Yarina Plus, pills, 84pcs

Composition

Film-coated tablets (active combined)

1 tablet contains:

active ingredients:

ethinyl estradiol (micronized, in the form of clathrate betadex) 30 µg,

drospirenone (micronized) 3 mg,

calcium levamelt (micronized) 451 µg

excipients:

lactose monohydrate – 45.319 mg,

microcrystalline cellulose – 24.8 mg,

croscarmellose sodium – 3.2 mg

of hyprolose (5 cP) 1.6 mg,

magnesium stearate – 1.6 mg.

the composition of the shell:

lac orange – 2 mg or (alternatively):

hypromellose (5 cP) – 1.0112 mg,

macrogol 6000-202.4 mcg,

talc-202.4 mcg,

titanium dioxide-527.1 mcg,

iron oxide yellow dye-44.6 mcg,

iron oxide red dye-12.3 mcg.

Film-coated tablets (auxiliary vitamin tablets)1 tablet contains:

active ingredients:

calcium levomefolate (micronized) 451 mg

excipients:

lactose monohydrate-48.349 mg,

microcrystalline cellulose-24.8 mg,

croscarmellose sodium-3.2 mg,

hyprolose (5 cP) – 1.6 mg,

magnesium stearate-1.6 mg

. shell composition:

light orange varnish – 2 mg or (alternatively):

hypromellose (5 cP) – 1.0112 mg,

macrogol 6000-202.4 mcg,

talc-202.4 mcg,

titanium dioxide-572.3 mcg,

iron oxide yellow dye-8.9 mcg,

iron oxide red dye-2.8 mcg.

Pharmacological action

Yarina®preparation Plus – a low-dose monophasic combined estrogen-progestogen contraceptive drug consisting of tablets containing hormones and auxiliary tablets containing calcium levomefolate.

Contraceptive effect of Yarina®Plus, it is mainly carried out by suppressing ovulation and increasing the viscosity of cervical secretions.

Women taking combined oral contraceptive medications( COCs) experience a more regular cycle, reduced soreness, intensity, and duration of menstrual-like bleeding, resulting in a reduced risk of iron-deficiency anemia. There is also evidence of a reduced risk of endometrial and ovarian cancer.

Two post-marketing studies were conducted to assess the risk of VTE when using Yarina® (ethinyl estradiol/drospirenone at doses of 0.03 mg/3 mg). The first prospective observational study showed that the incidence of VTE in women using Yarina®, in the presence or absence of other VTE risk factors, was in the same range as for women using levonorgestrel-containing and other COCs. A second prospective controlled database study, which compared women using Yarina® with women using other COCs, also confirmed a similar incidence of VTE among all cohorts of women.

Drospirenone, which is part of the Yarina Plus preparation, has antimineralocorticoid activity and helps prevent hormone-dependent fluid retention, which can manifest itself in a decrease in body weight and a decrease in the likelihood of peripheral edema.

Drospirenone also has antiandrogenic activity and helps reduce blackheads( acne), oily skin and hair (seborrhea). These features of drospirenone should be considered when choosing a contraceptive for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. According to its characteristics, drospirenone is similar to natural progesterone produced by the female body.

If the drug is used correctly, the Pearl index (an indicator that reflects the number of pregnancies in 100 women using the contraceptive during the year) is less than 1. If you skip pills or use the drug incorrectly, the Pearl index may increase.

The acidic form of calcium levomefolate is structurally identical to natural L-5-methyltetrahydrofolate (L-5-methyl-THF), the main folate form found in food. The average concentration of L-5-methyltetrahydrofolate in the blood plasma of people who do not use food enriched with folic acid is about 15 nmol/l.

Levomefolate, unlike folic acid, is a biologically active form of folate. Thanks to this, it is absorbed better than folic acid. Levomefolate is indicated to meet the increased need and provide the necessary folate content in a woman’s body during pregnancy and during breastfeeding.

