Yaren Plus

General characteristics. Structure:

Active agents: дроспиренон (micronized) 3,000 mg; ethinylestradiol бетадекс the clathrate (micronized) in terms of Ethinylestradiol of 0,030 mg, calcium левомефолат (micronized) 0,451 mg;
 Excipients: lactoses monohydrate of 45,319 mg, cellulose of microcrystallic 24,800 mg, croscarmellose sodium of 3,200 mg, hypro rod (5 Wednesday) of 1,600 mg, magnesium stearate of 1,600 mg; Cover
Varnish of orange 2,0000 mg or (alternatively): gipromelloza (5 Wednesday) of 1,0112 mg, macrogoal-6000 of 0,2024 mg, talc of 0,2024 mg, titanium dioxide of 0,5271 mg, dye ferrous oxide of yellow 0,0446 mg, dye ferrous oxide of red 0,0123 mg; Structure on one auxiliary vitamin tablet
Kernel
Active agent: calcium левомефолат (micronized)-0,451 mg; Excipients:    lactoses monohydrate of 48,349 mg, cellulose of microcrystallic 24,800 mg, croscarmellose sodium of 3,200 mg, hypro rod (5 Wednesday) of 1,600 mg, magnesium stearate of 1,600 mg.
Cover
Varnish of light orange 2,0000 mg or (alternatively): gipromelloza (5 Wednesday) of 1,0112 mg, macrogoal-6000 of 0,2024 mg, talc of 0,2024 mg, titanium dioxide of 0,5723 mg, dye ferrous oxide of yellow 0,0089 mg, dye ferrous oxide of red 0,0028 mg.

Description
The active combined tablets: round biconvex tablets, film coated orange color, on one party with a stamping of "Y+" in the correct hexagon.
Auxiliary vitamin tablets: round biconvex tablets, film coated light orange color, on one party with a stamping "M +" in the correct hexagon.

Pharmacological properties:

Pharmacodynamics

Yaren Plus - the combined estrogen-gestagenny low-dosed monophase peroral the contraceptive drug including the active tablets and auxiliary vitamin tablets containing calcium левомефолат.

The contraceptive effect of drug Yarina Plus is generally carried out due to suppression of an ovulation and increase in viscosity of cervical slime.

At the women accepting the combined oral contraceptives (COOK), the cycle becomes more regular, morbidity, intensity and duration of menstrualnopodobny bleedings therefore the risk of an iron deficiency anemia decreases decrease. Are available also this about decrease in risk of endometrial cancer and ovaries.

Drospirenon who is contained in drug Yarina Plus possesses antimineralokortikoidny action and promotes the prevention of a hormonedependent delay of liquid that can be shown in decrease in body weight and reduction of probability of emergence of peripheral hypostases. Drospirenon also has anti-androgenic activity and promotes reduction of an acne (eels), fat content of skin and hair. Such effect of a drospirenon is similar to effect of the natural progesterone produced in a female body. It should be considered at the choice of a contraceptive, especially to women with a hormonedependent delay of liquid, and also to women with an acne and seborrhea. At the correct use Perl's index (the indicator reflecting number of pregnancies at 100 women applying a contraceptive within a year) makes less than 1. At the admission of tablets or the wrong use Perl's index can increase.

Calcium левомефолат. The acid form of calcium of a levomefolat, on the structure is identical natural to L - 5-metiltetragidrofolatu (L-5-metil-TGF), the main folatny form which is contained in food. Average concentration in a blood plasma of the people who are not using the food enriched with folic acid makes near the 15th nmol/l. Levomefolat, unlike folic acid, is biologically active form of folate. Thanks to it it is acquired better, than folic acid. Levomefolat is shown for satisfaction of the increased requirement and ensuring necessary content of folates in the woman's organism during pregnancy and during feeding by a breast. Administration of calcium of a levomefolat in composition of peroral contraceptive drug reduces risk of development of defect of a neurotubule of a fruit if the woman becomes pregnant unexpectedly, at once after contraception phase-out (or, seldom or never, at use of peroral contraception).

Pharmacokinetics

• Drospirenon

Absorption

At oral administration дроспиренон quickly and almost it is completely absorbed. After a single dose inside the maximum concentration (Stakh) of a drospirenon in a blood plasma, equal 37 ng/ml, are reached in 1-2 hours. Bioavailability fluctuates from 76 to 85%. In comparison with reception of a drospirenon next the heart, meal does not influence its bioavailability.

