend on the average age in the sample and gynecological diseases, drugs used, methods for assessing the quality of sexual life. In general, 10-20 percent of women may experience a decrease in libido while taking drugs. In most patients, the use of GCs does not affect libido.

Acne and hirsutism usually have low levels of sex hormone-binding globulin (SHBG). COCs increase the concentration of this globulin, having a beneficial effect on the condition of the skin.


Subtleties of application

The estrogen in the composition of COCs promotes the elimination of LDL and an increase in HDL and triglycerides. Progestins counteract the estrogen-induced change in lipid levels in the body.

  1. For acne, preparations containing cyproterone acetate, drospirenone, or desogestrel as a progestin are prescribed. COCs containing cyproterone acetate and ethinylestradiol are more effective for acne than the combination of ethinylestradiol and levonorgestrel.
  2. With hirsutism, drugs containing progestogens with antiandrogenic properties are recommended: cyproterone acetate or drospirenone.
  3. Combinations of estradiol valerate and dienogest are more effective in reducing menstrual blood loss than ethinyl estradiol and levonorgestrel. In addition, an intrauterine system is indicated for the treatment of menorrhagia.
  4. Preparations containing drospirenone 3 mg and ethinylestradiol 20 mcg are recognized as the most effective combination for the correction of PMS symptoms, including psychogenic ones.
  5. Taking oral contraceptives increases systolic blood pressure (BP) by 8 mm Hg. Art., and diastolic - 6 mm Hg. Art. . There is evidence of an increased risk of cardiovascular events in women taking COCs. Due to the increased likelihood of myocardial infarction and stroke in patients with arterial hypertension, when prescribing COCs, the benefit / risk ratio must be carefully weighed.
  6. In non-smoking women under 35 years of age with compensated hypertension, COCs may be prescribed with careful monitoring of blood pressure during the first months of admission.
  7. In the case of an increase in blood pressure while taking COCs or women with severe hypertension, an intrauterine system or DMPA is indicated.
  8. The selection of a contraceptive for patients with dyslipidemia should be carried out taking into account the effect of drugs on lipid levels (see Table 5).
  9. Since the absolute risk of cardiovascular events in women with controlled dyslipidemia is low, COCs containing estrogen at a dosage of 35 mcg or less can be used in most cases. For patients with LDL levels above 4.14 mmol / l, alternative contraceptives are indicated.
  10. The use of COCs in women with diabetes associated with vascular complications is not recommended. A suitable hormonal contraceptive option for diabetes mellitus is the levonorgestrel-releasing intrauterine system, while dose adjustment of hypoglycemic drugs is usually not required.
  11. The results of epidemiological studies studying the risk of developing myocardial infarction when prescribing oral contraceptives to smoking women are contradictory. Due to the limited amount of convincing data, COCs are recommended to be used with caution in all women who smoke over 35 years of age.
  12. Obesity with a body mass index of 30 kg / m2 and above reduces the effectiveness of COCs and transdermal GCs. In addition, the use of COCs in obesity is a risk factor for venous thromboembolism. Therefore, the method of choice for such patients are mini-pills (gestagen-containing tablet contraceptives) and intrauterine contraceptives (levonorgesterel-releasing system).
  13. The use of COCs with an estrogen dosage of less than 50 micrograms in non-smoking, healthy women over the age of 35 years may have a beneficial effect on bone density and vasomotor symptoms in perimenopause. This benefit must be viewed through the lens of the risk of venous thromboembolism and cardiovascular factors. Therefore, COCs are prescribed individually for women of the late reproductive period.