The introduction of calcium levomefolate into an oral contraceptive reduces the risk of developing a fetal neural tube defect if a woman becomes pregnant immediately after stopping contraception (or, in very rare cases, when using oral contraception).

Indications

• Contraception intended primarily for women with symptoms of hormone-dependent fluid retention in the body.
• Contraception and treatment of moderate acne vulgaris.
• Contraception in women with folate deficiency.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy. If pregnancy is detected while taking Yarina Plus, the drug should be discontinued immediately.

Data on the results of taking Yarina Plus during pregnancy are limited, and do not allow us to draw any conclusions about the negative impact of the drug on pregnancy, fetal health and the newborn child.

At the same time, extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who took COCs before pregnancy or teratogenic effects in cases of taking COCs inadvertently in early pregnancy. No specific epidemiological studies have been conducted on Yarinaplus.

Lactation

The drug is contraindicated during breast-feeding. Taking COCs can reduce the amount of breast milk and change its composition, so their use is not recommended before stopping breastfeeding. Small amounts of sex hormones and / or their metabolites can be excreted in milk, but there is no evidence of their negative effects on the health of the child.

Contraindications

Yarina Plus is contraindicated in the presence of any of the conditions/diseases listed below. If any of these conditions / diseases develop for the first time while taking the drug, the drug should be discontinued immediately.

• Thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders.
• Conditions that precede thrombosis (including transient ischemic attacks, angina pectoris) at the present time or in the anamnesis.
• The presence of multiple or pronounced risk factors for venous or arterial thrombosis.
• Liver failure and severe liver diseases (until normalization of liver tests).
• Severe and / or acute renal failure.
• Liver tumors (whether benign or malignant) currently or in history.
• Migraines with present or previous focal neurological symptoms.
• Diabetes mellitus with vascular complications.
• Identified or suspected hormone-dependent malignancies (including those of the genitals or mammary glands).
• Vaginal bleeding of unknown origin.
• Hypersensitivity or intolerance to any of the components of Yarina Plus.
• Yarina Plus contains lactose, so it is contraindicated in patients with rare hereditary problems of lactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
• Pregnancy or suspected pregnancy.
• Breast-feeding period.

Caution should be exercised when evaluating the potential risk and expected benefit of using Yarina Plus on a case-by-case basis in the presence of the following diseases: /conditions and risk factors:

• Risk factors for developing thrombosis and thromboembolism: smoking, obesity, dyslipoproteinemia, controlled arterial hypertension, migraines without focal neurological symptoms, uncomplicated heart valve defects, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebral circulation disorders at a young age in one of the closest relatives);
• Other diseases that may cause peripheral circulatory disorders: diabetes mellitus without vascular complications, systemic lupus erythematosus, hemolytic-uremic syndrome, Crohn’s disease and ulcerative colitis, sickle cell anemia, phlebitis of superficial veins;
• Hereditary angioedema;
• Hypertriglyceridemia:
• Liver diseases that do not belong to contraindications (see “Contraindications”);
• Diseases that first occurred or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice and / or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing loss, porphyria, herpes of pregnant women, Sydenham’s chorea);
• Postpartum period.

Side effects

From the immune system: frequency unknown-hypersensitivity reactions.

From the side of metabolism and nutrition: infrequently – changes in body weight, fluid retention.

Mental disorders: often – depressed mood; infrequently-changes in libido; frequency unknown-mood swings.

Nervous system disorders: often – headache, migraine.

From the side of the visual organ:  frequency unknown-contact lens intolerance.

From the side of the hearing organ: rarely-hypoacoussis.

From the cardiovascular system: infrequently-increased blood pressure, decreased blood pressure; rarely-thromboembolism.

Respiratory system disorders: rarely-bronchial asthma.

From the gastrointestinal tract: often – nausea; infrequently-vomiting; frequency unknown-abdominal pain, diarrhea.

