JESS PLUS PILLS

Film Coated Tablets

Packaging

Set of two tablets, 28 pcs.

Mechanism of action

Jess Plus is a low-dose monophasic oral combined estrogen-progestin contraceptive drug, which includes active pills and auxiliary vitamin pills containing Calcium levomefolat.

The contraceptive effect of the drug Jess Plus 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, soreness, intensity and duration of menstrual-like bleeding decrease, resulting in a reduced risk of iron deficiency anemia. There is also evidence of a reduction in the risk of endometrial and ovarian cancer.

Drospirenone contained in the drug Plus Plus, has anti-mineralocorticoid action and helps prevent hormone-dependent fluid retention, which can manifest itself in weight loss and a decrease in the likelihood of peripheral edema. Drospirenone also has antiandrogenic activity and helps reduce acne (acne), oily skin and hair. This effect of drospirenone is similar to the action of natural Progesterone, produced in the female body.This should be considered when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. If used correctly, the Pearl Index (a measure reflecting the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. If you skip pills or misuse, the Pearl index may increase.

The acidic form of calcium levomefolata, in its structure is identical to the natural L-5-methyltetrahydrofolate (L-5-methyl-THF), the main folate form contained 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.

Levomefolat, unlike folic acid, is a biologically active form of folate. Because of this, it is absorbed better than folic acid. Levomefolat is indicated to meet the increased need and provide the necessary folate content in the woman’s body during pregnancy and during breastfeeding. The introduction of calcium levomefolata in the oral contraceptive reduces the risk of developing a defect in the fetal neural tube if a woman unexpectedly becomes pregnant immediately after discontinuation of the use of 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 administration Cmax Drospirenone in the blood plasma, equal to 35 ng / ml, is achieved in 1-2 hours. Bioavailability ranges from 76 to 85%. Compared with taking drospirenone on an empty stomach, eating does not affect its bioavailability.

Distribution. After oral administration, there is a two-phase decrease in serum level of the drug with T1/2 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 (CGC). Only 3-5% of the total concentration of the substance in the serum is present as a free hormone. An ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to plasma proteins. Average apparent vd makes (3,7 ± 1,2) l / kg.

Metabolism. After oral administration, drospirenone is extensively metabolized. Most plasma metabolites are represented by the acidic forms of drospirenone, which are formed without the involvement of the cytochrome P450 system. The cytochrome P4503A4 isoenzyme participates to a minimum extent in the metabolism of drospirenone, drospirenone is able to reduce the concentration of the enzyme in the blood plasma and the activity of cytochrome P4501A1, P4502С9 and P4502С19 in vitro.

Inference. The rate of metabolic clearance of drospirenone in plasma is (1.5 ± 0.2) ml / min / kg. In unchanged form, drospirenone is excreted only in trace amounts. The metabolites of drospirenone are excreted through the gastrointestinal tract and kidneys in a ratio of approximately 1.2: 1.4. T1/2 for excretion of metabolites - about 40 hours.

Equilibrium concentration. During the first course of use of the drug Css Drospirenone in plasma about 60 ng / ml is achieved from the 7th to the 14th day of the drug. There was an increase in the concentration of drospirenone in plasma approximately 2-3 times (due to cumulation), which was determined by the ratio T1/2 in the terminal phase and dosing interval. A further increase in the concentration of drospirenone in plasma is noted after 1-6 courses of use of the drug, after which there is no increase in concentration.

Impaired renal function. Plasma concentration of drospirenone when reaching an equilibrium state was comparable in women with mild renal dysfunction (Cl creatinine - 50-80 ml / min) and in women with intact kidney function (Cl creatinine> 80 ml / min). However, in women with moderate renal impairment (creatinine Cl - 30–50 ml / min), the average plasma concentration of drospirenone was 37% higher than in patients with intact kidney function. No marked changes in the concentration of potassium in the blood plasma when using drospirenone.

Liver dysfunction. In women with moderate hepatic impairment (Child-Pugh grade B), AUC is comparable to that in healthy women with similar C values.max in the phases of absorption and distribution. T1/2 drospirenone in patients with moderate liver dysfunction was 1.8 times higher than in healthy volunteers with intact liver function.

In patients with moderately impaired liver function, there was a decrease in the clearance of drospirenone by about 50% compared with women with intact liver function, and there were no differences in plasma potassium concentrations in the studied groups.Changes in the concentration of potassium were not observed 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 administration, ethinyl estradiol is rapidly and completely absorbed. Cmax - about 33 pg / ml - achieved within 1-2 hours. The drug is subjected to presystemic metabolism in the liver, its bioavailability when administered orally averages 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 the blood plasma decreases in 2 phases, T1/2 Ethinyl estradiol in the second phase is about 24 hours. Ethinyl estradiol has a nonspecific but strong binding to plasma albumin (about 98.5%) and induces an increase in plasma concentration of SHBG. Estimated Vd makes about 5 l / kg.

Metabolism. Ethinyl estradiol undergoes presystemic conjugation in the liver and in the mucosa of the small intestine. The main metabolic pathway of ethinyl estradiol is aromatic hydroxylation with the formation of numerous metabolites that are in both bound and unbound state. The rate of elimination of ethinyl estradiol is about 5 ml / min / kg.

Inference. Ethinyl estradiol is derived only in the form of metabolites by the kidneys and through the gastrointestinal tract in the ratio 4: 6 with T1/2 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 by about 1.4-2.1 times.

