Certificate of conformity (COC) Yaz Plus pills, 28pcs

Yaz Plus pills, 28pcs

$99.0

Active ingredient:	Calcium levomefolate, Drospirenone, Ethinylestradiol
Dosage form:	Pills
Indications for use:	Contraception

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Categories: Contraceptive, Medication, Obstetrics, gynecology

Description
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Composition

1 active combination tablet contains:

active ingredients:

drospirenone (micronized) 3 mg,

ethinyl estradiol betadex clathrate,

micronized (in terms of ethinyl estradiol) 0.02 mg,

calcium levomefolate (micronized) 0.451 mg;

excipients:

lactose monohydrate — 45,329 mg;

MCC-24.8 mg;

croscarmellose sodium-3.2 mg;

hyprolose (5 cP) – 1.6 mg;

magnesium stearate-1.6 mg

film shell:

pink nail polish — 2 mg or (alternatively): hypromellose (5 cP) — 1.0112 mg, macrogol 6000-0.2024 mg; talc-0.2024 mg; titanium dioxide-0.5580 mg; iron oxide red dye-0.026 mg

.1 auxiliary vitamin tablet contains:

active substance:

calcium levomefolate (micronized) 0.451 mg,

excipients:

lactose monohydrate — 48.349 mg;

MCC — 24.8 mg;

croscarmellose sodium-3.2 mg;

hyprolose (5 cP) – 1.6 mg;

magnesium stearate-1.6 mg,

film shell:

light orange varnish — 2 mg or (alternatively): hypromellose (5 cP) – 1.0112 mg, macrogol 6000-0.2024 mg; talc-0.2024 mg; titanium dioxide-0.5723 mg; iron oxide yellow dye-0.0089 mg; iron oxide red dye-0.0028 mg

Pharmacological action

Jess Plus — a low-dose monophasic oral combined estrogen-progestogen contraceptive drug, including active tablets and auxiliary vitamin tablets containing calcium levomefolate.

Contraceptive effect of Jes Plus, it is mainly carried out 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 Jes Plus, it 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.

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

Absorption. When taken orally, drospirenone is rapidly and almost completely absorbed. After a single oral dose, the cmax of drospirenone in blood plasma, equal to 35 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) after oral use, a two-phase decrease in serum levels of the drug is observed with T_1/2, respectively (1.6±0.7) h and (27.0±7.5) h. 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±1.2) l / kg.

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. The cytochrome P4503A4 isoenzyme is minimally involved in drospirenone metabolism; drospirenone is able to reduce the concentration of the enzyme in blood plasma and the activity of cytochrome P4501A1, P4502C9, and P4502C19 isoenzymes in vitro.

Output. The rate of metabolic clearance of drospirenone in blood plasma is (1.5±0.2) ml / min / kg. In unchanged form, drospirenone is excreted only in trace amounts. Drospirenone metabolites are excreted through the gastrointestinal tract and kidneys in a ratio of approximately 1.2: 1.4. T_1/2 for the excretion of metabolites is about 40 hours.

Equilibrium concentration. During the first course of use of the drug with_ss drospirenone in blood plasma, about 60 ng / ml is achieved from the 7th to the 14th day of use of the drug. There was an increase in the concentration of drospirenone in blood plasma by about 2-3 times (due to accumulation), which was due to the ratio of T_1/2 in the terminal phase and the dosage interval. A further increase in the concentration of drospirenone in blood plasma is noted after 1-6 courses of use of the drug, after which no increase in concentration is observed.

Impaired renal function. 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 >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.

Impaired liver function. In women with moderate hepatic impairment (Child-Pugh class B), AUC is comparable to that in 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).

Ethinyl Estradiol

Absorption. After oral use, ethinyl estradiol is rapidly and completely absorbed. _Cmax-about 33 pg / ml-is reached within 1-2 hours. The drug undergoes presystemic metabolism in the liver, its bioavailability when taken orally is on average about 60%. Simultaneous food intake in some cases is accompanied by a decrease in the bioavailability of ethinyl estradiol by 25%.

Distribution. The concentration of ethinyl estradiol in blood plasma decreases in 2 phases, T_1/2 of ethinyl estradiol in the second phase is about 24 hours. Ethinyl Estradiol has a non-specific but strong binding to plasma albumin (about 98.5%) and induces an increase in the plasma concentration of SHBG. The estimated Vd is about 5 l / kg.