Skin and subcutaneous tissue disorders: infrequently – acne, eczema, pruritus, alopecia; frequency unknown-rash, urticaria, erythema nodosum, erythema multiforme.

From the genitals and breast: often, breast pain (including breast engorgement), breast tenderness, whites (including vaginal discharge), vulvovaginal candidiasis, the lack of menstrualnopodobnoe bleeding, painful menstrualnopodobnoe bleeding, abundant menstrualnopodobnoe bleeding, poor menstrualnopodobnoe selection, the lack menstrualnopodobnoe bleeding, acyclic bleeding (usually decrease with long-term use of the drug); rarely, vaginitis; rare – discharge from the mammary glands; frequency unknown – breast enlargement.

Interaction

Effect of other medicinal products on Yarina®Plus

It is possible to interact with drugs that induce microsomal enzymes, as a result of which the clearance of sex hormones may increase, which, in turn, may lead to breakthrough uterine bleeding and/or a decrease in the contraceptive effect.

Women who receive treatment with such medications in addition to Yarina® In addition, it is recommended to temporarily use a barrier method of contraception or choose a different non-hormonal method of contraception. The barrier method of contraception should be used for the entire period of taking concomitant medications, as well as for 28 days after their cancellation. If the period of using a barrier method of contraception ends later than the orange (active) tablets in the Jarina®package Plus, you should skip taking the light orange (auxiliary) tablets and start taking tablets from the new Jarina® Plus package.

Agents that increase the clearance of Yarina® Plus (reducing efficiency by inducing enzymes): phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as preparations containing St. John’s wort.

Agents with different effects on the clearance of Yarina® Plus: when used in combination with Yarina® Plus, many HIV or hepatitis C protease inhibitors and non-nucleoside reverse transcriptase inhibitors can both increase or decrease the concentration of estrogens or progestins in blood plasma. In some cases, this effect may be clinically significant.

Drugs that reduce the effectiveness of calcium levomefolate: some medicines reduce the concentration of folate in the blood plasma and reduce the effectiveness of folate by inhibiting the enzyme dihydrofolate reductase (e. g., methotrexate, trimethoprim, triamterene, and sulfasalazine) or by reducing the absorption of folate (eg, cholestyramine) or by unknown mechanisms (e. g., antiepileptic drugs: carbamazepine, phenytoin, phenobarbital, primidon and valproic acid).

Drugs that reduce the clearance of combined oral contraceptives (enzyme inhibitors): strong to moderate CYP3A4 inhibitors, such as azole antifungal drugs (e. g., itraconazole, voriconazole, fluconazole), verapamil, macrolide antibiotics (e. g., clarithromycin, erythromycin), diltiazem, and grapefruit juice may increase plasma concentrations of estrogen or progestin, or both.

It was shown that etoricoxib at doses of 60 and 120 mg / day, when co-administered with combined oral contraceptives containing 0.035 mg of ethinyl estradiol, increases the concentration of ethinyl estradiol in blood plasma by 1.4 and 1.6 times, respectively.

Effect of combined oral contraceptives or calcium levomefolate on other medications

Combined oral contraceptives may interfere with the metabolism of other drugs, leading to an increase (for example, cyclosporine). or a decrease (for example, lamotrigine) in their concentration in blood plasma and tissues.

In vitro, drospirenone is able to slightly or moderately inhibit the cytochrome P450 enzymes CYP1A1, CYP2C9, CYP2C19, and CYP3A4.

Based on in vivo interaction studies in female volunteers treated with omeprazole, simvastatin, or midazolam as marker substrates, it can be concluded that a clinically significant effect of 3 mg of drospirenone on drug metabolism mediated by cytochrome P450 enzymes is unlikely.

