Expiration date: 01/2027

Release form

28 pcs. - blisters (1) - cardboard packs.

Dosage form

Round biconvex yellow film-coated tablets embossed with "EL” in a regular hexagon on one side. Cross-sectional view: the core is white to almost white in color, the shell is yellow.

Composition

The core

Active ingredients: estradiol hemihydrate (micronized) in terms of estradiol 0.500 mg, drospirenone (micronized) 0.250 mg;

Excipients: lactose monohydrate - 50,450 mg, corn starch -14,400 mg, pre-gelatinized corn starch - 9,600 mg, povidone - 4,000 mg, magnesium stearate - 0,800 mg;

Shell

Yellow varnish 2,0000 mg or (alternatively): hypromellose (5 cP) 1.0112 mg, macrogol-6000 0.2024 mg, talc 0.2024 mg, titanium dioxide 0.4640 mg, iron oxide yellow dye 0.100 mg.

Pharmacotherapeutic group

combined anti-climacteric agent (estrogen + progestogen)

Pharmacodynamics

Angelic Micro contains 17?-estradiol, chemically and biologically identical to endogenous human estradiol, and the synthetic progestogen drospirenone. 17?-estradiol provides hormone replacement during and after menopause. The addition of drospirenone provides control over bleeding and counteracts the development of estrogen-induced endometrial hyperplasia.

Effects of estradiol

The extinction of ovarian function, accompanied by a decrease in the production of estrogens and progesterone, leads to the development of menopausal syndrome, which is characterized by vasomotor and organic symptoms. Hormone replacement therapy (HRT) is indicated to treat these symptoms.

Of all natural estrogens, estradiol is the most active and has the greatest affinity (binding force) with respect to estrogen receptors. Target organs for estrogens include, in particular, the uterus, hypothalamus, pituitary gland, vagina, mammary glands, bones (osteoclasts).

Other effects of estrogens include: a decrease in the concentration of insulin and glucose in the blood, receptor-mediated vasoactive effects and receptor-independent effects on vascular smooth muscle cells. Estrogen receptors have been identified in the heart and coronary arteries.

Oral administration of natural estrogens has advantages in cases of hypercholesterolemia due to its more beneficial effect on lipid metabolism in the liver.

Estrogen monotherapy has a dose-dependent stimulating effect on mitosis and endometrial proliferation. thus, it increases the incidence of endometrial hyperplasia and, consequently, the risk of developing endometrial cancer. In order to avoid the development of endometrial hyperplasia, a combination with irogestogens is necessary.

Effects of drospirenone

Drospirenone has pharmacodynamic effects very similar to natural progesterone.

Progestogenic activity

Drospirenone is a potent progestogen with a central inhibitory effect on the hypothalamus-pituitary-gonadal system. In women of reproductive age, drospirenone has a contraceptive effect; when drospirenone is administered as a monopreparation, ovulation is suppressed. The threshold dose of drospirenone for ovulation suppression is 2 mg / day. Complete transformation of the previously exposed endometrium occurs after taking a dose of 4 or 6 mg / day for 10 days (= 40-60 mg per cycle).

Continuous hormone replacement therapy with Angelic Micro allows you to avoid regular "withdrawal" bleeding, which is observed with cyclic or phase HRT. During the first months of treatment, bleeding and "spotting" are quite common, but their frequency decreases over time.

Antimineralocorticoid activity

Drospirenone has the ability to compete with aldosterone antagonism. Women who received drospirenone in addition to estradiol in a clinical study were less likely to have peripheral edema than those who took estradiol alone.

Antiandrogenic activity

Like natural progesterone, drospirenone has antiandrogenic properties.

Effect on carbohydrate metabolism

Drospirenone has neither glucocorticoid nor antiglucocorticoid activity and has no effect on glucose tolerance and insulin resistance. When using Angelik Micro, glucose tolerance is not impaired.

Other properties

Observational studies suggest that among postmenopausal women, the incidence of colon cancer decreases when using HRT. The mechanism of action is still unclear.

Pharmacokinetics

Estradiol

Absorption

After oral administration, estradiol is rapidly and completely absorbed. During absorption and "first passage" through the liver, estradiol is largely metabolized, for example, into estrone, estriol and estrone sulfate. After oral administration, the bioavailability of estradiol is about 5%. The maximum plasma concentration of estradiol, approximately 16 pg/ ml, is usually reached 2-8 hours after taking the tablet. Food intake does not affect the bioavailability of estradiol.

