The preparation Angelique® Micro is not used for the purpose of contraception.
If you suspect a pregnancy, you should stop taking the pills until pregnancy is excluded (see "Pregnancy and Breastfeeding").
In the presence or deterioration of any of the following conditions or diseases or risk factors, before you start or continue taking Angelica® Micro, you should assess the relationship between individual risk and the benefits of treatment, given the possible need for withdrawal.
When HRT is prescribed for women who have several risk factors for thrombosis or a high degree of severity of one of the risk factors, consideration should be given to the possibility of a mutually reinforcing effect of risk factors and prescribed treatment on the development of thrombosis. In such cases, the total value of the available risk factors is increased. If there is a high risk, the preparation Angelique® Micro is contraindicated.
In a number of controlled randomized, as well as epidemiological studies, an increased relative risk of venous thromboembolism (VTE), i.deep vein thrombosis or pulmonary embolism, against the background of HRT. Therefore, with the appointment of Angelica® Micro to women with risk factors for VTE, the risk-benefit ratio of treatment should be carefully weighed and discussed with the patient.
Factors of high risk of VTE development include individual and family history (the presence of VTE in close relatives at a relatively young age may indicate a genetic predisposition) and obesity with a body mass index of more than 30 kg / sq. m. 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 post-traumatic surgeries or extensive trauma. In case of prolonged immobilization or planned surgical intervention, the drug should be stopped 4 to 6 weeks before the operation, the resumption of reception is possible only after the full restoration of the motor activity of the woman.
It should immediately stop treatment if symptoms of thrombotic disorders occur or if they are suspected.
It is necessary to estimate the ratio of individual risk and benefit of treatment in women using HRT drugs together with anticoagulants.
In randomized controlled trials with long-term use of conjugated equine estrogens (EEG) and medroxyprogesterone acetate (MPA), there was no evidence of a positive effect on the cardiovascular system. In a large-scale clinical study of the combination of CLA and MPA, a possible increase in the risk of coronary heart disease (CHD) in the first year of use was observed with a subsequent lack of positive effect. In one major clinical study, using only EFE, a potential reduction in the incidence of coronary artery disease 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 EFS, both in monotherapy and in combination with MPA, the risk of stroke was increased by 30-40%.Therefore, it is not known whether this increased risk extends to preparations for HRT containing other types of estrogens and progestogens or to non-oral uses.
With prolonged monotherapy with estrogens, the risk of developing hyperplasia or endometrial carcinoma increases. The addition of drospirenone prevents estrogen-induced development of endometrial hyperplasia. In the presence of endometrial hyperplasia in an anamnesis, estrogen alone or in combination with gestagens should be used with caution.
According to clinical and 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 therapy, but may be absent or 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. Increased risk is gradually reduced to the usual level at for several years after discontinuation of HRT.
Assumptions for an increased risk of developing breast cancer are based on the results of more than 50 epidemiological studies (the risk varies from 1 to 2).
In two large-scale, randomized trials with EFS as monotherapy or in combination with MPA, estimated risk values of 0.77 (95% confidence interval: 0.59-1.01) or 1.24 (95% confidence interval: 1 , 01-1.54) after approximately 6 years of HRT use. It is not known whether this increased risk also extends to other drugs for HRT.
HRT increases the mammographic density of the mammary glands, which in some cases may have a negative impact on the radiographic detection of breast cancer.
When prescribing Angelz® To micro-women with risk factors for the occurrence of estrogen-dependent tumors (for example, relatives of the first degree of kinship with breast cancer), the risk-benefit ratio should be carefully weighed and discussed with the patient.
A study of estrogen in combination with a progestin showed a statistically insignificant increase in the risk of developing ovarian cancer. The relative risk of ovarian cancer in the use of conjugated estrogens with MPA versus placebo was 1.58 (95% confidence interval: 0.77-3.24) after an average follow-up period of 5.6 years. The absolute risk for the use of conjugated estrogens with MPA versus placebo was 4 vs. 3 cases per 10 000 women-years. Long-term use of drugs for HRT containing estrogens alone (5-10 years) was associated with a slightly increased risk of ovarian cancer. Long-term use of combined drugs for HRT may have the same or slightly lower risk of developing ovarian cancer.
