Yarina® Plus

Compound

• One active tablet of Yarina Plus contains 3 mg of drospirenone , 30 mcg of ethinyl estradiol , 451 mcg of calcium levomefolate . Additional substances: microcrystalline cellulose, lactose monohydrate, hyprolose, croscarmellose sodium, magnesium stearate, orange varnish.
• One vitamin supplement tablet of Yarina Plus contains 451 mcg of calcium levomefolate . Additional substances: microcrystalline cellulose, lactose monohydrate, hyprolose, croscarmellose sodium, magnesium stearate, light orange varnish.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Monophasic low-dose combined oral estrogen-progestin contraceptive drug, which includes active and auxiliary tablets with calcium levomefolate .

The contraceptive effect of Yarina Plus is carried out by suppressing ovulation and increasing the viscosity of cervical mucus. In patients taking such oral contraceptives, the cycle is normalized, pain, intensity and duration of bleeding are reduced, and as a result, the risk of iron deficiency anemia . There is also evidence of a decreased likelihood of endometrial and ovarian tumors.

Drospirenone exhibits an antimineralocorticoid effect and prevents fluid retention, which can reduce body weight and reduce the risk of peripheral edema. It has antiandrogenic activity and helps relieve acne , reduce oily hair and skin. These facts must be taken into account when choosing a contraceptive for women with hormonal fluid retention, as well as acne .

Calcium levomefolate is an active form of folate that is absorbed better than folic acid . Necessary to meet the increased need for folate during pregnancy and lactation. The presence of calcium levomefolate in the oral contraceptive reduces the likelihood of neural tube defects in the fetus if pregnancy occurs after discontinuation of contraception.

Pharmacokinetics

Drospirenone

After administration it is quickly absorbed. The highest level in the blood is reached after an hour and a half. Bioavailability is 76-85%. Binds to albumin and does not react with hormone binding globulin . Only 3-5% of the substance circulating in the blood is in free form. With systematic use of the drug, the concentration of drospirenone in the blood increases by 2-3 times. Most metabolites are represented by acid derivatives of drospirenone. Excreted through the kidneys and intestines.

Ethinyl estradiol

Rapidly absorbed after oral administration. The maximum level in the blood is reached after an hour and a half. Food reduces bioavailability by 25%. Ethinyl estradiol reacts actively with blood albumin. It is transformed in the liver by aromatic hydroxylation with the production of numerous metabolites. Excreted as metabolic in urine and feces. The half-life reaches 24 hours.

Calcium levomefolate

Rapidly absorbed after entering the digestive tract. In the form of L-5-methyl-THF, it is delivered to organs and peripheral tissues. Folates are involved in the biosynthesis of thymidine, purines, DNA, RNA, methionine and glycine . It is excreted mainly by the kidneys in its original form and in the form of metabolites.

Pharmacokinetics

Drospirenone

When taken orally, drospirenone is rapidly and almost completely absorbed. After a single oral dose, the serum Cmax of drospirenone, equal to 37 ng/ml, is achieved within 1–2 hours. Bioavailability ranges from 76 to 85%. Food intake does not affect the bioavailability of drospirenone.

Drospirenone binds to serum albumin (0.5–0.7%) and does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG). Only 3–5% of the total concentration in the blood serum is found in free form. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to plasma proteins.

After oral administration, drospirenone is completely metabolized.

Most metabolites in plasma are represented by acidic forms of drospirenone, which are formed without the involvement of cytochrome P450.

The concentration of drospirenone in blood plasma decreases in 2 phases. Drospirenone is not excreted unchanged. Drospirenone metabolites are excreted by the kidneys and intestines in a ratio of approximately 1.2–1.4. T1/2 for excretion of metabolites in urine and feces is approximately 40 hours.

During cyclic treatment, the maximum steady-state serum concentration of drospirenone is achieved in the second half of the cycle.

A further increase in the serum concentration of drosperinone is observed after 1–6 cycles of administration, after which no increase in concentration is observed.