Distribution

Drospirenon contacts a seralbumin and the corticosteroid-the connecting globulin (CCG) does not contact the globulin, connecting sex hormones (G,CSH), or. Only 3-5% of the general concentration of substance in serum are present at quality of free hormone. 95-97% nonspecific contact albumine. The increase in GSPG induced etini.testradioly does not influence binding of a drospirenon proteins of a blood plasma. The average seeming volume of distribution makes 3,7-4,2 l/kg.

Metabolism

After oral administration дроспиренон it is completely metabolized. The majority of metabolites in plasma are presented by acid forms of a drospirenon, derivatives of a drosperinon which are formed without involvement of system of P450 cytochrome. According to studying of in vitro the isoenzyme of P450 ZA4 cytochrome participates in the minimum degree in metabolism of a drospirenon. The clearance of a drospirenon makes 1,2-1,5 ml/min. At simultaneous use with ethinylestradiol it is not established interactions.

Removal

Concentration of a drospirenon in a blood plasma decreases in 2 phases. The second, final phase has an elimination half-life (T1/2) about 31 hour. In an invariable look дроспиренон it is not excreted. Its metabolites are removed through digestive tract and kidneys in the ratio about 1,2:1,4. An elimination half-life for excretion of metabolites - about 1.7 days.

Equilibrium concentration

Concentration of GSPG does not exert impact on indicators of pharmacokinetics of a drospirenon. At daily use of drug inside concentration of a drospirenon in a blood plasma increases by 2-3 times, the equilibrium state is reached in the second half of cyclic treatment.

At a renal failure

Concentration of a drospirenon in a blood plasma at achievement of an equilibrium state was comparable at women to an easy renal failure (the clearance of creatinine (CC) - 50-80 ml/min.) and at women to safe function of kidneys (KK - more than 80 ml/min.). Nevertheless, at women with a moderate renal failure (KK - 30-50 ml/min.) average concentration of a drospirenon in a blood plasma was 37% higher, than at patients with safe function of kidneys. Change of potassium concentration in a blood plasma at use of a drospirenon is noted.

At an abnormal liver function

At women with a moderate abnormal liver function (a class B on a scale of Chayld-Pyyu) the area under a curve "concentration time" (AUC) is comparable to the corresponding indicator at healthy women with close values Stakh in phases of absorption and distribution. T1/2 of a drospirenon at patients with a moderate abnormal liver function was 1.8 times higher, than at healthy volunteers with safe function of a liver. At patients with a moderate abnormal liver function about 50% in comparison with women with safe function of a liver are noted decrease in clearance of a drospirenon, at the same time distinctions in potassium concentration in a blood plasma in the studied groups are noted. At identification of a diabetes mellitus and the accompanying use of Spironolactonum (both states are regarded as the factors contributing to development of a hyperpotassemia), increases in potassium concentration in a blood plasma it is not established. Portability of a drospirenon at women with an easy and moderate abnormal liver function good (a class B on a scale of Chayld-Pyyu).

• Ethinylestradiol

Absorption

After intake these the estrabottom of l is quickly and completely absorbed by l. Stakh is 54-100 pg/ml, it is reached within 1-2 hours. Drug is exposed to presistemny metabolism in a liver, its bioavailability at intake averages about 45% at high interindividual variability - from 20 to 65%. The concomitant use of food in some cases is followed by decrease in bioavailability of ethinylestradiol by 25%.

Distribution

Ethinylestradiol possesses nonspecific, but strong linkng with blood plasma albumine (about 98%>) and induces increase in concentration in GSPG plasma. The estimated volume of distribution makes about 2,8 - 8,6 l/kg.

Metabolism

Ethinylestradiol is exposed to presistemny conjugation in a liver and in a mucous membrane of a small bowel. The main way of metabolism of ethinylestradiol - an aromatic hydroxylation with formation of numerous metabolites which are as in connected with glucuronides and sulfate, and an untied state. Ethinylestradiol removal speed - about 2,3 - 7 ml/min.

Removal

Ethinylestradiol is removed only in the form of metabolites by kidneys and through digestive tract in the ratio 4:6 with an elimination half-life about 24 hours.

Equilibrium concentration

The equilibrium state is reached in the second half of a course of treatment when concentration of ethinylestradiol in a blood plasma increases by 40-110% in comparison with use of a single dose.

