Yarina Plus, pills, 28pcs

Composition

Film-coated tablets (active combined)

1 tablet contains:

active ingredients:

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

drospirenone (micronized) 3 mg,

calcium levomefolate (micronized) 451 mcgsupport substances:

lactose monohydrate – 45.319 mg,

microcrystalline cellulose-24.8 mg,

croscarmellose sodium-3.2 mg,

hyprolose (5 cP) – 1.6 mg,

magnesium stearate-1.6 mg

. shell composition:

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 Plus is a low-dose monophasic oral combined estrogen-progestogen contraceptive drug that includes active tablets and auxiliary vitamin tablets containing calcium levomefolate.

The contraceptive effect of Yarina Plus is mainly achieved by suppressing ovulation and increasing the viscosity of cervical mucus.

In women taking combined oral contraceptives (COCs), the cycle becomes more regular, the soreness, intensity and duration of menstrual-like bleeding decreases, resulting in a reduced risk of iron deficiency anemia. There is also evidence of a reduced risk of endometrial and ovarian cancer.

Drospirenone, contained in the preparation Yarina Plus, has an antimineralocorticoid effect 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 acne (blackheads), greasiness of the skin and hair. This effect of drospirenone is similar to the effect of natural progesterone produced in the female body. This should be taken into account when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. When used correctly, the Pearl index (a measure that reflects the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. If you skip pills or use them incorrectly, the Pearl index may increase.

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

Pharmacokinetics

Drospirenone

Suction

After oral use, drospirenone is rapidly and almost completely absorbed. After a single oral dose, the Cmax of drospirenone in blood plasma, equal to 37 ng / ml, is reached in 1-2 hours. Bioavailability ranges from 76 to 85%. Compared to taking drospirenone on an empty stomach, food intake does not affect its bioavailability.

Distribution

Drospirenone binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CSG). Only 3-5% of the total concentration of the substance in the serum is present as a free hormone. Ethinylestradiol-induced increase in SHBG does not affect the binding of drospirenone to plasma proteins. The average apparent Vd is 3.7±4.2 l / kg.

SHBG concentrations do not affect the pharmacokinetics of drospirenone. With daily oral use of the drug, the concentration of drospirenone in the blood plasma increases 2-3 times, the equilibrium state is reached in the second half of the cycle treatment.

Metabolism

After oral use, drospirenone is extensively metabolized. Most of the metabolites in plasma are acidic forms of drospirenone, which are formed without the involvement of the cytochrome P450 system. According to an in vitro study, cytochrome P450 isoenzyme 3A4 is minimally involved in the metabolism of drospirenone. No interaction has been established when co-administered with ethinyl estradiol.

Deduction

The clearance of drospirenone is 1.2-1.5 ml / min / kg. The concentration of drospirenone in blood plasma decreases in 2 phases. T1 / 2 of drospirenone in the second phase is about 31 hours. Drospirenone is not excreted unchanged. Its metabolites are excreted through the gastrointestinal tract and kidneys in a ratio of approximately 1.2: 1.4. T1 / 2 of metabolites – about 1.7 days.

Pharmacokinetics in special clinical cases

The concentration of drospirenone in blood plasma at steady state was comparable in women with mild renal impairment (creatinine clearance 50-80 ml / min) and in women with preserved renal function (creatinine clearance more than 80 ml/min). However, in women with moderate renal impairment (creatinine clearance 30-50 ml/min), the average concentration of drospirenone in blood plasma was 37% higher than in patients with preserved renal function. There was no change in the concentration of potassium in the blood plasma when using drospirenone.

In women with moderate hepatic impairment (Child-Pugh class B), the AUC is comparable to that of healthy women with similar Cmax values in the absorption and distribution phases. T 1/2 of drospirenone in patients with moderate hepatic impairment was 1.8 times higher than in healthy volunteers with preserved liver function.

