Angeliq Micro tabs #28

Angeliq Micro instruction for use

You can buy Angeliq Micro here

pharmachologic effect

Angeliq Micro contains 17-estradiol, chemically and biologically identical to endogenous human estradiol, and 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 estrogen and progesterone, leads to the development of the menopausal syndrome, which is characterized by vasomotor and organic symptoms. Hormone replacement therapy (HRT) is indicated for the treatment of these symptoms.
Of all the natural estrogens, estradiol is the most active and has the highest affinity (binding force) for estrogen receptors. Target organs for estrogens include, in particular, the uterus, hypothalamus, pituitary, vagina, mammary glands, bones (osteoclasts).
Other effects of estrogen include: a decrease in the concentration of insulin and glucose in the blood, receptor-mediated vasoactive effects, and receptor-independent effects on smooth muscle cells of the vascular walls. Estrogen receptors have been identified in the heart and coronary arteries.
Oral administration of natural estrogens has advantages in cases of hypercholesterolemia due to a more favorable effect on lipid metabolism in the liver.
Estrogen monotherapy has a dose-dependent stimulating effect on mitoses and endometrial proliferation and. thus, it increases the incidence of endometrial hyperplasia and, consequently, the risk of endometrial cancer. In order to avoid the development of endometrial hyperplasia, a combination with irogestagens is necessary.

Effects of Drospirenone

Drospirenone has very similar pharmacodynamic effects to natural progesterone.

Progestogenic activity

Drospirenone is a powerful progestogen with a central inhibitory effect on the hypothalamus-pituitary-gonad system. In women of reproductive age, drospirenone has a contraceptive effect; With the introduction of drospirenone monopreparation ovulation is suppressed. The threshold dose of drospirenone to suppress ovulation is 2 mg / day. Complete transformation of the endometrium exposed to estrogen occurs after taking a dose of 4 or 6 mg / day for 10 days (= 40-60 mg per cycle).
Continuous hormone replacement therapy with Angeliq Micro allows you to avoid the regular “withdrawal” bleeding that occurs with cyclic or phase HRT. During the first months of treatment, bleeding and "spotting" are fairly common, but their frequency decreases with time.

Antimineralocorticoid activity

Drospirenone is capable of competitive antagonism with aldosterone. Women who, in the framework of a clinical study, received drospirenone in addition to estradiol, less frequently experienced peripheral edema than estradiol.

Antiandrogenic activity

Like natural progesterone, drospirenone has antiandrogenic properties.

Effect on carbohydrate metabolism

Drospirenone does not have PI glucocorticoid or anti-glucocorticoid activity and does not affect glucose tolerance and insulin resistance. When using the drug Angeliq Micro glucose tolerance is not violated.

Other properties

Observational studies suggest that among women in postmenopausal women with HRT, the incidence rate of colon cancer is reduced. The mechanism of action is still unclear.

Indications for Angeliq Micro

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

Contraindications

Angeliq Micro  is contraindicated in the presence of any of the following conditions / diseases. If any of these conditions / diseases occur while taking Angeliq Micro, then you should immediately stop using the drug.
- pregnancy or breastfeeding period (see 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 at the present time 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) currently 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, deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);
- adrenal insufficiency;
- untreated hyperplasia;
- porphyria;
- severe hypertriglyceridemia;
- Hypersensitivity to the components of Angeliq Micro;
- children's and teenage age up to 18 years;
- congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Precautions: Angeliq Micro should be prescribed with caution in the following diseases: congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), cholestatic jaundice or cholestatic itch during a previous pregnancy, endometriosis, uterine fibroids, 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, relatives of the 1st degree of relationship with breast cancer), history of endometrial hyperplasia, smoking, hypercholesterolemia, obesity, systemic lupus erythematosus, dementia, gallbladder disease, retinal vascular thrombosis, moderate hypertriglyceridemia, edema in chronic heart failure, severe hyeocalcemia, endometriosis, bronchial asthma, epilepsy, migraine, liver hemangioma, hyperkalemia, conditions predisposing causing hyperkalemia - potassium-saving diuretics, potassium preparations, ACE inhibitors, apgioteizin II receptor antagonists and heparin.

