Drospyrenon, estradiol | Angelica tablets, 28 pcs.

Release form

Film-coated tablets.

Packing

28 pcs

Pharmacological action

Pharmacodynamics

Antifungal drug.

For external use, terbinafine is active against: dermatophytes - Trichophyton. Microsporum. Epidermophyton yeast fungi of the genus Candida, for example: Candida albicans.

For external use, terbinafine is also active against: Pityrosporum orbiculare (Malassezia furfur).

Pharmacokinetics

Absorption

When topically applied, less than 5% of the dose is absorbed.

Distribution of

Plasma protein binding is 99%. For external use, it quickly penetrates the dermal layer of the skin and accumulates in the lipophilic stratum corneum. Terbinafine also penetrates the secretion of the sebaceous glands, which leads to the creation of high concentrations in the hair follicles and nails.

Terbinafine is excreted in breast milk.t is about 1-12%, and the associated GPSS is 40-45%. The apparent Vd after a single iv injection is about 1 L / kg. After repeated use, the concentration of estradiol is approximately 2 times higher than after a single dose, with Css ranging from 20 pg / ml to 43 pg / ml. After cessation of use, estradiol and estrone levels return to their initial values ​​within approximately 5 days.

Metabolism

Estradiol is metabolized mainly in the liver, partially in the intestines, kidneys, skeletal muscles and in target organs with the formation of estrone, estriol, catecholesterogens, as well as sulfate and glucuronide conjugates of these compounds, which have significantly lower estrogenic activity compared to estrogen or generally inactive.

Excretion of

Serum estradiol clearance - about 30 ml / min / kg. Estradiol metabolites are excreted in urine and bile. T1 / 2 is approximately 24 hours.

Drospirenone

Absorption

After oral administration, drospirenone is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 76-85% and does not depend on food intake. Eating does not affect the bioavailability of drospirenone.

Distribution of

After a single or multiple dose of 2 mg Cmax in serum is reached after 1 h and is about 22 ng / ml. After this, a two-phase decrease in the concentration of drospirenone in serum with a final T1 / 2 of about 35-39 hours is observed. Drospirenone binds to albumin and does not bind to SHGC and corticoid-binding globulin (CSH) about 3-5% - free fraction. Due to the prolonged T1 / 2 Css, it is achieved after 10 days of daily administration of the preparation Angelique® and exceeds the concentration after a single dose by 2-3 times.

Metabolism

The 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 P450 cytochrome system.

Excretion of

The clearance of drospirenone from serum is 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 postmenopausal women.

Prevention of postmenopausal osteoporosis.

Contraindications

It is not recommended to start taking the drug Angelik® in the presence of any of the following conditions, if any of these conditions occurs while taking the drug Angelik®, you should immediately stop using the drug:

hypersensitivity to the components of the preparation Angelica®

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 tumor of

benign a history of)

severe liver disease

severe kidney disease currently or in history or acute renal failure sufficiency (before normalization of renal function indices)

acute arterial thrombosis or thromboembolism (including those leading to myocardial infarction, stroke)

deep vein thrombosis in the acute stage, venous thromboembolism at present or in the history of

the presence of a high risk of venous and arterial thrombosis

pulmonary embolism

severe hypertriglyceridemia

pregnancy and lactation

childhood and adolescence, lactose malignancy, 18 years old, lactose malignancy, sorblosis

Angelic® should be prescribed with caution in the following diseases: arterial hypertension, congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), cholestatic jaundice or cholestatic pruritus during a previous pregnancy, endometriosis, uterine fibroids, diabetes mellitus. It must be taken into account that estrogens alone or in combination with progestogens should be used with caution in the following diseases and conditions: smoking, hypercholesterolemia, obesity, systemic lupus erythematosus, dementia, gallbladder disease, retinal vascular thrombosis, moderate hypertriglyceridemia, edema in chronic heart failure, severe hypocalcemia, endometriosis, bronchial asthma, epilepsy, migraine, porphyria, hemangiomas, hemangiomas, hemangiomas, hemangiomas the development of hyperkalemia, the use of drugs that cause hyperkalemia (potassium-sparing diuretics, potassium preparations, ACE inhibitors, angiotensin II receptor antagonists and hepari a).

