Yarina Plus, 28 pcs.

How to take, the dosage

The tablets should be taken orally in the order listed on the package at the same time every day, without chewing, with a small amount of water. Take 1 tablet/day continuously for 28 days. Taking pills from the next package starts as soon as the previous one is finished.

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

If vomiting or diarrhea occurs before 4 hours after taking the pills, absorption may not be complete, and additional precautions should be taken to prevent an unwanted pregnancy.

The efficacy and safety of Yarina Plus as a contraceptive has been studied in women of reproductive age. It is assumed that efficacy and safety of the drug in postpubertal age up to 18 years old are similar to those in women after 18 years old. The use of the drug before the onset of menarche is not indicated.

Yarina Plus is not used after menopause.

The drug is contraindicated in women with severe liver dysfunction.

The drug is contraindicated in women with severe renal dysfunction and acute renal failure.

Interaction

The interaction of oral contraceptives with other medications may lead to uterine bleeding breakthroughs and/or decreased contraceptive reliability.

Interactions leading to decreased effectiveness of the drug Yarina Plus

Impacts on hepatic metabolism: the use of drugs that induce microsomal liver enzymes may 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 drugs containing St. John’s wort. HIV protease inhibitors (e.g., ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine) and combinations thereof can also potentially affect metabolism in the liver.

Influence on intestinal-hepatic recirculation: Some antibiotics (e.g., penicillins and tetracyclines) may decrease intestinal-hepatic recirculation of estrogen, thereby decreasing ethinyl estradiol concentrations, according to individual studies.

When taking drugs that affect microsomal liver enzymes and for 28 days after their withdrawal, an additional barrier method of contraception should be used.

Impact on intestinal-hepatic recirculation: According to some studies, some antibiotics (e.g., penicillins and tetracyclines) can decrease intestinal-hepatic recirculation of estrogen, thereby reducing the concentration of ethinylestradiol.

When taking drugs that affect microsomal liver enzymes, and for 28 days after their withdrawal, an additional barrier method of contraception should be used.

An additional barrier method of contraception should be used while taking antibiotics (except rifampicin and griseofulvin) and for 7 days after their withdrawal. If the barrier method of contraception ends later than the hormone-containing orange pills in the package, you should skip taking the remaining supporting light orange pills and start taking Yarina Plus from the new package without interruption of the pills.

Interactions decreasing the effectiveness of calcium levomepolate

Influence on folate metabolism: some drugs decrease the blood folate concentration or decrease the effectiveness of calcium levomepolate by inhibiting the dihydrofolate reductase enzyme (e.g. methotrexate. trimethoprim, sulfasalazine and triamterene) or by reducing folate absorption (e.g., cholestyramine) or by unknown mechanisms (e.g., antiepileptic drugs: carbamazepine, phenytoin, phenobarbital, primidone and valproic acid).

The effect on metabolism of OCs (enzyme inhibitors)

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

The effect of OCs or calcium levometholate on the activity of other drugs

C OCs can affect the metabolism of other drugs, resulting in an increase (e.g., cyclosporine) or decrease (e.g., lamotrigine) in their plasma and tissue concentrations.

Based on interaction studies as well as studies with female volunteers taking omeprazole, simvastatin and midazolam as 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 can change the pharmacokinetics or pharmacodynamics of some drugs that affect folate metabolism, such as antiepileptic drugs (phenytoin), mstotrexate or pyrimethamine. this can be accompanied by a reduction (mostly reversible, if the dose of the folate-affecting drug is increased) of their therapeutic effect. Administration of folate against the background of treatment with these drugs is recommended mainly to reduce the toxicity of the latter.

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Special Instructions

If any of the conditions, diseases, and risk factors listed below are present, the potential risks and expected benefits of Yarin Plus should be carefully weighed on a case-by-case basis and discussed with the woman before she decides to start taking this medication.

Cardiovascular disease

The results of epidemiological studies suggest Epidemiologic studies suggest an association between MTCT use and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular events) with combined oral contraceptive use. These diseases are rare.

The risk of venous thromboembolism (VTE) is highest in the first year of taking these drugs. An increased risk is present after initial use of combined oral contraceptives or renewed use of the same or different combined oral contraceptives (after a break of 4 weeks or more between doses). Data from a large prospective study involving 3 groups of patients show that this increased risk is predominantly present during the first 3 months.

The overall risk of venous VTE thromboembolism in patients taking low-dose combination oral contraceptives (

The data from a large prospective study involving 3 groups of patients show that in women with or without risk factors for VTE using ethinylestradiol/drospirenone containing contraceptives at doses 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 (1-2% of cases).

