Анжелик®

General characteristics. Structure:

Active agents:
Oestradiol гемигидрат, in terms of oestradiol of 1,0 mg, дроспиренон 2 mg. Excipients:
lactoses monohydrate - 48,2 mg, starch corn - 14,4 mg, starch corn prezhelatinizirovanny - 9,6 mg, K25 povidone - 4 mg, magnesium stearate - 0,8 mg, a gipromelloza - 1,0112 mg, a macrogoal of 6000 - 0,2024 mg, talc - 0,2024 mg, titanium dioxide of-0,5438 mg, dye ferrous oxide red - 0,0402 mg.

Description. Round, biconvex, grayish-pink tablets film coated with a stamping of "DL" in the correct hexagon on one party.

Pharmacological properties:

Pharmacodynamics. The drug Anzhelik® contains estrogen - oestradiol which in a human body turns into natural 17v-oestradiol. Also is a part of the drug Anzhelik® derivative Spironolactonum - дроспиренон, possessing gestagenny, anti-gonadotropic and anti-androgenic, and also antimineralokortikoidny action.
Анжелик® represents the combined drug for the replacement hormonal therapy (RHT) at climacteric frustration in postmenopauses the alny period (a natural menopause, a hypogonadism, castration or premature exhaustion of ovaries), including vasculomotor symptoms (such as heat inflows, the increased sweating), sleep disorders, decrease in mood, irritability, atrophic changes of an urinogenital path at women with an unextracted uterus. Continuous replacement hormonal therapy by the drug Anzhelik® allows to avoid regular bleedings of cancellation which are observed at cyclic or phase ZGT.
Oestradiol fills shortage of estrogen in a female body after approach of a menopause and provides effective treatment of psychoemotional and vegetative climacteric symptoms (such as "inflows", the increased sweating, a sleep disorder, the increased nervous irritability, irritability, heartbeat, cardialgias, dizziness, a headache, decrease in a libido, muscular and joint pains); involution of skin and mucous membranes, especially mucous urinogenital system (an urine incontience, dryness and irritation mucous vaginas, morbidity at the sexual intercourse).
Oestradiol prevents the loss of bone weight caused by deficit of estrogen. Mainly it is connected with suppression of function of osteoclasts and shift of process of bone remodeling towards formation of a bone. It was proved that prolonged use of ZGT allows to reduce risk of fractures of peripheral bones at women after approach of a menopause. At cancellation of ZGT rates of decrease in bone weight are comparable with the indicators characteristic of the period directly after a menopause. It is not proved that, applying ZGT, it is possible to achieve recovery of bone weight to premenopausal level.
ZGT also has salutary effect on the content of collagen in skin, as well as on its density, and also can slow down process of formation of wrinkles.
Besides, thanks to anti-androgenic properties of a drospirenon, Anzhelik® makes therapeutic impact on androgenzavisimy diseases, such as an acne, seborrhea, an androgenic alopecia.
Drospirenon has antimineralokortikoidny activity, increases removal of sodium and water that can prevent increase in arterial pressure, body weight, the hypostases, morbidity of mammary glands and other symptoms connected with a liquid delay. After 12 weeks of use of the drug Anzhelik® the small lowering of arterial pressure is noted (systolic - on average on 2-4 mm hg, diastolic - on 1-3 mm hg). The exerted impact on the ABP is more expressed at women with boundary arterial hypertension. In 12 months of use of the drug Anzhelik® the average value of body weight remains invariable or decreases by 1,1 - 1,2 kg.
Drospirenon is deprived of any androgenic, oestrogenic, glucocorticosteroid and anti-glucocorticosteroid activity, also insulin resistance does not influence tolerance to glucose. It, in combination with antimineralokortikoidny and anti-androgenic action, provides to a drospirenon the biochemical and pharmacological profile similar to natural progesterone.
Reception of Anzhelik® leads to decrease in level of the general cholesterol and cholesterol of lipoproteids of the low density (LPNP), and also slight increase of level of triglycerides. Drospirenon weakens growth of concentration of triglycerides caused by oestradiol.
Addition of a drospirenon prevents development of a hyperplasia and endometrial cancer.
The observation researches give the grounds to believe that among women in a postmenopause when using ZGT the indicator of cancer cases of a large intestine decreases. The action mechanism is not clear so far.
Pharmacokinetics. •  Oestradiol
Absorption
After intake oestradiol is quickly and completely absorbed. During absorption and the first passing through a liver oestradiol substantially is exposed to a metabolization, for example, in estrone, estriol and estrone sulfate. After oral administration bioavailability of oestradiol about 5%. Meal does not influence bioavailability of oestradiol.
Distribution
The maximum concentration of oestradiol in serum making about 22 pg/ml is usually reached in 6-8 hours after reception of a tablet. Oestradiol contacts albumine and the globulin connecting sex hormones (GSP 11). The free fraction of oestradiol in serum makes about 1-12%, and the fraction of the substance connected by GSPG is in limits of 40 — 45%. The seeming volume of distribution of oestradiol after single intravenous administration makes about 1 l/kg.
Metabolism
Oestradiol is metabolized preferential in a liver, and also partially and in intestines, kidneys, skeletal muscles and target organs. These processes are followed by formation of estrone, estriol, katekholestrogen, and also sulphatic and glyukuronidny conjugates of these connections, all from which have significantly smaller oestrogenic activity or have no oestrogenic activity at all.
Elimination
Clearance of oestradiol from serum - about 30 ml/min. Metabolites of oestradiol are removed with kidneys and through intestines with the elimination half-life equal
about 24 h.
Equilibrium concentration
Concentration of oestradiol in blood serum after repeated introduction is approximately twice higher, than after introduction of a single dose. On average concentration of oestradiol is in blood serum ranging from 20 pg/ml (minimum level) to 43 pg/ml
(maximum level). After the termination of reception of Anzhelik® levels of oestradiol and estrone are returned to reference values within about five days.
•  Drospirenon
Absorption
After intake with the broad range of doses дроспиренон it is quickly and completely absorbed. Bioavailability after oral administration makes 76-85%. Meal does not influence bioavailability of a drospirenon.
Distribution
The maximum concentration of a drospirenon in serum making about 22 ng/ml
it is reached approximately in 1 hour after single and multiple dose of 2 mg of a drospirenon. After that two-phase decrease in concentration of a drospirenon in serum with a final elimination half-life is observed about 35-39 hours.
Drospirenon contacts a seralbumin and does not contact the globulin, connecting sexual steroids (G,CSS) and the kortikoid-connecting globulin (KSG). About 3-5% of the general concentration of a drospirenon in serum are not connected with protein.
Biotransformation
The main metabolites in serum of the person are the acid form of a drospirenon and 4,5-dihydro-drospirenon-3-sulfate. Both metabolites are formed without participation of system of P450 cytochrome.
Elimination
The clearance of a drospirenon makes 1,2-1,5 ml/min. of serum. Some part of the received dose is removed in an invariable look. The most part of a dose is removed by kidneys and through intestines in the form of metabolites in the ratio 1,2:1,4, with an elimination half-life about 40 hours.
Equilibrium concentration
Equilibrium concentration is reached approximately in 10 days of daily administration of drug of Anzhelik®. Owing to a long elimination half-life of a drospirenon equilibrium concentration by 2-3 times exceeds concentration after a single dose.