Ethnicity. The effect of ethnicity on pharmacokinetic parameters was studied in single and multiple dosing studies of drospirenone and ethinyl estradiol in healthy women of the European race, as well as in Japanese women. The effect of ethnicity on the pharmacokinetic parameters of drospirenone and ethinyl estradiol has not been established.

Calcium levomefolat

Absorption. After ingestion of calcium, levomefolat is rapidly absorbed and incorporated into the body folate pool. After a single dose of 0.451 mg of calcium levomefolat after 0.5-1.5 hours Cmax becomes 50 nmol / l higher than the initial concentration.

Distribution. Folate pharmacokinetics has a biphasic character: folate pool is determined with a fast and slow metabolism. A fast metabolized pool is likely to represent folate re-ingested, which is consistent with T1/2 calcium levomefolat, which is about 4-5 hours after a single oral administration in a dose of 0.451 mg. A slow metabolism pool reflects polyglutamate folate conversion, T1/2 which is about 100 days. Inbound folates and folates, going through the enterohepatic cycle, maintain 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 they are delivered to peripheral tissues to participate in cellular folate metabolism.

Metabolism. L-5-methyl-THF is the main folate transported form in plasma.When comparing 0.451 mg of calcium levomefolata and 0.4 mg of folic acid, similar mechanisms of metabolism were established for other significant folates. Folate coenzymes are involved in 3 major 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.

Inference. 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 the blood plasma after ingestion of 0.451 mg of calcium levomefolat is achieved in 8-16 weeks and depends on its initial concentration. In red blood cells Css is achieved at a later date due to the life span of red blood cells, which is about 120 days.

• 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).

• Jess 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 receiving, the drug should be immediately canceled:
• hypersensitivity or intolerance to any of the components of the drug Jess Plus;
• Thrombosis (venous and arterial) and thromboembolism at present or in history (including deep vein thrombosis, thromboembolism of the pulmonary artery, myocardial infarction, stroke), cerebrovascular disorders;
• the conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history;
• the presence of multiple or pronounced risk factors for venous or arterial thrombosis;
• migraine with focal neurological symptoms now or in history;
• diabetes with vascular complications;
• liver failure and severe liver disease (until normalization of liver tests);
• severe and / or acute renal failure ;
• liver tumors (benign or malignant) now or in history;
• identified hormone-dependent malignant neoplasms (including the genitals or mammary glands) or suspicion of them;
• bleeding from the vagina of unknown origin;
• pregnancy or suspicion of it;
• breastfeeding period;
• the presence of rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

CAREFULLY

• The potential risk and the expected benefit of using the drug Jess Plus in each individual case should be assessed with the following diseases / conditions and risk factors:
• risk factors for thrombosis and thromboembolism: smoking, obesity, dyslipoproteinemia, controlled arterial hypertension,migraine without focal neurological symptoms, uncomplicated valvular heart disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebral circulation at a young age in any of the closest relatives);
• other diseases in which disorders of the peripheral circulation can be observed: 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 first arisen or aggravated during pregnancy or against the background of previous intake of sex hormones (for example jaundice and / or itching associated with cholestasis, cholelithiasis, otosclerosis with impaired hearing, porphyria, herpes of pregnant women, Sydenhamma chorea);
• postpartum period.

Pregnancy

The drug is contraindicated during pregnancy. If pregnancy is detected while taking the drug Jess plus, the drug should be immediately canceled. Data on the results of taking the drug Jess Plus during pregnancy is limited, and do not allow to draw any conclusions about the negative impact of the drug on pregnancy, the health of the fetus 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 COCs before pregnancy or are teratogenic in cases of COC carelessness in the early stages of pregnancy. No specific epidemiological studies have been conducted on Jess plus.

Lactation

The drug is contraindicated during lactation. Taking COCs can reduce the amount of breast milk and alter its composition, so their use is not recommended until breastfeeding is stopped. A small amount of sex hormones and / or their metabolites may be excreted in milk, but there is no evidence of their negative impact on the health of the child.

If any of the conditions, diseases, and risk factors listed below are presently present, the potential risk and the expected benefits of using the drug should be carefully weighed.® Plus in each individual case and discuss it with a 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 PDA and an increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders) when taking combined oral contraceptives. These diseases are rare.

The risk of venous thromboembolism (VTE) is maximum in the first year of taking such drugs. Increased risk is present after the initial use of combined oral contraceptives or the resumption of the use of the same or different combined oral contraceptives (after a break between taking the drug in 4 weeks or more). 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 thromboembolism of VTE in patients taking low-dose combined oral contraceptives (<50 μg of ethinyl estradiol) is 2-3 times higher than in non-pregnant patients who do not take PDA, however, this risk remains lower compared to the risk of VTE during pregnancy and childbirth.

VTE can be life threatening or fatal (1-2% of cases).

VTE, which is manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any combination oral contraceptives.

Thrombosis of other blood vessels, such as the hepatic, mesenteric, renal, cerebral veins and retinal arteries or vessels, is extremely rare with combined oral contraceptives. There is no consensus regarding the relationship between the occurrence of these events and the use of combined oral contraceptives.

Symptoms of deep vein thrombosis (DVT): one-sided swelling of the lower limb or along the vein of the lower limb, pain or discomfort in the lower limb only in a vertical position or when walking, a local temperature increase in the affected lower limb, redness or discoloration of the skin on the lower limb.

Symptoms of pulmonary thromboembolism (pulmonary embolism): difficulty or rapid breathing; sudden cough, incl. with hemoptysis; acute pain in the chest, which may increase with a deep breath; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of this