Additional information for special categories of patients

Patients with liver disorders. In women with moderate liver dysfunction (class B on the Child-Pugh scale), AUC is comparable to the corresponding indicator in healthy women with similar Cmax values ​​​​in the absorption and distribution phases. T1/2 of drospirenone in patients with moderate liver dysfunction was 1.8 times higher than in healthy volunteers with intact liver function.

In patients with moderate liver dysfunction, a 50% decrease in the clearance of drospirenone was observed compared with women with preserved liver function, while there were no differences in the concentration of potassium in the blood plasma in the studied groups. When diabetes mellitus is detected and concomitant use of spironolactone (both conditions are regarded as factors predisposing to the development of hyperkalemia), an increase in the concentration of potassium in the blood plasma has not been established.

It should be concluded that drospirenone is well tolerated in women with mild to moderate liver dysfunction (Child-Pugh class B).

Patients with kidney disorders. The concentration of drospirenone in the blood plasma when reaching a steady state was comparable in women with mild renal impairment (Cl creatinine - 50-80 ml/min) and in women with preserved renal function (Cl creatinine - > 80 ml/min). However, in women with moderate renal impairment (Cl creatinine 30–50 ml/min), the average plasma concentration of drospirenone was 37% higher than in patients with preserved renal function. Drospirenone was well tolerated by all groups of patients. There were no changes in the concentration of potassium in the blood plasma when using drospirenone.

Ethinyl estradiol

After oral administration, ethinyl estradiol is rapidly and completely absorbed. Cmax in blood plasma, equal to approximately 54–100 pg/ml, is achieved in 1–2 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, resulting in its oral bioavailability, on average, about 45%.

Ethinyl estradiol is almost completely (approximately 98%), although nonspecifically, bound by albumin. Ethinyl estradiol induces the synthesis of SHBG.

Ethinyl estradiol undergoes presystemic conjugation, both in the mucous membrane of the small intestine and in the liver. The main route of metabolism is aromatic hydroxylation.

The decrease in the concentration of ethinyl estradiol in the blood plasma is biphasic. It is not excreted from the body unchanged. Metabolites of ethinyl estradiol are excreted in urine and bile in a ratio of 4:6 with T1/2 for about 24 hours.

Css is achieved during the second half of the cycle.

Contraindications

Taking the medication is contraindicated if any of the following diseases are present or appear while taking the medication:

• the presence of several or one pronounced risk factor for vascular thrombosis ;
• pre-thrombosis conditions in the past or present;
• thrombosis or thromboembolism in the past or present, cerebrovascular disorders;
• diabetes mellitus with concomitant vascular disorders;
• migraine with focal neurological symptoms in the past or present;
• liver failure or liver disease;
• liver tumors in the past or present;
• decompensated or acute renal failure;
• malignant hormone-dependent tumors or suspicion of their presence;
• lactation;
• pregnancy or possible but not confirmed pregnancy;
• hereditary lactose intolerance lactase or impaired absorption of glucose and galactose ;
• bleeding from the vagina of unknown origin;
• hypersensitivity to the components of the drug.

Take the drug with extreme caution if you have at least one of the following conditions:

• risk factors for thrombosis : obesity , smoking, dyslipoproteinemia, migraine, arterial hypertension , heart valve defects, hereditary thrombosis
• diseases that may cause peripheral circulatory disorders: diabetes mellitus, sickle cell anemia, hemolytic-uremic syndrome, systemic lupus erythematosus, Crohn's disease, phlebitis ;
• hypertriglyceridemia;
• angioedema of a hereditary nature;
• diseases that arose or intensified during pregnancy or against the background of the use of sex hormones ( cholelithiasis , jaundice due to cholestasis , otosclerosis, herpes of pregnant women, porphyria, Sydenham chorea );
• liver diseases not listed as contraindications;
• postpartum period.

