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

film sheath: Opadrai II Pink 85F34048 (macrogol 3350-0.404 mg, titanium dioxide 0.496 mg, polyvinyl alcohol 0.8 mg, talc 0.296 mg, iron oxide red oxide 0.0036 mg, iron oxide oxide yellow 0.0004 mg 2.0) mg.

4 tablets of white color, film-coated (placebo)

Active substances: do not contain.

Excipients:

core: lactose monohydrate - 73.4 mg, polacrilin potassium - 1.6 mg, povidone-K30 - 4.00 mg, silicon dioxide colloid - 0.2 mg, magnesium stearate - 0.80 mg;

film sheath: Foam II white 85F18422 (macrogol 3350 0.8 mg, titanium dioxide 0.5 mg, polyvinyl alcohol 0.404 mg, talc 0.296 mg) 2.0 mg.

Description:Round, biconvex tablets, covered with a film shell of pink color.

Placebo tablets: round, biconvex tablets, covered with a film shell of white color.

Pharmacotherapeutic group:contraceptive combination (estrogen + progestogen)

ATX: & nbsp

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

Pharmacodynamics:

Lei is a monophasic combined oral contraceptive (COC), which includes ethinyl estradiol and progestogen drospirenone. The contraceptive effect of Leia's drug is based on the interaction of various factors,of which the most important are suppression of ovulation and a change in the properties of the cervical secret, as a result of which it becomes impermeable to spermatozoa. In therapeutic doses, drospirenone also has antiandrogenic and moderate antimineralocorticoid properties, which gives drospirenone a pharmacological profile similar to that of natural progesterone. Drospirenone helps to reduce the symptoms of acne (acne), the fatness of the skin and hair, prevents weight gain and the appearance of swelling associated with estrogen-induced fluid retention, which provides a very good tolerance of the drug Leia. The positive effect and clinical effectiveness of drospirenone in alleviating symptoms of severe premenstrual syndrome (PMS) such as severe psychoemotional disorders, breast engorgement, headache, muscle and joint pain, weight gain and other symptoms associated with the menstrual cycle are shown. In combination with ethinyl estradiol, drospirenone demonstrates a beneficial effect on the lipid profile, characterized by an increase in high-density lipoprotein (HDL) in the blood plasma.

In women taking COC, the menstrual cycle becomes more regular, less painful menstruation is observed, the intensity of bleeding decreases, which reduces the risk of anemia. In addition, according to epidemiological studies, the use of COC reduces the risk of developing endometrial cancer and ovarian cancer.

Pharmacokinetics:

Drospirenone

Absorption

When administered orally, drospirenone quickly and almost completely absorbed. After a single oral intake, the maximum concentration in the blood plasma, about 38 ng / ml, is reached after about 1-2 hours. Bioavailability is 76-85%. Eating does not affect the bioavailability of drospirenone.

Distribution

After oral administration, the concentration of drospirenone in the blood plasma decreases biphasally, with a half-life (t_1/2) in the second phase - 31 hours. Drospirenone binds to plasma albumin and does not bind to sex hormone binding globulin (SHBG), or corticosteroid-binding globulin (CSG). Only 3-5% of the total concentration of the substance in the blood plasma is present as a free steroid. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone with plasma proteins. The average apparent volume of distribution is 3.7 ± 1.2 l / kg.

Metabolism

After ingestion, drospirenone is extensively metabolized. Most metabolites in the plasma are represented by acid forms of drospirenone.

Excretion from the body

The metabolic clearance rate of drospirenone in blood plasma is 1.5±0.2 ml / min / kg. In unmodified form, drospirenone is excreted only in trace amounts. Metabolites of drospirenone are excreted through the intestine and kidneys in a ratio of approximately 1.2: 1.4. The half-life of excretion of metabolites is approximately 24 hours.

The equilibrium concentration

During the cyclic treatment, the maximum equilibrium concentration of drospirenone in the blood plasma is achieved after 8 days of administration and is approximately 70 ng / ml. There was an increase in the concentration of drospirenone in the blood plasma by approximately 2-3 times (due to cumulation), which was due to the ratio of the half-life in the terminal phase and the dosing interval. A further increase in the plasma concentration of drospirenone occurs between 1 and 6 cycles of administration, after which no increase in concentration is observed.