Indications to use:

• The Replacement Hormonal Therapy (RHT) at climacteric frustration in a postmenopause.
• Prevention of post-menopausal osteoporosis.

Route of administration and doses:

If the woman does not accept estrogen or passes to Anzhelik® from other combined drug for continuous reception, then it can begin treatment at any time. Patients who pass to Anzhelik® from the combined drug for the ZGT cyclic mode have to begin reception after the termination of bleeding of cancellation.
Each packaging is counted on 28-day reception.
Daily it is necessary to accept on one tablet. After the end of reception of 28 tablets from the current packaging, begin new packaging of Anzhelik® (continuous ZGT) next day, taking the first pill of week on the same day, as the first tablet from the previous packaging.
The tablet is swallowed entirely, washing down with a small amount of liquid. Time of day when the woman accepts drug, does not matter, however, if she began to take a pill in any specific time, she has to adhere to this time further. The forgotten medicine needs to be taken as soon as possible. If after usual time of reception there passed more than 24 hours, the additional pill should not be taken. At the admission of several tablets development of vaginal bleeding is possible.

Features of use:

The drug Anzhelik® is not used for the purpose of contraception.
In need of contraception, it is necessary to apply non-hormonal methods (except for calendar and temperature methods). At suspicion on pregnancy, it is necessary to suspend reception of tablets until pregnancy is not excluded (see the section "Pregnancy and Lactation").
At existence or deterioration any of the states or risk factors provided below before beginning or continuing administration of drug of Anzhelik® it is necessary to estimate a ratio of individual risk and advantage of treatment.
At purpose of ZGT the women having several risk factors of development of thrombosis or high degree of manifestation of one of risk factors should consider a possibility of mutual strengthening of action of risk factors and the appointed treatment on development of thrombosis. In similar cases total value of the available risk factors increases. With high risk the drug Anzhelik® is contraindicated.

• Venous thromboembolism
In a number of controlled randomized, and also epidemiological researches the increased relative risk of development of a venous thromboembolism (VTE) against the background of ZGT, i.e. a deep vein thrombosis or an embolism of a pulmonary artery is revealed. Therefore, at purpose of the drug Anzhelik® to women with risk factors of VTE the ratio of risk and advantage of treatment has to be carefully weighed and discussed with the patient.
Risk factors of development of VTE include the individual and family anamnesis (existence of VTE at the immediate family at rather young age can indicate genetic predisposition) and heavy obesity. The risk of VTE also increases with age. The question of a possible role of a varicosity in development of VTE remains disputable.
The risk of VTE can temporarily increase at a long immobilization, "big" planned and traumatologic operations or a massive injury. Depending on the reason or duration of an immobilization it is necessary to resolve an issue of expediency of the temporary termination of administration of drug of Anzhelik®.
It is necessary to stop immediately treatment at emergence of symptoms of trombotichesky disturbances or at suspicion on their emergence.
• Arterial thromboembolism
During the randomized controlled researches at prolonged use of the conjugated horse estrogen (CHE) and медроксипрогестерон acetate (MPA) the evidence of positive influence on cardiovascular system was not obtained. In large-scale clinical tests of this connection possible increase of risk of the coronary heart disease (CHD) in the first year of use with the subsequent lack of positive effect was revealed. In one large clinical trial when using only KLE was found potential reduction of cases of an ischemic heart disease among women at the age of 50-59 years in the absence of the cumulative positive effect among cumulative population of a research. As secondary result in two large-scale clinical trials with use of KLE as monotherapies or in combination with MPA 30-40% increase of risk of development of a stroke were revealed. Therefore it is unknown whether this increased risk extends to the drugs for ZGT containing other types of estrogen and progestogens or on not peroral routes of administration.
• Endometrial cancer
At long monotherapy by estrogen the risk of development of a hyperplasia or a carcinoma of an endometria increases. Researches confirmed that addition of gestagen reduces risk of a hyperplasia and endometrial cancer.
• Breast cancer
According to clinical tests and to results of the observation researches increase in relative risk of development of a breast cancer in the women using ZGT within several years was revealed. It can be connected with earlier diagnosis, acceleration of growth of already available tumor against the background of ZGT or a combination of both factors.
The relative risk increases with increase in duration of therapy, but can be absent or be reduced at treatment only estrogen. This increase is comparable to increase in risk of developing of cancer of mammary glands at women at later approach of a natural menopause, and also at obesity and an alcohol abuse. The increased risk gradually decreases to usual level during several (mostly to five) years after the termination of ZGT.
Assumptions concerning increase in risk of development of a breast cancer are made on the basis of results of more than 50 epidemiological researches (the risk varies from 1 to 2).
In two large-scale randomized researches with KLE separately or at a constant combination to MPA the settlement indicators of risk equal 0,77 were received (95% a confidence interval: 0,59 - 1,01) or 1,24 (95% confidence interval: 1,01 -