In vitro, ethinyl estradiol is a reversible inhibitor of CYP2C19, CYP1A1, and CYP1A2, as well as an irreversible inhibitor of CYP3A4 / 5, CYP2C8, and CYP2J2. In clinical studies, the use of a hormonal contraceptive containing ethinyl estradiol did not lead to any increase or only led to a slight increase in plasma concentrations of CYP3A4 substrates (for example, midazolam), while plasma concentrations of CYP1A2 substrates may increase slightly (for example, theophylline) or moderately (for example, melatonin and tizanidine).

Folates can alter the pharmacokinetics or pharmacodynamics of certain drugs that affect folate metabolism, for example, antiepileptic drugs (phenytoin), methotrexate or pyrimethamine, which may be accompanied by a decrease (mostly reversible, if the dose of the drug that affects folate metabolism is increased) in their therapeutic effect. Folate supplementation with such drugs is recommended mainly to reduce the toxicity of the latter.

Other forms of interaction

In patients with undisturbed renal function, the combined use of drospirenone and ACE inhibitors or NSAIDs does not have a significant effect on the concentration of potassium in blood plasma. However, the combined use of the drug Yarina®Interaction with aldosterone antagonists or potassium-sparing diuretics has not been studied. In such cases, the concentration of potassium in the blood plasma should be monitored during the first cycle of use.

How to take, course of use and dosage

Tablets should be taken orally in the order indicated on the package, every day at the same time, without chewing, with a small amount of water. Take 1 tab. /day continuously for 28 days. Taking tablets from the next package should be started immediately after completing the previous package.

Withdrawal bleeding usually begins 2-3 days after the start of taking inactive tablets and may not yet be completed before taking tablets from the next package.

In the Jarina®package Plus 1 or 3 blisters are included, which contain 21 active tablets and 7 auxiliary tablets (the last row). The package also includes a reception calendar consisting of 7 self-adhesive strips with the names of the days of the week marked on them. You must select a strip where the first day of the week is indicated, which starts taking pills. For example, if you start taking pills on a Wednesday, you should use a strip that starts with “Wed”.

The strip should be pasted along the top of the package, so that the designation of the first day is located above the tablet on which the arrow with the inscription “Start” is directed. This way, you will see on which day of the week you should take each pill.

Start of taking Yarina® Plus

In the absence of taking any hormonal contraceptives in the previous month, taking the drug Yarina® Plus, you should start on the 1st day of your menstrual cycle (i. e., on the 1st day of menstrual bleeding). Yarina®preparation Plus, it starts working immediately, so there is no need to use additional barrier methods of contraception.

It is allowed to start taking the drug on the 2nd-5th day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking tablets from the first package.

When switching from other combined contraceptive medications, a vaginal ring or transdermal patch, it is preferable to start taking Yarina® Plus the day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break (for drugs containing 21 tablets) or after taking the last inactive tablet (for drugs containing 28 tablets in a package). Taking Yarina® Plus, you should start on the day of removal of the vaginal ring or patch, but not later than the day when a new ring is to be inserted or a new patch is to be applied.

When switching from progestogen-only contraceptives (mini-pili, injectable forms, implant), or from an intrauterine therapeutic system with progestogen release, you can switch from mini-pili to Yarina® Plus on any day (without a break), from the implant or IUD with progestogen – on the day of its removal, from the injectable contraceptive-on the day when the next injection should be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion (including spontaneous) in the first trimester of pregnancy, you can start taking the drug immediately. If this condition is met, the woman does not need additional contraception.

After delivery (in the absence of breastfeeding) or abortion (including spontaneous) in the second trimester of pregnancy, it is recommended to start taking the drug no earlier than 21-28 days after delivery (in the absence of 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. If sexual contact took place before the start of taking Yarina® Plus, it is necessary to exclude pregnancy or wait for the first menstruation.

Taking missed pills

Skipping inactive pills can be ignored. However, they should be discarded, so as not to accidentally extend the period of taking inactive pills. The following recommendations apply only to skipping active tablets:

If the delay in taking any active tablet is less than 12 hours, the contraceptive protection of Yarina®is recommended. Plus is saved. You should take the missed pill as soon as possible, and take the next pill at the usual time.