Side effects

• Nervous disorders: migraine , headache .
• Mental disorders: changes in libido , depressed mood.
• Circulatory disorders: changes in blood pressure , thromboembolism .
• Respiratory disorders: bronchial asthma .
• Digestive disorders: abdominal pain, nausea, diarrhea , vomiting.
• Skin disorders: erythema multiforme, eczema, acne , rash, itching , erythema nodosum, urticaria .
• Visual disturbances: discomfort when wearing contact lenses.
• Hearing disorders: hypoacusia .
• Reproductive disorders: pain or enlargement of the mammary glands, vaginal candidiasis leucorrhoea , non-cyclic bleeding, changes in the menstrual cycle, vaginitis .
• Other disorders: weight changes, fluid retention, allergic reactions .

Severe side effects of Yarina Plus, which have been reported from people using combined oral contraceptives:

• thromboembolic venous and arterial disorders;
• cerebrovascular disorders;
• increased blood pressure;
• hypertriglyceridemia;
• hyperkalemia;
• impaired glucose tolerance ;
• changes in liver function indicators;
• liver tumors;
• angioedema in persons with a hereditary type of this disease;
• chloasma;
• the appearance or worsening of conditions arising from the use of oral combined contraceptives - jaundice, cholelithiasis, porphyria, herpes of pregnancy , hearing loss, Sydenham's chorea, systemic lupus erythematosus, hemolytic-uremic syndrome, Crohn's disease , cervical cancer .

Side effects

The most commonly reported adverse reactions to Yarina® include nausea and breast pain. They occurred in more than 6% of women using this drug.

Serious adverse reactions include arterial and venous thromboembolism.

The table below shows the frequency of adverse reactions. reported during clinical trials of Yarina® (N=4897). Within each group, allocated depending on the frequency of occurrence of an adverse reaction, adverse reactions are presented in order of decreasing severity. Based on frequency, they are divided into frequent (≥1/100 and <1/10), infrequent (≥1/1000 and <1/100) and rare (≥1/10000 and <1/1000). For additional adverse reactions identified only during post-marketing studies, and for which it was not possible to estimate the frequency of occurrence, “frequency unknown” is indicated (see Table 1).

Table 1

Adverse events during clinical trials were codified using the MedDRA dictionary (Medical Dictionary for Regulatory Activities, version 12.1). Different MedDRA terms reflecting the same symptom were grouped together and presented as a single adverse reaction to avoid diluting or diluting the true effect.

* — Approximate frequency based on the results of epidemiological studies covering the group of combined oral contraceptives. The frequency bordered on very rare.

— Venous or arterial thromboembolism includes the following entities: peripheral deep vein occlusion, thrombosis and embolism/pulmonary vascular occlusion, thrombosis, embolism and infarction/myocardial infarction/cerebral infarction and stroke not defined as hemorrhagic.

For venous and arterial thromboembolism, migraine, see also “Contraindications” and “Special instructions”.

Additional Information

Listed below are adverse reactions with a very rare incidence or with delayed symptoms, which are believed to be associated with taking drugs from the group of combined oral contraceptives (see also “Contraindications” and “Special instructions”).

Tumors:

- The incidence of breast cancer diagnosis in women taking combined oral contraceptives is slightly increased. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women taking combined oral contraceptives is small relative to the overall risk of breast cancer.

- liver tumors (benign and malignant).

Other states:

- erythema nodosum;

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

- increased blood pressure;

- conditions that develop or worsen while taking combined oral contraceptives, but their connection with taking the drug has not been proven (jaundice and/or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea Sydenham; herpes of pregnant women; hearing loss associated with otosclerosis);

- in women with hereditary angioedema, taking estrogens can cause or aggravate its symptoms;

- liver dysfunction;

- impaired glucose tolerance or effect on insulin resistance;

- Crohn's disease, ulcerative colitis;

- chloasma;

- hypersensitivity (including symptoms such as rash, urticaria).