Ethnic origin

Influence of an ethnic origin on pharmacokinetics parameters in researches at single and repeated dosing of a drospirenon and ethinylestradiol at healthy women of Caucasian race was studied, and also at Japanese. It is not established influences of an ethnic origin on parameters of pharmacokinetics of a drospirenon and ethinylestradiol.

• Calcium левомефолат

Absorption

After calcium intake левомефолат quickly is absorbed and joins in a pool of folates of an organism. After a single dose in 0,451 mg of calcium of a levomefolat in 0,5 - 1,5 hours Stakh becomes 50 nmols/l higher than initial concentration.

Distribution

The pharmacokinetics of folates has two-phase character: decide a pool of folates with bystry and on slow metabolism. The pool with bystry metabolism is probably represented by the folates which again came to an organism that will be coordinated st1/2 calcium of a levomefolat which makes about 4-5 hours after its single dose inside in a dose of 0,451 mg. The pool with slow metabolism reflects transformation of a polyglutamate of folate which T1/2 makes about 100 days. The folates and folates passing an enterohepatic cycle arriving from the outside provide maintenance of constant concentration L-5-metil-TGF in an organism.

L-5-metil-TGF represents the main form of existence of folates in an organism in which they are delivered to peripheral fabrics for participation in cellular folatny metabolism.

Metabolism

L-5-metil-TGF represents the main folatny transported form in a blood plasma. When comparing 0,451 mg of calcium of a levomefolat and 0,4 mg of folic acid, similar mechanisms of metabolism and for other significant folates were installed, Coenzymes of folates are involved in 3 main interfaced a metabolism cycle in cytoplasm of cells. These cycles are necessary for synthesis of thymidine and purines, predecessors of deoxyribonucleic (DNA) and ribonucleic (RNA) of acids, and also for synthesis of methionine from a gomotsistein and transformation of serine into glycine.

Removal

L-5-metil-TGF it is removed by kidneys in not changed look and in the form of metabolites, and also through intestines.

Equilibrium concentration

Equilibrium state L-5-metil-TGF in a blood plasma after intake of 0,451 mg of calcium of a levomefolat is reached in 8-16 weeks and depends on its initial concentration. In erythrocytes equilibrium concentration is reached in later terms because of life expectancy of erythrocytes which makes about 120 days.

Indications to use:

The contraception  intended  , first of all, for women with symptoms of a hormonedependent delay of liquid in an organism. Contraception and treatment of a moderate form of eels (acne vulgaris) Contraception at women with deficit of folates.

Route of administration and doses:

How to accept Yarina Plus

Pill should be taken inside on the order specified on packaging, every day at the same time without chewing, washing down with a small amount of water. Accept on 1 tablet a day continuously within 28 days. Reception of tablets from the following packaging begins right after completion of reception of previous.

Beginning of administration of drug Yarina Plus

Administration of drug Yarina Plus begins in the first day of a menstrual cycle (i.e. in the first day of menstrual bleeding).

Recommendations in case of vomiting and diarrhea

In case of vomiting or diarrhea during the period till 4 o'clock after reception of active tablets, absorption can be incomplete, and additional measures of protection from undesirable pregnancy have to be taken.

Use for separate groups of patients

At children

Efficiency and safety of the drug Yarina®plus as contraceptive means are studied at women of reproductive age. It is supposed that efficiency and safety of drug at post-pubertal age to 18 letanalogichna that at women after 18 years. Use of drug before menarche is not shown.

At elderly

Drug Yarina*plus is not used after a menopause.

At abnormal liver functions

Drug is contraindicated to use for women with heavy abnormal liver functions.

At renal failures

Drug is contraindicated to use for women with heavy renal failures and at an acute renal failure.

Features of use:

