Drospirenone + Ethinyl estradiol - instructions for use, dose, side effects, contraindications

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

There is evidence of a reduced risk of developing endometrial and ovarian cancer when combined oral contraceptives are used.

Pharmacokinetics:

Drospirenone

Suction. After ingestion drospirenone quickly and completely absorbed from the digestive 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 repeated intake in a dose of 2 mg C_max in the serum is achieved after 1 h and is about 22 ng / ml. After this, there is a two-phase decrease in serum drospirenone concentration with a final half-life of about 35-39 hours. Drospirenone binds to albumin and does not bind to globulin binding sex steroids and corticoid-binding globulin; about 3-5% is a free fraction.

Due to the long half-life of C_ss is achieved after 10 days of daily intake of the drug and exceeds the concentration after a single dose of 2-3 times.

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

Excretion. The clearance of drospirenone from serum is 1.2-1.5 ml / min / kg. Some part of the received dose is displayed 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; the half-life is about 40 hours.

Ethinylestradiol

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

Distribution. Serum concentrations of ethinyl estradiol decrease biphasic, in the phase of the final distribution the half-life is approximately 24 hours. Ethinylestradiol good, but not specifically associated with serum albumin (approximately 98.5%) and induces an increase in serum concentrations globulin binding sex steroids. V_d - about 5 l / kg.

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

Excretion. Unchanged ethinyl estradiol practically not excreted from the body. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestine in a ratio of 4: 6. Half-life metabolites is about 24 h.

C_ss comes in the second half of the treatment cycle, and the serum concentration of ethinyl estradiol increases 2-2.3 times.

Special patient groups

In case of impaired renal function. C_ss drospirenone in the blood plasma in women with mild renal insufficiency (creatinine clearance 50-80 ml / min) was comparable with the corresponding parameters 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 concentration of drospirenone in the blood plasma was on average 37% higher than in women with normal renal function. Drospirenone was well tolerated in all groups. The intake of drospirenone did not have a clinically significant effect on the potassium content in the blood serum. Pharmacokinetics in severe renal failure has not been studied.

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

Indications:

Contraception.

ICD-10

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

XXI.Z30-Z39.Z30 Monitoring the use of contraceptives

Contraindications:

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

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

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

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

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

- pregnancy and suspicion of it;

- lactation period;

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

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

- severe chronic or acute renal failure;

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

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

- bleeding from the vagina of unknown origin;

- Migraine with focal neurologic symptoms in history;

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

Carefully:

Risk factors for thrombosis and thromboembolism are smoking at the age of 35 years, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated heart valve defects, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age one of the next of kin); diseases in which there may be violations of peripheral circulation (diabetes mellitus without vascular complications, systemic lupus erythematosus, haemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia,phlebitis of superficial veins); hereditary angioedema; hypertriglyceridemia; liver disease of severe degree (before normalization of functional liver samples); the disease first appeared or worsen during pregnancy, or on the background of the previous use of sex hormones (including jaundice and / or pruritus related to cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in history, chorea (disease Sidengam), chloasma, postpartum period.

Pregnancy and lactation:

The drug is contraindicated during pregnancy. If the pregnancy occurred during the use of the drug, it should be stopped immediately. Advanced epidemiological studies found no increased risk of birth defects in children born to women who took combined oral contraceptives before pregnancy, or teratogenic effect combined oral contraceptives when they are unintentionally taken during pregnancy. According to preclinical studies, we can not exclude adverse effects that influence the course of pregnancy and fetal development, due to hormonal action of the active components.

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

Dosing and Administration:

Daily, at about the same time, with a small amount of water, in the order indicated on the blister pack. Tablets are taken continuously for 28 days, 1 tablet per day. The taking of tablets from the next package begins after the last tablet from the previous package is received. The withdrawal bleeding usually begins on the 2nd-3rd day after the start of taking the placebo tablets (last row) and does not necessarily end at the beginning of the next package.

Procedure for taking the drug

Hormonal contraceptives were not used in the last month. Acceptance of the drug begins on the 1st day of the menstrual cycle (that is, on the 1st day of menstrual bleeding). The onset of admission is possible on the 2nd-5th day of the menstrual cycle, in which case an additional use of the barrier method of contraception is necessary during the first 7 days of taking the tablets from the first package.

