Recently, quite often, modern doctors prescribe the drug Klayra for certain diseases. Reviews of doctors, the pros, cons of this tool - we will consider all this below.
How do they work?
This drug is a combined oral contraceptive, which is based on the interaction of a number of factors. The most important among them are the suppression of ovulation, as well as the adjustment of the properties of cervical mucus - this is what the effect of the Klayra drug is based on. Doctors' reviews (experts always consider the pros, cons) often say that this remedy stands out among similar ones with its effect.
In addition to preventing unwanted pregnancy, this drug is also characterized by a number of additional beneficial properties, which, even taking into account any negative qualities, allow you to choose the best option for contraception. All contraindications are described to the Klayra preparation by the instruction. Doctors' reviews also include information about who is not advisable to take such a medication.
What gives a welcome?
Reducing the intensity and pain of menstrual bleeding, which ultimately leads to a significant reduction in the risk of iron deficiency anemia. This is precisely the main effect that Klaira provides. The doctors' reviews (the pros / cons of this drug, see below) indicate that all this is fully provided, and therefore the medication is recommended to be used so often. Among other things, it is often noted that taking this drug provides a significant reduction in the possibility of developing endometrial cancer. Also, taking the drug reduces the risk of ovarian cancer.
What do doctors say?
Regarding the drug “Klaira”, the reviews of doctors often note the fact that it has a very favorable effect on the endometrium, and therefore it is used in the treatment of prolonged or too severe menstrual bleeding that does not have an organic pathology. These symptoms periodically relate to dysfunctional uterine bleeding. It is this fact that is highlighted by the opinions of doctors available on the Klayra drug. With endometriosis, its use can also be prescribed.
Research
The safety and efficacy of using estradiol valerate / dienogest tablets in the treatment of various symptoms of uterine dysfunctional bleeding have been identified in two clinical trials.
Both studies used the same packaging design and analysis plan. Ultimately, 269 patients were selected for use with the Klayra drug. The reviews of the doctors (the pros / cons are described in detail) participating in the study suggest that in addition to this, 152 patients were tested in whom the placebo effect was tested . In these studies, it was determined that the drug was much more effective compared to placebo in the treatment of these symptoms, and it is worth noting that the endpoint of response to the Klayra drug was more than 40% in each of the studies.
In addition, each of the studies clearly demonstrated a statistically and clinically significant decrease in menstrual blood loss, and subsequently this was accompanied by a statistically significant increase in iron metabolism, which at the moment is often noted about the Claira remedy by doctors (we consider the pros and cons of this drug) .
The estrogen in this preparation is estradiol variate, which is the precursor of natural human 17β-estradiol. The estrogen component used in this product is significantly different from estrogens, which are commonly used in combined oral contraceptives, which are standard synthetic estrogens such as mestranol or ethinyl estradiol, each of which contains an ethynyl group at position 17α. This group leads to significantly greater metabolic stability, but at the same time has a more pronounced effect on the liver, which is also quite important.
When describing the drug “Klayra,” the reviews of doctors often mention that its administration has a much less pronounced effect on the liver compared to other three-phase CPCs, which include levonorgestrel and ethinyl estradiol. In the process of research, it was determined that the effect on the concentration of globulin, designed to bind sex hormones, is less pronounced. In combination with estradiol dienogest, valerate shows a significant increase in HDL, while the overall concentration of LDL cholesterol decreases.
Dienogest is a progestogen that works when taken orally. It is characterized by additional antiandrogenic partial effects, while its antiestrogenic, androgenic and estrogenic properties are insignificant. Due to the unique chemical structure, a whole spectrum of pharmacological action is achieved, which includes the most significant advantages of 19-nor-progestogens, as well as various progesterone derivatives, which are often noted by reviews available on the Klaira remedy (pros / cons will be discussed later).
Even the preclinical data that were obtained in the process of conducting routine toxicity studies after multiple doses, as well as the carcinogenic potential and genotoxicity of this drug, did not show that there is any significant specific risk to humans. However, when describing the Klayra medication, the reviews of gynecologists often say that we should not forget about the possibility of stimulating a number of tumors and hormone-dependent tissues with sex hormones. In case of proper use, the so-called Pearl index (an indicator that determines the frequency of pregnancy in a hundred women during the year of using this or that drug) has a value of less than 1, but in case of missed tablets or improper use it can increase.
Next, the pharmacokinetics of the drug “Klayra” will be considered. The reviews of gynecologists almost completely confirm the information indicated by the manufacturer, in connection with which this tool is prescribed for many patients.
Dienogest
- Absorption After oral administration, this element is rapidly and at the same time almost completely absorbed. With max in serum, it reaches 90.5 ng / ml about an hour after taking the tablet (it contains 3 mg of dienogest and 2 mg of estradiol variate). Bioavailability in this case reaches an indicator of 91%. It is worth noting that the pharmacokinetics of dienogest in the dosage range from 1 to 8 mg is characterized by a direct dependence on the dose. If the drug is used simultaneously with food intake, this does not cause any clinically significant effect on the degree or rate of absorption of this element.
- Distribution . A considerable part of the circulating dienogest (10%) remains in an unbound form, while the rest has a non-specific connection with albumin. Dienogest alone does not directly bind to either corticosteroid-binding globulin or SHBG. It is for this reason that the risk of displacing testosterone from this connection with SHBG or cortisol from the connection of this element with CSG is completely eliminated. A particular effect on the various physiological processes of the movement of endogenous steroids, respectively, is almost impossible. At an equilibrium concentration, V d is 46 L as a result of the intravenous administration of 85 μg of dienogest labeled with tritium.
