Klimen® is not used for contraception.
In the presence of symptoms of estrogen deficiency due to the onset of natural menopause, HRT in cyclic mode is performed in women in the perimenopausal period (in women in the postmenopausal period, HRT is shown in continuous mode)
If contraception is necessary, non-hormonal methods should be used (with the exception of calendar and temperature methods). If you suspect a pregnancy, you should stop taking the pills until pregnancy is not ruled out (see "Pregnancy and lactation").
If any of the following conditions or risk factors are present or worsenable, the relationship between individual risk and benefit of treatment should be assessed before initiating or continuing to receive Climen®.
The appointment of Climen® to women who have several risk factors for thrombosis or a high degree of severity of one of the risk factors is contraindicated.
Venous thromboembolism
In a number of controlled randomized, as well as epidemiological studies, an increased relative risk of venous thromboembolism (VTE) in the background of the drug Klimen ®, i.e. deep vein thrombosis or pulmonary embolism. Therefore, with the appointment of Climen® to women with risk factors for VTE, the risk-benefit ratio should be carefully weighed and discussed with the patient.
Risk factors for VTE include individual and family history (the presence of VTE in close relatives at a relatively young age may indicate a genetic predisposition), a predisposed predisposition to venous or arterial thrombosis, including resistance to activated protein C, an antithrombin III deficiency, a protein deficiency C, a deficit protein S, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant), as well as multiple or expressed risk factors for veins or arterial thrombosis, including complications of valvular heart disease, atrial fibrillation,diseases of the vessels of the brain or coronary arteries; uncontrolled arterial hypertension, smoking over the age of 35, obesity with a body mass index> 30 kg / m2. The risk of VTE also increases with age. The question of the possible role of varicose veins in the development of VTE remains controversial.
The risk of VTE may temporarily increase with prolonged immobilization, "large" planned and traumatological operations or massive trauma. Depending on the cause or duration of immobilization, the expediency of temporary discontinuation of Climen®
It should immediately stop treatment if symptoms of thrombotic disorders occur or if they are suspected.
Arterial thromboembolism
In randomized controlled trials with prolonged use of combined conjugated equine estrogens (ELE) and medroxyprogesterone acetate, no evidence of a positive effect on the cardiovascular system was obtained. In large-scale clinical studies of this compound, a possible increase in the risk of coronary heart disease (CHD) in the first year of use was found with a subsequent lack of positive effect.In one large clinical study, using only EFE, a potential reduction in the incidence of coronary heart disease (CHD) among women aged 50-59 years was found in the absence of a common positive effect among the cumulative population of the study. As a secondary result, in two large-scale clinical studies using EML as monotherapy or in combination with MPA, a 30-40% increase in the risk of stroke was found. It is not known whether this increased risk extends to other HRT drugs, in particular to Climen®, containing other types of estrogens and progestogens, or to non-oral uses.
Endometrial cancer
With prolonged monotherapy with estrogen, the risk of developing hyperplasia or endometrial cancer increases. Studies have confirmed that the addition of gestagens inhibits the risk of hyperplasia and endometrial cancer.
Mammary cancer
According to clinical trials and the results of observational studies, an increase in the relative risk of breast cancer in women using HRT for several years has been found.This may be due to earlier diagnosis, the acceleration of growth of an already existing tumor in the background of HRT, or a combination of both. The relative risk increases with the duration of application, but may be absent or be reduced with estrogen alone. This increase is comparable to the increased risk of breast cancer in women with a later onset of natural menopause, as well as obesity and alcohol abuse. The increased risk gradually decreases to the usual level during the first few years after the discontinuation of taking HRT medications, to which Klimen® belongs. Assumptions regarding the increased risk of developing breast cancer are based on the results of more than 50 epidemiological studies.
There is a risk of breast cancer spreading beyond the breast.
In two large-scale, randomized trials with EFS alone, or with a consistent combination with MPA, hazard estimates were calculated equal to 0.77 (95% confidence interval: 0.59 to 1.01) or 1.24 (95% confidence interval: 1, 01 - 1.54) after approximately 6 years of use of this combination.It is not known whether this increased risk also extends to other products for HRT, in particular to Klimen®.
Preparations for HRT, to which Climen® refers, increases the mammographic density of the mammary glands, which in some cases may have a negative effect on the radiographic detection of breast cancer.