If the delay in taking any active pill is more than 12 hours, the contraceptive protection may be reduced. The more consecutive pills missed and the closer the skip is to the start or end of the dose, the more likely it is that pregnancy will occur.

In this case, you can follow the following two basic rules::

1. The drug should never be interrupted for more than 7 days.

2. To achieve adequate suppression of hypothalamic-pituitary-ovarian regulation,7 days of continuous use of active tablets are required.

Accordingly, if the delay in taking active tablets is more than 12 hours (the interval from the last tablet is more than 36 hours), we can recommend the following::

The first week of taking the drug

It is necessary to take the missed pill as soon as possible, as soon as the woman remembers about it (even if this means taking two tablets at the same time). The following tablets should be taken at the usual time. In addition, during the next 7 days, you must additionally use a barrier method of contraception (for example, a condom). If sexual contact took place within 7 days before skipping the pill, it is necessary to take into account the probability of pregnancy.

Second week of taking the drug

It is necessary to take the missed pill as soon as possible, as soon as the woman remembers about it (even if this means taking two tablets at the same time). The following tablets should be taken at the usual time. If you follow the pill regimen for 7 days prior to the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception for 7 days.

The third week of taking the drug

increases the risk of pregnancy due to the approaching phase of taking inactive tablets. You must strictly adhere to one of the following two options::

– if all pills were taken correctly during the 7 days preceding the first missed pill, there is no need to use additional contraceptive methods. When taking missed pills, you should follow points 1 or 2.

– if during the 7 days preceding the first missed pill, the pills were taken incorrectly, then during the next 7 days you must additionally use a barrier method of contraception (for example, a condom) and in this case you should follow point 1 for taking missed pills.

1. It is necessary to take the missed pill as soon as possible, as soon as the woman remembers about it (even if this means taking two tablets at the same time). The following tablets are taken at the usual time, until the orange (active) tablets in the package run out. Seven light orange (auxiliary) tablets should be discarded and immediately start taking orange (active) tablets from the new packaging. Until the orange (active) tablets from the second package run out, withdrawal bleeding is unlikely, but there may be spotting and / or breakthrough bleeding.

2. Stop taking orange (active) tablets from the current package, then take a break for 7 or less days (including days of skipping tablets), after which you should start taking the drug from the new package.

If a woman missed taking orange (active) tablets and no withdrawal bleeding occurred while taking light orange (auxiliary) tablets, it is necessary to make sure that there is no pregnancy.

Recommendations for gastrointestinal disorders

In severe gastrointestinal disorders, absorption may be incomplete, so you should additionally use a barrier method of contraception.

If vomiting or diarrhea develops within 3-4 hours after taking the active tablet, you should follow the recommendations when skipping tablets. If a woman does not want to change her usual intake schedule and postpone the onset of menstruation to another day of the week, an additional active tablet should be taken from a different package.

Delaying the onset of menstrual-like bleeding

In order to delay the onset of menstrual-like bleeding, you should skip taking 7 inactive (light orange) tablets from the current package and start taking active (orange) tablets from the next package of Yarina Plus. If a woman has taken all the active tablets from the second package, you should also take 7 inactive (light orange) tablets and immediately start taking tablets from the new package. Thus, the cycle can be extended at will for any period, up to 3 weeks, including until all active tablets from the second package are taken.

If it is necessary that menstrual-like bleeding begins earlier, you should stop taking active (orange) tablets from the second package, throw it away and take a break from taking the drug for no more than 7 days, and then start taking tablets from the new package. In this case, menstrual-like bleeding will begin approximately 2-3 days after taking the last active (orange) tablet from the second package. While taking Yarina® Plus, smearing discharge and/or breakthrough bleeding may occur from the second package.