VTE, manifesting as deep vein thrombosis, or pulmonary embolism, can occur with any combination oral contraceptive.

It is extremely rare for thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral veins and arteries, or retinal vessels, to occur with the use of combined oral contraceptives. There is no consensus on the association between the occurrence of these events and the use of combined oral contraceptives.

The symptoms of deep vein thrombosis (DVT) include unilateral swelling of the lower extremity or along the vein of the lower extremity, pain or discomfort in the lower extremity only when upright or walking, localized temperature rise in the affected lower extremity, redness or discoloration of the skin on the lower extremity.

Symptoms of pulmonary embolism (TELA): difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp chest pain, which may increase with deep breaths; anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (e.g., shortness of breath, coughing) are nonspecific and may be misinterpreted as signs of other more or less severe events (e.g., respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of stroke: 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-sided loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination of movements; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, swelling and mild bruising of the extremities, acute abdomen.

Symptoms of myocardial infarction: pain, discomfort, pressure, heaviness, compression or tumescence in the chest, arm or behind the chest; discomfort radiating to the back, cheekbone, throat, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; palpitations or irregularities.

Arterial thromboembolism can be life-threatening or fatal.

The risk of thrombosis (venous and/or arterial) and thromboembolism is increased:

– with age;

– in smokers (the risk increases with more cigarettes or greater age, especially in women over 35);

when:

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

– family history (e.g., venous or arterial thromboembolism ever in a close relative or parent at a relatively young age). If there is a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide whether she can take Yarin Plus;

– prolonged immobilization, major surgery, any surgery on the lower extremities or extensive trauma. In these situations, it is advisable to stop using Yarina Plus (if surgery is planned, at least 4 weeks before) and not to resume for 2 weeks after the end of immobilization;

– dyslipoproteinemia;

– arterial hypertension;

– migraine;

– heart valve disease;

– atrial fibrillation.

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

The increased risk of thromboembolism in the postpartum period should be considered.

Peripheral circulatory disorders may also be seen in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn’s disease or nonspecific 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 grounds for immediate discontinuation of this drug.

The biochemical indicators indicating an inherited or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When evaluating the risk-benefit ratio, it should be considered that adequate treatment of the condition in question can reduce the associated risk of thrombosis. It should also be considered that the risk of thrombosis and thromboembolism in pregnancy is higher than with low-dose oral contraceptives (< 50 mcg ethinylestradiol).

Tumors

The most significant risk factor for cervical cancer is persistent papillomavirus infection. There have been reports of some increased risk of cervical cancer with long-term use of CRPS. However, the association with PDA intake has not been proven. The possibility of a correlation between these data and cervical disease screening and patterns of sexual behavior (less frequent use of barrier methods of contraception) is being 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 CRC (relative risk 1.24). The increased risk gradually disappears within 10 years after stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women currently or recently taking CRPs is small relative to their overall risk of the disease. It has not been shown to be associated with taking CRPS. The increased risk observed may be a result of close monitoring and earlier diagnosis of breast cancer in women taking CRPs. Women who have ever used PDAs are found to have earlier stages of breast cancer than women who have never used them.

In rare cases, there have been benign and, in extremely rare cases, malignant liver tumors that have led to life-threatening intra-abdominal bleeding in some patients.

If severe abdominal pain, enlargement of the liver, or signs of intra-abdominal bleeding occur, this should be considered when making a differential diagnosis.

Other conditions

Clinical studies have shown no effect of drospirenone on plasma potassium concentrations in patients with mild to moderate renal impairment. However, in patients with impaired renal function and baseline potassium concentration at the upper limit of normal, the risk of hyperkalemia with potassium retention medications cannot be excluded.

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

While small increases in BP have been described in many women taking CRP, clinically significant increases have been rare. However, if a persistent, clinically significant increase in BP develops while taking Yarina Plus, the drug should be stopped and treatment for arterial hypertension should be initiated. The drug may be continued if normal BP values are achieved with hypotensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking PDA, but their association with taking PDA has not been proven: Jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus: hemolytic-uremic syndrome; Sydenham’s chorea; pregnancy herpes; hearing loss associated with otosclerosis. Cases of Crohn’s disease and ulcerative colitis have also been described with PDA.

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

While PDAs may affect 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 closely monitored while taking this drug.

Sometimes chloasma may develop, especially in women with a history of pregnancy chloasma. Women with a history of chloasma should avoid prolonged sun exposure and exposure to ultraviolet radiation while taking Yarina Plus.

The folate may mask vitamin B12 deficiency.