1,54) after about 6 years of use of ZGT. It is unknown whether this increased risk as well extends to other drugs for ZGT.
• ZGT increases the mammography density of mammary glands that in certain cases can exert a negative impact on radiological detection of a breast cancer.
• Liver tumor
Against the background of use of sexual steroids to which also means for ZGT belong were in rare instances observed high-quality, and is even more rare - malignant tumors of a liver. In some cases these tumors led to the intra belly bleeding posing a threat for life. At pains in an upper part of a stomach, the increased liver or symptoms of intra belly bleeding at differential diagnosis it is necessary to consider probability of existence of a tumor of a liver.
• Cholelithiasis
It is known that estrogen increases a bile litogennost. Some women are predisposed to development of cholelithiasis at treatment with use of estrogen.
• Dementia
There are limited data of clinical trials on possible increase in risk of development of dementia in the women beginning administration of drugs, containing KLE at the age of 65 years and are more senior. As it was observed in researches, the risk can be reduced if administration of drugs for ZGT containing KLE is begun in an early menopause. It is unknown whether it extends to other drugs for ZGT.
• Other states
It is necessary to stop immediately treatment, at emergence for the first time migrenepodobny or frequent and extraordinary severe headaches, and also at emergence of other symptoms - possible harbingers of a trombotichesky stroke of a brain.
The interrelation between ZGT and development is not established to clinically expressed arterial hypertension. At the women accepting ZGT small increase in arterial pressure is described, clinically significant increase is noted seldom. However, in some cases, at development against the background of reception of ZGT of persistent clinically significant arterial hypertension cancellation of ZGT can be considered. At women with the increased arterial pressure (AP) perhaps some decrease in the ABP against the background of administration of drug of Anzhelik®. At women does not happen to the normal arterial pressure of significant changes of the ABP.
At a renal failure ability of removal of potassium can decrease. Reception of a drospirenon does not influence potassium concentration in plasma at patients with the easy and moderated forms of a renal failure. The risk of development of a hyperpotassemia theoretically cannot be excluded only in group of patients at whom potassium concentration in plasma before treatment was defined on the upper bound of norm and who in addition accept kaliysberegayushchy drugs.
At not heavy abnormal liver functions, including various forms of a hyperbilirubinemia, such as syndrome the Cudgel Johnson or a syndrome of the Rotor, are necessary observation of the doctor, and also periodic researches of function of a liver. At deterioration in indicators of function of a liver the drug Anzhelik® should be cancelled.
At a recurrence of cholestatic jaundice or cholestatic itch, observed for the first time during pregnancy or the previous treatment by sex steroid hormones, administration of drug of Anzhelik® needs to be stopped immediately.
Special observation of women at increase in concentration of triglycerides is necessary. In similar cases use of ZGT can cause further increase of concentration of triglycerides in blood that increases risk of acute pancreatitis.
Though ZGT can influence peripheral insulin resistance and tolerance to glucose, need to change the scheme of treatment of patients with a diabetes mellitus when carrying out ZGT, usually does not arise. Nevertheless, the women suffering from a diabetes mellitus when carrying out ZGT have to be under observation.
At some patients undesirable manifestations of stimulation by estrogen, for example pathological uterine bleeding can develop. Frequent or persistent pathological uterine bleedings against the background of treatment are the indication for an endometria research for the purpose of an exception of a disease of organic character.
Under the influence of estrogen of a hysteromyoma can increase in sizes. In this case treatment has to be stopped.
It is recommended to stop treatment at development of a recurrence of endometriosis against the background of ZGT.
At suspicion on existence of a prolaktinoma before an initiation of treatment it is necessary to exclude this disease. In case of identification of a prolaktinoma, the patient has to be under fixed medical observation (including periodic assessment of concentration of prolactin).
In certain cases the hloazma, especially at women with hloazmy pregnant women in the anamnesis can be observed. During therapy by the drug Anzhelik® of the woman with tendency to emergence of a hloazma have to avoid long stay in the sun or ultraviolet radiation.
The following states can arise or be aggravated against the background of ZGT, and women with these states when carrying out ZGT have to be under observation of the doctor: epilepsy; benign tumor of a mammary gland; bronchial asthma; migraine; porphyria; otosclerosis; system lupus erythematosus, hysterical chorea.
At women with hereditary forms of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.
Additional information
Women have no data on need of dose adjustment up to 65 years. At use of the drug Anzhelik® for women 65 years are more senior it is necessary to take information provided in the subsection "Dementia" into account.
At women with a slight or moderate liver failure, дроспиренон it is transferred well.
At women with easy or moderate renal failures insignificant delay of removal of a drospirenon was observed that had no clinically significant character.

