Yaz Plus pills, 84pcs

Composition

of 1 tab. – ethinyl estradiol (micronized, in the form of betadex clathrate) 20 mcg;

drospirenone (micronized) – 3 mg;

calcium levomefolate (micronized) – 451 mcg.

Auxiliary substances:

lactose monohydrate – 45.329 mg,

microcrystalline cellulose-24.8 mg,

croscarmellose sodium-3.2 mg,

hyprolose (5 cP) – 1.6 mg,

magnesium stearate-1.6 mg.

Shell composition:

 pink nail polish – 2 mg or (alternatively):

hypromellose (5 cP) – 1.0112 mg,

macrogol 6000-202.4 mcg,

talc-202.4 mcg,

titanium dioxide-558 mcg,

iron oxide red dye-26 mcg.

Pharmacological action

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

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

In women taking combined oral contraceptives, 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 included in Jes® Plus, it has antimineralocorticoid activity and helps prevent hormone-dependent fluid retention, which can manifest itself in a decrease in body weight and a decrease in the likelihood of peripheral edema. Drospirenone also has antiandrogenic activity and helps reduce acne (blackheads), oily skin and hair (seborrhea). These features of drospirenone should be considered when choosing a contraceptive for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. According to its characteristics, drospirenone is similar to natural progesterone produced by the female body. 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 of L-5-methyltetrahydrofolate in the blood plasma of people who do not use food enriched with folic acid is about 15 nmol/l.

Levomefolate, unlike folic acid, is a biologically active form of folate. Thanks to this, it is absorbed better than folic acid. Levomefolate is indicated for women during pregnancy and lactation to meet the increased need for folate. 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).

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.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy. If pregnancy is detected during the use of Jes® Plus, the drug should be discontinued immediately. Data on the results of using the drug Jes® Advantages during pregnancy are limited, and do not allow us to draw any conclusions about the negative impact of the drug on pregnancy, fetal health and the newborn child.

At the same time, extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who took combined oral contraceptives before pregnancy, or teratogenic effects in cases of taking combined oral contraceptives due to carelessness in early pregnancy. Specific epidemiological studies in relation to the drug Jes® Plus, it wasn’t conducted.

The drug is contraindicated during breast-feeding. The use of combined oral contraceptives can reduce the amount of breast milk and change its composition, so the use of the drug Jes® Plus it is contraindicated before stopping breastfeeding. Small amounts of sex hormones and / or their metabolites can enter breast milk and affect the baby’s health.

Contraindications

Jes®Preparation 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 in the present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders;

— status of prior thrombosis (including transient ischemic attack, angina) in the present or in the anamnesis;

— identification of acquired or genetic predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, deficiency of protein C, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);

— the presence of a high risk of venous or arterial thrombosis;

— migraine with focal neurological symptoms in the present or in the anamnesis;

— pancreatitis with severe hypertriglyceridemia present or in the anamnesis;

— diabetes mellitus with vascular complications;

— liver failure and severe liver disease (up to normalization of liver tests);

— liver tumors (benign or malignant) at present or in the anamnesis;

— severe and/or acute renal failure;

— identification of hormone-dependent malignant tumors (including genitalia or mammary glands) or suspected them;

— vaginal bleeding of unknown origin;

— pregnancy or suspicion of it;

— the period of breastfeeding;

— a rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the lactose content);

— hypersensitivity or intolerance to any component of the drug Jess® Plus.

With caution

The potential risk and expected benefit of using Jes®should be evaluated Plus in each individual case in the presence of the following diseases/conditions and risk factors:

— risk factors for the 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 in which can be observed 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;

— diseases of new-onset or aggravated during pregnancy or in the background of previous use of sex hormones (e. g., jaundice and/or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes pregnant, chorea Sydenham);

— postpartum period (not earlier than 21-28 days after birth, in the absence of breast-feeding).

