Buy Yaz plus

Yaz® Plus is a low-dose, monophasic oral combination estrogen-progestin contraceptive drug consisting of hormone tablets and calcium levofefolat, and auxiliary tablets containing only calcium levofefolat.

The contraceptive effect of OCPs is based on the interaction of various factors, the most important of which are suppression of ovulation, increased viscosity of the cervical secretions and changes in the endometrium.

In women taking OCPs, the menstrual cycle becomes more regular, the pain, intensity and duration of menstrual bleeding decrease, reducing the risk of iron deficiency anemia. There is also evidence of a reduction in the risk of endometrial and ovarian cancer.

Drospirenone, which is included in Yaz® Plus, has anti-mineralocorticoid activity and helps prevent hormone-dependent fluid retention, which can manifest itself in weight loss and a reduced likelihood of peripheral edema, which ensures good tolerability of the drug. Drospirenone has a positive effect on PMS. In combination with ethinyl estradiol, drospirenone shows a favorable effect on the lipid profile, characterized by an increase in HDL. Drospirenone also has antiandrogenic activity and helps reduce acne (acne), 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.

Drospirenone does not possess androgenic, estrogenic, glucocorticoid, and antiglucocorticoid activity. All this, in combination with the anti-mineralocorticoid and anti-androgenic effects, provides Drospirenone with a biochemical and pharmacological profile similar to natural progesterone. With proper use of the drug, the Pearl Index (an indicator reflecting the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. If you skip the tablets or misuse, the Pearl index may increase.

The acidic form of calcium levomefolata is identical in structure to the natural L-5-methyltetrahydrofolate (L-5-methyl-THF), the main folate form found in food. The average concentration of L-5-methyl-THF in the blood plasma of people not using food enriched with folic acid is about 15 nmol / l.

Levomefolat, unlike folic acid, is a biologically active form of folate, making it more digestible than folic acid. Folate deficiency correlates with an increased risk of developing fetal neural tube defects. Calcium levomefolata recommended for women before pregnancy to meet the increased need for folate in the early stages of pregnancy. It may take several weeks to achieve optimal folate levels.

Drospirenone

 

• Absorption.

When ingested, drospirenone is rapidly and almost completely absorbed. After a single oral administration, Cmax of drospirenone in the blood plasma, equal to 38 ng / ml, is achieved in 1–2 hours. Eating does not affect its bioavailability, which ranges from 76 to 85%.

 

• Distribution.

After oral administration, a two-phase decrease in serum level of the drug is observed with T1 / 2, respectively (1.6 ± 0.7) h and (27 ± 7.5) h. Drospirenone binds to plasma albumin and does not bind to HSPG or corticosteroid binding globulin. 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. The average apparent Vd is (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. Drospirenone is also a substrate for oxidative metabolism catalyzed by the CYP3A4 isoenzyme.

 

• Derivation.

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 metabolites - about 40 hours.

 

• Css (equilibrium concentration).

During the first course of use of the drug Css Drospirenone in plasma, about 70 ng / ml is achieved 8 days after the start 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 T1 / 2 ratio in the terminal phase and the 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 the increase in concentration is not observed.

 

• Special patient groups

Impaired renal function. Studies have shown that the concentration of drospirenone in the blood plasma of women with mild renal insufficiency (Cl creatinine - 50–80 ml / min) when reaching equilibrium and comparable in women with normal kidney function (Cl creatinine - more than 80 ml / min). Nevertheless, in women with moderately severe renal insufficiency (Cl creatinine - 30–50 ml / min), the average concentration of drospirenone in the blood plasma was 37% higher than in patients with normal renal function. No marked changes in the concentration of potassium in the blood plasma when using drospirenone.

The pharmacokinetics of drospirenone have not been studied in patients with severe renal insufficiency.

 

• Liver dysfunction.

In women with moderate hepatic insufficiency (class B on the Child-Pugh scale), the AUC is comparable to the corresponding indicator in healthy women with similar Cmax values ​​in the absorption and distribution phases. T1 / 2 of drospirenone in patients with moderate liver failure was 1.8 times higher than in healthy volunteers with intact liver function.