Preclinical data on safety
The preclinical data obtained during the standard researches regarding detection of toxicity at multiple dose of doses of drug, and also genotoxicity, cancerogenic potential and toxicity for reproductive system do not indicate existence of extra risk for the person. Nevertheless, it is necessary to remember that sexual steroids can promote growth of some hormonedependent fabrics and tumors.
Medical examination and consultation
Before the beginning or resuming of administration of drug of Anzhelik® it is necessary to get acquainted in detail with a case history of the patient and to conduct physical and gynecologic examination. Frequency and the nature of such inspections have to be based on the existing norms of medical practice at the necessary accounting of specific features of each patient (but at least 1 time in 6 months) and have to include measurement of arterial pressure, assessment of a condition of mammary glands, abdominal organs and pelvic bodies, including a cytologic research of an epithelium of a neck of uterus.
In the presence of a prolaktinoma periodic definition of concentration of prolactin is required.
Influence on results of laboratory indicators.
Reception of sexual steroids can influence biochemical indicators of function of a liver, thyroid gland, adrenal glands and kidneys, the content in plasma of transport proteins, such as the globulin connecting sex hormones and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and a fibrinolysis. Анжелик® does not exert a negative impact on tolerance to glucose.
Influence on ability to drive the car and to use mechanisms
It is not revealed.