Special groups of patients

Patients with renal insufficiency

Equilibrium concentrations of drospirenone in blood plasma in women with mild renal insufficiency (creatinine clearance (CK) = 50-80 ml / min) were comparable with those in women with normal renal function (CK> 80 ml / min). In women with renal insufficiency of moderate severity (CK = 30-50 ml / min), the concentration of drospirenone in the blood plasma was on average 37% higher than in women with normal renal function. Treatment with drospirenone was well tolerated in all groups. The intake of drospirenone did not have a clinically significant effect on the potassium concentration in the blood plasma. Pharmacokinetics in severe renal failure has not been studied.

Patients with hepatic insufficiency

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

Ethinylestradiol

Absorption

After oral administration ethinyl estradiol quickly and completely absorbed. Peak plasma concentration after a single oral intake is achieved after 1-2 hours and is about 33 ng / ml.Absolute bioavailability as a result of presystemic conjugation and metabolism of the first passage is approximately 60%. Concomitant ingestion reduces the bioavailability of ethinylestradiol in about 25% of those surveyed, while in other patients no similar changes were noted.

Distribution

The concentration of ethinyl estradiol in blood plasma is reduced biphasic; the half-life is approximately 24 hours. Ethinylestradiol is largely and not specifically associated with plasma albumin (approximately 98.5%) and causes an increase in the concentration of SHBG in the blood plasma. The average apparent volume of distribution is about 5 l / kg.

Metabolism

Ethinyl estradiol is subjected to presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinylestradiol is first metabolized by aromatic hydroxylation, with the formation of a variety of hydroxylated and methylated metabolites, represented both as free metabolites and as conjugates with glucuronic and sulfuric acids. Ethinylestradiol completely metabolized; the rate of metabolic clearance is about 5 ml / min / kg.

Excretion from the body

Ethinyl estradiol is practically not excreted unchanged.Metabolites of ethinyl estradiol are excreted through the kidneys and intestines in a ratio of 4: 6; the half-life is approximately 1 day.

The equilibrium concentration

The state of equilibrium concentration is reached during the second half of the cycle of taking the drug, and the concentration of ethinyl estradiol in the blood plasma increases by approximately 1.4-2.1 times.

Preclinical safety data

Preclinical data obtained from routine studies to detect toxicity with multiple doses of the drug, as well as genotoxicity, carcinogenic potential, and toxicity to the reproductive system, do not indicate a particular risk to humans. Nevertheless, it should be remembered that sex hormones can promote the growth of some hormone-dependent tissues and tumors.

Indications:

- Contraception;

- contraception and acne treatment of moderate severity (acne vulgaris);

- contraception and treatment of severe premenstrual syndrome (PMS).

Contraindications:

Lei is contraindicated in the presence of any of the conditions listed below; if any of these conditions occur for the first time against the background of treatment with COCs, they should be stopped immediately:

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

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

- hereditary or acquired predisposition to the development of venous or arterial thrombosis, such as resistance to activated protein C. deficiency of antithrombin III, protein deficiency C, protein deficiency S, hyperhomocysteinemia and antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant);

- Migraine with focal neurologic symptoms at present or in the anamnesis;

- multiple or expressed risk factors for venous or arterial thrombosis, including complicated cardiac valve disease, atrial fibrillation; diseases of the vessels of the brain or coronary arteries; uncontrolled arterial hypertension; severe dyslipoproteinemia, diabetes mellitus with vascular complications,Serious surgical intervention with prolonged immobilization; smoking over the age of 35; Obesity with a body mass index (BMI) of more than 30 kg / m²; extensive trauma;

- hepatic failure, severe liver disease (before the normalization of liver function);

- liver tumors (benign or malignant), incl. in the anamnesis;

- severe renal failure, acute renal failure;

- adrenal insufficiency;

- pancreatitis, incl. in history, if associated with the presence of severe triglyceridemia;

- identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspected of them;

- bleeding from the vagina, unspecified etiology;

- pregnancy or suspected of it;

- the period of breastfeeding;

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

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption (lactose monohydrate is included).