Preclinical safety data

Preclinical data from standard studies for multiple-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity indicate no particular risk to humans. However, we should keep in mind that sex hormones can promote the growth of some hormone-dependent tissues and tumors.

Preclinical data from standard calcium levomepolate studies for multiple-dose toxicity and genotoxicity and reproductive toxicity indicate no special risk to humans.

Laboratory tests

The administration of Yarina Plus may affect the results of some laboratory tests, including liver, kidney, thyroid and adrenal function, plasma transport protein concentrations, carbohydrate metabolism, clotting and fibrinolysis parameters. The changes usually do not go beyond the normal values. Drospirenone increases plasma renin activity and aldosterone concentration, which is associated with its anti-mineralocorticoid effect.

There is a theoretical possibility of increased plasma potassium concentrations in women receiving Yarina Plus concomitantly with other drugs that may increase plasma potassium levels. These drugs include angiotensin II receptor antagonists, potassium-saving diuretics, and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone with ACE inhibitors or indomethacin, no significant difference was found between plasma potassium concentrations compared with placebo.

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

The frequency and severity of menstrual bleeding

Yarina Plus may cause irregular (acyclic) bleeding and vaginal bleeding (spotting or uterine breakthrough bleeding), 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 evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop “withdrawal” bleeding during a break in the pill. If Yarina Plus was taken as recommended, it is unlikely that the woman is pregnant. However, if irregular use of Yarina Plus and no two consecutive “withdrawal” bleeding events occur, the medication cannot be continued until pregnancy is ruled out.

Medical examinations

Before starting or resuming use of the drug, a woman’s life history, family history, a thorough physical examination (including measurement of BP, heart rate, body mass index, breast examinations), a gynecological examination, cervical cytology (Papanicolae test), and pregnancy should be performed. When you resume taking the drug Yarina Plus, the amount of additional studies and the frequency of follow-up examinations is determined individually, but at least once every 6 months.

Warn women that the drug Yarina Plus does not protect against HIV infection and other sexually transmitted diseases.

Impact on driving and operating ability

There have been no reported cases of adverse effects of Yarina Plus on psychomotor reaction speed; no studies have been conducted to study the effect of the drug on psychomotor reaction speed.

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, it should be stopped immediately.

• Thrombosis (venous and arterial) and thromboembolism at present or in the history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders.
• Conditions preceding thrombosis (including transient ischemic attacks, angina pectoris), current or history.
• Migraine with focal neurological symptoms, current or history.
• Diabetes mellitus with vascular complications.
• Hepatic failure and severe liver disease (until liver tests normalize).
• Severe and/or acute renal failure.
• Liver tumors (benign or malignant), current or history.
• Discovered or suspected hormone-dependent malignancies (including genital or mammary glands).
• Vaginal bleeding of unclear genesis.
• Pregnancy or suspected pregnancy.
• Breastfeeding period.
• High sensitivity or intolerance to any of the components of Yarina Plus.
• Yarina Plus contains lactose, so it is contraindicated in patients with rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
  

Side effects

Digestive system disorders: nausea, vomiting.

Perior genital system: changes in vaginal secretion.

Endocrine system disorders: mammary glands engorgement, pain, secretion of mammary glands; changes in body weight, changes in libido.

CNS disorders: decreased mood, headache, migraine.

Other: various skin reactions, poor tolerance of contact lenses, fluid retention in the body, allergic reactions.

Overdose

There have been no reported cases of overdose of the drug Yarina Plus.

Symptoms that may be observed in case of overdose: nausea, vomiting, oozing bloody vaginal discharge or metrorrhagia (more often in young women).

Treatment: there is no specific antidote, symptomatic treatment should be carried out. Calcium levomepholate and its metabolites are identical to folate contained in natural products, the daily consumption of which is not harmful to the body. Calcium levomepholate at a dose of 17 mg / day (37 times the dose contained in 1 tablet of the drug Yarina Plus) for 12 weeks was well tolerated.

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Pregnancy use

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

The data on the results of taking Yarina Plus in pregnancy are limited and do not allow drawing any conclusions about the negative effect of the drug on pregnancy, fetal and newborn health.

At the same time, extensive epidemiologic studies have not found an increased risk of developmental defects in children born to women who have taken CRP before pregnancy or teratogenic effects when CRP is taken inadvertently in early pregnancy.

There have been no specific epidemiological studies on Yarina Plus.

The drug is contraindicated during breastfeeding. Taking PDAs may decrease the amount of breast milk and change its composition, so their use is not recommended until you stop breastfeeding.

Small amounts of sex hormones and/or their metabolites may be excreted with milk, but there is no evidence of adverse effects on infant health.