Interaction. The interaction of combined oral contraceptives with other drugs (inducers of microsomal liver enzymes, some antibiotics) can lead to breakthrough bleeding and/or a decrease in contraceptive effectiveness (see “Interaction”).

Yarina Plus tablets, instructions for use (Method and dosage)

The tablets are taken orally in the order indicated on the package, at the same time every day, with water and without chewing.

Reception begins on the first day of the cycle (the first day of menstrual bleeding). Take one tablet per day continuously for 4 weeks. The use of tablets from the next pack begins immediately after the completion of the previous one.

If symptoms of vomiting or diarrhea occur within 5 hours after taking the medication, absorption of the active substance becomes ineffective. In the described case, it is necessary to use additional contraceptive measures.

Yarina Plus is not used during menopause.

The medicine is contraindicated for women with severe renal and liver dysfunction.

Directions for use and doses

Orally, in the order indicated on the package, every day at approximately the same time, with a small amount of water.

Take one tablet per day continuously for 21 days. Taking tablets from the next package begins after a 7-day break, during which menstrual-like bleeding usually develops (withdrawal bleeding). As a rule, it begins on the 2-3rd day after taking the last tablet and may not end until you start taking tablets from a new package.

How to start taking Yarina®

If you have not taken any hormonal contraceptives in the previous month

Taking Yarina® begins on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding). It is possible to start taking it 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 the tablets from the first package.

When switching from other combined oral contraceptives, vaginal ring or contraceptive patch

It is preferable to start taking Yarina® the next 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 containing 28 tablets per package). Taking Yarina® should begin on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied.

When switching from contraceptives containing only gestagens (mini-pills, injectable forms, implant), or from a gestagen-releasing intrauterine contraceptive (Mirena)

You can switch from the “mini-pill” to Yarina® on any day (without a break), from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from the injection form - from the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

You can start taking the drug immediately, on the day of the abortion. If this condition is met, the woman does not need additional contraception.

After childbirth or abortion in the second trimester of pregnancy

You should start taking the drug no earlier than 21–28 days after childbirth (in the absence of breastfeeding) or abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has already been sexually active, pregnancy should be excluded before starting to take Yarina® or she must wait until her first menstruation.

Taking missed pills

If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. The woman should take the pill as soon as possible, and the next one should be taken at the usual time.

If the delay in taking the pills is more than 12 hours, contraceptive protection is reduced. The more pills are missed and the closer the missed pill is to the 7-day break in taking pills, the greater the likelihood of pregnancy.

In this case, you can be guided by the following two basic rules:

- taking the drug should never be interrupted for more than 7 days;

— to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation, 7 days of continuous pill taking are required.

Accordingly, the following advice can be given if the delay in taking tablets exceeds 12 hours (the interval since the last tablet was taken is more than 36 hours).

First week of taking the drug

The last missed pill should be taken as soon as possible, as soon as the woman remembers (even if this means taking two pills at the same time). The next tablet is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) should be used for the next 7 days. If sexual intercourse took place within a week before missing the pill, the possibility of pregnancy must be taken into account.

Second week of taking the drug

The last missed pill should be taken as soon as possible, as soon as the woman remembers (even if this means taking two pills at the same time). The next tablet is taken at the usual time. Provided that the woman has taken the pills correctly for the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, or if you miss two or more tablets, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.

Third week of taking the drug

The risk of pregnancy increases due to the upcoming break in taking the pills. A woman must strictly adhere to one of the two options below. However, if during the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods.

1. It is necessary to take the last missed pill as soon as possible, as soon as the woman remembers it (even if this means taking two pills at the same time). The next tablets are taken at the usual time until the tablets in the current pack are gone. You should start taking the tablets from the next package immediately without interruption. Withdrawal bleeding is unlikely until the second pack is finished, but spotting and breakthrough bleeding may occur while taking the tablets.

2. You can stop taking tablets from the current package, thus starting a 7-day break (including the day you skipped tablets), and then start taking tablets from a new package.