Distribution

After oral administration of Angelik Micro, there is a gradual change in the concentration of estradiol in blood plasma for 24 hours. Due to the circulation of estrogen sulfates and glucuronides in a wide range on the one hand, intestinal-hepatic recirculation on the other, the half-life of estradiol is a complex parameter that depends on all these processes and is in the range of 13-20 h after ingestion.

Estradiol binds non-specifically to serum albumin and specifically to sex hormone binding globulin (SHBG). The free fraction of estradiol in plasma is approximately 1-2%, and the fraction of the substance bound by SHBG is in the range of 40-45%. After oral administration, estradiol causes the formation of SHBG, which affects the distribution of serum proteins, causing an increase in the SHBG-bound fraction and a decrease in albumin-bound and unbound fractions, indicating the non-linearity of the pharmacokinetics of estradiol after taking Angelic Micro. The apparent volume of estradiol distribution after a single intravenous injection is about 1 l/kg.

Metabolism

Estradiol is metabolized mainly in the liver, as well as partially in the intestines, kidneys, skeletal muscles and target organs. These processes are accompanied by the formation of estrone, estriol, catecholestrogens, as well as sulfate and glucuronide conjugates of these compounds, each of which has significantly less estrogenic activity or no estrogenic activity at all. The concentration of estrone in plasma is 6 times higher than estradiol. The plasma concentration of estrone conjugates is 26 times higher than the corresponding concentrations of free estrone.

Elimination

The clearance of estradiol from plasma is about 30 ml/min/kg. Estradiol metabolites are excreted by the kidneys and through the intestine with a half-life of approximately 24 hours.

Equilibrium concentration

With daily use of Angelic Micro, the equilibrium concentration of estradiol in blood plasma is reached after about 5 days. On average, the concentration of estradiol in blood plasma ranges from 12 pg/ml (minimum level) to 29 pg/ml (maximum level).Drospirenone

Absorption

After oral administration, drospirenone is rapidly and completely absorbed. Bioavailability after oral administration is 76-85%. Food intake does not affect the bioavailability of drospirenone.

Distribution

The maximum plasma concentration of drospirenone, which is about 3.35 ng / ml, is reached approximately 1 hour after a single and repeated intake of 0.25 mg of drospirenone. After that, there is a two-phase decrease in the concentration of drospirenone in plasma with a final half-life of about 35-39 hours. Drospirenone binds to serum albumin and does not bind to SHBG and corticoid-binding globulin. About 3-5% of the total plasma concentration of drospirenone is not associated with protein.

Metabolism

After oral administration, drospirenone is largely metabolized. The main metabolites in human plasma are the acidic form of drospirenone and 4.5-dihydro-drospirenone-Z-sulfate. Both metabolites are formed without the participation of the cytochrome P450 system. Based on in vitro data, drospirenone is slightly metabolized by the cytochrome P450 ZA4 system.

Elimination

The clearance of drospirenone from plasma is 1.2-1.5 ml/min/kg. Some part of the received dose is excreted unchanged. Most of the dose is excreted by the kidneys and through the intestine in the form of metabolites in a ratio of 1.2:1.4 with a half-life of about 40 hours.

Equilibrium concentration

The equilibrium concentration is reached after about 10 days of daily intake of the drug Angelic Micro. Due to the long half-life of drospirenone, the equilibrium concentration is 2-3 times higher than the concentration after a single dose.

Indications

— hormone replacement therapy for the treatment of moderate to severe vasomotor symptoms associated with menopause in women with an unopened uterus.

Contraindications

Taking Angelic Micro is contraindicated in the presence of any of the following conditions / diseases. If any of these conditions / diseases occur while taking Angelic Micro, then the use of the drug should be stopped immediately.

