Angelica coated pills 2mg N28
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Active ingredients
Drospirenone + Estradiol
Release form
Pills
Composition
1 tablet contains: Active substance: estradiol (in the form of hemihydrate) 1 mg, drospirenone 2 mg. Additional substances: lactose monohydrate - 48.2 mg, corn starch - 14.4 mg, corn starch, pregelatinized - 9.6 mg, povidone K25 - 4 mg, magnesium stearate - 0.8 mg, hypromellose - 1.0112 mg, macrogol 6000 - 0.2024 mg, talc - 0.2024 mg, titanium dioxide - 0.5438 mg, iron dye red oxide - 0.0402 mg.
Pharmacological effect
Anti-menopausal drug. Angelik's preparation contains estrogen - estradiol, which is identical to natural 17β-estradiol. Also, the drug Angelica contains a derivative of spironolactone - drospirenone, which has a gestagenic, antigonadotropic and antiandrogenic, as well as anti-mineralocorticoid action. ovarian depletion), including vasomotor symptoms (such as hot flashes, increased sweating), sleep disturbances, relieve mood mood, irritability, atrophic changes of the urinary tract in women with an unremoved uterus. Continuous hormone replacement therapy with Angelic helps to avoid regular withdrawal bleeding, which are observed with cyclical or phase HRT. Estradiol compensates for the estrogen deficiency in the female body after menopause and provides effective treatment of psycho-emotional and autonomic menopausal symptoms (such as tidal flow, increased sweats (such as tides, increased sweats), and increased edema symptoms sleep, increased nervous irritability, irritability, palpitations, cardialgia, dizziness, headache , decreased libido, muscle and joint pain); involution of the skin and mucous membranes, especially the urogenital system (urinary incontinence, dryness and irritation of the vaginal mucosa, pain during sexual intercourse). Estradiol prevents bone loss due to estrogen deficiency, which is mainly due to the suppression of osteoclast function and a shift in bone process remodeling in the direction of bone formation. It has been proven that prolonged use of HRT can reduce the risk of peripheral bone fractures in women after menopause.With the abolition of HRT, the rate of decrease in bone mass is comparable with the indicators characteristic of the period immediately after menopause. It is not proven that during HRT, it is possible to restore the bone mass to the premenopausal level. HRT also has a beneficial effect on the collagen content in the skin, as well as on its density, and can also slow down the formation of wrinkles. In addition, due to the antiandrogenic properties of drospirenone, Angelica has a therapeutic effect on androgen-dependent diseases such as acne, seborrhea, androgenic alopecia. Drospirenone has anti-mineralocorticoid activity, increases elimination atria and water, which can prevent the increase in blood pressure, weight gain, occurrence of edema, breast tenderness and other symptoms associated with fluid retention. After 12 weeks of using Angelic, there was a slight decrease in blood pressure (systolic - by an average of 2-4 mm Hg, diastolic - by 1-3 mm Hg). The effect on blood pressure was more pronounced in women with hypertension. After 12 months of use of the drug Angelica, the average body mass index remained unchanged or decreased by 1.1-1.2 kg. Drospirenone is deprived of any androgenic, estrogenic, glucocorticosteroid, and antiglucocorticosteroid activity, does not affect glucose tolerance and insulin resistance. This, combined with anti-mineralocorticoid and anti-androgenic effects, provides Drospirenone with a biochemical and pharmacological profile similar to natural progesterone. Taking Angezhek leads to a decrease in total cholesterol and LDL cholesterol, as well as a slight increase in triglycerides. Drospirenone reduces the increase in triglyceride concentration caused by estradiol. The addition of Drospirenone prevents the development of hyperplasia and endometrial cancer. Observational studies suggest that among postmenopausal women, the incidence of colon cancer is reduced among postmenopausal women. The mechanism of action is still unclear.