If any of the states, diseases and risk factors provided below are available in
the present, it is necessary to weigh carefully potential risk and the expected advantage of use of drug Yarina Plus in each individual case and to discuss it with the woman before she decides to begin reception of this drug. At disturbances from cardiovascular system
There are epidemiological data on increase in frequency of development of venous and arterial thromboses and thromboembolisms (such as deep vein thrombosis, thromboembolism of a pulmonary artery, myocardial infarction, stroke) at reception the COOK. These diseases are observed seldom.
The risk of development of a venous thromboembolism (VTE) is maximum in the first year of reception of such drugs. The increased risk is present after initial use of the combined oral  contraceptives or resuming of use same or the different combined oral contraceptives (after a break between administrations of drug in 4 weeks and more). Data of a large prospective research with participation of 3 groups of patients show that this increased risk is present preferential within the first 3 months. The general risk of VTE at the patients accepting the low-dosed combined oral contraceptives (<50 mkg of ethinylestradiol) is two-three times higher, than at nonpregnant patients who do not accept the COOK, nevertheless, this risk remains lower in comparison with risk of VTE at pregnancy and childbirth.
Data of a large prospective research with participation of 3 groups of patients show that at women with risk factors of VTE or without them using ethinylestradiol / дроспиренон the containing contraceptives in a dosage of 0,03 mg / 3 mg respectively, emergence frequency the same VTE as at use levonorgestrel - the containing oral contraceptives. VTE can lead to a lethal outcome (in 1-2% of cases).
VTE which is shown as a deep vein thrombosis, or an embolism of a pulmonary artery can occur when using of any combined oral contraceptives. Extremely seldom when using of the combined oral contraceptives there is thrombosis of other blood vessels, for example, hepatic, mesenteric,
renal, brain veins and arteries or vessels of a retina. A consensus concerning communication between emergence of these events and use of the combined oral contraceptives is absent.
Symptoms of the deep vein thrombosis (DVT) include the following: unilateral hypostasis of the lower extremity or along a vein on a leg, pain or discomfort in a leg only in vertical position or when walking, local temperature increase in the affected leg, reddening or change of coloring of integuments on a leg. Symptoms of a thromboembolism of a pulmonary artery (TELA) consist in the following: the complicated or hurried breathing; sudden cough, including with a pneumorrhagia; an acute pain in a thorax which can amplify at a deep breath; feeling of alarm; severe dizziness; the speeded-up or irregular heartbeat. Some of these symptoms (for example, "short wind", "cough") are nonspecific and can be interpreted incorrectly as signs of other more or less heavy events (for example, respiratory infection).
The arterial thromboembolism can lead to a stroke, occlusion of vessels or a myocardial infarction. Symptoms of a stroke are as follows: sudden weakness or anesthesia of the person, hand or leg, especially on the one hand bodies, sudden confusion of consciousness, problem with the speech and understanding; sudden one - or bilateral loss of sight; sudden disturbance of gait, dizziness, loss of balance or coordination of movements; sudden, heavy or long headache for no apparent reason; a loss of consciousness or a syncope with an epileptic seizure or without it. Other signs of occlusion of vessels: sudden pain, puffiness and weak posineniye of extremities, acute abdomen.
Symptoms of a myocardial infarction include: pain, discomfort, pressure, weight, feeling of compression or a raspiraniye in a breast, in a hand or behind a breast; discomfort with irradiation in a back, a cheekbone, a throat, a hand, a stomach; cold sweat, nausea, vomiting or dizziness, strong weakness, alarm or asthma; the speeded-up or irregular heartbeat. The arterial thromboembolism can lead to a lethal outcome. The risk of development of thrombosis (venous and/or arterial) and thromboembolisms increases:
- with age;
- at smokers (with increase in quantity of cigarettes or increase in age the risk increases, especially at women 35 years are more senior);
in the presence:
- obesity (index of body weight of more than 30 kg/sq.m);
- the family anamnesis (for example, a venous or arterial thromboembolism ever at close relatives or parents at rather young age). In case of the hereditary or acquired predisposition, the woman has to be examined by the corresponding specialist for the solution of a question of a possibility of reception
drug Yarina Plus;
- long immobilization, serious surgical intervention, any operation
standing or extensive injury. In these situations it is desirable to stop drug use Yarina Plus (in case of the planned operation, at least, in four weeks prior to it) and not to resume reception within two weeks after the termination of an immobilization;
- dislipoproteinemiya;
- arterial hypertension;
- migraines;
- diseases of valves of heart;
- fibrillations of auricles.
The question of a possible role of a varicosity and superficial thrombophlebitis in development of a venous thromboembolism remains disputable.
It is necessary to consider the increased risk of development of thromboembolisms in a puerperal period. Disturbances of peripheric circulation can be also noted at a diabetes mellitus, a system lupus erythematosus, a gemolitiko-uraemic syndrome, chronic inflammatory diseases of intestines (a disease Krone or nonspecific ulcer colitis) and a sickemia.
Increase in frequency and weight of migraine during drug Yarina®plus use (that can precede cerebrovascular disturbances) can be the basis for the immediate termination of reception of this drug.
The following belongs to the biochemical indicators indicating the hereditary or acquired predisposition to venous or arterial thrombosis: resistance to the activated protein C, a gipergomotsisteinemiya, a lack of antithrombin-III, a lack of protein C, a lack of protein S, anti-phospholipidic antibodies (anti-cardiolipin antibodies, lupus anticoagulant).
At assessment of a ratio of risk and advantage, it is necessary to consider that adequate treatment of the corresponding state can reduce the related risk of thrombosis. Also it is necessary to consider that the risk of thromboses and thromboembolisms at pregnancy is higher, than at reception of the low-dosed oral contraceptives (<0,05 mg of ethinylestradiol).
Tumors