Use during pregnancy and lactation

HRT is contraindicated during pregnancy or during breastfeeding. If pregnancy is detected while taking Angeliq Micro, the drug should be immediately canceled.
A small amount of sex hormones can be excreted in breast milk.

special instructions

Angeliq 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 to the benefit of treatment should be evaluated, taking into account the possible need for it to be canceled, before starting or continuing to take Angeliq Micro.
When prescribing HRT to women with several risk factors for thrombosis or a high degree of severity of one of the risk factors, the possibility of mutual reinforcement of the action of risk factors and prescribed treatment for 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, Angeliq 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 Angeliq 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 long-term immobilization or planned surgery, the drug should be stopped 4-6 weeks before the operation, resumption of treatment 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 who use HRT drugs in conjunction with anticoagulants.

Arterial Thromboembolism

In the course of randomized controlled trials with prolonged 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 HRT 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 studies 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 HRT It 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 can have a negative effect on the X-ray detection of breast cancer.
When Angeliq Micro Micro is prescribed to women with risk factors for the onset of estrogen-dependent tumors (for example, relatives of the 1st degree of relationship with breast cancer), the ratio of the 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 of using conjugated estrogens with MPA versus placebo was 4 versus 3 cases per 10,000 women-years. 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 slightly lower risk of developing ovarian cancer.

Liver tumor

Against the background of the use of sex hormones, which also include drugs for hormone replacement therapy, benign and, even more rarely, malignant tumors of the liver have been observed in rare cases. 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

Estrogens are known to increase 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 start taking 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 started 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 precursors of brain 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 excretion of potassium 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. The risk of development of hyperkalemi is theoretically impossible to exclude 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 mild abnormalities in 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 the deterioration of liver function indicators Angeliq Micro should be canceled.
When recurrent cholestatic jaundice or cholestatic pruritus, observed for the first time during pregnancy or prior sex hormone therapy, the administration of Angeliq 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, it is usually not necessary to change the treatment regimen for diabetics during HRT. However, women with diabetes during HRT should be monitored.
Some patients may develop undesirable manifestations of estrogen stimulation, such as 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 to stop treatment in case of endometriosis recurrence 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 Angeliq Micro Micro therapy, women with a tendency to chloasma should avoid prolonged exposure to the sun or ultraviolet radiation.
The following conditions / diseases can 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 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 administration of Angeliq 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 norms 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 condition of the mammary glands, abdominal organs and pelvic organs, including cytological examination of the cervical epithelium.
Impact on laboratory results.
The administration of sex hormones can affect the biochemical indicators of liver, thyroid, adrenal gland and kidney function, the plasma concentration of transport proteins such as globulin, sex hormone binding and lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis.
Angeliq Micro does not adversely affect glucose tolerance.

Composition

1 tab.
estradiol (in the form of hemihydrate) micronized 0.25 mg
drospirenone (micronized) 0.5 mg
Excipients: lactose monohydrate - 50.45 mg, corn starch - 14.4 mg, pregelatinized corn starch - 9.6 mg, povidone - 4 mg, magnesium stearate - 0.8 mg.

Dosage and administration

If a woman does not take estrogen or goes to Angeliq Micro from another combination drug for continuous use, she can start treatment at any time.
Patients who switch to Angeliq 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 tablet daily. After the end of the intake of 28 tablets from the current package, the next day, begin taking the tablets from the new package of Angeliq Micro (continuous HRT), taking the first tablet on the same day of the week as the first tablet from the previous package.
The pill is swallowed whole with a small amount of liquid. The tablets 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. When you skip a few pills, you may develop bleeding from the vagina.

Side effects of Angeliq Micro

Most often, with the use of Angeliq Micro, such undesirable drug reactions (NLR) were observed, such as breast tenderness, bleeding from the genital tract, 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.
In one placebo-controlled study, adverse reactions were reported with a frequency of> 2%: headache (6% of patients taking Angeliq 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).
The adverse reactions that occur in isolated cases, or the 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 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 Angeliq 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 exacerbate the 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".

Drug interactions

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

The interaction of the drug Angeliq Micro 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 Angeliq 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.

Overdose

Studies of acute toxicity did not reveal the risk of acute side effects if you accidentally take 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 / progestin preparations with a content of 4 mg of 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.

Storage conditions

At a temperature not higher than 30 ° C. Keep out of the reach of children.
Shelf life - 3 years.

Terms of sell

You can buy Angeliq micro without a prescription.