If a woman misses taking pills and then does not have withdrawal bleeding during the break, pregnancy must be ruled out.

Recommendations in case of vomiting and diarrhea

If vomiting or diarrhea occurs within 4 hours of taking the tablets, absorption may not be complete and additional measures should be taken to protect against unwanted pregnancy. In such cases, you should follow the above recommendations when skipping pills.

Changing the day of the onset of menstrual bleeding

In order to delay the onset of menstrual bleeding, it is necessary to continue taking tablets from the new package of Yarina® without a 7-day break. Tablets from the new package can be taken for as long as necessary, incl. until the tablets in the package run out. While taking the drug from the second package, spotting from the vagina or breakthrough uterine bleeding are possible. You should resume taking Yarina® from the next package after the usual 7-day break.

In order to move the day of the onset of menstrual bleeding to another day of the week, a woman should shorten the next break in taking pills by as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and will subsequently experience spotting and breakthrough bleeding while taking the second pack (just as if she would like to delay the onset of menstrual-like bleeding).

Additional information for special categories of patients

Children and teenagers. The drug Yarina is indicated only after the onset of menarche. Available data do not suggest dose adjustment in this group of patients.

Elderly patients. Not applicable. Yarina® is not indicated after menopause.

Patients with liver disorders. Yarina® is contraindicated in women with severe liver disease until liver function tests return to normal (see also “Contraindications” and “Pharmacokinetics”).

Patients with kidney disorders. Yarina® is contraindicated in women with severe renal failure or acute renal failure (see also “Contraindications” and “Pharmacokinetics”).

Interaction

The use of drugs that stimulate microsomal liver enzymes can lead to increased excretion of sex hormones. Similar medications include: barbiturates, Phenytoin, Primidone, Carbamazepine, Rifampicin and others.

Some antibiotics ( penicillins and tetracycline ) can reduce the concentration of ethinyl estradiol . During the period of use of drugs acting on microsomal liver enzymes, and another 4 weeks after their discontinuation, you must additionally use a barrier method of contraception.

During the use of antibiotics ( Rifampicin and Griseofulvin do not cause such a need) and for another week after their discontinuation, it is recommended to additionally use a barrier method of contraception.

A number of drugs lower blood folate of calcium levomefolate by blocking the enzyme dihydrofolate reductase ( Trimethoprim, Methotrexate, Triamterene and Sulfasalazine ), reducing folate ( Cholestyramine ) or through unknown mechanisms ( Phenobarbital, Carbamazepine, Primidone, Phenytoin, Valproic acid ).

Folates are capable of changing the pharmacokinetic parameters of antiepileptic drugs , Methotrexate, Pyrimethamine , which is accompanied by a decrease in the therapeutic effect of the latter.

special instructions

There is a proven connection between the use of contraceptives of the described type and an increased risk of vascular thrombosis , but these diseases develop rarely. The risk of venous thrombosis is greatest in the first 12 months of taking the drug. The overall likelihood of venous thrombosis in patients using combined low-dose oral contraceptives is approximately 2.5 times higher than in patients not using such drugs. Venous or arterial thrombosis can be life-threatening and cause death in approximately 1% of cases.

Venous thrombosis can manifest as main pulmonary embolism, deep vein thrombosis, and other disorders. Arterial thromboembolism can cause vascular occlusion, stroke or myocardial infarction .

The risk of developing such thrombosis increases:

• in smokers;
• with age;
• with lesions of the heart valves;
• in obese ;
• in the presence of a hereditary or acquired tendency to thrombosis ;
• for dyslipoproteinemia ;
• with prolonged immobilization, surgery, interventions on the lower extremities;
• for migraines ;
• for arterial hypertension ;
• with atrial fibrillation .

An increase in the frequency and severity of migraine may be grounds for immediate discontinuation of this drug.