— pregnancy or breastfeeding (see the section "Use during pregnancy and breastfeeding");

— bleeding from the vagina of unspecified etiology;

— confirmed or suspected diagnosis of breast cancer or a history of breast cancer;

— confirmed or suspected diagnosis of hormone-dependent precancerous disease or hormone-dependent malignant tumor;

— liver tumors currently or in the anamnesis (benign or malignant);

— severe liver diseases;

— severe kidney disease currently or in the anamnesis or acute renal failure (before normalization of renal function);

— acute arterial thrombosis or thromboembolism (for example, myocardial infarction, stroke), angina pectoris;

— deep vein thrombosis in the acute stage, venous thromboembolism (including pulmonary embolism) currently or in the anamnesis;

— the presence of a high risk of venous and arterial thrombosis (see the section "Special instructions");

— revealed predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);

— adrenal insufficiency;

— untreated hyperplasia;

— porphyria;

— severe hypertriglyceridemia;

— hypersensitivity to the components of the drug Angelic Micro;

— children and adolescents under 18 years of age;

— congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With caution: Angelique Micro should be prescribed with caution for the following diseases: congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), cholestatic jaundice or cholestatic itching during previous pregnancy, endometriosis, uterine fibroids, diabetes mellitus (see "Special instructions").

It should be taken into account that estrogens alone or in combination with progestogens should be used with caution in the following diseases and conditions: the presence of risk factors for thrombosis and thromboembolism in a family history (thromboembolic complications in close relatives at a young age), the presence of risk factors for the occurrence of estrogen-dependent tumors (for example, relatives of the 1st degree of kinship with breast cancer), a history of endometrial hyperplasia, smoking, hypercholesterolemia, obesity, systemic lupus erythematosus, dementia, gallbladder diseases, retinal vascular thrombosis, moderate hypertriglyceridemia, edema in chronic heart failure, severe hypocalcemia, endometriosis, bronchial asthma, epilepsy, migraine, liver hemangiomas, hyperkalemia, conditions predisposing to the development of hyperkalemia, taking medications that cause hyperkalemia - potassium-sparing diuretics, potassium preparations, ACE inhibitors, receptor antagonists apgiotheisin II and heparin.

Use during pregnancy and lactation

HRT is contraindicated during pregnancy or during breastfeeding. If pregnancy is detected while taking Angelic Micro, the drug should be discontinued immediately.

A small amount of sex hormones may be excreted in breast milk.

Method of administration and dosage

If a woman does not take estrogens or switches to Angelique Micro from another combination drug for continuous use, then she can start treatment at any time.

Patients who switch to Angelic Micro from a combination drug for a cyclic HRT regimen should start taking it after the end of the current cycle of therapy.

Each package is designed for a 28-day reception.

One tablet should be taken daily. After finishing taking 28 tablets from the current package, the next day they begin taking tablets from the new package of Angelik Micro (continuous HRT), taking the first tablet on the same day of the week as the first tablet from the previous package.

The tablet is swallowed whole, washed down with a small amount of liquid. The pills are taken regardless of the meal. The time of day when a woman takes the drug does not matter, however, if she started taking the pills at any particular time, she should stick to this time further.

The forgotten pill must be taken as soon as possible. If more than 24 hours have passed after the usual intake time, an additional tablet should not be taken. If you skip several pills, bleeding from the vagina may develop.

For more information, see the instructions

Side effects

The most common adverse drug reactions (NLR) observed when using Angelik Micro were breast tenderness, bleeding from the genital tract, abdominal pain (less than 2% of patients).

Irregular bleeding usually disappears with prolonged therapy. The frequency of bleeding decreases with increasing duration of treatment.

Serious adverse reactions include arterial and venous thromboembolic complications and breast cancer.

The NLR described in clinical trials using the drug Angelic Micro are presented in the table below. The following concepts are used to determine frequency: very frequent (> 1/10), frequent (from > 1/100 to < 1/10), infrequent (from > 1/1 000 to < 1/100) and rare (from > 1/10 000 to < 1/1 000).

Mental disorders emotional lability are often

Disorders of the nervous system migraine infrequently

Vascular disorders venous and arterial thromboembolic complications* infrequently

Gastrointestinal disorders abdominal pain is common

Disorders of the genitals and breast pain in the mammary glands (including discomfort in the mammary glands) often

bleeding from the genital tract cervical polyp is infrequent

breast cancer**

In clinical studies, adverse events were encoded using the MedDRA dictionary. Different MedDRA terms reflecting the same medical phenomenon were grouped into one adverse phenomenon in order to avoid duplication or ambiguity in describing the true effect.

* The concept of "venous and arterial thromboembolic complications" includes the following medical terms: occlusion of peripheral deep veins, thrombosis and embolism/occlusion of pulmonary vessels, thrombosis, embolism and infarction/myocardial infarction/cerebral infarction and stroke, with the exception of hemorrhagic.

** Data on the relationship with the use of the drug were obtained from the results of post-marketing observations; frequency data were obtained from clinical studies using the drug Angelik Micro.