Carefully:

If the patient has any of the conditions / risk factors listed below, the potential risk and expected benefits of using COC should be carefully weighed, including Leah's drug:

- risk factors for thrombosis and thromboembolism: smoking, thrombosis (incl.in anamnesis), myocardial infarction or cerebrovascular accident at a young age with someone from the next of kin; Obesity with a BMI of less than 30 kg / m²; dyslipoproteinemia; controlled arterial hypertension; migraine without focal neurological symptoms; heart valve disease without complications; heart rhythm disorder;

- other diseases in which there may be violations of peripheral circulation: diabetes mellitus; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease and ulcerative colitis; sickle-cell anemia; and phlebitis of superficial veins;

- hereditary angioedema;

- hypertriglyceridemia;

- liver disease;

- diseases that first appeared or worsened during pregnancy or against the background of previous reception of sex hormones (for example, jaundice, cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes pregnant, Sydenham's chorea);

- the postpartum period.

Pregnancy and lactation:

Pregnancy

Leia is contraindicated for use during pregnancy. When a pregnancy occurs against the background of taking Leah's drug, you must immediately stop taking it.The conducted epidemiological studies revealed neither an increase in the risk of birth defects in children born to mothers who had taken COC prior to pregnancy, or a teratogenic effect, when COCs were negligently taken early in pregnancy.

The available data on the use of the drug Leia during pregnancy are too limited and do not allow to draw a conclusion about its negative effect on pregnancy or on the health of the fetus or newborn.

Breast-feeding

Leia is contraindicated during breastfeeding. COCs can reduce the amount of breastmilk and change its quality. A small amount of sex hormones and / or their metabolites can penetrate into breast milk and, possibly, can affect the baby.

Dosing and Administration:

The drug Lei is intended for oral administration daily for 28 days without interruptions, approximately at the same time, with a small amount of water, in the order indicated on the blister pack. Receiving tablets from a new package begins the day after receiving the last tablet from the previous package.

How to take the drug Leia

If no hormonal contraceptives were taken in the previous month

Reception of Leah's drug begins on the first day of the menstrual cycle (ie on the first day of menstrual bleeding). It is allowed to start taking the menstrual cycle on the 2nd-5th day, but in this case it is recommended to use the barrier method of contraception in the first 7 days of taking the tablets from the new package.

Bleeding "cancellations", as a rule, begins on the 2nd-2nd day after the start of taking inactive tablets and may not end before taking pills from a new package.

When switching from other combined oral contraceptives (COC, vaginal ring or transdermal patch)

It is preferable to start taking Leah's drug the day after taking the last active tablet from the previous package, but in no case later than the day after the usual 7-day break (for preparations containing 21 active tablets) or after taking the last inactive tablet , containing 28 tablets in a package). Lei should be taken on the day of removal of the vaginal ring or contraceptive patch, but no later than the day when a new ring is to be inserted or a new patch is stuck.

When switching from contraceptives containing only gestagens ("mini-pili", injectable forms, implant or intrauterine contraceptive)

A woman can switch from a "mini-drink" to taking Leah's drug any day (without interruption), with an implant or an intra-uterine therapeutic system releasing progestogen - on the day of removal, from the injection contraceptive - on the day the next injection is to be taken. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.

After abortion in the first trimester of pregnancy

A woman can start taking Leah's drug from the first day after the abortion. If this condition is met, the woman does not need additional contraceptive measures.

After childbirth or abortion in the second trimester of pregnancy

It is recommended to start taking Leah's drug on the 21-28th day after giving birth, without breastfeeding, or abortion in the second trimester of pregnancy. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if a woman already had sex life, pregnancy should be excluded before Leia's reception.

Acceptance of missed tablets

Skipping inactive tablets can be ignored. Nevertheless, they should be thrown away, so as not to accidentally prolong the period of intake of inactive tablets.