In patients with moderate hepatic impairment, the clearance of drospirenone decreased by about 50% compared to women with preserved liver function, while there were no differences in the concentration of potassium in blood plasma in the studied groups. There were no changes in the potassium concentration even in the case of a combination of factors predisposing to its increase (concomitant diabetes mellitus or treatment with spironolactone). Drospirenone is well tolerated in women with mild to moderate hepatic impairment (Child-Pugh class B).

Ethinyl Estradiol

Suction

After oral use, ethinyl estradiol is rapidly and completely absorbed. Cmax is about 54-100 pg / ml, reached within 1-2 hours. The drug undergoes presystemic metabolism in the liver, its oral bioavailability is on average about 45%, with high interindividual variability – from 20 to 65%. Simultaneous food intake in some cases is accompanied by a decrease in the bioavailability of ethinyl estradiol by 25%.

Distribution

Ethinyl Estradiol has a non-specific but strong binding to plasma albumin (about 98%) and induces an increase in the concentration of SHBG in plasma. The estimated Vd is about 2.8-8.6 l / kg.

The equilibrium state is reached in the second half of the course of treatment, when the concentration of ethinyl estradiol in the blood plasma increases by 40-110% compared to the use of a single dose.

Metabolism

Ethinyl estradiol undergoes presystemic conjugation in the liver and in the mucosa of the small intestine. The main pathway of ethinyl estradiol metabolism is aromatic hydroxylation with the formation of numerous metabolites that are both bound (with glucuronides and sulfate) and unbound. The rate of elimination of ethinyl estradiol is about 2.3-7 ml / min / kg.

Deduction

Ethinylestradiol is excreted only as metabolites by the kidneys and through the gastrointestinal tract in a ratio of 4: 6. T1 / 2 of ethinylestradiol is about 24 hours

. Pharmacokinetics in special clinical cases

The influence of ethnicity on pharmacokinetic parameters was studied in studies with single and multiple doses of drospirenone and ethinyl estradiol in healthy Caucasian women, as well as in Japanese women. The effect of ethnicity on the pharmacokinetics of drospirenone and ethinyl estradiol was not established.

Calcium Levomefolate

Suction

After oral use, calcium levomefolate is rapidly absorbed and incorporated into the body’s folate pool. After a single oral dose of 451 mcg of calcium levomefolate in 0.5-1.5 hours, Cmax becomes 50 nmol / l higher than the initial concentration.

The distribution

of folate pharmacokinetics is biphasic: the pool of folates with fast and slow metabolism is determined. The pool with a fast metabolism is probably represented by newly ingested folate, which is consistent with the T1/2 of calcium levomefolate, which is about 4-5 hours after a single oral dose of 451 mcg. The slow-metabolizing pool reflects the conversion of folate polyglutamate, which has a T 1/2 of about 100 days.Folates coming from outside and folates passing through the intestinal-hepatic cycle ensure the maintenance of a constant concentration of L-5-methyl-TTF in the body.

L-5-methyl-THF is the main form of folate in the body, in which it is delivered to peripheral tissues to participate in cellular folate metabolism.

The equilibrium state of L-5-methyl-THF in blood plasma after oral use of 451 mcg of calcium levomefolate is reached after 8-16 weeks and depends on its initial concentration. In red blood cells, Css is achieved at a later time due to the life span of red blood cells, which is about 120 days.

Metabolism

L-5-methyl-THF is the main folate transportable form in the blood plasma. When comparing 451 mcg of calcium levomefolate and 400 mcg of folic acid, similar mechanisms of metabolism were established for other significant folates. Folate coenzymes are involved in 3 main conjugated metabolic cycles in the cytoplasm of cells. These cycles are necessary for the synthesis of thymidine and purines, precursors of DNA and RNA acids, as well as for the synthesis of methionine from homocysteine and the conversion of serine to glycine.

Elimination

of L-5-methyl-TTF is excreted unchanged by the kidneys and as metabolites, as well as through the intestine.

Indications

Contraception intended primarily for women with symptoms of hormone-dependent fluid retention in the body.

Contraception and treatment of moderate acne (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 found 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 Yarina Plus.