Side effects

The most common adverse reactions reported in connection with the use of the drug are: nausea, breast pain, irregular uterine bleeding, bleeding from the genital tract of unspecified origin (more than 3% of women using the drug for indications “Contraception” and “Contraception and treatment of moderate acne (acne vulgaris)”); nausea, breast pain, irregular uterine bleeding (more than 10% of women using the drug for indications “Contraception”and” Contraception and treatment of moderate acne (acne vulgaris)”). ” Contraception and treatment of severe premenstrual syndrome (PMS)”).

Serious adverse reactions include arterial and venous thromboembolism.

The frequency of adverse reactions reported in clinical trials with Jes® and Jes®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 (PMS) “(n=289) for Jes®. Within each group, divided according to the frequency of occurrence, adverse reactions are presented in order of decreasing severity. By frequency, they are divided as follows: often (≥1/100 and <1/10), infrequently (≥1/1000 and <1/100), and rarely (≥1/10,000 and For additional adverse reactions identified only in the course of post-marketing observations, and for which it was not possible to estimate the frequency of occurrence, “frequency unknown”is indicated.

Infectious and parasitic diseases:  rarely-candidiasis.

From the side of metabolism and nutrition: infrequently-weight gain; rarely-weight loss, increased appetite, anorexia, hyperkalemia, hyponatremia.

From the side of the psyche: often-mood swings; infrequently-decreased or lost libido 2, drowsiness, depression/depressed mood; rarely-anorgasmia, insomnia.

Nervous system disorders: often – headache; infrequently-dizziness, paresthesia.

From the cardiovascular system: infrequently-increased blood pressure, migraine; rarely-tachycardia, venous and arterial thromboembolism*, syncope, nosebleeds.

From the side of the visual organ: rarely-conjunctivitis, dryness of the eye mucosa, visual impairment.

From the gastrointestinal tract: often – nausea 1; infrequently-abdominal pain, vomiting, gastritis, diarrhea, dyspepsia, flatulence; rarely-bloating, constipation, dry mouth.

Liver and biliary tract disorders: rarely-pain in the right hypochondrium.

From the immune system: rarely-allergic reactions; frequency unknown-hypersensitivity.

Skin and subcutaneous tissue disorders: infrequently-acne, pruritus, rash; rarely-alopecia, hypertrichosis, eczema, dry skin, contact dermatitis, acneform dermatosis; frequency unknown-erythema multiforme.

Musculoskeletal disorders: infrequently – back pain, pain in the extremities, muscle cramps.

From the genitals and breast: often – breast pain 1, breast tenderness, acyclic spotting/bleeding from the vagina 1, bleeding from the genital tract of unspecified origin, absence of menstrual – like bleeding; infrequently-pelvic pain, hot flashes, fibrocystic mastopathy, candida vulvovaginitis, vaginal discharge, heavy menstrual – like bleeding, scanty menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, rare menstrual-like bleeding, menstrual-like bleeding, painful menstrual-like bleeding, dryness of the vaginal mucosa, abnormal Pap test result; rarely-breast hyperplasia, cervical polyp, ovarian cyst, endometrial atrophy.

From the hematopoietic system: rarely-anemia, thrombocythemia.

Other: infrequently-asthenia, increased sweating, generalized or peripheral edema; rarely-malaise.

Adverse events were classified using the MedDRA 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.

* 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 nosological units: peripheral deep vein occlusion, thrombosis and embolism / pulmonary vascular occlusion, thrombosis, embolism and infarction / myocardial infarction / cerebral infarction and hemorrhagic stroke.

1 The incidence of cases in studies evaluating PMS was very frequent >10/100>

2 The incidence of cases in studies evaluating PMS was frequent ≥1/100

Additional information

Listed below are adverse reactions with very rare frequency or delayed symptoms that are believed to be associated with the use of drugs from the group of combined oral contraceptives.