The following recommendations apply only to the omission of active tablets:

- if the delay in taking the drug was less than 24 hours, contraceptive protection is not reduced. The woman should take the missed tablet as soon as possible, and the next take at the usual time;

- if the delay in taking the tablets is more than 24 hours, contraceptive protection can be reduced. The more pills are missed, and the closer the skipping of tablets to the phase of taking inactive tablets, the higher the probability of pregnancy.

In doing so, you can follow the following basic rules:

- the drug should never be interrupted for more than 7 days (the recommended interval for taking inactive tablets is 4 days);

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

Thus, if the delay in taking active tablets is more than 24 hours, you can recommend the following:

From the 1st to the 7th day:

A woman should take the last missed pill right away, as soon as she remembers it, even if it means taking two pills at the same time. The following tablets she continues to take at the usual time. In addition, during the next 7 days, the barrier method of contraception (for example, a condom) needs to be additionally used. If sexual intercourse has occurred within 7 days before passing the pill, you should consider the possibility of pregnancy.

From the 8th to the 14th day:

A woman should take the last missed pill right away, as soon as she remembers it, even if it means taking two pills at the same time. The following tablets should be taken at the usual time.

Provided that the woman took the tablets correctly for 7 days preceding the first missed tablet, there is no need for additional contraceptive measures. Otherwise, as well as when two or more tablets are missed, barrier methods of contraception (for example, a condom) should be used additionally within 7 days.

From the 15th to the 24th day:

The risk of a decrease in reliability is inevitable due to the approaching phase of taking inactive tablets. A woman should strictly adhere to one of the following two options.In this case, if in the 7 days preceding the first missed tablet, all the pills were taken correctly, there is no need to use additional contraceptive methods. Otherwise, she must use the first of the following schemes and additionally use the barrier method of contraception (for example, a condom) for 7 days.

1 option:

The woman should take the last missed pill as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The following tablets are taken at the usual time, until the active tablets in the package run out. Four inactive tablets should be discarded and immediately begin taking the tablets from the next package. Bleeding "cancellation" is unlikely until the active pills in the second package run out, but "smearing" discharge and "breakthrough" bleeding may occur during taking the tablets.

2 option:

A woman can also interrupt the taking of tablets from the current package. Then she should take a break no more than 4 days, including the days of missing the tablets, and then start taking the tablets from the new package.If a woman missed active pills, and during the reception of inactive bleeding pills "cancellation" did not occur, it is necessary to exclude pregnancy.

Recommendations for gastrointestinal disorders

In severe gastrointestinal disorders, absorption of the drug may be incomplete, therefore additional contraceptive measures should be taken.

If vomiting occurs within 4 hours after taking the active pill, recommendations should be followed when skipping tablets. If a woman does not want to change her usual schedule of taking and transfer the onset of menstruation on another day of the week, an additional active pill should be taken from another package.

Change in the day of menstrual bleeding

In order to delay the onset of menstrual bleeding, a woman should continue taking the tablets from the next package, skipping the inactive tablets from the current package. Thus, the cycle can be extended, if desired, for any period, until the active tablets from the second package run out. Against the background of taking tablets from the second package, a woman may have "spotting" discharge or "breakthrough" uterinebleeding. Regular intake of the drug Lei resumes after the end of the phase of taking inactive tablets.

In order to transfer the day of the onset of menstrual bleeding to another day of the week, the woman should shorten the next phase of taking inactive tablets for the desired number of days. The shorter the interval, the higher the risk that it will not have the bleeding of "withdrawal" and thereafter there will be "spotting" bleeding and "breakthrough" bleeding during the second package (as well as in the case when it would like to delay the onset of menstrual-like bleeding).

How to delay the bleeding of "cancellation"

To delay the onset of menstruation, a woman should proceed to receive tablets from a new package of Leah's drug, skipping the reception of the placebo tablets. Such extension of the cycle can be continued until the active tablets of the second package run out. During this prolongation, a woman may have "breakthrough" bleeding or spotting. In the future, regular use of Lei's drug should be resumed after a normal interval without pills, which is 7 days.To postpone the onset of menstruation for another day, more suitable for a woman's usual schedule, you can shorten the second phase of taking placebo tablets for as many days as needed. The shorter this phase, the higher the risk that the bleeding of the "cancellation" will not develop, and that there will be "breakthrough" bleeding or spotting during the taking of the tablets from the second package (and also during the delay in menstruation).