- Metabolism . The dienogest element is almost completely metabolized in full accordance with the currently known metabolic pathways of steroid hormones, as well as with the formation of metabolites, which in the majority of cases are hormone inactive. These metabolites are excreted extremely quickly, therefore, the predominant fraction in the blood plasma is the unchanged dienogest. The total clearance after intravenous use of tritium-labeled dienogest is 5.1 l / h.
- Elimination . As a result of taking this element inside at a dose of 0.1 mg / kg, the dienogest completely comes out in the form of metabolites excreted by the kidneys and intestines in an approximate ratio of 3: 1. After oral use, approximately 42% of the dose is completely excreted during the first day, while 63% during 6 days through renal excretion. In addition, after 6 days, approximately 86% of the dose is excreted through the intestines and kidneys.
- Equilibrium concentration. In this case, the pharmacokinetics of dienogest does not depend on the concentration of SHBG. C ss is achieved approximately three days after using the same dose, which is 3 mg of dienogest in combination with 2 mg of estradiol valerate.
Estradiol valerate
- Absorption As a result of taking the drug, estradiol is quick enough and completely absorbed. Cleavage into valerianic acid and estradiol itself is carried out in the process of absorption of this element in the gastrointestinal mucosa or during the first passage through the liver, as a result of which estradiol and its metabolites appear. If the drug is taken simultaneously with food, this does not have any clinically significant effect on the degree or rate of absorption of this element.
- Metabolism . Valerianic acid has an extremely fast metabolism. After ingestion of approximately 3% of the dose, it becomes completely bioavailable in the form of pure estradiol, which undergoes the intense effect of the initial passage through the liver, as a result of which a significant portion of the administered dose begins to be metabolized already in the mucosa of the gastrointestinal tract. In combination with a presystemic metabolism directly in the liver, approximately 95% of the total oral dose is ultimately metabolized before it enters the systemic circulation. The main metabolites here are estrone sulfate, estrone and estrone glucuronide.
- Distribution . In blood serum, about 38% of estradiol is directly associated with SHBG, while 60% is associated with albumin, and only 2-3% is constantly circulated in an unbound state. It is worth noting that estradiol may slightly increase the total concentration of SHBG in the blood serum, and this effect directly depends on the pleasant dose. On the 21st day of taking this drug, the total concentration of SHBG reached approximately 146% of the initial one, while by the 28th day, which is the end of the phase of application of inactive tablets, it was already reduced to 141%.
- Elimination . Due to the sufficiently large circulating pool of glucuronides and sulfates, as well as due to hepatic-intestinal recirculation of T 1/2 estradiol after oral use in the terminal phase, it is a complex characteristic that directly depends on all these processes.
- Equilibrium concentration. The pharmacokinetics of estradiol is directly dependent on the concentration of SHBG. In women, the concentration of estradiol in the blood plasma is a complex of endogenous estradiol, as well as the estradiol that comes in the process of taking this drug. During the phase of taking the tablets, which contain 3 mg of dienogest and 2 mg of estradiol valerate, the average concentration of estradiol in blood serum in an equilibrium state is 51.6 pg / ml.
When is this drug used?
First of all, Klaira is prescribed for menopause. Reviews of doctors say that this is the best choice for the treatment of women suffering from heavy or prolonged menstrual bleeding in the absence of any organic pathology.
Also, this drug is usually used for oral contraception.
Contraindications
About the drug "Klayra" reviews of doctors (side effects are to blame) are not always positive. So, there are some contraindications. We note several conditions in which this drug should not be used, and the reception should be completely canceled if one of them begins to develop during therapy:
- excessive sensitivity to any active substances or to a certain auxiliary component;
- thromboembolism or thrombosis at present or in history;
- conditions that are prior to thrombosis, both in history and at present;
- pronounced hereditary or acquired predisposition to arterial or venous thrombosis, including also antithrombin III deficiency, protein S and C deficiency, antibodies to phospholipids and hyperhomocystsinemia;
- the presence of an increased risk of arterial or venous thrombosis;
- the presence of migraine with any neurological focal symptoms both at the moment and in history;
- diabetes mellitus, characterized by various vascular complications;
- pancreatitis having severe hypertriglyceridemia at the moment or in history;
- severe liver disease or liver failure;
- manifested hormone-dependent malignant tumors or a suspicion of their occurrence;
- liver tumors;
- pregnancy or suspicion of it;
- vaginal bleeding of unknown origin;
- lactose intolerance, glucose-galactose malabsorption, or lactase deficiency.
Among other things, it is worth noting another case in which Klaira birth control pills cannot be used. Reviews of doctors say that they should not be taken during breastfeeding.
Special warnings
If certain diseases, conditions or risk factors listed below are observed in a person at the present time, it will be necessary to carefully consider the potential risk and benefits of taking this drug in each case. In particular, this applies to the following situations:
- risk factors for subsequent development of thromboembolism and thrombosis;
- other diseases in which various peripheral circulatory disorders can be noticed;
- hypertriglyceridemia;
- the presence of hereditary angioedema;
- various diseases that first appeared or worsened during pregnancy or during the previous use of sex hormones.
In all these cases, you can not take pills "Klayra". Reviews of doctors in this situation will help maintain health.
Pregnancy and the period of breastfeeding
The use of this drug is contraindicated during pregnancy. In this case, such situations occur when conception occurs against the background of admission, which also mentions the instructions for use for the drug “Klayra”. Reviews of doctors say that in this case, you need to immediately stop the subsequent intake. However, in the process of conducting large-scale studies, an increase in the risk of developing any birth defects in children born to women who took CPC both before conception and when they were accidentally taken at the beginning of pregnancy was not determined.
CPC sometimes have an effect on lactation, as they can negatively affect the volume of milk produced or even change its composition, which is often mentioned by the doctors about the drug “Klayra”. After 40 years, for this reason its use is especially not recommended.