Pharmacokinetics
Estradiol Absorption After taking the drug inside estradiol is rapidly and completely absorbed from the gastrointestinal tract.Subjected to the effect of the first passage with the formation of estrone, estriol and estrone sulfate. Bioavailability when administered is about 5% and does not depend on food intake. Serum estradiol Cmax is approximately 22 pg / ml and is reached after 6–8 hours. Food intake does not affect the bioavailability of estradiol. Distribution Associated with albumin and globulin that binds sex steroids (GSPS). The free fraction of estradiol in serum is about 1-12%, and the associated GSPS 40-45%. The apparent Vd after a single IV injection is about 1 l / kg. After repeated use, the concentration of estradiol is about 2 times higher than after a single dose, while Css varies from 20 pg / ml to 43 pg / ml. After discontinuation of use, estradiol and estrone levels return to their original values within about 5 days. Metabolism Estradiol is metabolized mainly in the liver, partly in the intestine, kidneys, skeletal muscles and in target organs with the formation of estrone, estriol, catechol estrogen, and sulphate and glucuronide conjugates of these compounds, which have significantly less estrogenic activity compared to estradiol or are inactive at all. Intake of serum estradiol clearance is about 30 ml / min / k . Estradiol metabolites are excreted in the urine and bile. T1 / 2 is approximately 24 hours. Drospirenone Absorption After ingestion, drospirenone is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 76-85% and does not depend on food intake. Meal does not affect the bioavailability of drospirenone. Distribution After a single or multiple dose of 2 mg Cmax in serum is reached after 1 hour and is about 22 ng / ml. After that, there is a biphasic decrease in the concentration of drospirenone in serum with a final T1 / 2 of about 35-39 hours. Drospirenone binds to albumin and does not bind to GSM and corticoid-binding globulin (KSG); about 3-5% - free fraction. Due to long T1 / 2 Css it is reached after 10 days of taking the drug Angelica and exceeds the concentration after a single dose by 2-3 times. MetabolismThe main metabolites are the acidic form of drospirenone and 4,5-dihydro-drospirenone- 3-sulfate, which are formed without the participation of isoenzymes of the cytochrome P450 system. Injection The serum clearance of drospirenone from 1.2-1.5 ml / min / kg. Some of the dose received is displayed unchanged.Most of the dose is excreted by the kidneys and through the intestines in the form of metabolites in a ratio of 1.2: 1.4; T1 / 2 - about 40 hours.
Indications
- Hormone replacement therapy for menopausal disorders in postmenopause; - Prevention of postmenopausal osteoporosis.
Contraindications
It is not recommended to start taking the drug Angelique in the presence of any of the following conditions; If any of these conditions occur while taking the Angelic drug, you should immediately stop using the drug: - vaginal bleeding of unknown etiology; - confirmed or suspected breast cancer or a history of breast cancer; - confirmed or suspected diagnosis of a hormone-dependent precancerous disease or hormone-dependent malignant tumors; - benign or malignant tumors of the liver (including history); - severe liver disease; - serious kidney disease EC currently or in history or acute renal failure (before normalization of renal function); - acute arterial thrombosis or thromboembolism (including those leading to myocardial infarction, stroke); - deep vein thrombosis in the acute stage, venous thromboembolism in present or in history; high risk of venous and arterial thrombosis; thromboembolism of the pulmonary artery; severe hypertriglyceridemia; pregnancy; lactation; children and adolescence under 18; congenital lactate deficiency PS, lactose intolerance, glucose-galactose malabsorption - hypersensitivity to the components of the drug Anzhelik. previous pregnancy, endometriosis, uterine myoma, diabetes mellitus. It is necessary to take into account that estrogens alone or in combination with gestagens should be used with following diseases and conditions: smoking, hypercholesterolemia, obesity, systemic lupus erythematosus, dementia, gallbladder disease, retinal thrombosis, moderate hypertriglyceridemia, edema in chronic heart failure,severe hypocalcemia, endometriosis, bronchial asthma, epilepsy, migraine, porphyria, liver hemangiomas, hyperkalemia, conditions predisposing to the development of hyperkalemia, administration of drugs that cause hyperkalemia (potassium-sparing diuretics, potassium preparations, ACE inhibitors, antagonists of anhydro-angiographers, antagonists, and I have already been in an outpatient group, and I have already been undergoing anesthesia.