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 intra-abdominal bleeding, which poses a threat to life. 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.
It is known that estrogens increase the lithogenicity of bile. The risk of developing cholelithiasis is increased 2-4 times when treated with estrogens.
There are limited data from clinical studies on the possible increase in the risk of dementia in women starting to take drugs containing EML at the age of 65 years and over. As observed in the studies, the risk may be reduced if the use of drugs for HRT containing PLE is started in early menopause.
- Other conditions or diseases
Immediately discontinue treatment when migraine-like pain occurs for the first time, or a frequent and unusually severe headache, as well as other symptoms-possible precursors of thrombotic cerebral stroke.
The relationship between HRT and the development of clinically significant arterial hypertension has not been established. Women taking HRT, described a small increase in blood pressure, a clinically significant increase is noted rarely. However, in some cases, with the development of HRT in the presence of a clinically significant hypertension, cancellation of HRT can be considered.
With renal insufficiency, the potassium excretion ability can decrease. The intake of drospirenone does not affect the concentration of potassium in the blood plasma in patients with mild and moderate forms of renal insufficiency. The risk of developing hyperkalemia theoretically can not be excluded only in the group of patients in whom the concentration of potassium in blood plasma before treatment was determined at the upper limit of the norm and which additionally take potassium-sparing drugs.
In case of mild violations of the 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.
If the liver function is worsening, the preparation Angelique® Micro should be canceled.
In case of recurrence of cholestatic jaundice or cholestatic pruritus observed for the first time during pregnancy or previous treatment with sex hormones, the preparation of Angelica® Micro must be discontinued immediately.
Special monitoring of women is necessary with an increase in the concentration of triglycerides. In such cases, the use of HRT may cause a further increase in the concentration of triglycerides in the blood, which increases the risk of acute pancreatitis.
Although HRT may affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the regimen for the treatment of diabetic patients with HRT. However, women with diabetes mellitus should be monitored for HRT.
Some patients may develop unwanted estrogen stimulation, for example, a pathological uterine bleeding. Frequent or persistent abnormal uterine bleeding on the background of treatment is an indication for endometrial research in order to eliminate organic diseases.
Under the influence of estrogen, uterine fibroids may increase in size. In this case, treatment should be discontinued.
It is recommended to stop treatment with the development of recurrence of endometriosis in the background of HRT.
If you suspect a prolactinoma before starting treatment, you should exclude this disease. In case of detection of prolactinoma, the patient should be under close medical supervision (including periodic evaluation of prolactin concentration).
In some cases, there may be a chloasma, especially in women with a history of pregnant women with chloasma.During Angelge® treatment, micro women with a tendency to develop chloasma should avoid prolonged sun exposure or ultraviolet radiation.
The following conditions or diseases can occur or worsen in the presence of HRT, and women with these conditions or diseases should be under the supervision of a physician during epilepsy: epilepsy; benign breast tumor; 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.
Preclinical safety data
Preclinical data obtained from routine studies to detect toxicity with multiple doses of the drug, as well as genotoxicity, carcinogenic potential, and toxicity to the reproductive system, do not indicate a particular risk to humans. Nevertheless, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.
Medical examination and counseling
Before starting or resuming the use of Angelica® Micro, you should familiarize yourself with the history of the patient's illness and conduct a general medical and gynecological examination. The frequency and nature of such surveys should be based on existing standards of medical practice, with the necessary consideration of the individual characteristics of each patient (but at least every 6 months) and include a measurement of blood pressure, assessment of the mammary glands, abdominal organs and pelvic organs, including cytological study of the epithelium of the cervix.
Effect on the results of laboratory indicators.
Admission of sex hormones can affect the biochemical parameters of the liver, thyroid, adrenal and kidney functions, plasma concentrations of transport proteins such as globulin, binding sex hormones and lipid or lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis. Angelica® Micro does not adversely affect glucose tolerance.