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.
• Migraines with present or previous focal neurological symptoms.
• Diabetes mellitus with vascular complications.
• 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.
• Identified or suspected hormone-dependent malignancies (including those of the genitals or mammary glands).
• Vaginal bleeding of unknown origin.
• Pregnancy or suspected pregnancy.
• Breast-feeding period.
• 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.

Side effects

From the digestive system: nausea, vomiting.

From the side of the reproductive system: changes in vaginal secretion.

From the endocrine system: engorgement, soreness of the mammary glands, secretion from them; change in body weight, change in libido.

From the central nervous system: decreased mood, headache, migraine. Other services: various skin reactions, poor tolerance of contact lenses, fluid retention in the body, allergic reactions.

Interaction

The interaction of oral contraceptives with other medications can lead to” breakthrough ” uterine bleeding and/or reduce the reliability of contraception.

Interactions leading to a decrease in the effectiveness of Yarina Plus

Effects on hepatic metabolism: the use of drugs that induce microsomal liver enzymes can lead to an increase in the clearance of sex hormones. These drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, possibly also-oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John’s wort. HIV protease inhibitors (for example, ritonavir) and non-nucleoside reverse transcriptase inhibitors (for example, nevirapine) and their combinations can also potentially affect liver metabolism.

Effect on intestinal-hepatic recirculation: according to separate studies, some antibiotics (such as penicillins and tetracycline) can reduce the intestinal-hepatic recycling of estrogens, thereby reducing the concentration of ethinyl estradiol.

When taking medications that affect microsomal liver enzymes, and for 28 days after their withdrawal, a barrier method of contraception should also be used.

Effect on intestinal-hepatic recirculation: some antibiotics (such as penicillins and tetracycline) can reduce the intestinal-hepatic recycling of estrogens, thereby reducing the concentration of ethinyl estradiol.

When taking medications that affect microsomal liver enzymes, and for 28 days after their withdrawal, a barrier method of contraception should also be used.

When taking antibiotics (with the exception of rifampicin and griseofulvin) and for 7 days after their withdrawal, a barrier method of contraception should also be used. If the period of using the barrier method of contraception ends later than the hormone-containing orange tablets in the package, you should skip taking the remaining auxiliary light orange tablets and start taking Yarina Plus from the new package without a break in taking tablets.

Interactions that reduce the effectiveness of calcium levomefolate

Effects on folate metabolism: some medications reduce the concentration of folate in the blood or reduce the effectiveness of calcium levomefolate by inhibiting the enzyme dihydrofolate reductase (for example, methotrexate. trimethoprim, sulfasalazine and triamterene) or by reducing folate absorption (for example, cholestyramine) or by unknown mechanisms (for example, antiepileptic drugs: carbamazepine, phenytoin, phenobarbital, primidone and valproic acid).

Effect on the metabolism of COCs (enzyme inhibitors)

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

Effect of COCs or calcium levomefolate on the activity of other drugs

COCs can affect the metabolism of other drugs, which leads to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their concentration in blood plasma and tissues.

Based on interaction studies, as well as studies involving female volunteers taking omeprazole, simvastatin and midazolam as the study substrates, it can be concluded that the effect of drospirenone at a dose of 3 mg on the metabolism of other drugs is unlikely.

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

How to take, the course of use and dosage

of abletka 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 begins immediately after completing the previous one.

Yarina Plus is started on the 1st day of the menstrual cycle (i. e., on the 1st day of menstrual bleeding).

In case of vomiting or diarrhea within 4 hours after taking the tablets, absorption may be incomplete, and additional measures should be taken to prevent unwanted pregnancy.

The efficacy and safety of Yarina Plus as a contraceptive have been 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 before the onset of menarche is not indicated.

Yarina Plus is not used 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

No cases of overdose of Yarina Plus have been reported.

Symptoms that 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 natural products, daily consumption of which does not harm the body. Taking calcium levomefolate at a dose of 17 mg / day (the dose is 37 times higher than that contained in 1 tablet of Yarina Plus) for 12 weeks was well tolerated.