Special groups of patients

Children and teens

The drug Leia is shown only after the onset of menarche. The available data do not suggest correction of the dose in this group of patients.

Older patients

Not applicable. Leia is not indicated after menopause.

Patients with hepatic impairment

Leia is contraindicated in women with severe liver disease until the liver function test results are normal. (See the sections "Contraindications" and "Pharmacological properties").

Patients with impaired renal function

The drug Leia is contraindicated in women with severe renal failure or with acute renal failure. (Cm.sections "Contraindications" and "Pharmacological properties").

Side effects:

Clinical Trials Data

The frequency of unwanted reactions is presented in accordance with the classification of the Medical Dictionary for Regulatory Activities (MedDRA):

Very often (≥ 10%),

Often ( ≥1% < 10%),

Infrequently ( ≥ 0,1% < 1%),

Rarely (≥ 0,01% <0,1%),

Rarely ( < 0,01%),

The frequency is unknown (it is not possible to determine the frequency of occurrence according to the available data).

Infectious and parasitic diseases

Infrequently: candidiasis of the oral mucosa, vaginal candidiasis, herpes simplex.

Immune system disorders

Infrequent: allergic reactions.

Rarely: bronchial asthma.

Frequency is unknown: hypersensitivity reactions.

Violations of the blood and lymphatic system

Rarely: anemia, thrombocytopenia.

Disorders of the psyche

Often: emotional lability.

Infrequently: depression, nervousness, sleep disorder.

Rarely: anorgasmia.

Disturbances from the nervous system

Often: headache.

Infrequently: paresthesia, dizziness, migraine.

Rarely: a tremor.

Disturbances on the part of the organ of sight

Infrequent: conjunctivitis, dry eye syndrome, visual impairment.

Hearing disorders and labyrinthine disorders

Rarely: hearing loss.

Heart Disease

Infrequently: extrasystoles, tachycardia.

Vascular disorders

Infrequent: pulmonary embolism, increased blood pressure, lower blood pressure, varicose veins.

Rarely: arterial and venous thromboembolism, fainting.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: pharyngitis.

Disorders from the gastrointestinal tract

Often: nausea.

Infrequent: vomiting, gastroenteritis, diarrhea.

Rarely: constipation, abdominal pain, bloating.

Disturbances from the liver and bile ducts

Rarely: cholecystitis.

Disturbances from the skin and subcutaneous tissues

Infrequent: itchy skin, rash, seborrhea, acne.

Rarely: alopecia, dry skin, eczema, photodermatitis, acneiform dermatosis, hypertrichosis, striae, nodal erythema, erythema multiforme.

Disturbances from musculoskeletal and connective tissue

Infrequent: pain in the neck, in the extremities, lumbar region; muscle cramps.

Disorders from the kidneys and urinary tract

Infrequently: cystitis.

Violations of the genitals and mammary gland

Often: pain in the mammary glands, engorgement of the mammary glands, metrorrhagia, absence of menstrual bleeding.

Infrequently: neoplasms of the mammary glands, galactorrhea, ovarian cyst, "hot flashes", leucorrhoea, dry vaginal mucosa, pelvic pain, pap smear changes, decreased libido, mammary glands, painful menstrual bleeding, scanty menstrual-like bleeding.

Rarely: fibrocystic mastopathy, vaginitis, cervical polyp, cervical neoplasia, endometrial atrophy, copious menstrual bleeding, dyspareunia, postcoital bleeding, bleeding "cancellation", enlargement of the uterus.

Disorders from the endocrine system

Very rarely: changes in glucose tolerance or influence on insulin resistance.

General disorders and disorders at the site of administration

Often: weight gain.

Infrequent: increased appetite, weight loss, anorexia, edema, asthenia, excessive thirst, sweating.

Laboratory and instrumental data

Infrequently: hyperkalemia, hyponatremia.