The most essential risk factor of development of cancer of neck of uterus is the persistent human papillomavirus infection. There are messages on some increase in risk of development of cancer of neck of uterus at prolonged use the COOK. However communication with reception the COOK is not proved. The possibility of interrelation of these data with screening of diseases of a neck of uterus and is discussed with features of a sexual behavior (more rare use of barrier methods of contraception).
Meta-analysis of 54 epidemiological researches showed that there is a little increased relative risk of development of the breast cancer diagnosed for the women accepting the COOK now (relative risk 1,24). The increased risk gradually disappears within 10 years after the termination of reception of these drugs. Because the breast cancer is noted seldom at women to 40 years, increase in number of diagnoses of a breast cancer at the women accepting the COOK now or accepting recently is insignificant in relation to the general risk of this disease. Its communication with reception the COOK is not proved. Observed increase in risk can be a consequence of careful observation and earlier diagnosis of a breast cancer at the women applying the COOK. At the women ever applying the COOK earlier stages of a breast cancer, than at women, never their applying come to light.
In rare instances against the background of use the COOK development high-quality, and in extremely exceptional cases - malignant new growths of a liver which at certain patients led to life-threatening intra belly bleeding was observed. At emergence of severe pains in a stomach, increase in a liver or symptoms of intra belly bleeding, it it is necessary to consider Other states when carrying out the differential diagnosis
Clinical trials showed lack of influence of a drospirenon on potassium concentration in plasma of patients with a slight and moderate renal failure. Nevertheless, at patients with a renal failure and initial potassium concentration on the upper bound of norm it is impossible to exclude risk of development of a hyperpotassemia against the background of reception of the medicines leading to a potassium delay in an organism.
At women with a gipertriglitseridemiya (or existence of this state in the family anamnesis) increase in risk of development of pancreatitis is possible during reception the COOK. In spite of the fact that small increase in the ABP was described at many women accepting the COOK, clinically significant increases were noted seldom. Nevertheless,
if during administration of drug Yarina Plus develops permanent, clinically significant increase in the ABP, it is necessary to cancel this drug and to begin treatment of arterial hypertension. Administration of drug can be continued if by means of hypotensive therapy the ABP normal values are reached.
The following states as it was reported, develop or worsen both during pregnancy, and at reception the COOK, but their communication with reception the COOK is not proved: jaundice and/or the itch connected with a cholestasia; formation of stones in a gall bladder; porphyria; system lupus erythematosus; gemolitiko-uraemic syndrome; Sydenham's chorea; herpes of pregnant women; the hearing loss connected with an otosclerosis. Disease cases Krone and ulcer colitis against the background of use the COOK are also described.
At women with hereditary forms of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.
Acute or chronic abnormal liver functions can demand the termination of administration of drug Yarina Plus until indicators of function of a liver do not return to norm. Recurrent cholestatic jaundice which develops for the first time in time of pregnancy or previous reception of sex hormones demands the reception termination
drug Yarina Plus.
Though the COOK can exert impact on resistance to insulin and tolerance to glucose, patients with sugar have no need of change of the therapeutic mode
diabetes, using the drug Yarina®plus. Nevertheless, women with sugar
have to be observed by diabetes carefully during reception of this drug.
The hloazma can sometimes develop, especially women with existence in the anamnesis have hloazma
pregnant women. Women with tendency to a hloazma during administration of drug of Yarina®
Plus have to avoid long stay to the sun and influences of ultraviolet radiation.
Folates can mask shortage of vitamin B 12.
Laboratory tests
Administration of drug Yarina Plus can influence results of some laboratory tests, including indicators of function of a liver, kidneys, a thyroid gland, adrenal glands, concentration of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of a blood coagulation and fibrinolysis. Changes usually do not overstep the bounds of normal values. Drospirenon increases activity of a renin of plasma and concentration of Aldosteronum that is connected with its antimineralokortikoidny effect.
There is a theoretical possibility of increase in potassium concentration in a blood plasma for the women receiving drug Yarina Plus along with other drugs which can increase the content of potassium in a blood plasma. Antagonists of receptors of angiotensin II, kaliysberegayushchy diuretics and antagonists of Aldosteronum treat these drugs. However in the researches estimating interaction of a drospirenon with inhibitors of an angiotensin-converting enzyme (APF) or indometacin reliable distinction between potassium concentration in plasma in comparison with placebo was not revealed.
Decrease in efficiency
Efficiency of drug Yarina Plus can be reduced in the following cases: at the admission of tablets, at vomiting and diarrhea or as a result of medicinal interaction.
Frequency and expressiveness of menstrualnopodobny bleedings.
Against the background of administration of drug Yarina Plus within the first several months irregular (acyclic) bleedings from a vagina (the smearing bloody allocations or "breakthrough" uterine bleedings) can be observed. Apply means of hygiene and continue reception of tablets, as usual. Irregular bleedings usually stop in process of adaptation of your organism to drug (usually after 3 cycles of reception of tablets). If they proceed, intensity amplifies or renew after the termination, see a doctor. Absence of the next menstrualnopodobny bleeding
If you took all pill correctly, and you had no vomiting during reception
tablets or a concomitant use of other medicines, the probability of pregnancy is small. Continue administration of drug Yarina Plus, as usual.
If there are no 2 menstrualnopodobny bleedings in a row, immediately address
to the doctor. Do not begin reception of the following packaging until the doctor excludes pregnancy.
When it is necessary to consult with the doctor
Regular surveys