Transition from other combined contraceptives (in the form of tablets, vaginal ring or transdermal patch). The drug should be started on the day after the last inactive tablet (for preparations containing 28 tablets) or on the day after the last active tablet from the previous package (possibly the day after the end of the usual 7-day break) containing 21 tablets in a package. If a woman uses a vaginal ring or a transdermal patch, it is preferable to start taking the drug on the day of removal or, at the latest, on the day when a new ring or replacement of the patch is planned.

Transition from contraceptives containing only progestogens (mini-pili, injections, implants), or from the intrauterine system that secretes progestogens. A woman can switch from taking a mini-drink to taking the drug any day (from the implant or from the intrauterine system - on the day of removal, from the injectable form of the drugs - the day the next injection was to be made), but in all cases it is necessary to use additionally barrier method of contraception during the first 7 days of taking the tablets.

After abortion in the first trimester of pregnancy. The drug can be taken at the doctor's prescription on the day of termination of pregnancy. In this case, the woman does not need to take additional measures of contraception.

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

Acceptance of missed tablets

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

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

If the delay exceeds 12 hours, the contraceptive protection can be reduced. In doing so, you can follow two basic rules:

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

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

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

Days 1-7th. A woman should take the missed pill as soon as she remembers it, even if it means taking two tablets at the same time. Then she should take the pill at the usual time. In addition, during the next 7 days, a barrier method, such as a condom, should be used. If sexual contact occurs in the previous 7 days, the possibility of pregnancy should be considered. The more pills are missed and the closer this pass to the 7-day break in taking the drug, the higher the risk of pregnancy.

Days 8-14th. A woman should take the missed pill as soon as she remembers it, even if it means taking two tablets at the same time. Then she should take the pill at the usual time.If within 7 days preceding the first missed tablet, a woman took the pill as expected, there is no need for additional contraceptive measures. However, if she missed more than 1 tablet, an additional method of contraception (barrier, for example, a condom) is needed for 7 days.

Days of the 15-24th. The reliability of the method inevitably decreases, as the phase of the placebo tablets approaches. However, correction of the pill regimen can still help in preventing pregnancy. When one of the two following schemes, unless the previous 7 days before passing woman tablets complied dosing regimen, the need for additional contraceptive measures would not arise. If this is not the case, she must perform the first of the two schemes and use additional precautions for the next 7 days.

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

2. A woman can also interrupt the taking of active tablets from the started package. Instead, she should take placebo tablets from the last row for 4 days, including the days of missing the tablets, and then start taking the tablets from the next package. If a woman missed taking the pills and subsequently had no withdrawal bleeding in the phase of the placebo tablets, the possibility of pregnancy should be considered.

Use of the drug in case of gastrointestinal upset

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

Postponement of menstrual-like withdrawal bleeding

To delay bleeding, a woman should miss taking placebo tablets from the started package and begin taking the tablets drospirenone + ethinylestradiol from the new packaging. The delay can be prolonged until the active tablets in the second package run out. During the delay, a woman may experience acyclic copious or spotting spotting from the vagina. Regular reception of the drug resumes after the placebo phase. To shift the bleeding for another day of the week, it is recommended to shorten the forthcoming phase of taking tablets for the desired number of days. If the cycle is shortened, it is more likely that the woman will not have a menstrual bleeding cancellation, but there will be acyclic copious or spotting spotting from the vagina with the next package (the same as with the lengthening cycle).

Side effects:

The most frequently reported adverse reactions to the drug include nausea and pain in the mammary glands. They were found in more than 6% of women who use this drug.

Severe adverse reactions are arterial and venous thromboembolism.

The following are adverse reactions with a very rare incidence or with delayed symptoms that are believed to be associated with taking medications from the group of combined oral contraceptives.

Tumors:

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

- liver tumors (benign and malignant).

Other conditions:

- erythema nodosum;

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

- increased blood pressure;

- conditions developing or worsening during the administration of combined oral contraceptives, but their association with the drug has not been proven (jaundice and / or pruritus associated with cholestasis, gallstones, porphyria, systemic lupus erythematosus, haemolytic uremic syndrome, Sydenham's chorea herpes of pregnant women, hearing loss associated with otosclerosis);

- in women with hereditary angioedema, estrogen use may cause or aggravate its symptoms;

- impaired liver function;

- impaired glucose tolerance or influence on insulin resistance;

- Crohn's disease, ulcerative colitis;

- Chloasma;

- Hypersensitivity (including symptoms such as rash, hives).