Tumors

– women using combined oral contraceptives have a very slightly increased rate of breast cancer detection. Because breast cancer is rare in women younger than 40, the increase in cancer incidence in women using combined oral contraceptives is insignificant relative to the overall risk of breast cancer. The causal relationship with the use of combined oral contraceptives is unknown;

– liver tumors (benign and malignant).

Other state

– erythema nodosum;

hypertriglyceridemia (increased risk of pancreatitis during use of combined oral contraceptives);

– increase in blood pressure;

– state, developing or worsens during the use of combined oral contraceptives, but their relationship has not been proven (jaundice and/or pruritus associated with cholestasis; the formation of stones in the gallbladder; epilepsy; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham chorea; herpes during pregnancy; hearing loss associated with otosclerosis);

– in women with hereditary angioedema estrogen can cause or aggravate the symptoms;

– disorders of the liver;

– changes in glucose tolerance or effect on insulin resistance;

– Crohn’s disease, ulcerative colitis;

– chloasma;

– hypersensitivity (including symptoms such as rash, hives).

Interaction

Interaction of oral contraceptives with other drugs (enzyme inducers) can lead to breakthrough bleeding and / or a decrease in contraceptive effectiveness.

Interaction

Effect of other medications on Jes® Plus

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

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

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

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

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

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

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

Effect of combined oral contraceptives or calcium levomefolate on other medications

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

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

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

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

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

Other forms of interaction

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

How to take, course of use and dosage

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

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

Instructions for handling the packaging of Jes® Plus

In a fold-out package of Jes® Plus, a blister is pasted containing 24 active (pink) tablets and 4 auxiliary (light orange) tablets (bottom row). The package also contains a sticker block consisting of 7 self-adhesive strips with the names of the days of the week marked on them, which is necessary for registration of the reception calendar.

You must select a strip where the first day of the week is indicated, which starts taking pills. For example, if you start taking pills on a Wednesday, you should use a strip that starts with “Wed. ” The strip is pasted along the top of the package so that the designation of the first day is located above the tablet on which the arrow with the inscription “Start” is directed. Thus, it becomes clear on which day of the week you should take each tablet.

Start of taking the drug

In the absence of taking any hormonal contraceptives in the previous month

Taking Jes® Plus start on the 1st day of the menstrual cycle (i. e., on the 1st day of menstrual bleeding). On this day, you must take one pink (active) tablet, which is marked with the corresponding day of the week. Then you should take the pills in order. Jes®Preparation Plus, it starts working immediately, so there is no need to use additional barrier methods of contraception.

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

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

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

When switching from progestogen-only contraceptives (“mini-pills”, injectable forms, implants), or from an intrauterine therapeutic system with the release of a progestogen

Switch from mini-pili to Jes® Plus, you can do it on any day (without a break), from the implant or IUD with progestogen – on the day of their removal, from the injectable contraceptive-on the day when the next injection should be made. In all cases, during the first 7 days of taking Jes® Plus, you need to additionally use a barrier method of contraception (for example, a condom).

After an abortion (including spontaneous) in the first trimester of pregnancy

You can start taking the drug immediately. If this condition is met, no additional contraceptive measures are required.

After childbirth (in the absence of breastfeeding) or abortion (including spontaneous) in the second trimester of pregnancy

It is recommended to start taking the drug on the 21st-28th day after delivery or abortion (including spontaneous) in the second trimester of pregnancy. If the drug is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if sexual contact has taken place, before starting taking Jes® Plus, you should exclude pregnancy.

Taking missed pills

Skipping the light orange auxiliary pills can be ignored. However, missed pills should be discarded, so as not to accidentally extend the period of taking auxiliary pills. The following recommendations apply only to skipping active pink tablets (1-24 tablets per pack).

If the delay in taking any pink (active) pill is less than 24 hours, the contraceptive protection is not reduced. A woman should take the missed pill as soon as possible, and take the next one at the usual time.

If the delay in taking any pink (active) pill is more than 24 hours, the contraceptive protection may be reduced. The more pills you skip and the closer you get to the light orange (auxiliary) pill phase, the more likely you are to get pregnant.