If you accept drug Yarina Plus, the doctor will report to you about need of carrying out regular surveys, at least, at least 1 time in 6 months. Consult with the doctor as soon as possible
• At any changes in health, especially any states listed in a leaf insert (see also "Contraindications" and "Use with care");
• At local consolidation in a mammary gland;
• If you are going to use other medicines (see also "Interaction with other medicines");
• If the long immovability (for example, gypsum is imposed on a leg) is expected, hospitalization or operation is planned (consult with the doctor, at least, in 3-4 weeks prior to alleged operation);
• When developing unusually severe bleeding from a vagina;
• If you forgot to take a pill in the first week of reception of packaging and had the sexual intercourse in seven or less days before;
• You twice in a row had no next menstrualnopodobny bleeding or you suspect that are pregnant (do not begin reception of the following packaging, you will not consult with the doctor yet).
Stop reception of tablets and immediately consult to the doctor if you noticed possible symptoms of thrombosis, myocardial infarction or stroke: unusual cough; unusually severe pain behind a breast giving to the left hand; unexpectedly arisen short wind, an unusual, severe and long headache or an attack of migraine; partial or total loss of sight or doubling in eyes; inarticulate speech; sudden changes of hearing, sense of smell or taste; dizziness or faint; weakness or an anesthesia in any part of a body; severe pain in a stomach; severe pain in a leg or
suddenly arisen swelled any of legs.