Post-marketing application data

It reported the following serious adverse reactions with unknown frequency in women taking COCs: venous thromboembolism, arterial thromboembolic complications, high blood pressure, liver tumors.

Communication with COC use is not convincing with the appearance or worsening of the following diseases: Crohn's disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice, chloasma.

Acute and chronic liver dysfunction may require cancellation of COCs until the hepatic function markers return to normal.

In women with hereditary angioedema, exogenous estrogens can cause the manifestation of the disease or its aggravation.

The frequency of diagnosis of breast cancer among women taking COC is slightly increased, although the causal relationship with the use of COC is not established.

Overdose:

Until now, there has been no case of overdose of Leah's drug.Given the clinical experience of using COCs, in the event of an overdose of the drug, the following symptoms may occur: nausea, vomiting, spotting spotting or metrorrhagia. Antidote does not exist, treatment is symptomatic.

Interaction:

The interaction of oral contraceptives with other drugs can lead to "breakthrough" bleeding and / or a decrease in contraceptive reliability. Women taking these drugs should temporarily use barrier methods of contraception in addition to taking Leah's drug or choosing another method of contraception.

The use of drugs that induce microsomal enzymes of the liver can lead to an increase in the clearance of sex hormones. Such medicines include: phenytoin, barbiturates, primidon, carbamazepine, rifampicin; There are also suggestions for oxcarbazepine, topiramate, felbamate, griseofulvin, and preparations containing St. John's Wort.

HIV proteases (for example, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and their combinations also have the potential to affect hepatic metabolism.

According to separate studies, some antibiotics (for example, penicillins and tetracycline) can reduce intestinal hepatic recycling of estrogens, thereby lowering the concentration of ethinylestradiol.

During the administration of drugs that affect microsomal enzymes, and within 28 days after their withdrawal, the barrier method of contraception should be used additionally.

During the administration of antibiotics (such as ampicillins and tetracyclines) and within 7 days after their withdrawal, the barrier method of contraception should be used additionally. If active (pink) tablets terminate during these 7 days of using the barrier method of contraception, you should skip the placebo (white) tablets from the current package and start taking the tablets from the next Leah preparation.

The main metabolites of drospirenone are formed in the plasma without the participation of cytochrome P450 isoenzymes. Therefore, the effect of inhibitors of cytochrome P450 isoenzymes on the metabolism of drospirenone is unlikely.

COCs can affect the metabolism of other drugs, leading to an increase (for example, ciclosporin) or decrease (for example, lamotrigine) of their concentration in plasma and tissues.

Based on interaction studies in vitro, as well as studies in vivo among women volunteers omeprazole, simvastatin and midazolam as markers, it can be concluded that the effect of drospirenone in a dose of 3 mg on the metabolism of other drugs is unlikely.

There is a theoretical possibility of increasing the concentration of potassium in the blood plasma in women receiving Lei simultaneously with other drugs that can increase the concentration of potassium in the blood plasma. These drugs include ACE inhibitors, angiotensin II receptor antagonists, some non-steroidal anti-inflammatory drugs, potassium-sparing diuretics and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone with ACE inhibitors or indomethacin, there was no significant difference between plasma potassium concentration in comparison with placebo. Nevertheless, in women taking drugs that can increase the concentration of potassium in the blood plasma, it is recommended to determine the concentration of potassium in the blood plasma during the first cycle of taking Leah's drug.

To determine possible interactions with drugs taken concomitantly with Leah's preparation, you should read the instructions for using these medications.

Special instructions:

If any of the conditions / risk factors listed below are present, careful consideration should be given to the potential risk and expected benefit of using COCs in each individual case and to discuss it with the patient prior to taking the drug. In case of weighting, strengthening, or the first manifestation of any of these conditions or risk factors, a woman should consult with her doctor who can decide whether to cancel the drug.

Diseases of the cardiovascular system

The results of epidemiological studies indicate the existence of a relationship between the use of COCs and an increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders) with COCs. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is maximal in the first year of taking such drugs. The increased risk is present after the initial use of COCs or the resumption of use of the same or different COCs (after a break between doses of 4 weeks or more), mainly during the first 3 months.