It is necessary to remember:

— the drug should never be interrupted for more than 7 days (please note that the recommended interval of reception of light orange (secondary) tablets is 4 days);

— to achieve adequate suppression of the hypothalamic-pituitary-ovarian system required 7 days continuous use of active (pink) tablets.

Accordingly, if the delay in taking active (pink) tablets was more than 24 hours, we can recommend the following::

From day 1 to day 7

, a woman should take the last missed pill as soon as she remembers it, even if it means taking two pills at the same time. The following tablets should be taken at the usual time. In addition, during the next 7 days, you must additionally use a barrier method of contraception (for example, a condom). If sexual contact took place within 7 days before skipping the pill, the possibility of pregnancy should be considered.

From day 8 to day 14

, a woman should take the last missed pill as soon as she remembers it, even if it means taking two pills at the same time. She continues to take the next pills at the usual time.

If you follow the pill regimen for 7 days prior to the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for the next 7 days.

From day 15 to day 24

, the risk of reduced contraceptive reliability is unavoidable due to the approaching phase of taking light orange (auxiliary) tablets. In this case, you must follow the following algorithms::

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

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

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

2. Stop taking pink (active) tablets from the current package, then take a break for 4 or less days (including days of skipping tablets), and then start taking the drug from the new package.

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

It is allowed to take no more than two tablets in one day.

Recommendations for gastrointestinal disorders

In severe gastrointestinal disorders, the absorption of the drug may be incomplete, so additional contraceptive measures should be taken.

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

Discontinuation of Jes® Plus

Taking Jes® Plus, you can stop it at any time. If a woman is not planning a pregnancy, you should take care of other methods of contraception.If pregnancy is planned, you should simply stop taking Jes® Plus, wait for natural menstrual bleeding, and then try to get pregnant. This will help you more accurately calculate the duration of pregnancy and the time of delivery.

Delaying the onset of menstrual-like bleeding

To delay the onset of withdrawal bleeding, you should skip taking 4 light orange (auxiliary) tablets from the current package and start taking pink (active) tablets from the next package of Yaz ® Plus. If all 24 pink tablets from the second package were taken, then 4 light orange tablets should also be taken. Only then can you start taking tablets from the new packaging. Thus, the cycle can be extended, if desired, for any period, up to 3 weeks, including until all the pink tablets from the second package are taken. If a woman wants menstrual bleeding to start earlier, you should stop taking the pink pills from the second package, throw it away and take a break from taking all the pills for no more than 4 days, and then start taking the pills from the new package. In this case, menstrual-like bleeding will begin approximately 2-3 days after taking the last pink pill from the second package. While taking Jes® Plus, from the second package, smearing discharge and/or breakthrough bleeding may occur on the days of taking tablets.

Changing the day of onset of menstrual-like bleeding

If the tablets of the drug are taken in accordance with the recommendations, menstrual-like bleeding will occur approximately on the same day every 4 weeks. If a woman wants to change the day of the onset of menstrual-like bleeding, you should stop taking light orange pills for as many days as the woman wants to change the onset of menstrual-like bleeding. For example, if the cycle usually starts on Friday, and in the future the woman wants it to start on Tuesday (3 days earlier), then you should start taking pills from the next package 3 days earlier than usual, that is, do not use the last 3 light orange pills from the current package and start taking pills from the next package. The fewer light orange pills a woman takes, the more likely it is that menstrual-like bleeding will not occur. While taking Jes® Plus, smearing discharge and/or breakthrough bleeding may occur from the following package.

Efficacy and safety of Jes® Plus as a contraceptive have been studied in women of reproductive age. The use of the drug in children and adolescents is contraindicated until regular menstrual cycles are established.

Jes®Preparation Plus does not apply after menopause.

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

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

Overdose

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

use of calcium levomefolate at a dose of 17 mg / day (the dose is 37 times higher than that contained in 1 tablet of 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 this drug.