Changing the day of onset of menstrual-like bleeding

If a woman takes the pills as recommended, menstrual-like bleeding will occur approximately on the same day every 4 weeks.

If a woman wants to change the day of the onset of menstrual-like bleeding, you should stop taking inactive (light orange) tablets for as many days as you need to change the onset of menstrual-like bleeding.

For example, if the cycle usually starts on Friday, and in the future the woman wants it to start on Tuesday (3 days earlier), then the pills from the next package should start 3 days earlier than usual, i. e. do not take the last 3 inactive (light orange) pills from the current package and start taking pills from the next package. The fewer inactive (light orange) pills a woman takes, the more likely it is that menstrual-like bleeding will not occur.

While taking Yarina® Plus, smearing discharge and/or breakthrough bleeding may occur from the following package.

Discontinuation of Yarina® Plus

You can stop taking Yarina® Plus at any time. If pregnancy is not planned, you should take care of other methods of contraception. If pregnancy is planned, you should simply stop taking the drug.

Special patient categories

Efficacy and safety of Yarina® Plus studied in women of reproductive age. It is assumed that the efficacy and safety of the drug in post-puberty age up to 18 years are similar to those in women after 18 years. The use of the drug is contraindicated until the menstrual cycle is established.

The drug is not indicated after menopause.

The drug is contraindicated for use in women with severe hepatic impairment.

The drug is contraindicated for use in women with severe renal impairment and acute renal failure.

Overdose

About cases of overdose of the drug Yarina® Plus, it wasn’t reported.

Symptomsthat may occur with an overdose: nausea, vomiting, spotting spotting from the vagina or metrorrhagia (more often in young women).

Treatment: There is no specific antidote, and symptomatic treatment should be performed. Calcium levomefolate and its metabolites are identical to folate, which is part of food products, daily consumption of which does not harm the body. use of calcium levomefolate at a dose of 17 mg / day (the dose is 37 times higher than that contained in 1 tablet of Yarina® Plus) was well tolerated for 12 weeks.

Special instructions

If any of the conditions, diseases, and risk factors listed below are currently present, the potential risk and expected benefit of using Yarina®should be carefully weighed. Plus in each individual case and discuss it with the woman before she decides to start taking this drug.

Diseases of the cardiovascular system

There are epidemiological data on an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) when taking combined oral contraceptives. These diseases are rarely observed.

The risk of developing venous thromboembolism (VTE) is maximal in the first year of using such drugs. An increased risk is present after the initial use of combined oral contraceptives or the resumption of use of the same or different combined oral contraceptives (after a break between doses of the drug for 4 weeks or more). Data from a large prospective study involving 3 groups of patients show that this increased risk is present mainly during the first 3 months.

Overall risk of VTE in patients taking low-dose combined oral contraceptives (

VTE can be fatal (in 1-2% of cases).

VTE, which manifests as deep vein thrombosis or pulmonary embolism, can occur with any combination of oral contraceptives.

Very rarely, when using combined oral contraceptives, thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels. There is no consensus on the association between the occurrence of these events and the use of combined oral contraceptives.

Symptoms of deep vein thrombosis (DVT): unilateral swelling of the lower limb or along the vein of the lower limb, pain or discomfort in the lower limb only when standing upright or walking, local fever in the affected lower limb, redness or discoloration of the skin on the lower limb.

Symptoms of pulmonary embolism (PE): difficulty or rapid breathing; sudden coughing, including with hemoptysis; acute chest pain, which may increase with deep breathing; anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (for example, shortness of breath, cough) are non-specific and may be misinterpreted as signs of other more or less severe events (for example, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Stroke symptoms: sudden weakness or loss of sensation in the face, upper or lower extremities, especially on one side of the body; sudden confusion, problems with speech and understanding; sudden one – or two-way loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination; 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, swelling and slight blueness of the extremities, a symptom complex “acute abdomen”.