The overall risk of VTE in patients taking low-dose COCs (<50 mcg ethinyl estradiol) is two to three times higher than in non-pregnant patients who do not take COC, however, this risk remains lower compared with the risk of VTE during pregnancy and childbirth . VTE may be life threatening or fatal (in 1-2% of cases). Venous thromboembolism, manifested as deep vein thrombosis, or pulmonary embolism, can occur when using any COCs. It is extremely rare when using COC occurs thrombosis of other blood vessels, for example, liver, mesenteric, renal, cerebral veins and arteries or vessels of the retina.

Symptoms of deep vein thrombosis (DVT) include the following: a one-sided swelling of the lower limb or along the vein on the lower limb,pain or discomfort only in the vertical position or walking, local temperature increase, redness or discoloration of the skin on the lower limb.

Symptoms of thromboembolism of the pulmonary artery (PE) are as follows: shortness of breath or rapid breathing; sudden cough, including hemoptysis; acute pain in the chest, which can increase with a deep breath; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (eg, dyspnea, coughing) are nonspecific and may be incorrectly interpreted as signs of other more or less severe conditions (e.g., respiratory infection).

Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction.

Symptoms of stroke are as follows: sudden weakness or loss of sensitivity of the face, hands or feet, especially on one side of the body, sudden confusion, problems with speech and understanding; sudden one- or two-sided loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination of movements; sudden,severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, puffiness and weak blueing of the extremities, symptomatology of the "acute abdomen".

Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of contraction or raspiraniya in the chest or behind the breastbone; discomfort with irradiation in the back, jaw, left upper limb, epigastric region; cold sweats, nausea, vomiting or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat. Arterial thromboembolism can be life threatening or fatal.

The risk of developing thrombosis (venous and / or arterial) and thromboembolism increases:

- with age;

- smokers (with the increase in the number of cigarettes or an increase in the age of the risk increases, especially in women older than 35 years);

in the presence of:

- obesity (BMI more than 30 kg / m²);

- dyslipoproteinemia;

- arterial hypertension;

- migraine;

- heart valve diseases;

- atrial fibrillation;

- family history (for example, venous or arterial thromboembolism ever at close relatives or parents at a relatively young age).In the case of a hereditary or acquired predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking COC;

- prolonged immobilization, serious surgical intervention, any surgical intervention on the lower extremities, the pelvic area, neurosurgical operations or extensive trauma. In these cases, the COCs should be discontinued (in the case of a planned operation, at least four weeks before) and do not resume admission within two weeks of immobilization.

It should be borne in mind that temporary immobilization (for example, air travel lasting more than 4 hours) is also a risk factor for venous thromboembolism.

The risk of developing thrombosis and thromboembolism with a combination of several high-risk factors is mutually reinforcing.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. You should consider the increased risk of thromboembolism in the postpartum period.

Violations of the peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus,hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular disorders) is the reason for the immediate withdrawal of these drugs.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia. deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When assessing the risk-benefit ratio, it should be borne in mind that adequate treatment of the relevant condition can reduce the risk of thrombosis associated with it. It should also be taken into account that the risk of thrombosis and thromboembolism in pregnancy is higher than when taking low-dose oral contraceptives (<0.05 mg of ethinyl estradiol).

According to some data, preparations containing drospirenone have a higher risk of developing thromboembolic complications,compared with drugs containing levonorgestrel, norgestimate or norethindrone.

Tumors

The most significant risk factor for developing cervical cancer is persistent papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with prolonged use of COCs. The connection with the reception of the COC has not been proved. There are contradictions as to the extent to which these findings are associated with screening for cervical pathology or with peculiarities of sexual behavior (more rare use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COC (relative risk 1.24). The increased risk gradually disappears within 10 years after discontinuation of these medications. Due to the fact that breast cancer is rarely seen in women under 40 years of age, an increase in the number of diagnoses of breast cancer in women who are currently taking COCs or who have recently taken COC is insignificant in relation to the overall risk of this disease.The observed increase in risk may be the result of an earlier diagnosis of breast cancer in women using COC, the biological effect of oral contraceptives, or a combination of both. Women who use COC have earlier stages of breast cancer than women who have never used them.