Side effects:

Most often at use of the drug Anzhelik® such undesirable medicinal reactions (UMR) as morbidity of mammary glands, bleedings from a genital tract, gastrointestinal pains and abdominal pains were observed. These reactions develop at> 6% of the women using the drug Anzhelik®.
Irregular bleedings usually disappear at long therapy. Frequency of bleedings decreases with increase in duration of treatment.
Serious undesirable reactions include arterial and venous tromboembolic episodes and a breast cancer.
NLR described in clinical trials using the drug Anzhelik® are presented in the table as weight reduction. For determination of frequency the following concepts are used: very frequent (> 1/10), frequent (from> 1/100 to <1/10), infrequent (from> 1/1000 to <1/100) and rare (from> 1/10 000 to <1/1 000).

Class of systems of bodies        Very frequent                Frequent                       Infrequent

Mental                                                      It is emotional
frustration                                                    lability
Pathology nervous                                               Migraine
systems
Pathology of vessels                                                                                            Venous and arterial
                                                                                                                            thromboembolic
                                                                                                                            complications *
Pathology gastro                                            Gastrointestinal
intestinal path                                                     of pain and pain
                                                                                   in a stomach
                        Bol's pathology in milk          the Polyp of a neck of uterus       the Breast cancer
reproductive              glands (Including
systems and milk      discomfort in milk
glands                                 glands)
                                         Bleedings from
                                         genital tract

The concept "venous and arterial tromboembolic episodes" includes the following medical terms: occlusion of peripheral deep veins, fibrinferments and embolism/occlusion of pulmonary vessels, fibrinferments, an embolism and a heart attack/heart attack a myocardium/heart attack of a brain and a stroke,  except for hemorrhagic.

** Data on interrelation using drug were obtained by results of post-marketing observations; data on frequency are obtained from clinical trials using the drug Anzhelik®.
In addition about venous and arterial tromboembolic episodes, a breast cancer and migraine also look in the sections "Contraindications" and "Special Instructions".
Undesirable reactions which arise in isolated cases or symptoms which develop through very long time after the beginning of therapy and which are considered connected using drugs from group of the combined means for continuous replacement hormonal therapy are listed below:

• Liver tumors (high-quality and malignant)
• Hormonedependent malignant tumors or hormonedependent precancerous diseases (if it is known that the patient has similar states, it serves as a contraindication to drug Anzhelik® use)
• Cholelithiasis
• Dementia
• Endometrial cancer
• Arterial hypertension
• Abnormal liver functions
• Gipertriglitseridemiya
• Changes of tolerance to glucose or influence on resistance of peripheral fabrics to insulin
• Increase in the sizes of a hysteromyoma
• Reactivation of endometriosis
• Prolaktinoma
• Hloazma
• The jaundice and/or an itch connected with a cholestasia

• Emergence or deterioration in states for which the interrelation using ZGT is definitely not proved: epilepsy; benign diseases of mammary glands; bronchial asthma; porphyria; system lupus erythematosus; otosclerosis, hysterical chorea.
• At women with a hereditary Quincke's disease exogenous estrogen can promote an aggravation of symptoms.
• Hypersensitivity (including such symptoms as rash and urticaria)

In addition about the serious undesirable phenomena connected with replacement hormonal therapy look in the section "Special Instructions".