Use during pregnancy and lactation
HRT is contraindicated during pregnancy and lactation. If pregnancy is detected while taking the drug Angelique, the drug should be immediately canceled. A small amount of sex hormones can be excreted in the mother's milk.
Dosage and administration
If a woman does not take estrogen or goes to Angelique from another combination drug for continuous use, she can start treatment at any time. Patients who switch to Angelique from the combined drug for cyclic HRT should begin taking after the end of the bleeding withdrawal. Each package is designed for a 28-day reception. The drug should be taken daily for 1 tab. After the end of taking 28 pills from the current package, the next day, Angelic is started, taking the first tablet on the same day of the week as the first tablet from the previous package. The tablet is swallowed whole with a small amount of liquid. During the day, when the woman takes the drug, it doesn't matter, but if she started taking the pills at any particular time, she should stick to that time and beyond. When you skip taking the missed pill, you should take it as soon as possible. If more than 24 hours have elapsed after the usual reception time, an additional pill should not be taken. If you skip a few pills, vaginal bleeding may develop.
Side effects
Most often, when using the drug Angelique, such undesirable drug reactions as breast tenderness, bleeding from the genital tract, gastrointestinal pain and abdominal pain were observed. These reactions develop in ≥ 6% of women using the drug Angelik. Irregular bleeding usually disappears with long-term therapy. The frequency of bleeding decreases with increasing duration of treatment. Serious adverse reactions include arterial and venous thromboembolic complications and breast cancer. The undesirable drug reactions described in clinical studies using Angelica are presented in order of decreasing severity.The frequency of occurrence of adverse events was classified as follows: very often (≥1 / 10), often (≥1 / 10, <1/10), infrequently (≥1 / 1000, <1/100), rarely (<1/10 000 ). Mental disorders: often - emotional lability. On the CNS side: often - migraine. On the cardiovascular system: infrequent - venous and arterial thromboembolic complications (occlusion of peripheral deep veins, thrombosis and pulmonary embolism / occlusion of the pulmonary vessels, thrombosis, embolism and heart attack / myocardial infarction / cerebral infarction and stroke, except for hemorrhagic) From the digestive system: often - gastrointestinal pain, abdominal pain. From the reproductive system: very often - pain in the mammary glands (including discomfort in the mammary glands), bleeding from the genital tract; often - cervical polyp; infrequently - breast cancer *. * - Data on the relationship with the use of the drug were obtained from the results of post-marketing observations; frequency data obtained from clinical studies using the drug Angelik. For more information on venous and arterial thromboembolic complications, breast cancer and migraine, see Contraindications and Specific Instructions. Adverse reactions that occur in isolated cases, or whose symptoms develop very long after initiation of therapy and which are considered to be associated with the use of drugs from the group of combined agents for continuous HRT: liver tumors (benign and malignant e); hormone-dependent malignant tumors or hormone-dependent precancerous diseases (if it is known that the patient has similar conditions, this is a contraindication to the use of the drug Angelica); cholelithiasis; dementia; endometrial cancer; arterial hypertension; abnormal liver function; hypertriglyceridemia; changes in glucose tolerance or the effect on peripheral insulin resistance; increase in the size of uterine fibroids; reactivation of endometriosis; prolactinoma; chloasma; jaundice and / or pruritus associated with cholestasis. Occurrence or worsening of conditions for which the relationship with the use of HRT is not exactly proven: epilepsy; benign breast diseases; bronchial asthma; porphyria; systemic lupus erythematosus; otosclerosisminor chorea. In women with hereditary angioedema, exogenous estrogens can exacerbate symptoms. Hypersensitivity reactions have also been noted (including symptoms such as rash and urticaria). For more information about serious adverse events associated with hormone replacement therapy, see Special Instructions.
Overdose
Studies of acute toxicity 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 / progestin drugs containing 4 mg of estradiol was well tolerated. Symptoms that can occur during overdose: nausea, vomiting, bleeding from the vagina. Treatment: There is no specific antidote, if necessary, symptomatic therapy is used.