Yarina Plus does not protect drug from infection with HIV infection (AIDS) or
any other disease, sexually transmitted.

Drug Yarina Plus is recommended by the doctor personally to you, do not report drug to others!

Influence on ability of control of vehicles and mechanisms

It was not reported about cases of adverse influence of drug Yarina Plus on the speed of psychomotor reactions; researches on studying of influence of drug on the speed of psychomotor reactions were not conducted.

Side effects:

At administration of drug Yarina Plus, as well as any other medicines, side reactions can be observed though their emergence is not obligatory at all patients.

Serious side reactions:
You watch the sections "With Care" and "Special Instructions". Please, read these sections attentively and, in case of manifestation of side reactions, including serious, consult with the doctor.
Frequency of side reactions about which it was reported during clinical trials of the drug Yarina® is included below. These side reactions can also be referred also to the drug Yarina®plus.
Frequent side reactions (more than 1/100 and less than 1/10):
- the suppressed mood
- headache
- migraine
- nausea
- mammary gland pain
- bleach
- vaginal candidiasis
- disturbance of a cycle
- acyclic bleedings
Infrequent side reactions (more than 1/1000 and less than 1/100):
- change of body weight
- liquid delay
- change of a libido
- increase in the arterial pressure (AP)
- decrease in the ABP
- vomiting
- acne
- eczema
- itch
- vaginitis
Rare side reactions (more than 1/10000 and less than 1/1000):
- gipoakuziya
- thromboembolism
- bronchial asthma
- allocations from mammary glands

Side reactions about which it was reported during use Yarina Plus, but assessment of frequency of emergence of which to carry out it was not represented possible: hypersensitivity reaction, differences of mood, intolerance of contact lenses, abdominal pains, diarrhea, rash, urticaria, knotty erythema, multiformny erythema, increase in mammary glands.
At women with hereditary forms of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.
If any of side reactions becomes serious or if you noticed some side reactions which are not specified in the instruction, please, report about it
To your doctor.

Interaction with other medicines:

Interaction of oral contraceptives with other medicines can lead to "breakthrough" uterine bleedings and/or decrease in reliability of contraception.

The interactions leading to decrease in efficiency of drug Yarina Plus Influence on hepatic metabolism: use of the drugs inducing microsomal enzymes of a liver can lead to increase of clearance of sex hormones. Treat such medicines: Phenytoinum, barbiturates, Primidonum, carbamazepine, rifampicin, it is possible also - окскарбазепин, топирамат, фелбамат, the griseofulvin and drugs containing the St. John's Wort which is made a hole. HIV protease inhibitors (for example, ритонавир) and nenukleozidny inhibitors of the return transcriptase (for example, not Virapinum) and their combinations also potentially can influence metabolism in a liver.
Influence on enterohepatic recirculation: according to separate researches, some antibiotics (for example, penicillin and tetracycline) can reduce enterohepatic recirculation of estrogen, thereby reducing concentration of ethinylestradiol.
During administration of drugs, influencing microsomal enzymes of a liver, and within 28 days after their cancellation it is necessary to apply a barrier method of contraception in addition.
Influence on enterohepatic recirculation: according to separate researches, some antibiotics (for example, penicillin and tetracycline) can reduce entero hepatic recirculation of estrogen, thereby reducing concentration of ethinylestradiol.
During administration of drugs, influencing microsomal enzymes of a liver, and within 28 days after their cancellation it is necessary to apply a barrier method of contraception in addition.
During reception of antibiotics (except for rifampicin and griseofulvin) and within 7 days after their cancellation it is necessary to apply a barrier method of contraception in addition. If the period of use of a barrier method of contraception comes to an end later, than gormonosoderzhashchy orange tablets in packaging, it is necessary to miss reception remained auxiliary light orange to begin tabletok administration of drug Yarina Plus from new packaging without interruption in reception of tablets. The interactions reducing efficiency of calcium of a levomefolat Influence on metabolism of folates: some medicines reduce concentration of folates in blood or reduce efficiency of calcium of a levomefolat by digidrofolatreduktaza enzyme inhibition (for example, a methotrexate, Trimethoprimum, Sulfasalazinum and Triamterenum) or due to reduction of absorption of folates (for example, холестирамин) or at the expense of unknown mechanisms (for example, antiepileptic drugs: carbamazepine, Phenytoinum, phenobarbital, Primidonum and valproic acid).
Influence on metabolism COOK (inhibitors of enzymes)
The main metabolites of a drospirenon are formed in plasma without participation of system of P450 cytochrome. Therefore influence of inhibitors of system of P450 cytochrome on metabolism of a drospirenon is improbable.
Influence the COOK or calcium of a levomefolat on activity of other medicines
The COOK can influence metabolism of other drugs that leads to increase (for example, cyclosporine) or to decrease (for example, ламотриджин) their concentration in a blood plasma and fabrics.
On the basis of interaction researches, and also researches it is possible to conclude with participation of the female volunteers accepting омепразол, симвастатин and midazolam as the studied substrates that influence of a drospirenon in a dose of 3 mg on metabolism of other medicines is improbable.
Folates can change pharmacokinetics or a pharmacodynamics of some drugs influencing exchange of folates, for example, of antiepileptic drugs (Phenytoinum), a methotrexate or Pyrimethaminum that can be followed by decrease (generally reversible, under a condition increase in a dose of the drug influencing exchange of folates) their therapeutic action. Purpose of folates against the background of treatment by such drugs is recommended, mainly, for decrease in toxicity of the last.