Interaction with other medicines:

Prolonged treatment by the drugs inducing liver enzymes (for example, some anticonvulsant and germicides) can increase clearance of sex hormones and reduce their clinical performance. Similar property was revealed to induce enzymes of a liver at hydantoins, barbiturates, Primidonum, carbamazepine and rifampicin, existence of this feature is also supposed at an okskarbazepin, a topiramat, a felbamat and griseofulvin. The maximum induction of enzymes is usually observed not earlier, than in 2-3 weeks, but then it can remain still, at least, within 4 weeks after the termination of administration of drug.
In rare instances against the background of the accompanying reception of some antibiotics (for example, penicillinic and tetracycline groups) decrease in level of oestradiol was observed.
The main metabolites of a drospirenon are formed in plasma without participation of system of P450 cytochrome. Therefore influence of inhibitors of system of P450 cytochrome on metabolism of a drospirenon is a little probable. Nevertheless, CYP3A4 inhibitors (for example, Cimetidinum, кетоконазол, etc.) can inhibit oestradiol metabolism.
On the basis of researches of interaction in vitro, and also the research in vivo on women the volunteers accepting омепразол, симвастатин and midazolam as markers it is possible to conclude that influence of a drospirenon in a dose of 3 mg on metabolism of other medicinal substances it is improbable.
Use Anjelica at the women receiving anti-hypertensive therapy (for example, APF inhibitors, antagonists of receptors of angiotensin II, a hydrochlorothiazide) can increase anti-hypertensive effect several.
Increase in level of serumal potassium at the combined reception Anjelica and non-steroidal anti-inflammatory drugs (NPVS) or anti-hypertensive drugs is improbable. Combined use of three above-stated types of drugs can lead to the slight increase of level of serumal potassium which was more expressed at the women suffering from a diabetes mellitus 1 and 2 types.
• Interaction with alcohol
Overconsumption of alcohol during ZGT can lead to increase in level of the circulating oestradiol.

Contraindications:

It is not recommended to begin administration of drug of Anzhelik® in the presence of any of the listed below states. If any of these states arises during administration of drug of Anzhelik®, then it is necessary to stop drug use immediately.
• Pregnancy and lactation
• Bleeding from a vagina of not clear origin
• The confirmed or estimated diagnosis of a breast cancer or a breast cancer in the anamnesis
• The confirmed or estimated diagnosis of a hormonedependent precancerous disease or hormonedependent malignant tumor
• Liver tumors now or in the anamnesis (high-quality or malignant)
• Serious illness of a liver
• A serious illness of kidneys now or in the anamnesis or an acute renal failure (before normalization of indicators of renal function)
• The acute arterial thrombosis or a thromboembolism including leading to a myocardial infarction, a stroke
• A deep vein thrombosis in aggravation stages, venous thromboembolisms now or in the anamnesis
• Existence of high risk of venous and arterial thromboses
• Thromboembolism of a pulmonary artery
• The expressed gipertriglitseridemiya
• Hypersensitivity to drug Anzhelik® components
• Children's and teenage age up to 18 years
• Inborn deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption.

Use with care
Анжелик® it is necessary to appoint with care at the following diseases: arterial hypertension, inborn hyperbilirubinemias (Gilbert's syndromes, the Cudgel Johnson and the Rotor), cholestatic jaundice or a cholestatic itch during the previous pregnancy, endometriosis, a hysteromyoma, a diabetes mellitus (see. "Special instructions").
It is necessary to take into account that are oestrogenic separately or in combination with gestagena it is necessary to apply with care at the following diseases and states: smoking, a hypercholesterolemia, obesity, a system lupus erythematosus, dementia, diseases of a gall bladder, fibrinferments of vessels of a retina, a moderate gipertriglitseridemiya, hypostases at HSN, a heavy hypocalcemia, endometriosis, bronchial asthma, epilepsy, migraine, a porphyria, the liver hemangiomas, a hyperpotassemia, states contributing to development of a hyperpotassemia, reception of the HP causing a hyperpotassemia - kaliysberegayushchy diuretics, drugs of potassium, APF inhibitors, antagonists of receptors of angiotensin II and heparin.
Pregnancy and lactation
ZGT is contraindicated during pregnancy or feeding by a breast. If pregnancy comes to light during administration of drug of Anzhelik®, drug should be cancelled at once.
A small amount of sex hormones can be allocated with maternal milk.

Overdose:

Researches of acute toxicity did not reveal risk of acute side effects at accidental administration of drug in the quantity which is repeatedly exceeding a daily therapeutic dose. In clinical trials use of a drospirenon to 100 mg or the drugs combined estrogen / гестагенных with the maintenance of 4 mg of oestradiol well was transferred. Symptoms which can be noted at overdose: nausea, vomiting, bleeding from a vagina. There is no specific antidote, a symptomatic treatment.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets are film coated. On 28 tablets in the blister from PVC and aluminum foil. 1 or 3 blisters together with a pocket for carrying the blister and the application instruction place in a cardboard pack.