Symptoms of myocardial infarction: pain, discomfort, pressure, heaviness, a feeling of compression or fullness in the chest, arm, or behind the sternum; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting, or dizziness; severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat.

Arterial thromboembolism can be life-threatening or fatal.

In women with a combination of several risk factors or a high severity of one of them (for example, complicated diseases of the valvular heart apparatus, uncontrolled arterial hypertension, extensive surgical interventions with prolonged immobilization), the possibility of their mutual strengthening should be considered. In such cases, the total value of the available risk factors increases. In this case, the use of the drug Yarina® Plus it is contraindicated.

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

— with age;

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

in the presence of:

– obesity (BMI greater than 30 kg / m2);

– indications in the family history (for example, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of a hereditary or acquired predisposition, the woman should be referred to a specialist to decide on the possibility of using the drug Yarina® Plus;

– prolonged immobilization, serious surgical intervention, any operation on the lower extremities or extensive trauma. In these situations, it is advisable to discontinue the use of Yarina® Plus (in the case of planned surgery, at least 4 weeks before it) and do not resume taking it for 2 weeks after the end of immobilization;

— dyslipoproteinemia;

— arterial hypertension;

— migraines;

— heart valve diseases;

— atrial fibrillation.

The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.

The increased risk of developing thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders can also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or UC) and sickle cell anemia.

Increased frequency and severity of migraines during Yarina®usePlus (which may precede cerebrovascular disorders) may be a reason for immediate discontinuation of this drug.

Biochemical parameters that indicate a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant).

When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition can reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (

Tumors

The most significant risk factor for cervical cancer is persistent papillomavirus infection. There are reports of a slight increase in the risk of cervical cancer with prolonged use of combined oral contraceptives. However, the association with the use of combined oral contraceptives has not been proven. The possibility of interrelation of these data with screening of cervical diseases and with the peculiarities of sexual behavior (more rare use of barrier methods of contraception) is discussed.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women currently taking combined oral contraceptives (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 rare in women under the age of 40, the increase in breast cancer diagnoses in women who are currently or have recently taken combined oral contraceptives is insignificant relative to the overall risk of this disease. Its association with the use of combined oral contraceptives has not been proven. The observed increased risk may be due to careful monitoring and earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are more likely to develop early-stage breast cancer than women who have never used them.

In rare cases, against the background of the use of combined oral contraceptives, the development of benign, and in extremely rare cases, malignant neoplasms of the liver was observed, which in individual patients led to life-threatening intra-abdominal bleeding.

If you experience severe abdominal pain, enlarged liver, or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

Other states

Clinical studies have shown no effect of drospirenone on the plasma potassium concentration in patients with mild to moderate renal insufficiency. However, in patients with impaired renal function and an initial potassium concentration at the upper limit of normal, the risk of hyperkalemia cannot be excluded against the background of taking medications that lead to potassium retention in the body.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking combined oral contraceptives.

Although a small increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically significant increases have rarely been observed. However, if during the use of the drug Yarina® If a persistent, clinically significant increase in blood pressure develops, you should cancel this drug and start treatment for arterial hypertension.The drug 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 with combined oral contraceptives, but their association with combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus: hemolytic-uremic syndrome; Sydenham’s chorea; herpes of pregnancy; hearing loss associated with otosclerosis. Crohn’s disease and ulcerative colitis have also been reported with combined oral contraceptives.

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

Acute or chronic hepatic impairment may require discontinuation of Yarina® Plus, until the liver function indicators return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or during a previous intake of sex hormones, requires discontinuation of Yarina Plus.

Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using Yarina Plus. However, women with diabetes should be carefully monitored while taking this medication.

Sometimes chloasma can develop, especially in women with a history of chloasma in pregnant women. Women with a tendency to chloasma while taking Yarina® Plus, you should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Folate can mask a lack of vitamin B12.