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 Plus should be carefully weighed on a case-by-case basis and discussed with the woman before she decides to start taking this medication.

Diseases 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, and cerebrovascular disorders) when taking combined oral contraceptives. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is highest in the first year of taking these medications. 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 venous thromboembolism VTE in patients taking low-dose combined oral contraceptives (

Data from a large prospective study involving 3 groups of patients show that in women with or without VTE risk factors using ethinyl estradiol/drospirenone-containing contraceptives at a dosage of 0.03 mg/3 mg, respectively, the incidence of VTE is the same as with levonorgestrel-containing oral contraceptives.

VTE can be life-threatening or 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 coughing up blood; 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 limbs, 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 include sudden pain, swelling and slight blueness of the extremities, and a sharp stomach.

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.

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);

– family history (for example, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide whether to take the drug Yarina Plus;

– prolonged immobilization, serious surgery, any operation on the lower extremities or extensive trauma. In these situations, it is advisable to stop using Yarina Plus (in the case of planned surgery, at least 4 weeks before it) and 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 with diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraines during the use of Yarina Plus (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, antiphospholipid antibodies (anti-cardiolipin antibodies, lupus anticoagulant).

When assessing the risk-benefit ratio, consider that adequate treatment of the condition may 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 developing cervical cancer with prolonged use of COCs. However, the association with PDA use 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 developing breast cancer diagnosed in women currently taking COCs (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 40, the increase in breast cancer diagnoses among women who are currently or have recently taken COCs is insignificant relative to the overall risk of this disease. Its association with PDA use has not been proven. The observed increased risk may be due to careful monitoring and earlier diagnosis of breast cancer in women using COCs. Women who have ever used COCs 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 COCs, the development of benign, and in extremely rare cases – malignant neoplasms of the liver was observed, which in some 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 COCs.

Although a small increase in blood pressure has been reported in many women taking COCs, clinically significant increases have rarely been observed. However, if a persistent, clinically significant increase in blood pressure develops while taking Yarina Plus, this drug should be discontinued and treatment for arterial hypertension should be initiated. 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 when taking COCs, but their association with COCs 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. Cases of Crohn’s disease and ulcerative colitis associated with the use of COCs are also described.

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 liver function returns to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of Yarina Plus.

Although COCs 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 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.

Preclinical data obtained during standard studies of calcium levomefolate for the detection of toxicity with multiple doses of the drug, as well as genotoxicity and toxicity to the reproductive system, do not indicate the presence of a special risk to humans.

Laboratory tests

Taking Yarina Plus may 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 the blood plasma in women receiving Yarina Plus at the same time as 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 ACE inhibitors or Indometacin, there was no significant difference between the concentration of potassium in plasma compared with placebo.

Reduced efficiency

The effectiveness of Yarina Plus may be reduced in the following cases:: when skipping pills, vomiting and diarrhea, or as a result of a drug interaction.

Frequency and severity of menstrual-like bleeding

While taking Yarina Plus, irregular (acyclic) spotting and bleeding from the vagina (spotting spotting or “breakthrough” uterine bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be evaluated 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 was taken according to the recommendations, it is unlikely that the woman is pregnant. However, with irregular use of Yarina Plus and 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, body mass index determination, breast examination), gynecological examination, cytological examination of the cervix (Pap test), and exclude pregnancy. When you resume taking Yarina Plus, the volume of additional studies and the frequency of follow-up examinations are determined individually, but at least once every 6 months.

A woman should be warned that the drug Yarina Plus does not protect against HIV infection and other sexually transmitted diseases.

Influence on the ability to drive motor vehicles and manage mechanisms

No adverse effects of Yarina Plus on the rate of psychomotor reactions have been reported; no studies have been conducted on the effect of the drug on the rate of psychomotor reactions.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Drospirenone, Ethinyl Estradiol, Calcium Levomefolinate

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For women of childbearing age, For women

Indications

Contraception