Ancelic® is not used for contraception.
If it is necessary to use contraception, non-hormonal methods should be used (with the exception of calendar and temperature methods). If you suspect a pregnancy, you should stop taking tablets until pregnancy is excluded (see section "Pregnancy and lactation").
If any of the following conditions or risk factors are present or worsened, the relationship between individual risk and benefit of treatment should be assessed before initiating or continuing to take Angelz®.
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 increases. If there is a high risk, Angelic® is contraindicated.
Venous thromboembolism
In a number of controlled randomized as well as epidemiological studies, an increased relative risk of venous thromboembolism (VTE) in background HRT, i.e. deep vein thrombosis or pulmonary embolism.Therefore, with the appointment of Angelz® 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 (availability VTE in close relatives at a relatively young age may indicate a genetic predisposition) and severe obesity. The risk of VTE also increases with age. 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 temporarily stopping the use of Angelz® should be addressed.
It should immediately stop treatment if symptoms of thrombotic disorders occur or if they are suspected.
Arterial thromboembolism
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 large-scale clinical trials 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 artery disease in women aged 50-59 years was found in the absence of a common positive effect among the population of the study. As a secondary result, in two large-scale clinical studies using EFS as monotherapy or in combination with MPA, a 30-40% increase in the risk of stroke was found. 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.
Endometrial cancer
With prolonged monotherapy with estrogens, the risk of developing hyperplasia or endometrial carcinoma increases. Research has confirmed, that the addition of gestagens reduces the risk of hyperplasia and endometrial cancer.
Mammary cancer
According to clinical trials 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 an earlier diagnosis, acceleration of the 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. The increased risk gradually decreases to the usual level for several (mostly five) years after the termination 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 alone or in a consistent combination with MPA,equal to 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 applies to other preparations 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.
Tumor of the liver
Against the background of the use of sex steroids, 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 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 studies, the risk can be reduced, if the use of drugs for HRT, containing EML, started in early menopause. It is not known whether this applies to other drugs for HRT.
Other states
Treatment should be discontinued immediately at the first appearance of migraine or frequent and unusually severe headaches, as well as the appearance of other symptoms - possible precursors of thrombotic stroke brain. The relationship between HRT and the development of clinically significant arterial hypertension not installed. 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 a clinically significant hypertension with the use of HRT, the abolition of HRT can be considered. In women with high blood pressure (BP), there may be some reduction in blood pressure when taking Angelz®. In women with normal arterial pressure, no significant changes in blood pressure occur.
With renal insufficiency, the potassium excretion ability can decrease.The intake of drospirenone does not affect the concentration of potassium in the plasma in patients with mild and moderate forms of renal insufficiency. The risk of hyperkalemia theoretically can not be excluded only in a group of patients in whom the concentration of potassium in plasma before treatment was determined at the upper limit of the norm, and which additionally take potassium-sparing drugs. With mild violations of liver function, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, it is necessary to observe the doctor, as well as periodic studies of liver function.
If the liver function indicators worsen, the preparation Angelique® 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 steroid hormones, the use of Angelz® should be stopped 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. Nevertheless, women suffering from diabetes mellitus should be monitored during HRT.
Some patients may develop unwanted estrogen stimulation, such as abnormal uterine bleeding. Frequent or persistent abnormal uterine bleeding against 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 assessment of the concentration prolactin).
In some cases, there may be a chloasma, especially in women with a history of pregnant women with chloasma. During therapy with Angelic®, women with a tendency to develop chloasma should avoid prolonged sun exposure or ultraviolet radiation.
The following conditions may occur or worsen in the background of HRT, and women with these conditions should be under the supervision of a doctor when carrying out HRT: 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.
Additional Information
There is no data on the need for dose adjustment in women up to 65 years of age. When using Angelz® in women older than 65 years, the information in the section "Dementia" should be taken into account.
In women with mild or moderate hepatic impairment, drospirenone is tolerated well.
In women with mild to moderate renal impairment, there was a slight slowdown in drospirenone excretion, which was not clinically significant.
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 steroids can promote the growth of some hormone-dependent tissues and tumors.
Medical examination and counseling
Before starting or resuming the use of Angelz® it is necessary to get acquainted with the history of the patient's illness and conduct a physical 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 not less than once in 6 months) and should include measurement of blood pressure, assessment of the state of the mammary glands, abdominal organs and pelvic organs, including cytological examination of the cervical epithelium.
In the presence of prolactinoma, a periodic determination of the concentration of prolactin is required.
Effect on the results of laboratory indicators.
Reception of sex steroids can affect the biochemical parameters of the function of the liver, thyroid, adrenal and kidney, on the content of plasma transport proteins, such as globulin, binding sex hormones and lipid or lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis. Angelica® does not adversely affect glucose tolerance.