Preclinical safety data sheet

Preclinical data obtained in the course of standard studies for detecting toxicity with multiple doses of the drug, as well as genotoxicity, carcinogenic potential and reproductive toxicity, do not indicate the presence of a particular risk to humans. However, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.

Laboratory tests

Taking Yarina® Plus, it can affect the results of certain laboratory tests, including liver, kidney, thyroid, and adrenal function, plasma transport protein concentrations, carbohydrate metabolism, blood clotting, and fibrinolysis parameters. Changes usually do not exceed the limits of normal values. Drospirenone increases plasma renin activity and aldosterone concentration, which is associated with its antimineralocorticoid effect.

There is a theoretical possibility of increasing the concentration of potassium in blood plasma in women receiving Yarina® Plus, at the same time with other drugs that can increase the potassium content in the blood plasma. These drugs include angiotensin II receptor antagonists, potassium-sparing diuretics, and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone with ACE inhibitors or Indometacin, there was no significant difference between the concentration of potassium in plasma compared with placebo.

Reduced efficiency

Effectiveness of Yarina® Plus can be reduced in the following cases:: when skipping pills, with gastrointestinal disorders, or as a result of drug interaction.

Frequency and severity of menstrual-like bleeding

Against the background of the use of the drug Yarina® Plus, there may be irregular (acyclic) spotting and bleeding from the vagina (spotting spotting or breakthrough uterine bleeding), especially during the first months of use. You should use hygiene products and continue taking the pills as usual. Evaluation of any irregular bleeding should be performed after an adjustment period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to rule out malignancies or pregnancy.

Some women may not develop withdrawal bleeding during the pill break. If the drug Yarina® Plus it was taken according to the recommendations, it is unlikely that the woman is pregnant. However, if the drug Yarina®is used on an irregular basis Plus, in the absence of two consecutive withdrawal bleeds, the drug can not be continued until pregnancy is excluded.

Medical examinations

Before starting or resuming the use of the drug, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough physical examination (including blood pressure measurement, heart rate, BMI determination, breast examination), gynecological examination, cytological examination of the cervix (Pap test), and exclude pregnancy. When you resume taking Yarina® Plus, the amount of additional research and the frequency of follow-up examinations is determined individually, but at least once every 6 months.

You should warn the woman that the drug Yarina® Plus, it doesn’t protect against HIV infection and other sexually transmitted diseases.

Condition requiring a doctor’s advice

– any changes in health, especially the emergence of the States listed in the sections “Contraindications” and “carefully”;

local a lump in the breast;

– simultaneous reception of other medicines (see “Drug interactions”);

– if expected prolonged immobility (for example, on the lower limb in plaster), planned hospitalization or surgery (at least 3-4 weeks before the proposed transaction);

unusual bleeding from the vagina;

– missed a pill in the first week of receiving the package and took place intercourse for 7 days or less before;

– the lack of regular menstrualnopodobnoe bleeding 2 times in a row or suspected pregnancy (you should not start taking the pills from the next pack before consulting a doctor).

You should stop taking the pills and consult your doctor immediately if there are possible signs of thrombosis, myocardial infarction, or stroke: unusual cough; unusually severe pain behind the sternum radiating to the left arm; sudden shortness of breath, unusual, severe, and prolonged headache, or migraine attack; partial or complete loss of vision or double vision; slurred speech; sudden changes in hearing, smell, or taste; dizziness or fainting; weakness or loss of sensation in any part of the body; severe pain abdominal pain; severe pain in the lower extremity or sudden swelling of any of the lower extremities.

Influence on the ability to drive motor vehicles and manage mechanisms

No adverse effects of Yarina®have been reported Plus on the speed of psychomotor reactions; studies on the effect of the drug on the speed of psychomotor reactions have not been conducted.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf life

2 years

Active ingredient

Drospirenone, Ethinyl Estradiol, Calcium Levomefolinate

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For women, For women of childbearing age

Indications

Contraception