Use during pregnancy and lactation

HRT is contraindicated during pregnancy and during lactation.

If pregnancy is detected while taking AngelikВ®, the drug should be discontinued immediately.

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

Composition

1 tablet contains:

Active substances:

estradiol (in the form of hemihydrate) 1 mg

drospirenone 2 mg.

Excipients:

lactose monohydrate - 48.2 mg,

corn starch - 14.4 mg,

pregelatinized corn starch - 9.6 mg,

povidone K25 - 4 mg,

magnesium stearate - 0.8 mg,

- 1.0112 mg,

macrogol 6000 - 0.2024 mg,

talc - 0.2024 mg,

titanium dioxide - 0.5438 mg,

dye iron oxide red - 0.0402 mg.

Dosage and administration of

If a woman does not take estrogen or switches to Angelica® from another combination drug for continuous use, she can start treatment at any time. Patients who switch to Angelic® with a combined preparation for cyclic HRT should start taking it after the withdrawal bleeding has ended.

Each pack has a 28-day intake.

The drug should be taken daily at 1 tab. After taking 28 tablets from the current package, the next day begin a new package of Angelik®, 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.

The time of day when a woman is taking the drug does not matter however, if she started taking the pill at any particular time, she should stick to that time further.

If you skip a dose, you must take the missed tablet as soon as possible. If after the usual time of administration more than 24 hours have passed, an additional tablet should not be taken. If you miss a few tablets, vaginal bleeding may develop.

Drug Interaction

Long-term treatment with drugs that induce liver enzymes (for example, some anticonvulsants and antimicrobials) may increase the clearance of sex hormones and reduce their clinical efficacy. A similar property - to induce liver enzymes - has been found in hydantoins, barbiturates, primidone, carbamazepine and rifampicin, the presence of this feature is also assumed in oxcarbazepine, topiramate, felbamate and griseofulvin.

Maximum induction of enzymes is usually observed no earlier than 2-3 weeks, but then it may persist for at least another 4 weeks after discontinuation of the drug.

In rare cases, a decrease in estradiol levels has been observed with concomitant administration of some antibiotics (eg, penicillins and tetracyclines).

The major metabolites of drospirenone are formed in the plasma without the involvement 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 (eg, cimetidine, ketoconazole) can inhibit estradiol metabolism.

Based on in vitro interaction studies, and in vivo studies in female volunteers taking omeprazole, simvastatin and midazolam as markers, it can be concluded that 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 (eg, ACE inhibitors, angiotensin II receptor antagonists, hydrochlorothiazide) may slightly increase the antihypertensive effect.

An increase in serum potassium when combined with Angelica and NSAIDs or antihypertensive drugs is unlikely. Co-administration of the three above-mentioned types of drugs can lead to a slight increase in serum potassium, more pronounced in women with type 1 and type 2 diabetes.

Excessive alcohol intake during HRT can increase circulating estradiol levels.

Overdose

Acute toxicity studies have not identified a risk of acute side effects when administered accidentally in excess of the daily therapeutic dose.

In clinical studies, the use of drospirenone up to 100 mg or combination estrogen / gestagen preparations containing 4 mg estradiol was well tolerated.

Symptoms that can be observed with overdose: nausea, vomiting, bleeding from the vagina.

Treatment: no specific antidote, if necessary, conduct symptomatic therapy.

Storage conditions

Keep out of the reach of children at a temperature not exceeding 25 РC.

Expiration

5 years.

Deystvuyuschee substances

Drospyrenon, estradiol

dosage form

dosage form

tablets

Bayer Pharma AG, Germany