In very rare cases, when using contraceptives of the described type, the appearance of benign, and even less often, malignant liver tumors .

If severe abdominal pain occurs, liver enlargement, or symptoms of intra-abdominal bleeding, the possibility of a neoplasm should be taken into account during differential diagnosis.

In patients with deteriorating kidney function and elevated levels of potassium in the blood, the possibility of developing hyperkalemia as a result of the use of drugs that lead to a slowdown in the excretion of potassium from the body.

In patients with hypertriglyceridemia, pancreatitis may increase when taking combined contraceptives .

If during the period of use of Yarina Plus a persistent increase in blood pressure is detected, the medicine should be discontinued and therapy for arterial hypertension . It is allowed to continue taking the drug if, thanks to antihypertensive therapy, the blood pressure level has returned to normal.

Liver dysfunction may require discontinuation of Yarin Plus until the corresponding functional indicators return to normal levels. The resulting cholestatic jaundice requires discontinuation of the drug.

Taking folate may mask vitamin B12 .

Taking Yarin Plus can influence the results of a number of laboratory tests: indicators of the adrenal glands, liver, thyroid gland, kidneys, the level of transport proteins, coagulation and fibrinolysis .

The effectiveness of the medicine may be reduced if the tablets are not taken regularly, vomiting or diarrhea due to drug interactions.

While using the drug, discharge or non-cyclic bleeding from the vagina may occur, especially during the first months of taking it. Based on this, evaluation of any non-cyclic bleeding is carried out after completion of the adaptation period, which lasts 3 cycles.

If you do not take the drug regularly and there are no 2 consecutive bleedings during the withdrawal period, pregnancy must be excluded.

Before using the product, it is necessary to collect the patient’s medical history, conduct a general examination, gynecological examination, cytological diagnostics, examination of the cervix, and exclude pregnancy.

Yarina® Plus

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

For disorders of the cardiovascular system

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

The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking COCs.

An increased risk is present after initial use of a COC or resumption of use of the same or a different COC (after a dosing interval of 4 weeks or more). Data from a large prospective study involving 3 groups of patients indicate that this increased risk is predominantly present during the first 3 months.

The overall risk of VTE in women taking low-dose COCs (<0.05 mg ethinyl estradiol) is two to three times higher than in non-pregnant patients not taking COCs, although the risk remains lower than the risk of VTE in pregnancy and childbirth

VTE can be life-threatening or lead to death (in 1-2% of cases).

VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any COC.

It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels.

Symptoms of deep vein thrombosis: unilateral swelling of the lower limb or along a vein in the lower limb, pain or discomfort in the lower limb only in an upright position or when walking, local increase in temperature in the affected lower limb, redness or discoloration of the skin of the lower limb.

Symptoms of pulmonary embolism: difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more common and less severe conditions (eg, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke include: sudden weakness or loss of sensation in the face or limbs, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without convulsions. Other signs of vascular occlusion: sudden pain, swelling and slight cyanosis of the extremities, “acute” abdomen.

Symptoms of myocardial infarction:

pain, discomfort, pressure, heaviness, a feeling of compression or swelling in the chest or behind the sternum, radiating to the back, jaw, left upper limb, epigastric region; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.

Arterial thromboembolism can be life-threatening or fatal.

In women with a combination of several risk factors or high severity of one of them (for example, complicated heart valve diseases, uncontrolled arterial hypertension, extensive surgical interventions with prolonged immobilization, etc.), the possibility of their mutual reinforcement should be considered. In such cases, the total value of the existing risk factors increases. In this case, taking Yarina® Plus is contraindicated (see section “Contraindications”).

The risk of developing thrombosis (venous and/or arterial), thromboembolism or cerebrovascular disorders 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 old);

in the presence of:

— obesity (body mass index more than 30 kg/m2);

- family history (for example, venous or arterial thromboembolism ever in close relatives or parents under the age of 50 years).

In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking the drug Yarina® Plus;

- prolonged immobilization, major surgery, any operation on the lower extremities or major trauma.