Contraindications:

Drug Yarina Plus is contraindicated in the presence of any of the states/diseases which are listed below. If any of these states / diseases develop for the first time against the background of reception, drug has to be immediately cancelled.
• Thrombosis (venous and arterial) and a thromboembolism now or in the anamnesis (including a deep vein thrombosis, a thromboembolism of a pulmonary artery, a myocardial infarction, a stroke), cerebrovascular disturbances.
• The states preceding thrombosis (including, the tranzitorny ischemic attacks, stenocardia) now or in the anamnesis.
• Existence of the multiple or expressed risk factors of venous or arterial thrombosis.
• Migraine with focal neurologic symptoms now or in the anamnesis.
• A diabetes mellitus with vascular complications.
• A liver failure and a serious illness of a liver (before normalization of hepatic tests).
• Heavy and/or acute renal failure.
• Liver tumors (high-quality or malignant) now or in the anamnesis.
• The revealed hormonedependent malignant new growths (including generative organs or mammary glands) or suspicion on them.
• Bleeding from a vagina of not clear genesis.
• Pregnancy or suspicion on it.
• Feeding period breast.
• Hypersensitivity or intolerance of any of drug components Yarina Plus.

• The drug Plus of Yaren contains lactose therefore it is contraindicated to patients with a rare hereditary lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption.

With care
It is necessary to estimate potential risk and the expected advantage of use of drug
Yaren Plus in each individual case in the presence of the following diseases / states and risk factors:
• Risk factors of development of thrombosis and thromboembolisms: smoking, obesity, a dislipoproteinemiya, controlled arterial hypertension, migraine without focal neurologic symptomatology, uncomplicated defects of valves of heart, genetic predisposition to thrombosis (thromboses, a myocardial infarction or disturbance of cerebral circulation at young age at any of the immediate family);
• Other diseases at which disturbances of peripheric circulation can be noted: a diabetes mellitus without vascular complications, a system lupus erythematosus, a gemolitiko-uraemic syndrome, a disease Krone and ulcer colitis, a sickemia, phlebitis of superficial veins;
• Hereditary Quincke's disease;
• Gipertriglitseridemiya;
• The liver diseases which are not relating to contraindications (see. "Contraindications");
• The diseases which for the first time arose or aggravated during pregnancy or against the background of the previous reception of sex hormones (for example, the jaundice and / or an itch connected with a cholestasia, a cholelithiasis, an otosclerosis with deterioration in hearing, a porphyria, herpes of pregnant women, Sydenham's trochee);
• Puerperal period.

Use at pregnancy and in the period of a lactation
Drug is contraindicated during pregnancy. If pregnancy comes to light during administration of drug Yarina Plus, drug should be cancelled at once. Data on results of administration of drug Yarina Plus during pregnancy are limited, and do not allow to draw any conclusions on a negative impact of drug to pregnancy, health of a fruit and the newborn child. At the same time, extensive epidemiological researches did not reveal the increased risk of defects of development in the children born by the women accepting the COOK before pregnancy or teratogenic action in cases
reception the COOK on imprudence in early durations of gestation. Specific epidemiological researches concerning drug Yarina Plus were not conducted. Lactation
Drug is contraindicated during feeding by a breast. Reception the COOK can reduce amounts of breast milk and change its structure therefore their use is not recommended before the breastfeeding termination. A small amount of sex hormones and/or their metabolites can be removed with milk, however there is no confirmation of their negative impact on health of the child.

Overdose:

About drug overdose cases Yarina Plus it was not reported.
Symptoms which can be noted at overdose: the nausea, vomiting smearing bloody allocations from a vagina or a metrorrhagia (is more often at young women). There is no specific antidote, it is necessary to carry out a symptomatic treatment. Calcium левомефолат and its metabolites are identical to the folates which are a part of foodstuff which daily consumption does not do harm to an organism. Calcium reception
levomefolata in a dose of 17 mg / дн (the dose is 37 times higher contained in 1 tablet of drug Yarina Plus) within 12 weeks it was well transferred.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets are film coated. Set: on 21 active combined tablet with 7 auxiliary vitamin tablets in a blister strip packaging (blister) from multilayer material - PVC-PE-EVOH-PE-PCTFE seal aluminum foil. On 1 or 3 blisters (set) complete with the block of self-adhesive stickers for registration of a calendar of reception together with the application instruction place in a cardboard pack.