In rare cases, the development of benign, and extremely rare, malignant liver tumors, which in some cases led to life-threatening intraabdominal hemorrhage, was observed with the use of COCs. 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. Tumors can endanger life or lead to death.

Other states

Clinical studies have shown no effect of drospirenone on the potassium concentration in blood plasma in patients with mild and moderate renal insufficiency. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial concentration of potassium at the upper limit of the norm, simultaneously taking medications leading to a delay in potassium in the body.Nevertheless, in women with an increased risk of developing hyperkalemia, it is recommended to determine the concentration of potassium in the blood plasma during the first cycle of taking Leah's drug.

Women with hypertriglyceridemia (or having this condition in a family history) may have an increased risk of developing pancreatitis while taking COC.

Although a small increase in blood pressure was described in many women taking COC, clinically significant increases were rarely seen. Nevertheless, if a persistent, clinically significant increase in blood pressure develops during the administration of COC, these drugs should be discontinued and the treatment of hypertension should begin. Reception of COCs can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions have been reported to develop or worsen, both during pregnancy and when taking COCs, according to their relationship with the administration of COC has not been proven: jaundice and / or pruritus associated with cholestasis; formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes pregnant; hearing loss associated with otosclerosis.Cases of Crohn's disease and ulcerative colitis are also described against the background of COC use.

In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require cancellation of the COC until the liver function returns to normal. Recurrence of cholestatic jaundice, which developed for the first time during previous pregnancy or previous reception of sex hormones, requires discontinuation of COCs.

Although COCs may have an effect on insulin resistance and glucose tolerance, the need for dose adjustment for hypoglycemic drugs in patients with diabetes mellitus using low-dose COCs (<0.05 mg ethinylestradiol) generally does not occur. Nevertheless, women with diabetes should be under the close supervision of the endocrinologist while taking COC.

Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma while taking COC should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Described cases of depression and epilepsy on the background of the COC.

Laboratory Tests

Acceptance of COC may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal, transport protein levels in the plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the limits of normal values. Drospirenone increases the activity of plasma renin and aldosterone, which is associated with its antimineralocorticoid effect.

Medical examinations

Before the start or resumption of use of the drug Leia should be familiar with the history of life, a family history of a woman, a thorough medical (including measurement of blood pressure, heart rate, body mass index) and gynecological examination (including breast examination and cytological examination of cervical mucus), exclude pregnancy. The frequency and nature of the follow-up examinations should be determined individually for each woman, but not less than 1 time and 6 months.

A woman should be warned that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases!

Decreased efficiency

The effectiveness of Lei's drug can be reduced in the following cases: when missing active tablets (pink), with vomiting, diarrhea, or as a result of drug interactions.

Insufficient control of the menstrual cycle

Against the background of taking Leah's drug, irregular bleeding ("spotting" spotting or "breakthrough" bleeding) can occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be conducted to exclude malignant neoplasms or pregnancy.

Some women during the break in taking active tablets (pink) may not develop a bleeding "cancellation". If the drug Leah was taken according to the instructions, it is unlikely that a woman is pregnant. If the drug Leia was taken irregularly or if there are no consecutive two bleeding "cancellations", then to continue taking the drug should be excluded pregnancy.

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

Effects of the drug Leia on the ability to manage vehicles and mechanisms is not established.

Form release / dosage:

Tablets, film-coated, 3 mg + 0.02 mg.

Packaging:

For 24 active tablets together with 4 tablets in a blister of PVC / PVDC / Alu.

For 1, 2, 3 or 6 blisters together with a pocket for wearing a blister and instructions for use in a cardboard bundle.

Storage conditions:

Store in a dry place, at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the product after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003298

Date of registration:10.11.2015

Date of cancellation:2020-11-10

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

CYNDEA PHARMA SL Spain

Representation: & nbspZENTIVA PHARMA, LLCZENTIVA PHARMA, LLC

Information update date: & nbsp21.01.2016

Illustrated instructions

Instructions

Lei (Lea)