Diseases of the cardiovascular system

The results of epidemiological studies indicate a relationship between the use of combined oral contraceptives 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 combined oral contraceptives. An increased risk is present after the initial use of combined oral contraceptives or the resumption of use of the same or different combined oral contraceptives (after a break between doses of the drug for 4 weeks or more). Data from a large prospective study involving 3 groups of patients show that this increased risk is present mainly during the first 3 months.

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

VTE can be 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.

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: sudden pain, swelling and slight blueness of the extremities, a symptom complex “acute abdomen”.

Symptoms of myocardial infarction: pain, discomfort, pressure, heaviness, a feeling of compression or fullness in the chest or behind the sternum with radiating to the back, jaw, left upper limb, epigastrium; cold sweat, nausea, vomiting or dizziness; severe weakness, anxiety or shortness of breath; rapid or irregular heartbeat.

Arterial thromboembolism can be life-threatening or fatal.

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

The risk of developing thrombosis (venous and/or arterial) and 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 of age);

in the presence of:

– obesity (BMI greater than 30 kg / m%^%2);

– indications in the family history (for example, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of a hereditary or acquired predisposition, the woman should be 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 4 weeks before it) and do not resume admission for 2 weeks after the end of immobilization. Temporary immobilization (for example, air travel lasting more than 4 hours) may also be a risk factor for venous thromboembolism, especially in the presence of other risk factors;

— 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) is a reason for immediate discontinuation of the 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 (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 cervical cancer with prolonged use of combined oral contraceptives. However, the association with the use of combined oral contraceptives has not been proven. The possibility of interrelation of these data with screening of cervical diseases and with the peculiarities of sexual behavior (more rare use of barrier methods of contraception) is discussed.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk 1.24). The increased risk gradually disappears within 10 years after discontinuation of these medications. Because breast cancer is rare in women under the age of 40, the increase in breast cancer diagnoses among women who are currently or have recently taken combined oral contraceptives is insignificant relative to the overall risk of this disease. Its association with the use of combined oral contraceptives has not been proven. The observed increased risk may be due to careful monitoring and earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are more likely to develop early-stage breast cancer than women who have never used them.

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

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

Other states

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

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

Although a small increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically significant increases have rarely been observed. However, if 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 with combined oral contraceptives, but their association with combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus: hemolytic-uremic syndrome; Sydenham’s chorea; herpes of pregnancy; hearing loss associated with otosclerosis. Cases of worsening of the course of Crohn’s disease and ulcerative colitis, endogenous depression, and epilepsy with the use of combined oral contraceptives 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 combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to adjust the dose of hypoglycemic drugs in patients with diabetes mellitus who use low-dose combined oral contraceptives ( However, women with diabetes should be carefully monitored during the use of combined oral contraceptives.

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.

Reduced efficiency

Effectiveness of Jes® Plus can be reduced in the following cases:: when skipping pink (active) tablets, gastrointestinal disorders while taking pink (active) tablets, or as a result of drug interaction.

Frequency and severity of menstrual-like bleeding

While taking Jes® Plus, during the first few months, there may be irregular (acyclic) bleeding from the vagina (spotting spotting and / or breakthrough uterine bleeding). You should use hygiene products and continue taking the pills as usual. Evaluation of any irregular bleeding should be performed after an adjustment period of approximately three cycles.

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

No regular menstrual-like bleeding

Some women may not develop withdrawal bleeding while taking the auxiliary light orange pills. 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, BMI determination, breast examination), gynecological examination, cytological examination of the cervix (Pap test), and exclude pregnancy. When you resume taking Jes® Plus, the volume of additional studies and the frequency of follow-up examinations are determined individually, but at least once every 6 months.

It is necessary to warn the woman that the drug Jes® Plus, it doesn’t protect against HIV infection and other sexually transmitted diseases.

Conditions that require a doctor’s consultation

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

local a lump in the breast;

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

– if expected