In these situations, taking Yarina® Plus should be stopped (in the case of a planned operation at least four weeks before it) and not resumed for two weeks after the end of immobilization.

Temporary immobilization (eg, air travel lasting more than 4 hours) may also be a risk factor for the development of venous thromboembolism, especially in the presence of other risk factors;

- dislipoproteinemia;

- arterial hypertension;

- migraine;

— diseases of the heart valves;

- atrial fibrillation.

The use of any combined hormonal contraceptives increases the risk of developing VTE. The use of drugs containing levonorgestrel, norgestimate or norethisterone carries the lowest risk of developing VTE.

The use of other drugs, such as Yarina® Plus, can lead to a twofold increase in risk. The choice to use a COC with a higher risk of developing VTE can only be made after consultation with the patient to ensure that she fully understands the risk of VTE associated with the use of Yarina® Plus, the effect of the drug on her existing risk factors and that The risk of developing VTE is greatest during the first year of using the drug. The possible role of varicose veins and superficial thrombophlebitis in the development of VTE remains controversial.

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

Peripheral circulatory disorders may 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 use of Yarina® Plus (which may precede cerebrovascular events) is grounds for immediate discontinuation of this drug.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antibodies to phospholipids (anticardiolipin 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 (<0.05 mg ethinyl estradiol).

Tumors

The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs. However, the connection with taking COCs has not been proven. The possibility of the relationship of these data with screening for cervical diseases and with characteristics of sexual behavior (less frequent 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 developing breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in current or recent COC users is small relative to the overall risk of breast cancer. Its connection with COC use has not been proven. The observed increased risk may be a consequence of careful monitoring and earlier diagnosis of breast cancer in women using COCs, the biological effects of sex hormones, or a combination of both factors. Women who have ever used COCs are diagnosed with earlier stages of breast cancer than women who have never used them.

In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors was observed, which in some patients led to life-threatening intra-abdominal bleeding. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.

Other states

Clinical studies have shown no effect of drospirenone on plasma potassium concentrations in patients with mild to moderate renal failure. However, in patients with impaired renal function and an initial potassium concentration at the upper limit of normal, the risk of developing hyperkalemia cannot be excluded while 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 COCs.

Although slight increases in blood pressure (BP) have been described in many women taking COCs, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in blood pressure develops while taking Yarina® Plus, this drug should be discontinued and treatment of arterial hypertension should be started. 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 while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of worsening the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis during the use of COCs have also been described.

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

Acute or chronic liver dysfunction may require discontinuation of Yarina® Plus until liver function tests return to normal. Recurrence of cholestatic jaundice, which developed for the first time during a previous pregnancy or previous use of sex hormones, requires discontinuation of taking Yarina® Plus.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is usually no need to adjust the dose of hypoglycemic drugs in patients with diabetes mellitus using low-dose oral contraceptives (<0.05 mg ethinyl estradiol). However, women with diabetes mellitus should be carefully monitored while taking COCs.

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

Folates may mask vitamin B12 deficiency.

Laboratory tests

Taking Yarina® Plus may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of blood coagulation and fibrinolysis. Changes usually do not go beyond normal values. Drospirenone increases plasma renin activity and aldosterone concentrations, which is associated with its antimineralocorticoid effect.

There is a theoretical possibility of increasing the concentration of potassium in the blood plasma in women receiving Yarina® Plus simultaneously with other drugs that can increase the content of potassium 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 angiotensin-converting enzyme (ACE) inhibitors or indomethacin, there was no significant difference in plasma potassium concentrations compared with placebo.

Reduced efficiency

The contraceptive effectiveness of Yarina® Plus may be reduced in the following cases: if a dose is missed or gastrointestinal disorders occur while taking tablets containing hormones (orange tablets), or as a result of drug interactions.