In patients with moderately severe liver failure, 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 the concentration of potassium in the blood plasma in the studied groups. Changes in the concentration of potassium are not observed even in the case of a combination of factors predisposing to its increase (concomitant diabetes mellitus or treatment with spironolactone).

The pharmacokinetics of drospirenone has not been studied in patients with severe hepatic insufficiency.

 

• Ethnicity.

The effect of ethnicity (a study conducted on a cohort of women of the Caucasian race and Japanese women) on the pharmacokinetic parameters of drospirenone and ethinyl estradiol has not been established.

 

 

Ethinyl Estradiol

 

• Absorption.

After oral administration, ethinyl estradiol is rapidly and completely absorbed. Cmax - about 33 pg / ml - is achieved within 1–2 hours after a single ingestion. The absolute bioavailability as a result of presystemic conjugation and metabolism of the first passage is approximately 60%. Concomitant food intake reduces the bioavailability of ethinyl estradiol in about 25% of the patients, while other subjects did not observe similar changes.

 

• Distribution.

The concentration of ethinyl estradiol in plasma decreases biphasic, T1 / 2 of ethinyl estradiol in the second phase is about 24 hours. Ethinyl estradiol nonspecifically, but strongly binds to plasma albumin (about 98.5%) and induces an increase in plasma concentration of SHBG. Estimated Vd is about 5 L / kg.

 

• Metabolism.

Ethinyl estradiol undergoes significant primary metabolism in the intestine and liver. Ethinyl estradiol and its oxidative metabolites are primarily conjugated to glucuronides or sulfate. The rate of metabolic clearance of ethinyl estradiol is about 5 ml / min / kg.

 

• Derivation.

Ethinyl estradiol is practically not displayed unchanged. Ethinyl estradiol metabolites are excreted by the kidneys and through the intestine at a ratio of 4: 6. T1 / 2 metabolites is approximately 24 h.

 

• Css (equilibrium concentration).

Css is achieved in the second half of the cycle of the drug, the concentration of ethinyl estradiol in the blood plasma increases by about 1.4-2.1 times.

 

Calcium levomefolat

 

• Absorption.

After ingestion of calcium, levomefolat is rapidly absorbed and incorporated into the body folate pool. After a single oral administration, 0.451 mg of calcium levomefolat after 0.5–1.5 hr 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 pool with a fast metabolism is likely to represent folates that have been re-ingested, which is consistent with T1 / 2 of calcium levomefolat, which is about 4–5 hours after it has been taken once orally at a dose of 0.451 mg. The slow metabolism pool reflects the conversion of polyglutamate to folate, whose T1 / 2 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 represents the main form of folate in the body, in which they are delivered to peripheral tissues for participation 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 metabolic mechanisms 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, the precursors of DNA and RNA, as well as for the synthesis of methionine from homocysteine ​​and the conversion of serine to glycine.

 

• Derivation.

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

Css. 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 erythrocytes, Css is reached at a later date due to the life span of red blood cells, which is about 120 days.

• Contraception, especially in women with symptoms of hormone-dependent fluid retention in the body;
• contraception and treatment of acne (acne vulgaris) of moderate severity;
• contraception in women with folate deficiency;
• contraception and treatment of severe PMS.