Overdose:

Cases of drug overdose have not yet been described.

Based on the general experience of application combined oral contraceptives Potential symptoms of an overdose can be: nausea, vomiting, slightly pronounced bleeding from the vagina.

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

Interaction:

The interaction between oral contraceptives and other drugs may result in acyclic bleeding and / or ineffectiveness of contraception.The interactions described below are reflected in the scientific literature.

The mechanism of interaction with hydantoin, barbiturates, primidon, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, and 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 this is maintained for a minimum of 4 weeks after discontinuation of drug therapy.

Inefficiency of contraception was also noted when taking antibiotics, for example, ampicillin and tetracycline. The mechanism of this phenomenon is unclear. Women with short-term treatment (up to one week) by any of the above groups of drugs or mono drugs should temporarily use (during the simultaneous intake of other medicines and for another 7 days after the end), in addition to combined oral contraceptives, barrier methods of contraception.

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

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

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

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

In patients without renal failure, simultaneous administration of drospirenone and ACE inhibitors or non-steroidal anti-inflammatory drugs does not significantly affect the serum potassium content. However, simultaneous use of the drug with aldosterone antagonists or potassium-sparing diuretics has not been investigated. In this case, during the first cycle of treatment, the concentration of serum potassium should be monitored.

Special instructions:

If there are any states / risk factors among the ones mentioned below, the benefit of taking combined oral contraceptives should be evaluated individually for each woman and discussed with her before the application. In case of an exacerbation of an undesirable phenomenon, or in case of any of these conditions or risk factors, a woman should contact the attending physician. The doctor must decide whether to interrupt the reception combined oral contraceptives.

Circulatory disorders

Admission 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 taking low doses of estrogens (<0.05 mg of ethinyl estradiol) as part of combined oral contraceptives, is approximately 20 cases per 100,000 women-years (for levonorgestrel-containing combined oral contraceptives second generation) or 40 cases per 100,000 women-years (for desogestrel / gestodene-containing combined oral contraceptives third generation). In women who do not use combined oral contraceptives, 5-10 venous thromboembolism occur and 60 pregnancies per 100,000 women-years. Venous thromboembolism is fatal in 1-2% of cases.

Data from a large, prospective, three-pronged study showed that the incidence of venous thromboembolism in women with other risk factors for venous thromboembolism or without them, using a combination of ethinyl estradiol and drospirenone,0.03 + 3 mg, coincides with the frequency of venous thromboembolism in women using levonorgestrel-containing oral contraceptives and others combined oral contraceptives. The risk of venous thromboembolism is currently not established.

Epidemiological studies also revealed a connection between admission combined oral contraceptives with an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic disorders).

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

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

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

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

- sudden shortness of breath;

- sudden appearance of cough;

- any unusual severe prolonged headache;

- sudden partial or complete loss of vision;

- diplopia;

- broken speech or aphasia;

- vertigo;

- a collapse with partial epileptic seizures or without them;

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

- motor disorders;

- an acute abdomen.

Before starting reception combined oral contraceptives a woman should consult a specialist. Risk of venous thromboembolic disturbances in admission combined oral contraceptives increases:

- with increasing age;

- hereditary predisposition;

- prolonged immobilization, extended surgical intervention, any surgical intervention on the lower limbs or major trauma. In such situations it is recommended to stop taking the drug (in the case of planned surgical intervention for at least 4 weeks) and not to resume until two weeks after the full recovery of mobility. If the drug has not been discontinued in advance, an anticoagulant treatment should be considered;

- obesity (body mass index more than 30);

- there is no consensus on the possible role of varicose veins and superficial thrombophlebitis with the appearance or exacerbation of venous thrombosis.

Risk of arterial thromboembolic complications or acute impairment of cerebral circulation upon admission combined oral contraceptives increases with:

- increasing age;

- smoking (women older than 35 years are strongly advised to stop smoking if they want to take combined oral contraceptives);

- dyslipoproteinemia;

- arterial hypertension;

- migraine without focal neurological symptoms;

- obesity (body mass index more than 30);

- hereditary predisposition (arterial thromboembolism ever in the sibling brothers or parents at a relatively early age). If a hereditary predisposition is possible, a woman should consult a specialist before starting the treatment combined oral contraceptives;

- defeat of the valvular heart;

- atrial fibrillation.