List of sources

  1. Van Vliet H. A. A. M. et al. Biphasic versus triphasic oral contraceptives for contraception //The Cochrane Library. - 2006.
  2. Omnia M Samra-Latif. contraception. Available from http://emedicine.medscape.com
  3. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347(9017):1713–1727.
  4. Carlborg L. Cyproterone acetate versus levonorgestrel combined with ethinyl estradiol in the treatment of acne. Results of a multicenter study. Acta Obstetricia et Gynecologica Scandinavica 1986;65:29–32.
  5. Batukan C et al. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol 2007;23:38–44.
  6. Fruzzetti F, Tremollieres F, Bitzer J. An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest. Gynecol Endocrinol 2012;28:400–8.
  7. Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev 2012.
  8. Armstrong C, Coughlin L. ACOG releases guidelines on hormonal contraceptives in women with coexisting medical conditions. - 2007.
  9. Carr BR, Ory H. Estrogen and progestin components of oral contraceptives: relationship to vascular disease. Contraception 1997; 55:267–272.
  10. Burrows LJ, Basha M, Goldstein AT. The effects of hormonal contraceptives on female sexuality: a review. The journal of sexual medicine 2012; 9:2213–23.

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 spironolactone derivative 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 estrogens or is switching from another combination hormone product for continuous use, then she can start treatment at any time. Patients who are switching from a 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 digestive system: dyspepsia, bloating, nausea, vomiting, abdominal pain, relapse of cholestatic jaundice.

On the part of the 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 with 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. The question of the possible role of varicose 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, no long-term randomized controlled trials have been conducted 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. If pain occurs in the upper abdomen, an enlarged liver, or signs of intra-abdominal bleeding, differential diagnosis should take into account the likelihood 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 abolition of 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 breast tumors, bronchial asthma, migraine, porphyria, otosclerosis, systemic lupus erythematosus, chorea minor.

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 a cytological examination of cervical mucus), to exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. Control examinations should be carried out periodically.

The intake of sex hormones can affect the biochemical parameters of the liver, thyroid gland, adrenal glands and kidneys, the plasma content of transport proteins such as SHBG and lipid / lipoprotein fractions, indicators of 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.

Preparations based on drospirenone (drospirenone) in combination with estradiol are used in hormone replacement therapy, as a contraceptive and in the treatment of androgen-dependent conditions (hirsutism, seboria, acne, seborrhea). Drospirenone and are the main active ingredients with antiandrogenic activity, which are prescribed by gynecologists for hirsutism. Trade names of drugs containing drospirenone: Yarina/ Yarina, Jess/ Yaz, Simitsia / Symicia, Dailla / Dailla, Midiana / Midiana, Dimia / Dimia, Leah, Anabella, Vidora (drospirenone + ethinyl estradiol), Angelique/ Angeliq (drospirenone + estradiol hemihydrate).

Drospirenone is a derivative of 17α-spirolactone with progestogenic, antimineralocorticoid and antiandrogenic activity, presumably has no estrogenic, androgenic, glucocorticosteroid and antiglucocorticosteroid activity, does not affect glucose tolerance and insulin resistance, which, in combination with antimineralocorticoid and antiandrogenic action, provides drospirenone with a biochemical and pharmacological profile, similar to natural progesterone.

Antiandrogenic activity is due to two mechanisms: on the one hand, the drug reduces the secretion of testosterone in the adrenal glands and ovaries due to antigonadotropic action, and on the other hand, it competes with androgens for a place on their receptors. At the same time, drospirenone does not interfere with the conversion of free testosterone to dihydrotestosterone and does not affect the activity of the 5α-reductase enzyme in any way.

Like cyproterone, drospirenone-based drugs should not be taken with adrenal insufficiency due to antimineralocorticoid activity. However, unlike cyproterone, drospirinone has a diuretic effect: by increasing the excretion of sodium and water, the drug can prevent an increase in blood pressure, body weight, edema, breast tenderness, and other symptoms associated with fluid retention.