Also, for venous and arterial thromboembolic complications, breast cancer and migraine, see the sections "Contraindications" and "Special instructions".

In one placebo-controlled study, adverse reactions were reported with a frequency of > 2%: headache (6% of patients taking Angelic Micro and 5% of patients receiving placebo), nausea (3.3% and 1.1%, respectively), diarrhea (2.2% and 0.6%, respectively), candidiasis vulvovaginitis (5.5% and 0.6%, respectively), peripheral edema (2.2% and 1.1%, respectively).

Adverse reactions that occur in isolated cases, or symptoms that develop very long after the start of therapy and which are considered to be associated with the use of drugs from the group of combined drugs for continuous hormone replacement therapy, are listed below:

— liver tumors (benign and malignant);

— hormone-dependent malignant tumors or hormone-dependent precancerous diseases (if it is known that the patient has similar conditions / diseases, this serves as a contraindication to the use of the drug Angelic Micro)

— cholelithiasis;

— dementia;

— endometrial cancer;

— arterial hypertension;

— impaired liver function;

— hypertriglyceridemia;

— changes in glucose tolerance or insulin resistance;

— an increase in the size of uterine fibroids;

— reactivation of endometriosis;

— prolactinoma;

— Chloasma;

— jaundice and/or itching associated with cholestasis;

— the occurrence or deterioration of conditions/ diseases for which the relationship with the use of HRT has not been precisely proven: epilepsy; benign breast diseases; bronchial asthma; porphyria; systemic lupus erythematosus; otosclerosis; minor chorea;

— in women with hereditary angioedema, exogenous estrogens may contribute to exacerbation of symptoms;

— hypersensitivity (including symptoms such as rash and urticaria).

For more information about serious adverse events associated with hormone replacement therapy, see the section "Special instructions".

Drug interaction

Long-term treatment with drugs that induce liver enzymes (for example, some anticonvulsants and antimicrobials) can increase the clearance of sex hormones and reduce their clinical effectiveness, which is manifested by irregular bleeding. A similar property of inducing liver enzymes has been found in hydantoines, barbiturates, primidone, carbamazepine and rifampicin, the presence of this feature is also assumed in oxcarbazepine, topiramate, felbamate and griseofulvin. The maximum induction of enzymes is usually observed no earlier than 2-3 weeks, but then it can persist for at least another 4 weeks after discontinuation of the drug.

In rare cases, against the background of concomitant administration of certain antibiotics (for example, penicillin and tetracycline groups), a decrease in the concentration of estradiol was observed.

The main metabolites of drospirenone are formed in plasma without the participation of the cytochrome P450 system. Therefore, the effect of cytochrome P450 inhibitors on the metabolism of drospirenone is unlikely. However, CYP3A4 inhibitors (e.g. cimetidine, ketoconazole, etc.) can inhibit estradiol metabolism.

Interaction of the drug Angelic Micro with other drugs

Based on in vitro interaction studies, as well as an in vivo study on female volunteers taking 3 mg of drospirenone per day in combination with omeprazole, simvastatin or midazolam, it can be concluded that a clinically significant interaction of drospirenone with cytochrome P450 on the metabolism of other medicinal substances is unlikely.

Pharmacodynamic interaction with antihypertensive agents and nonsteroidal anti-inflammatory drugs (NSAIDs)

An increase in serum potassium concentration is unlikely when taking Angelic Micro and nonsteroidal anti-inflammatory drugs (NSAIDs) or antihypertensive drugs in combination. The combined use of the three above types of drugs may lead to a slight increase in serum potassium concentration, more pronounced in women with diabetes mellitus.

Interaction with alcohol

Excessive alcohol consumption during HRT can lead to an increase in the concentration of circulating estradiol.

Special instructions

The drug Angelic Micro is not used for the purpose of contraception.

If pregnancy is suspected, you should stop taking the pills until pregnancy is excluded (see the section "Use during pregnancy and breastfeeding").

If any of the following conditions / diseases or risk factors are present or worsen, before starting or continuing to take Angelik Micro, the ratio of individual risk and benefit of treatment should be assessed, taking into account the possible need for its cancellation.

When prescribing HRT to women who have several risk factors for thrombosis or a high degree of severity of one of the risk factors, the possibility of mutual enhancement of the effect of risk factors and prescribed treatment on the development of thrombosis should be considered. In such cases, the total value of the existing risk factors increases. If there is a high risk, Angelic Micro is contraindicated.

Venous thromboembolism

A number of controlled, randomized, and epidemiological studies have revealed an increased relative risk of venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism, against the background of HRT. Therefore, when prescribing Angelik Micro to women with VTE risk factors, the risk-benefit ratio of treatment should be carefully weighed and discussed with the patient.

High risk factors for VTE include an 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/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" elective and post-traumatic surgeries, or extensive trauma. In case of prolonged immobilization or planned surgical intervention, the drug should be discontinued 4-6 weeks before surgery, resumption of administration is possible only after full recovery of the woman's motor activity.

Treatment should be stopped immediately if symptoms of thrombotic disorders appear or if they are suspected of occurring.

It is necessary to assess the ratio of individual risk and benefit of treatment in women using HRT drugs in combination with anticoagulants.

Arterial thromboembolism

In the course of randomized controlled trials with long-term use of conjugated equine estrogens (CLE) and medroxyprogesterone acetate (MPA), no evidence of a positive effect on the cardiovascular system was obtained. In large-scale clinical studies of the combination of CLE and MPA, a possible increase in the risk of coronary heart disease (CHD) in the first year of use was revealed, followed by the absence of a positive effect. In one large clinical study using only CLE, a potential decrease in the number of cases of coronary heart disease among women aged 50-59 years was found in the absence of an overall positive effect among the total study population. As a secondary result, two large-scale clinical trials using CLE both in the form of monotherapy and in combination with MPA revealed an increase in the risk of stroke by 30-40%. Therefore, it is not known whether this increased risk applies to HRT drugs containing other types of estrogens and irogestogens or to oral methods of administration.

Endometrial cancer

With prolonged monotherapy with estrogens, the risk of developing endometrial hyperplasia or carcinoma increases. The addition of drospirenone prevents the development of endometrial hyperplasia caused by estrogens. If there is a history of endometrial hyperplasia, estrogens alone or in combination with progestogens should be used with caution.

Breast cancer

According to clinical and observational studies, an increase in the relative risk of breast cancer has been found in women using HRT for several years. This may be due to earlier diagnosis, accelerated growth of an existing tumor on the background of HRT, or a combination of both factors. The relative risk increases with increasing duration of therapy, but may be absent or reduced with estrogen-only treatment. This increase is comparable to an increase in the risk of breast cancer in women with a later onset of natural menopause, as well as with obesity and alcohol abuse. The increased risk gradually decreases to the usual level within a few years after the cessation of HRT.

Assumptions about the increased risk of breast cancer are made based on the results of more than 50 epidemiological studies (the risk varies from 1 to 2).

In two large-scale randomized trials with CLE as monotherapy or in combination with MPL, calculated risk indicators were obtained equal to 0.77 (95% confidence interval: 0.59 - 1.01) or 1.24 (95% confidence interval: 1.01 - 1.54) after about 6 years of HRT use. It is not known whether this increased risk also applies to other HRT drugs. HRT increases the mammographic density of the mammary glands, which in some cases may have a negative effect on the X-ray detection of breast cancer.

When prescribing Angelik Micro to women with risk factors for the occurrence of estrogen-dependent tumors (for example, relatives of the 1st degree of kinship with breast cancer), the risk-benefit ratio of treatment should be carefully weighed and discussed with the patient.

Ovarian cancer

A study of estrogen in combination with progestin showed a statistically insignificant increase in the risk of ovarian cancer. The relative risk of ovarian cancer when using conjugated estrogens with MPA compared with placebo was 1.58 (95% confidence interval: 0.77-3.24) after an average follow-up period of 5.6 years. The absolute risk when using conjugated estrogens with MPA compared with placebo was 4 versus 3 cases per 10,000 women-years. Long-term use of estrogen-only HRT drugs (5-10 years) was associated with a slightly increased risk of ovarian cancer. Long-term use of combined HRT drugs may have the same or slightly lower risk of ovarian cancer.

Liver tumor

Against the background of the use of sex hormones, which include HRT drugs, benign and even less often malignant liver tumors were observed in rare cases. In some cases, these tumors led to intra-abdominal bleeding, which is life-threatening. In case of pain in the upper abdomen, enlarged liver or signs of intra-abdominal bleeding, differential diagnosis should take into account the likelihood of a liver tumor.

Cholelithiasis

Estrogens are known to increase the lithogenicity of bile. The risk of developing cholelithiasis increases 2-4 times with estrogen treatment.

Dementia

There is limited clinical research data on a possible increased risk of dementia in women starting to take drugs containing CLE at the age of 65 and older. As has been observed in studies, the risk may be reduced if the use of HRT drugs containing CLE is started in early menopause.

Other conditions/diseases

Treatment should be stopped immediately if migraine-like pain or frequent and unusually severe headache appear for the first time, as well as if other symptoms appear - possible precursors of a thrombotic stroke of the brain.

The relationship between HRT and the development of clinically pronounced hypertension has not been established. In women taking HRT, a slight increase in blood pressure has been described, a clinically significant increase is rarely noted. However, in some cases, with the development of persistent clinically significant arterial hypertension on fne taking HRT, the abolition of HRT may be considered.

With renal insufficiency, the ability to remove potassium may decrease. Taking drospirenone does not affect the concentration of potassium in blood plasma in patients with mild and moderate forms of renal insufficiency. Theoretically, the risk of developing hyperkalemia cannot 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 who additionally take potassium-sparing drugs.

In case of mild liver dysfunction, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, medical supervision is necessary, as well as periodic studies of liver function.

If liver function indicators deteriorate, the drug Angelik Micro should be discontinued.

In case of recurrence of cholestatic jaundice or cholestatic itching, observed for the first time during pregnancy or previous treatment with sex hormones, Angelic Micro should be stopped immediately.

Special monitoring of women is necessary when the concentration of triglycerides increases. In such cases, the use of HRT can cause a further increase in the concentration of triglycerides in the blood, which increases the risk of acute pancreatitis.

Although HRT can affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the treatment regimen for diabetic patients during HRT. However, women with diabetes mellitus should be monitored during HRT.

Some patients may develop undesirable manifestations of estrogen stimulation, for example, abnormal uterine bleeding. Frequent or persistent pathological uterine bleeding during treatment is an indication for endometrial examination in order to exclude an organic disease.

Under the influence of estrogens, uterine fibroids can increase in size. In this case, the treatment should be discontinued

It is recommended to discontinue treatment with the development of a recurrence of endometriosis on the background of HRT.

If prolactinoma is suspected, this disease should be excluded before starting treatment. If prolactinoma is detected, the patient should be under close medical supervision (including periodic assessment of prolactin concentration).

In some cases, chloasma may occur, especially in women with a history of pregnant chloasma. During therapy with Angelic Micro, women with a tendency to develop chloasma should avoid prolonged exposure to the sun or ultraviolet radiation.

The following conditions/diseases may occur or worsen against the background of HRT, and women with these conditions /diseases should be under the supervision of a doctor during HRT: epilepsy; benign breast tumor; bronchial asthma; migraine; porphyria; otosclerosis; systemic lupus erythematosus, chorea minor.

In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen the symptoms of aigioedema.

Preclinical safety data

Preclinical data obtained during standard studies for the detection of toxicity with repeated doses of the drug, as well as genotoxicity, carcinogenic potential and toxicity to the reproductive system, do not indicate the presence of a special risk to humans. However, 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 taking Angelik Micro, you should familiarize yourself in detail with the patient's medical history and conduct a general medical and gynecological examination. The frequency and nature of such examinations should be based on existing standards of medical practice, with the necessary consideration of the individual characteristics of each patient (but at least once every 6 months) and should include blood pressure measurement, assessment of the condition of the mammary glands, abdominal organs and pelvic organs, including cytological examination of the cervical epithelium.

The effect on the results of laboratory parameters.

The intake of sex hormones can affect the biochemical parameters of liver, thyroid, adrenal and kidney function, the plasma concentration of transport proteins such as globulin binding sex hormones and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis.

Angelique Micro has no negative effect on glucose tolerance.

Influence on the ability to drive vehicles and mechanisms

It has not been revealed.

Overdose

Acute toxicity studies have not revealed the risk of acute side effects when accidentally taking the drug in an amount many times higher than the daily therapeutic dose.

In clinical studies, the use of drospirenone up to 100 mg or combined estrogen/progestogenic drugs containing 4 mg of estradiol was well tolerated.

Symptoms that may occur in case of overdose: nausea, vomiting, bleeding from the vagina.

There is no specific antidote, the treatment is symptomatic.

Storage temperature

from 2℃ to 25℃