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 in a bound and unbound state. The rate of elimination of ethinyl estradiol is about 5 ml / min / kg.

Output. Ethinyl Estradiol is excreted only as metabolites by the kidneys and through the gastrointestinal tract in a ratio of 4: 6 with T_1/2 about 24 hours.

Equilibrium concentration. The equilibrium state is reached in the second half of the course of treatment, the concentration of ethinyl estradiol in the blood plasma increases approximately 1.4-2.1 times.

Ethnicity. 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

Absorption. After oral use, calcium levomefolate is rapidly absorbed and incorporated into the body’s folate pool. After a single oral dose of 0.451 mg of calcium levomefolate in 0.5-1.5 hours_{, max} becomes 50 nmol / l higher than the initial concentration.

Distribution. The pharmacokinetics of folates 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 T_1/2 of calcium levomefolate, which is about 4-5 hours after a single oral dose of 0.451 mg. The pool with slow metabolism reflects the conversion of folate polyglutamate, T_1/2 of which is about 100 days. External folates and folates that pass through the intestinal-hepatic cycle ensure the maintenance of a constant concentration of L-5-methyl-THF 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.

Metabolism. L-5-methyl-THF is the main folate transportable form in blood plasma. When comparing 0.451 mg of calcium levomefolate and 0.4 mg 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 deoxyribonucleic (DNA) and ribonucleic (RNA) acids, as well as for the synthesis of methionine from homocysteine and the conversion of serine to glycine.

Output. L-5-methyl-THF is excreted by the kidneys unchanged and in the form of metabolites, as well as through the gastrointestinal tract.

Equilibrium concentration. The equilibrium state of L-5-methyl-THF in blood plasma after oral use of 0.451 mg of calcium levomefolate is reached after 8-16 weeks and depends on its initial concentration. In red blood cells, C_ss is achieved at a later time due to the life span of red blood cells, which is about 120 days.

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;
contraception and treatment of severe premenstrual syndrome (PMS).

Contraindications

The drug Jes 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:
hypersensitivity or intolerance to any of the components of the drug Jes Plus;
thrombosis (venous and arterial) and thromboembolism in the present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders;
status, previous thrombosis (including transient ischemic attack, angina) at present or in history;
the presence of multiple or severe risk factors for venous or arterial thrombosis;
migraine with focal neurological symptoms in the present or in the anamnesis;
diabetes mellitus with vascular complications;
liver failure and severe liver disease (up to normalization of liver tests);
severe and/or acute renal failure;
liver tumors (benign or malignant) at present or in history;
identification of hormone-dependent malignant tumors (including genitalia or mammary glands) or suspicion of them;
vaginal bleeding of unknown origin;
pregnancy or suspicion of it;
the breast-feeding period;
the presence of rare hereditary lactose intolerance, of lactase deficiency or glucose-galactose malabsorption.

WITH CAUTION

The potential risk and expected benefit of using Yaz Plus should be evaluated on a case-by-case basis in the presence of the following diseases:/conditions and risk factors:
risk factors for development of thrombosis and thromboembolism: Smoking, obesity, dislipoproteinemia, controlled hypertension, migraine without focal neurologic symptoms, uncomplicated valvular disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin);
other diseases, which may include peripheral circulatory disorders: diabetes mellitus without vascular complications, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn’s disease and ulcerative colitis, sickle cell anemia, phlebitis of superficial veins; hereditary angioedema;
hypertriglyceridemia;
liver disease not related to contraindications;
disease, new-onset or aggravated during pregnancy or in the background of previous use of sex hormones (such as jaundice and/or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes pregnant, Sydenham’s chorea);
postpartum period.

Side effects

The most common adverse reactions reported in connection with the use of Yaz are as follows: :

— nausea, pain in the Breasts, irregular uterine bleeding, bleeding from the genital tract of unspecified origin (more than 3% of women who use the drug for indications of “Contraception'” and “Contraception and the treatment of moderate forms of acne /acne vulgaris/”);

— nausea, pain in the Breasts, irregular uterine bleeding (more than 10% of women who use the drug for the indication of “Contraception and treatment of severe premenstrual syndrome”).

Serious adverse reactions include arterial and venous thromboembolism. The frequency of adverse reactions reported in clinical trials with Yaz and Yaz is shown below Plus for the indication “Contraception”, as well as for the indications “Contraception and treatment of moderate acne (acne vulgaris)” (n=3565) and ” Contraception and treatment of severe premenstrual syndrome “(n=289) for the drug Jes. Within each group, divided according to the frequency of occurrence, adverse reactions are presented in order of decreasing severity. The frequency of adverse events was classified as follows: frequent (≥1/100 and

From the central nervous system: often-migraines.