Interaction with other drugs
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. 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 concomitant use of certain antibiotics (for example, penicillins and tetracyclines) a decrease in estradiol was observed. 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) can inhibit estradiol metabolism. On the basis of in vitro interaction studies, as well as an in vivo study in female volunteers who take omeprazole, simvastatin and midazolam as markers, we can concludethat the effect of drospirenone at a dose of 3 mg on the metabolism of other medicinal substances is unlikely. The use of Angelica in women receiving antihypertensive therapy (for example, ACE inhibitors, angiotensin II receptor antagonists, hydrochlorothiazide) may slightly increase the antihypertensive effect. and NSAIDs or antihypertensive drugs unlikely. Combined use of the above three types of drugs can lead to a slight increase in serum potassium, more pronounced in women with type 1 and 2 diabetes. Excessive alcohol consumption during HRT may lead to an increase in circulating estradiol.
special instructions
Angelica is not used for contraception. If contraception is necessary, non-hormonal methods should be used (except for calendar and temperature methods). If you suspect a pregnancy, you should stop taking the pills until pregnancy is excluded. If any of the following conditions or risk factors are present or worsen, you should evaluate the ratio of individual risk and benefit of treatment before starting or continuing to take Angelica. . When prescribing HRT to women with several risk factors for thrombosis or a high degree of severity of one of the risk factors, one should consider the possibility of mutual enhancement of the effects of rice factors. and a prescribed treatment on the development of thrombosis. In such cases, the total value of the existing risk factors increases. If there is a high risk, Angelica is contraindicated. Venous thromboembolism In a number of controlled randomized, as well as epidemiological studies, an increased relative risk of developing venous thromboembolism (VTE) was revealed in the presence of HRT, i.e. deep vein thrombosis or pulmonary embolism. Therefore, when prescribing Angelique to women with risk factors of VTE, the ratio of risk and benefits of treatment should be carefully weighed and discussed with the patient. Risk factors for developing VTE include an individual and family history (the presence of VTE in next of kin at a relatively young age may indicate a genetic predisposition) and severe obesity. 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 trauma operations, or massive trauma. Depending on the cause or duration of immobilization, the question of whether to temporarily discontinue taking Angelik should be resolved. Treatment should be stopped immediately if symptoms of thrombotic disorders appear or if they are suspected. Arterial thromboembolism medroxyprogesterone acetate (MPA) was not obtained evidence of a positive effect on cardiovascular if it was revealed the system. In large-scale clinical trials of this compound, a possible increase in the risk of coronary artery disease in the first year of use was revealed, followed by the absence of a positive effect. In a large clinical study using only CEE, a potential reduction in the incidence of coronary artery disease among women aged 50–59 years was found, with no overall positive effect among the cumulative study population. As a secondary result in two large-scale clinical studies using CEA as monotherapy or in combination with MPA, a 30–40% increase in the risk of stroke was detected. Therefore, it is not known whether this increased risk covers drugs for hormone therapy containing other types of estrogens and progestogens or non-oral methods of use. Endometrial cancer. With prolonged estrogen monotherapy, the risk of endometrial hyperplasia or carcinoma increases. Studies have confirmed that adding progestogens reduces the risk of endometrial hyperplasia and cancer. Breast cancer According to clinical trials 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, acceleration of 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 treatment only. This increase is comparable to the increased risk of breast cancer in women with a later onset of natural menopause, as well as obesity and alcohol abuse. The increased risk gradually decreases to the usual level for several (but most of the five) years after the termination of HRT. Assumptions regarding the increased risk of developing breast cancer are made on the basis of more than 50 epidemiological studies (the risk varies from 1 to 2). large-scale randomized studies with KLE, separately or with constant combination with MPA, were obtained calculated risk indicators equal to 0.77 (95% confidence interval: 0.59-1.01) or 1.24 (95% confidence interval: 1.01-1.54) riblizitelno 6 years of use of HRT. It is not known whether this increased risk also extends to other products 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. Liver tumor Against the use of sex steroids, which include and HRT, in rare cases, benign, and even more rarely - malignant liver tumors were observed. In some cases, these tumors led to life threatening intra-abdominal bleeding. When pain in the upper abdomen, enlarged liver or signs of intra-abdominal bleeding with