Yaz® Plus is contraindicated in the presence of any of the conditions / diseases / risk factors 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 drospirenone, ethinyl estradiol, calcium levomefolata or any of the excipients of the drug Yaz Plus;
• thrombosis (venous and arterial) and thromboembolism (including deep vein thrombosis, pulmonary thromboembolism, myocardial infarction, stroke), cerebrovascular disorders - now or in history;
• the conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history;
• revealed acquired or hereditary susceptibility to venous or arterial thrombosis, including resistance to activated protein C, deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);
• high risk of venous or arterial thrombosis;
• migraine with focal neurological symptoms now or in history;
• pancreatitis with severe hypertriglyceridemia now or in history;
• diabetes with vascular complications;
• liver failure, severe acute or severe chronic liver disease (before normalization of liver tests);
• combined use with direct-acting antiviral drugs (DAAs) containing ombitasvir, paritaprevir, dasabuvir, or a combination of these substances;
• severe and / or acute renal failure;
• liver tumors (benign or malignant) now or in history;
• identified hormone-dependent malignant neoplasms (including genitals or mammary glands) or suspicion of them;
• bleeding from the vagina of unknown origin;
• rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption (Yaz® Plus contains lactose);
• pregnancy or suspicion of it;
• breastfeeding period.

 

Carefully

 

• The potential risk and the expected benefit of using the drug Yaz® Plus in each individual case should be assessed with the following diseases / conditions and risk factors:
• thrombosis risk factors and venous thromboembolism: smoking, obesity, dislipoproteinemia controlled hypertension, migraine without focal neurological symptoms, uncomplicated valvular disease, a genetic predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at the age of less than 50 years from someone from close relatives);
• diseases that may cause violations of the peripheral blood circulation: 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 of mild and moderate severity in history with normal indicators of functional liver samples;
• diseases first arisen or aggravated during pregnancy or against the background of previous intake of sex hormones (including jaundice and / or pruritus associated with cholestasis, cholelithiasis, otosclerosis with impairment of hearing, porphyria, pregnant women herpes, Sydengam chorea);
• postpartum period.

The drug is contraindicated during pregnancy. If pregnancy is detected while taking the drug Yaz® Plus, the drug should be stopped immediately.

Available data on the use of the drug Yaz® 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 OCPs before pregnancy or are teratogenic in cases of OCPs carelessness in the early stages of pregnancy. No specific epidemiological studies have been conducted on Yaz® Plus.

The drug is contraindicated during breastfeeding. Taking the drug can reduce the amount of breast milk and change its composition, therefore, the use of the drug Yaz Plus is contraindicated until breast feeding is stopped. A small amount of sex hormones and / or their metabolites can penetrate into breast milk and affect the health of the baby.

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

 

Take 1 tab. per day, continuously, for 28 days. Taking the pills from the next pack starts immediately after taking the pills from the previous one.

Withdrawal bleeding, as a rule, begins on the 2nd or 3rd day after the start of taking inactive tablets and may not finish yet before the start of taking the tablets from the next package.

 

Taking tablets from the first package of the drug Yaz®Plus

 

When no hormonal contraceptive was applied in the previous month. Reception of the drug Yaz®Plus should be started on the first day of the menstrual cycle, i.e. on the first day of menstruation. On this day, you must take one pink (hormone-containing) pill, which is labeled with the corresponding day of the week.

Then you should take the pills in order. It is allowed to start taking the drug on the 2–5 day of the menstrual cycle, but in this case, during the first 7 days of taking pink pills, you must use an additional barrier method of contraception (for example, a condom).

 

When switching from other combined contraceptive drugs (OCPs, vaginal ring contraceptive or contraceptive patch). It is preferable to start taking the drug Yaz®Plus on the next day after taking the last pill containing hormones from the package of the previous OCPs, but in no case later than the next day after the usual 7-day break (for preparations containing 21 tablets) or after taking the last pill that does not contain hormones (for drugs containing 28 tablets. per pack). Yaz Plus Plus should be started after the usual interruption in the use of active tablets in the event of a switch from contraceptive drugs with a prolonged use regimen. The administration of Yaz® Plus should be started on the day of removal of the vaginal ring or patch, but no later than the day when a new patch is to be inserted or a new patch is pasted.

 

When moving from contraceptives containing only gestagens (mini-pili, injection forms, implant), or from the intrauterine therapeutic system with the release of the gestagen. You can switch from mini-pill to Yaz® Plus on any day (without a break), from an implant or an intrauterine contraceptive with a gestagen — on the day of their removal, from an injection contraceptive — on the day when the next injection should be made. In all cases, during the first 7 days of taking Yaz®Plus, you must additionally use a barrier method of contraception (for example, a condom).