The effectiveness of Yarina in the treatment of hirsutism was observed during the year on 52 young women (25±6 years). The results were evaluated every 3-6-12 months according to the hormonal blood test (LH, FSH, androstenedione, testosterone, estradiol, SHBG, DHEA-S; blood sampling on the 3rd-6th day from the onset of bleeding). Results in the picture:

We see that, on the Ferriman-Galloway scale, women, on average, became half as hairy. The hormonal profile shows a significant increase in SHBG (sex hormone-binding globulin) and an associated decrease in free testosterone. The rest of the hormones remained virtually unchanged. The authors conclude that the use of drugs based on drospirenone is promising in the treatment of hirsutism, since in addition to reducing free testosterone, the drug helps to remove excess fluid and does not have a negative effect on metabolism, which is especially important for. However, the authors warn about the risks of thromboembolism associated with taking drospirenone.

In another study involving 15 women with PCOS, hormonal changes in the blood showed much more significant changes after starting Yarina tablets. We see that in addition to an increase in sex hormone-binding globulin (SHBG), cortisol increases significantly, 17-OH-progesterone (17OHP) and dehydroepiandrosterone sulfate (DHEAS) decrease, estradiol and androstenedione (A) decrease. Tests for glucose tolerance did not reveal any changes, but there was a trend towards an increase in cholesterol, triglycerides and high and low density lipoproteins.

A 12-month blind experiment with 91 women showed that drospirinone and cyproterone-based drugs are similar in effectiveness. The authors of the study, however, believe that due to the diuretic effect (and, therefore, pressure reduction), drospirinone-containing contraceptives are preferable. Below is a diagram of the reduction in the Ferriman-Galloway hairiness score in various areas of the body:


Like other hormone replacement drugs with progestogenic activity, taking drospirenone increases the risk of developing venous thromboembolism. Controlled randomized trials show that hormone replacement therapy increases the risks of the following diseases: endometrial hyperplasia or carcinoma, benign and malignant liver tumors, cholelithiasis, stroke, pancreatitis, jaundice, uterine bleeding, etc. Contraceptives are not used in the presence of any benign or malignant tumors. For a complete list of contraindications, see

1,2-dihydrospirorenone, (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))

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, its properties are close to natural, a derivative . 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 of drugs 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 , and . Drospirenone stimulates excretion sodium ions and other fluids from the body, as a result of which blood pressure normalizes, swelling and soreness in the mammary glands subside, and 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 occurrence is significantly reduced, 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 blood level decreases 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 ) - 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

The tool is prescribed:

  • as part of complex therapy for the prevention of postmenopausal;
  • 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 , 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 for contraception.

Contraindications

The medicine is contraindicated:

  • patients with Drospirenone;
  • at porphyria ;
  • persons with a penchant for education;
  • with severe liver failure;
  • during lactation;
  • with or in severe form;
  • if the patient has vaginal bleeding of unknown origin;
  • with 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 cerebral vessels;
  • thrombophlebitis , blood clots in the veins of the retina;
  • arterial hypertension , swelling, headaches;
  • ,apathy , ;
  • decreased visual acuity, vomiting, weight gain or loss;
  • galactorrhea , nausea, ;
  • , pain and swelling of the mammary glands;
  • bloody or unusual vaginal discharge;
  • decreased sex drive, chloasma ;
  • , reduced seizure threshold, .

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 medicine does not have a specific one, the treatment is symptomatic.

Interaction

With long-term treatment with drugs that induce liver enzymes ( barbiturates , , oscarbazepine , hydantoin derivatives , , , , 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

Need a prescription.

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, 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 signs of this disease, pain in the area under the ribs, an increase in the organ and intra-abdominal bleeding, then treatment should 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 .acne to remove excess fluid from the body. Be aware of the increased risk of developing and hyperkalemia during treatment with drospirenone.

Desogestrel or Drospirenone, which is better?

Desogestrel, like Drospirenone, belongs to the latest generation of hormonal contraceptives. By analogy with Gestodene, the substance is used to eliminate dysmenorrhea . It should also be noted that in the course of clinical studies it was found that the risk of weight gain is higher during treatment with Drospirenone. In any case, the decision as to which of the above substances should be chosen should be made by the attending physician.

Similar posts