The presence of one major risk factor for venous disease or several risk factors for artery disease can also becontraindication. You should also consider the possibility of anticoagulant therapy. Women taking combined oral contraceptives, should be properly instructed about the need to inform the attending physician in case of suspicion of the symptoms of thrombosis. In the event that thrombosis is suspected or confirmed, admission combined oral contraceptives should be discontinued. It is necessary to begin adequate alternative contraception due to teratogenicity of anticoagulant therapy with indirect anticoagulants - coumarin derivatives.

An increased risk of thromboembolism in the postpartum period should be considered.

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

Increased frequency or severity of migraine on the background of admission combined oral contraceptives may be an indication to their immediate cancellation.

Tumors

The most significant risk factor for developing cervical cancer is infection with the human papillomavirus. Some epidemiological studies have reported an increased risk of developing cervical cancer with prolonged use combined oral contraceptives, but there are conflicting views as to the extent to which these findings are related factors, for example, research on cervical cancer or the use of barrier methods of contraception.

A meta-analysis of the results of 54 epidemiological studies revealed a slight increase in the relative risk of developing breast cancer in women who are currently taking combined oral contraceptives. Risk gradually decreases within 10 years after discontinuation of admission 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 combined oral contraceptives little affects the overall probability of breast cancer.In these studies, there was no sufficient evidence of a cause-effect relationship. The increase in risk may be a consequence of an earlier diagnosis of breast cancer in combined oral contraceptives, biological action combined oral contraceptives or a combination of both. Diagnosed breast cancer in women who have ever taken combined oral contraceptives, was clinically less severe, which is due to early diagnosis of the disease.

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

Other

The progestogen component of the drug is an aldosterone antagonist that retains potassium in the body. In most cases, an increase in the potassium content is not expected.However, in a clinical study, in some patients with mild or moderate renal disease who took potassium-sparing drugs, the serum potassium content increased slightly during the administration of drospirenone. Therefore, it is recommended that the serum potassium content be monitored during the first treatment cycle in patients with renal insufficiency, whose serum potassium concentration before treatment was at the upper limit of the norm and, especially, with simultaneous intake of potassium-sparing drugs. In women with hypertriglyceridemia or a hereditary predisposition to this, the risk of pancreatitis in admission may be increased 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 it justified to immediately stop taking combined oral contraceptives. If you receive combined oral contraceptives in patients with concomitant arterial hypertension, the blood pressure is constantly increased or significantly elevated blood pressure can not be corrected by antihypertensive drugs, combined oral contraceptives should be discontinued. After normalization of arterial pressure with the help of antihypertensive medications combined oral contraceptives you can resume.

The following diseases appeared or worsened during pregnancy and admission combined oral contraceptives: jaundice and / or itching associated with cholestasis, stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; rheumatic chorea (Sydenham's chorea); herpes during pregnancy; otosclerosis with loss of hearing. However, evidence of their relationship with the reception combined oral contraceptives unconvincing.

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

Acute or chronic liver disease may be an indication of discontinuation combined oral contraceptives before the normalization of liver function. The recurrence of cholestatic jaundice and / or cholestasis-related pruritus that developed during an earlier pregnancy or with earlier use of sex hormones,serve as an indication to stop taking combined oral contraceptives.

Although combined oral contraceptives can affect peripheral insulin resistance and glucose tolerance, a change in the treatment regimen in patients with diabetes mellitus on the background of admission combined oral contraceptives with a low content of hormones (containing <0.05 mg of ethinyl estradiol) is not shown. However, women with diabetes mellitus should be closely monitored, especially in the early stages of admission combined oral contraceptives.

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

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

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

Allergic reactions may occur in women who are allergic to soy lecithin.

The efficacy and safety of the drug as a contraceptive is studied in women of reproductive age. It is assumed that in the post-pubertal period up to 18 years, the effectiveness and safety of the drug are similar to those in women after 18 years of age.

Medical examinations

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

Decreased efficiency

Efficiency combined oral contraceptives can be reduced, for example, when you miss taking pills drospirenone + ethinylestradiol, gastrointestinal disorders at the time of taking tablets drospirenone + ethinylestradiol or simultaneous administration of other medications.

Insufficient cycle control

As with the application of other combined oral contraceptives, a woman may have acyclic bleeding (smearing or bleeding cancellation), especially in the first months of admission. Therefore, any irregular bleeding should be assessed after a three-month adaptation period.

Instructions

Drospirenone + Ethinylestradiol (Drospirenonum + Aethinyloestradiolum)