Liver tumors
Against the background of the use of sex hormones, which include and means for HRT, in rare cases, there were benign, and even less often, malignant liver tumors. In some cases, these tumors led to a life-threatening intra-abdominal bleeding. With pain in the upper abdomen, enlarged liver, or signs of intra-abdominal bleeding in differential diagnosis, the probability of a liver tumor should be taken into account.
Cholelithiasis
It is known that estrogens increase the lithogenicity of bile. Some women are predisposed to the development of cholelithiasis in treatment with estrogen.
Dementia
There are limited data showing an increased likelihood of dementia risk in women starting hormone replacement therapy at the age of 65 and older.The risk can be reduced if the use of HRT is started in early menopause, as observed in studies. It is not known whether this applies to other HRT drugs, to which Klimen® refers.
Other states
Immediately discontinue treatment with the appearance of the first appeared migraine-like or frequent and unusually severe headaches, as well as with the appearance of other symptoms - possible precursors of thrombotic stroke of the brain.
The relationship between the administration of Climen ® and the development of clinically significant arterial hypertension is not established. Women taking medications for HRT, including Klimen®, described a slight increase in blood pressure, a clinically significant increase (over 140/90 mm Hg) is rare. However, in some cases, with the development of a clinically significant hypertension in the presence of Climen®, a withdrawal of the drug may be considered.
In case of mild violations of liver function, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, a doctor's supervision is necessary,as well as periodic studies of liver function. With worsening of the liver function parameters, Climen® should be discarded.
In case of recurrence of cholestatic jaundice or cholestatic pruritus observed for the first time during pregnancy or previous treatment with sex steroid hormones, it is necessary to immediately stop taking Climen®.
Special care is required for women with moderately elevated concentrations of triglycerides. In such cases, the use of Climen ® can cause a further increase in the concentration of triglycerides in the blood, which increases the risk of acute pancreatitis.
Although the administration of Climen ® may affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the regimen for treatment of patients with diabetes mellitus. Nevertheless, women with diabetes mellitus should be supervised when using Climen®.
In some patients under the influence of the drug Climen®, unwanted manifestations of estrogen stimulation, for example, bleeding from the vagina, can develop.Frequent or persistent bleeding from the vagina on the background of treatment is an indication for the study of the endometrium.
If treatment of irregular menstrual cycles does not give results, a survey should be conducted to eliminate the organic disease.
Under the influence of estrogens, the myomatous nodes of the uterus can increase in size. In this case, treatment should be discontinued.
It is recommended to stop treatment with the development of recurrence of endometriosis on the background of the drug Klimen ®.
In case of detection of prolactinoma, the patient should be under close medical supervision (including periodic determination of prolactin concentration).
In some cases, there may be a chloasma, especially in women with a history of pregnant women with chloasma. During the application of Climen®, women with a tendency to develop chloasma should avoid prolonged sun exposure or ultraviolet radiation. The following conditions can occur or worsen when taking drugs for HRT, to which Klimen® refers. Although their relationship with the use of the drug Klimen® is not proven,women with these conditions with the use of the drug Klimen® should be under the supervision of a doctor: epilepsy; benign breast diseases; bronchial asthma; migraine; porphyria; otosclerosis; systemic lupus erythematosus, small chorea.
In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.
Additional Information
There is no data on the need for dose adjustment in women up to 65 years of age. When using Climen ® in women older than 65 years, the information provided in the section "Special instructions" should be taken into account.
The use of Climen ® in women with impaired liver function has not been studied. The use of Climen ® in women with impaired renal function has not been studied. The available data indicate that there is no need for dose adjustment in such patients.
Medical examination and counseling
Before starting or resuming the use of Klimen®, you should familiarize yourself with the patient's medical history and conduct a physical and gynecological examination.The frequency and nature of such surveys should be based on existing standards of medical practice, with due consideration for the individual characteristics of each patient (but not less than once in 6 months) and should include blood pressure measurement, assessment of the mammary glands, abdominal and pelvic organs, including cytological examination of the epithelium of the cervix.
Influence on the results of laboratory studies
Admission of sex hormones can affect the biochemical parameters of the liver, thyroid, adrenal and kidney functions, for the transport of plasma proteins such as corticosteroid-binding globulin and lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis.