Angelica micro pill №28

Indications

- hormone replacement therapy for the treatment of moderate to severe vasomotor symptoms associated with menopause in women with a untreated uterus.

Dosage and administration

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

Patients who switch to Angelique Micro from the combined drug for cyclic HRT regimen should begin reception after the end of the current cycle of therapy.

Each package is designed for a 28-day reception.

Take one pill daily. After the end of taking 28 pills from the current package, the next day they start taking the pills from the new package of Angelic Micro Micro (continuous HRT), taking the first pill on the same day of the week as the first pill from the previous package.

A pill is swallowed whole 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 pills at any particular time, she should stick to that time and beyond.

The forgotten pill must be taken as soon as possible. If more than 24 hours have elapsed after the usual reception time, an additional pill should not be taken. With the omission of several pills may develop bleeding from the vagina.

Use in some patient groups

In children

The drug is contraindicated for use in children and adolescents under 18 years of age.

In the elderly

Data indicating the need for dose adjustment in elderly patients are not available. Information on the use of the drug in women aged 65 years and older is presented in the section "Special Instructions".

With abnormal liver function

In women with impaired liver function, mild and moderate severity of drospirenone is well tolerated.

The drug is contraindicated for use in women with severely impaired liver function (see section "Contraindications").

In case of impaired renal function

In women with impaired mild to moderate renal function, there was a slight increase in the exposure of drospirenone, but it is assumed that it will not have clinical significance.

The drug is contraindicated for use in women with severely impaired renal function (see section "Contraindications").

Side effect

Most often, when using the Angelic Micro Micro, such undesirable drug reactions (NLR) were observed as breast tenderness, bleeding from the genital tract, and abdominal pain (less than in 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.

NLR described in clinical studies with the use of the drug Angelik Micro, 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).

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

* The term “venous and arterial thromboembolic complications” includes the following medical terms: peripheral deep vein occlusion, thrombosis and pulmonary embolism / occlusion, thrombosis, embolism and myocardial infarction / cerebral infarction and stroke, except for 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 Angelic Micro.

Also on 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 Angelica Micro and 5% of patients receiving placebo), nausea (3.3% and 1.1%, respectively), diarrhea ( 2.2% and 0.6%, respectively), vulvovaginal candidiasis (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 that are considered to be associated with the use of drugs from the group of combined agents 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 is a contraindication to the use of the drug Angelique Micro)

- cholelithiasis;

- dementia;

- endometrial cancer;

- arterial hypertension;

- abnormal liver function;

- hypertriglyceridemia;

- changes in glucose tolerance or insulin resistance;

- 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 is not exactly proven: epilepsy; benign breast diseases; bronchial asthma; porphyria; systemic lupus erythematosus; otosclerosis; chorea;

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

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

In addition to serious adverse events associated with hormone replacement therapy, see the section "Special instructions".

Contraindications

Angelic Micro Micro is contraindicated in the presence of any of the following conditions / diseases.If any of these conditions / diseases occur while taking Angelik Micro, then you should immediately stop using the drug.

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

- bleeding from the vagina of unspecified etiology;

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

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

- Liver tumors at present or in history (benign or malignant);

- severe liver disease;

- severe kidney disease now or in history or acute renal failure (until 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 thromboembolism of the pulmonary artery) now or in history;

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

- identified susceptibility 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 Angelic Micro;

- children's and teenage age up to 18 years;

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

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

It is necessary to take into account that estrogens alone or in combination with gestagens should be used with caution in the following diseases and conditions: the presence of risk factors for thrombosis and thromboembolism in the family history (thromboembolic complications of close relatives at a young age), the presence of risk factors for the emergence of estrogen-dependent tumors (for example,family 1st-degree relatives with breast cancer), endometrial hyperplasia history, smoking, hypercholesterolemia, obesity, systemic lupus erythematosus, dementia, gall bladder disease, thrombosis of the retinal vessels, moderate hypertriglyceridemia, edema in chronic heart failure , severe giiokaltsiemiya, endometriosis , bronchial asthma, epilepsy, migraine, liver hemangiomas, hyperkalemia, conditions predisposing to the development of hyperkalemia, medication that causes hyperkalemia - kalisbe diuretics, potassium preparations, ACE inhibitors, apioteizin II receptor antagonists and Heparin .

Use during pregnancy and lactation

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

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

Application for violations of the liver

In women with impaired liver function, mild and moderate severity of drospirenone is well tolerated.

The drug is contraindicated for use in women with severely impaired liver function.

Application for violations of kidney function

In women with impaired mild to moderate renal function, there was a slight increase in the exposure of drospirenone, but it is assumed that it will not have clinical significance.

The drug is contraindicated for use in women with severely impaired renal function.

Use in children

The drug is contraindicated for use in children and adolescents under 18 years of age.

special instructions

Angelic Micro Micro is not used for contraception.

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

If any of the following conditions / diseases or risk factors are present or worsening, the ratio of the individual risk and the benefits of treatment should be assessed, taking into account the possible need for it to be canceled, before starting or continuing to take Angelica Micro.

When prescribing HRT to women with several risk factors for thrombosis or a high degree of severity of one of the risk factors, consider the possibility of mutual enhancement of the action of risk factors and prescribed treatment for the development of thrombosis. In such cases, the total value of the existing risk factors increases. If there is a high risk, Angelique Micro is contraindicated.

Venous thromboembolism

In a number of controlled randomized, as well as epidemiological studies, an increased relative risk of venous thromboembolism (VTE) has been identified, i.e. deep vein thrombosis or pulmonary embolism, against the background of HRT. Therefore, when administering Angelique Micro to women with VTE risk factors, the ratio of the risk and benefit 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 immediate 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” planned and post-traumatic operations or extensive trauma. In the case of prolonged immobilization or planned surgical intervention, the drug should be stopped 4-6 weeks before the operation; resumption of administration is possible only after the woman’s physical activity is fully restored.

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

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

Arterial Thromboembolism

In the course of randomized controlled studies with long-term use of conjugated equine estrogens (CEE) 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 KLE 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 TLE, a potential decrease in the number of cases of IHD among women aged 50–59 years was found in the absence of a general positive effect among the cumulative population of the study. As a secondary result in two large-scale clinical studies using CEH, both in the form of monotraphy and in combination with MPA, an increase in the risk of developing a stroke by 30-40% was found. Therefore, it is not known whether this increased risk extends to drugs for hormone therapy containing other types of estrogens and irogestagens or nsperoralny ways of use.

Endometrial cancer

Long-term estrogen monotherapy increases the risk of endometrial hyperplasia or carcinoma. The addition of drospirenone prevents the development of estrogen-induced endometrial hyperplasia. If there is a history of endometrial hyperplasia, estrogens alone or in combination with gestagens should be used with caution.

Mammary cancer

According to clinical and observational studies, an increase in the relative risk of developing breast cancer in women using HRT for several years was found. This may be due to an 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 be reduced when treated 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 is gradually reduced to the usual level for several years after the termination of HRT.

Assumptions regarding the increase in the risk of developing breast cancer are made on the basis of 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, risk estimates of 0.77 (95% confidence interval: 0.59 - 1.01) or 1.24 (95% confidence interval: 1.01 - 1.54) were obtained after approximately 6 years of use HRTIt is not known whether this increased risk also applies to other drugs for HRT. 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 Angelique Micro for women with risk factors for the emergence of estrogen-dependent tumors (for example, relatives of the 1st degree of relationship with breast cancer), the ratio of risk and benefits 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 developing ovarian cancer. The relative risk of developing ovarian cancer with conjugated estrogens with MPA versus placebo was 1.58 (95% confidence interval: 0.77–3.24) after an average follow-up of 5.6 years. The absolute risk with conjugated estrogens with MPA versus placebo was 4 versus 3 cases per 10,000 women-years. The long-term use of estrogen-only drugs for HRT (5-10 years) has been associated with a slightly increased risk of ovarian cancer. Prolonged use of combined drugs for HRT may have the same or somewhat lower risk of developing ovarian cancer.

Liver tumor

Against the background of the use of sex hormones, which include drugs for hormone replacement therapy, in rare cases benign and, even more rarely, malignant tumors of the liver have been observed. In some cases, these tumors led to intra-abdominal bleeding, which is life threatening. For pain in the upper abdomen, an enlarged liver, or signs of intra-abdominal bleeding, a differential diagnosis should take into account the likelihood of a liver tumor.

Cholelithiasis

It is known that estrogen increases the lithogenicity of bile. The risk of developing cholelithiasis increases 2-4 times with estrogen therapy.

Dementia

There is limited data from clinical studies on the possible increase in the risk of dementia in women who are beginning to receive drugs containing CLE, 65 years of age and older. As observed in studies, the risk can be reduced if the administration of drugs for HRT containing KLE is begun in early menopause.

Other conditions / diseases

Treatment should be discontinued immediately for the first time when a migraine-like pain or frequent and unusually severe headache occurs, as well as with the appearance of other symptoms — possible harbingers of a cerebral thrombotic stroke.

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

In renal failure, the ability of potassium excretion may decrease. Receiving drospirenone does not affect the concentration of potassium in the blood plasma in patients with mild and moderate forms of renal failure. Theoretically, the risk of developing hyperkali-emipi cannot be excluded only in the group of patients whose plasma potassium concentration before treatment was determined at the upper limit of normal, and who additionally take potassium-sparing drugs.

In cases of non-severe abnormal liver function, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, physician observation is required, as well as periodic liver function tests.

With a deterioration in liver function performance, Angelicus Micro should be withdrawn.

When recurrent cholestatic jaundice or cholestatic itching, observed for the first time during pregnancy or prior sex hormone treatment, the administration of Angelicus Micro should be stopped immediately.

Special attention should be paid to women with increasing triglyceride concentrations. 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, the need to change the treatment regimen for diabetics during HRT does not usually occur. However, women with diabetes during HRT should be monitored.

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 the study of the endometrium in order to exclude diseases of an organic nature.

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

It is recommended that treatment be discontinued if endometriosis recurs with HRT.

If you suspect the presence of prolactinomas before the start of treatment, this disease should be excluded. If prolactinomas are detected, the patient should be under close medical supervision (including periodic assessment of prolactin concentration).

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

The following conditions / diseases may occur or be aggravated against the background of HRT, and women with these conditions / diseases during HRT should be under the supervision of a physician: 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 the symptoms of aygioedema.

Preclinical safety data

Preclinical data obtained in the course of standard studies to identify 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 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 taking of Angelique Micro, you should familiarize yourself 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, taking into account the individual characteristics of each patient (but not less than 1 time in 6 months) and should include blood pressure measurement, assessment of the mammary glands, abdominal organs and pelvic organs, including cytological examination of the cervical epithelium.

The impact on the results of laboratory parameters.

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

Angelique Micro does not adversely affect glucose tolerance.

Influence on ability to drive vehicles and mechanisms

Not found.

Overdose

Studies of acute toxicity did not reveal the risk of acute side effects if you accidentally take the drug in an amount that exceeds many times the daily therapeutic dose.

In clinical studies, the use of drospirenone up to 100 mg or combined estrogen / gestagen preparations with a content of 4 mg estradiol was well tolerated.

Symptoms that may occur with an overdose: nausea, vomiting, bleeding from the vagina.

There is no specific antidote, the treatment is symptomatic.

Drug interaction

Long-term treatment with drugs that induce liver enzymes (for example, some anticonvulsant and antimicrobial drugs) can increase the clearance of sex hormones and reduce their clinical efficacy, which is manifested by irregular bleeding. A similar property to induce liver enzymes has been found in hydantoins, barbiturates, primidone, Carbamazepine and rifampicin, the presence of this feature is also expected in oxcarbazepine, topiramate , felbamate and Griseofulvin . The maximum induction of enzymes is usually observed not earlier than in 2-3 weeks, but then it can persist for at least 4 weeks after stopping the drug.

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

The major 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 (for example, cimetidine, Ketoconazole , etc.) can inhibit estradiol metabolism.

The interaction of the drug AngelicaMicro with other drugs

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

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

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

Alcohol Interaction

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

Pharmacy sales terms

On prescription.

Terms and conditions of storage

At a temperature not higher than 30 ° C. Keep out of the reach of children.