Frequency and severity of menstrual-like bleeding

While taking Yarina® Plus during the first few months, irregular (acyclic) bleeding from the vagina may be observed (“spotting” spotting or “breakthrough” uterine bleeding). You should use hygiene products and continue taking your pills as usual. Any irregular bleeding should be assessed after an adaptation period of approximately 3 cycles of dosing.

If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.

No regular menstrual bleeding

Some women may not develop bleeding while taking auxiliary light orange tablets “ooContraindications” and “With caution”;

— Local compaction in the mammary gland;

- Concomitant use of other medications (see also section “Interaction with other medications and other types of interactions”);

- If prolonged immobility is expected (for example, a cast is applied to the lower limb), hospitalization or surgery is planned (at least 4 weeks before the proposed operation);

- Unusually heavy bleeding from the vagina;

- Missed a pill in the first week of taking the package and had sexual intercourse seven days or less before;

— Absence of regular menstrual-like bleeding two times in a row or suspicion of pregnancy (you should not start taking pills from the next package before consulting your doctor).

You should stop taking the tablets and seek medical help 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; unexpected 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 abdominal pain; severe pain in the lower limb or sudden swelling of any of the lower limbs.

Analogs

Level 4 ATC code matches:
Ovidon

Rigevidon

Non-Ovlon

Mercilon

Yarina

Miniziston 20 fem

Novinet

Microgynon

Janine

Lindineth

Cyclo-Proginova

Regulon

Logest

Midiana

Belara

Femoden

Jess Plus

Jess

Zoely

The closest analogue of the described product is a drug called Jazz Plus .

Reviews about Yarina Plus

Reviews about Yarina Plus on forums are generally positive. Of the associated effects, the most often noted is the appearance or elimination of acne , deterioration or improvement in the condition of hair and nails. Based on the reports of patients, we can say that unplanned pregnancy does not occur if the rules of administration are followed.

Reviews from doctors focus on the presence of calcium levomefolate , which reduces the likelihood of fetal development defects if pregnancy occurs after discontinuation of Yarina Plus.

Use during pregnancy and breastfeeding

The drug is not prescribed during pregnancy and breastfeeding. If pregnancy is detected while taking Yarina®, it should be discontinued immediately. However, extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who received sex hormones before pregnancy or teratogenic effects in cases of inadvertent use of sex hormones in early pregnancy. At the same time, data on the results of taking Yarina® during pregnancy are limited, which does not allow us to draw any conclusions about the negative impact of the drug on pregnancy, the health of the newborn and the fetus. Currently, no significant epidemiological data are available.

Taking combined oral contraceptives may reduce the amount of breast milk and change its composition, so their use is not recommended until you stop breastfeeding. Small amounts of sex steroids and/or their metabolites may be excreted in milk.

Yarina Plus price, where to buy

The price of Yarina Plus in Russian pharmacies averages 890-940 rubles for package No. 28.

In Ukraine, a similar form of release will cost 250-320 hryvnia, depending on the region.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine

ZdravCity

• Yarina plus tab.
  p.p.o. 3mg+0.03mg+0.451mg n28 Bayer Weimar/Bayer Pharma RUB 1,141 order
• Yarina plus tab. p.p.o. 3mg+0.03mg+0.451mg n84 Bayer Weimar/Bayer Pharma

  RUB 3,037 order

Pharmacy Dialogue

• Yarina plus (table p/o No. 28x3) Bayer

  RUR 3,080 order

• Yarina plus (tab. No. 28) Bayer

  RUB 1,197 order

• Yarina plus (tab. No. 28) Bayer

  1200 rub. order

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Pharmacy24

• Yarina plus N28 tablets - 3 packs Promotion of Bayer Pharma AG, Nimecchina/Bayer Weimar GmbH i Co.
  KG, Nimechchyna 631 UAH.order
• Yarina plus No. 28 tablets Bayer Pharma AG, Nimechchina/Bayer Weimar GmbH i Co. KG, Nimechchyna

  261 UAH. order