Mental disorders: often – mood swings, depression/depressed mood; infrequently-decreased or lost libido.

From the cardiovascular system: rarely-venous or arterial thromboembolism (approximate frequency based on the results of epidemiological studies covering the group of combined oral contraceptives. The frequency bordered on very rare. The term includes the following nosological units: peripheral deep vein occlusion, thrombosis and embolism / pulmonary vascular occlusion, thrombosis, embolism and infarction, myocardial infarction, cerebral infarction and hemorrhagic stroke).

From the digestive system: often – nausea.

From the side of the skin: frequency unknown-erythema multiforme.

From the side of the reproductive system and mammary glands: often – pain in the mammary glands, irregular uterine bleeding, bleeding from the genital tract of unspecified origin.

Adverse events were classified using the MedDRA (Medical Dictionary of Regulatory Activity) dictionary. Different MedDRA terms reflecting the same symptom were grouped together and presented as a single adverse reaction, in order to avoid diluting or blurring the true effect.

Interaction

Interaction of oral contraceptives with other drugs can lead to breakthrough uterine bleeding and / or reduce the reliability of contraception.

Interactions leading to a decrease in the effectiveness of Jes® Plus

Effect 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 (e. g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e. g. nevirapine) and their combinations may also potentially affect liver metabolism.

Effect on intestinal-hepatic recirculation. Some antibiotics (such as penicillins and tetracycline) may reduce the intestinal-hepatic recycling of estrogens, according to separate studies. 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 pink tablets in the package, you should skip taking the remaining auxiliary light orange tablets and start taking Jes® Plus from a new package without a break in taking pills.

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 studied 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, such as antiepileptic drugs (phenytoin), methotrexate, or pyrimethamine, which may be accompanied by a decrease (mostly reversible, provided the dose of the drug that affects folate metabolism is increased) in their therapeutic effect. Folate supplementation with such drugs is recommended mainly to reduce the toxicity of the latter.

How to take, course of use and dosage

Inside, in the order indicated on the package, every day at approximately the same time, without chewing, with a small amount of water.

Take 1 table each. per day, continuously, for 28 days. Taking tablets from the next package begins immediately after completing the previous one.

Start of taking the drug Jes Plus

Taking the drug Jes Plus begins on the first day of the menstrual cycle (i. e., the first day of menstrual bleeding).

Recommendations for vomiting and diarrhea

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.

Use in certain groups of patients

Children. Efficacy and safety of Jes 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.

Elderly patients. The drug Jes Plus, it doesn’t apply after menopause.

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

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

Overdose

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

Symptoms: nausea, vomiting, spotting of blood from the vagina, or metrorrhagia (more common 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 per day (the dose is 37 times higher than that contained in 1 tablet of the drug Jes Plus) was well tolerated for 12 weeks.

Special instructions

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

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 (

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

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction.

Stroke symptoms: sudden weakness or loss of sensation in the face, upper or lower 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 (body mass index 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 a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide whether to take Jes®. Plus;

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

Increased frequency and severity of migraines during the use of Jes® 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.

Tumors can be life-threatening or fatal.

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 while taking the drug Jes® If a persistent, clinically significant increase in blood pressure develops, you should cancel this drug and start treatment for arterial hypertension. The drug can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and 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 Jes® Plus, until the liver function indicators return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of Yaz 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 Yaz 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 Jes® You should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Folate can mask a lack of vitamin_B12.

Preclinical safety data sheet

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

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

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

Reduced efficiency

Effectiveness of Jes® Plus can 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 Jes® Plus, there may be irregular (acyclic) spotting and bleeding from the vagina (spotting spotting or “breakthrough” uterine bleeding), especially during the first months of use. 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 Jes® Plus it was taken according to the recommendations, it is unlikely that the woman is pregnant. However, if Jes®is used on an irregular basis Plus, in the absence of two consecutive “withdrawal” bleeds, the drug can not be continued until pregnancy is excluded.

Medical examinations

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

The woman should be warned that the drug Jes® Plus, it doesn’t protect against HIV infection and other sexually transmitted diseases.

Influence on the ability to drive motor vehicles and manage mechanisms

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