a differential diagnosis should take into account the likelihood of a liver tumor. Gastrointestinal disease It is known that estrogens increase the lithogenicity of bile. Some women are susceptible to the development of cholelithiasis during treatment with estrogens. Dementia There are limited data from clinical studies about a possible increase in the risk of dementia in women who are starting treatment with KLE, 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. It is not known whether it is spreading to other drugs for HRT. Other conditions It should be stopped immediately when migraine-like or frequent and unusually severe headaches appear for the first time,as well as the appearance of other symptoms - possible precursors of cerebral thrombotic stroke. The relationship between HRT and the development of clinically significant 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 persistent clinically significant arterial hypertension while receiving HRT, the withdrawal of HRT may be considered. In women with elevated blood pressure, a slight decrease in blood pressure is possible while taking the drug Angelique. In women with normal blood pressure, significant changes in blood pressure are not expected. In case of renal failure, the ability to excrete potassium may decrease. Drospirenone intake does not affect serum potassium concentration in patients with mild or moderate renal failure. Theoretically, the risk of developing hyperkalemia cannot be excluded only in the group of patients whose serum potassium concentration before treatment was determined on VGN and who additionally take potassium-sparing drugs. For mild abnormalities in liver function, incl. various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, require physician supervision as well as periodic liver function tests. If your liver function deteriorates, Angelique should be canceled. When cholestatic jaundice or cholestatic itch recurs, was observed for the first time during pregnancy or prior steroid hormone treatment, Angelica should be stopped immediately. Special attention should be paid to women with an increase in triglyceride concentration. In such cases, the use of HRT may cause a further increase in the concentration of triglycerides in the blood, which increases the risk of acute pancreatitis. Although HRT may affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the treatment regimen for diabetics during HRT. However, women with diabetes mellitus should be monitored when performing HRT. In some patients, unwanted estrogen stimulation may develop under the effect of HRT, 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 to stop treatment if endometriosis recurs in the presence of HRT. If you suspect a prolactinoma, before the start of treatment, this disease should be excluded. In the case of prolactinomas, the patient should be under close medical supervision (including periodic assessment of the drug concentration). In some cases, chloasma can be observed, especially in women with a chloasma of pregnant women in history. During therapy with Angelica, women with a tendency to develop chloasma should avoid prolonged exposure to the sun or ultraviolet radiation. The following conditions may occur or worsen during HRT, and women with these conditions should be monitored by a doctor during episodic diseases: epilepsy, benign lactic tumor glands, bronchial asthma, migraine, porphyria, otosclerosis, systemic lupus erythematosus, minor chorea. In women with hereditary forms of angioedema, exogenous edema Estrogens may cause or worsen the symptoms of angioedema. Additional informationNo data on the need for dose adjustment in women under 65 years of age. When using the drug Angelica in women older than 65 years, the information provided in the subsection Dementia should be taken into account. Drospirenone is well tolerated in women with mild or moderate hepatic insufficiency. Women with mild and moderate renal impairment showed a slight slowdown in the elimination of drospirenone, which was not clinically significant nature. Pre-clinical safety data Pre-clinical data obtained in the course of standard studies to identify toxicity in many atnom receiving doses of the drug, as well as genotoxicity, carcinogenic potential and toxicity to the reproductive system, do not indicate a particular risk to humans. Nevertheless, it should be remembered that sex steroids can promote the growth of certain hormone-dependent tissues and tumors. Medical examination Before starting or resuming taking the drug Angelica, you should familiarize yourself with the patient's medical history and conduct a physical 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 measurement of blood pressure, assessment of the mammary glands, abdominal organs and pelvic organs, including cytological examination of the cervical epithelium. In the presence of prolactinoma, periodic determination of the concentration of prolactin is required. Effect on the results of laboratory parameters. The use of sex steroids can affect on biochemical parameters of liver, thyroid, adrenal glands and kidney function, on plasma content of transport proteins, such as globulin, hormone binding and lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis. Angelique does not adversely affect glucose tolerance. Impact on the ability to drive vehicles and control mechanismsNot identified.