 

After 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 in the II trimester. It is recommended to start taking the drug on the 21-28th day after birth or abortion (including spontaneous) in the second trimester of pregnancy. If taking the drug started later, you must use an additional barrier method of contraception during the first 7 days of taking the pills. However, if sexual intercourse took place, pregnancy should be excluded before taking the drug Yaz Plus.

• Skipping auxiliary light orange pills can be ignored. However, the missed pills should be thrown away in order not to accidentally extend the period of taking the auxiliary pills.

 

The following recommendations apply only to skipping pink tablets (tablets 1-24 per pack).

 

• If the delay in taking the pink pill was 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 the pink pill is more than 24 hours, contraceptive protection may be reduced. The more pills are missed, and the closer the skip pills to the phase of taking light orange (auxiliary) tablets, the higher the probability of pregnancy.

 

It should be remembered:

 

• taking the drug should never be interrupted for more than 7 days (it is necessary to pay attention to the fact that the recommended interval for taking light orange (auxiliary) tablets is 4 days);

 

• to achieve adequate suppression of the hypothalamic-pituitary-ovarian system requires 7 days of continuous administration of pink tablets.

 

Accordingly, if the delay in taking pink pills was more than 24 hours, we can recommend the following.

 

• From 1st to 7th day.

It is necessary to take the last missed pill as soon as the patient remembers this, even if it means taking 2 tablets. at the same time. The following tablets must be taken at the usual time. In addition, over the next 7 days, you must additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before the tablet is missed, the possibility of pregnancy should be considered.

 

• From the 8th to the 14th day.

It is necessary to take the last missed pill as soon as the patient remembers this, even if it means taking 2 tablets. at the same time. The following tablets must be taken at the usual time. Subject to the admission pills for 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as skipping two or more pills, it is necessary to additionally use barrier methods of contraception (for example, a condom) for the next 7 days.

 

• From the 15th to the 24th day.

The risk of a decrease in contraceptive reliability is inevitable due to the approaching phase of taking light orange (auxiliary) tablets. In this case, you must adhere to the following algorithms:

 

•  if within the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods. When taking the missed pills should be guided by paragraphs 1 or 2;
• if during the 7 days preceding the first missed pill, the pills were taken incorrectly, then over the next 7 days you must additionally use a barrier method of contraception (for example, a condom) and in this case, you should be guided by paragraph 1 for taking the 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 tablets in the package run out. Four light orange (auxiliary) tablets should be discarded and the pink tablets should be taken from the new package immediately. Until the pink tablets from the second package run out, withdrawal bleeding is unlikely, but there may be spotting and / or breakthrough bleeding.

 

2. Stop taking the pink pills from the current package, then take a break for 4 days or less (including the days of skipping the tablets), then start taking the drug from the new package. If a woman misses taking pink pills and during taking light orange (auxiliary) pills, no withdrawal bleeding has occurred, it is necessary to make sure that there is no pregnancy.

 

 

Allowed to take no more than 2 tablets in a day.

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

To delay the onset of withdrawal bleeding, skip taking 4 light orange (auxiliary) tablets from the current package and start taking pink tablets from the next package of Yaz® Plus. If the woman has taken all 24 pink tablets from the second package, in this case 4 light orange tablets should also be taken.

Only after that you can start taking pills from the new package. Thus, the cycle can be extended, at will, for any period of time, until all pink tablets from the second package are taken.

If a woman wants menstrual-like bleeding to start earlier, you should stop taking the pink pills from the second pack, throw it away and take a break in taking all the pills for no more than 4 days, and then start taking the pills from the new pack. In this case, menstrual bleeding will begin approximately 2-3 days after taking the last pink pill from the second package. While taking the drug Yaz® Plus from the second package, spotting and / or breakthrough bleeding may occur on the days of taking the pills.