Femoston mini pills 2,5/0,5mg №28

Composition

active ingredients: 1 pill contains didgesterone micronized 2.5 mg of estradiol micronized hemihydrate, which is equivalent to 0.5 mg estradiol;

excipients: lactose, monohydrate; hypromellose (HPMC 2910); corn starch; colloidal anhydrous silicon dioxide; Magnesium stearate; film shell Yellow 1 (macrogol 3350, polyvinyl alcohol, talc, titanium dioxide (E171), iron yellow oxide (E172)).

Pharmacodynamics. Estradiol

Suction

The absorption of estradiol depends on the size of the particles, micronized estradiol is easily absorbed from the gastrointestinal tract.

Distribution

Estradiol (as well as other estrogens) can be found both in the bound and in the free state. About 98-99% of the dose of estradiol binds to plasma proteins, of which 30-52% is with albumin and about 46-69% is with the sex hormone-binding globulin (GSPH).

Metabolism

After oral administration, estradiol is actively metabolized in the liver. The main unconjugated and conjugated metabolites are estrone and estrone sulfate, possessing estrogenic activity. Estrone sulfate may be subject to enterohepatic recirculation.

Removal

Estrone and estradiol are excreted in a state conjugated with glucuronic acid by the kidneys. The half-life (T1 / 2) is 10-16 hours. Estrogens enter breast milk.

The dependence of the concentration of estradiol on time and dose

With daily intake of Femoston® mini, plasma estradiol concentration reaches a constant value in about 5 days. Usually this indicator is achieved within 8-11 days after the start of therapy.

Didrogesterone

Suction

After oral administration, dydrogesterone is rapidly absorbed. The time of onset of the maximum concentration (T max) for didrogesterone varies from 30 minutes to 2.5 hours. The bioavailability of didrogesterone is 28%.

Distribution

More than 90% of dydrogesterone and 20a-dihydrodrodosterone (DHD) are bound to plasma proteins.

Metabolism

After oral administration, dydrogesterone is rapidly metabolized to DHD. The maximum concentration of DHD in the blood plasma is reached approximately 1.5 hours after taking the drug.Plasma DGD concentration significantly exceeds the initial concentration of didrogesterone, the ratio of the area under the concentration-time curve (AUC) and the maximum concentration (Cmax) of DGD to didrogesterone are about 40 and 25, respectively. The half-life for didrogesterone is 5-7 hours, for DGD it is 14-17 hours.

A common characteristic of all metabolites of dydrogesterone is the preservation of the 4,6-dien-3-one configuration of the original substance and the absence of 17α-hydroxylation, which leads to the absence of estrogenic and androgenic activities.

Removal

Completely dydrogesterone is eliminated after 72 hours. On average, 63% of the accepted dose is excreted by the kidneys. Total plasma clearance - 6.4 l / min. DGD is determined in the urine mainly in the form of a conjugate of glucuronic acid.

The dependence of the concentration of dydrogesterone on time and dose

Comparison of the kinetics of single and multiple doses (from 2.5 to 10 mg) shows that the pharmacokinetic properties of didrogesterone and DHD do not change when taking multiple doses.

The equilibrium concentration of didrogesterone was reached 3 days after the start of administration.

Hormone replacement therapy of disorders caused by estrogen deficiency in postmenopausal women (no earlier than 12 months after the last menstruation).

- Hypersensitivity to the drug.

- Diagnosed or suspected breast cancer.

- Diagnosed or suspected estrogen-dependent malignant tumors (for example, endometrial cancer).

- Diagnosed or suspected progestogen-dependent neoplasms (for example, meningioma).

- Bleeding from the vagina of unknown etiology.

- Untreated endometrial hyperplasia.

- Thrombosis (arterial and venous) and thromboembolism currently or in history (including thrombosis, deep vein thrombosis; thromboembolism of the pulmonary artery, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders).

- Acute or chronic liver disease is currently or in history (prior to normalization of indicators of functional liver tests), including malignant tumors of the liver.

- Porphyria.

- Multiple or expressed factors arterial or venous thrombosis associated with congenital or acquired predisposition, e.g., lack of protein C, protein deficiency S, deficiency of antithrombin III, the presence of antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant), angina pectoris, prolonged immobilization, heavy obesity forms (body mass index more than 30 kg / m2), diseases of cerebral vessels or coronary arteries, transient ischemic attacks, complicated clap lesions atrial apparatus, atrial fibrillation.

- Pregnancy and breastfeeding period.

- Galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

- Meningioma.

Reception of the drug Femoston® mini should be discontinued when contraindications are detected and / or when the following conditions occur:

- jaundice and / or abnormal liver function;

- uncontrolled arterial hypertension;

- first appeared on the background of the use of drugs for hormone replacement of migraine-like headache.

Pregnancy and Breastfeeding

The drug is contraindicated during pregnancy and during breastfeeding.

The results of most epidemiological studies with the analysis of data on the unintentional use of combinations of estrogens and progestogens by pregnant women indicate the absence of teratogenic and fetotoxic effects of drugs on the fetus. Available data on estradiol / didrogesterone intake by pregnant women is limited.

In the event of pregnancy during treatment with Femoston®, mini-therapy should be immediately discontinued.

The drug is prescribed only if there are symptoms that adversely affect the quality of life. Therapy should continue until the benefits of taking the drug outweigh the risk of side effects.

Experience with the use of the drug in women over 65 is limited.

The drug is taken orally daily, in continuous mode, 1 pill per day (preferably at the same time of day), regardless of the meal.

Patients who make a transition from another continuous sequential or cyclic drug regimen should complete the current cycle,and then go to the drug Femoston ® mini. The patients who are not receiving drugs for ZGT or passing from a continuous regimen of use of the combined drugs for ZGT can begin reception of the drug Femoston® pass on any day.

If the patient misses taking the pill, it must be taken within 12 hours after the usual time of admission; otherwise, the missed pill should not be taken, and the next day it is necessary to take the pill at the usual time. Skipping the drug can increase the likelihood of "breakthrough" uterine bleeding or spotting bleeding.

To start and continue therapy for postmenopausal disorders, the smallest effective dose should be taken within the shortest period of time (see section "Special Instructions").

Continuous combination therapy can be started with Femoston® mini or Femoston® product with 5 mg didrogesterone and 1 mg estradiol per tablet, depending on the time after menopause and the severity of symptoms.

Reception of the combined drug for hormone therapy Femoston mini in women with natural menopause can be started no earlier than 12 months after the last menstruation.

Women whose menopause is due to surgery can start taking the drug right away (as prescribed by the doctor if symptoms are present).

Adverse reactions

In clinical trials, patients receiving therapy with the estradiol / didrogesterone combination most often encountered: headache, abdominal pain, breast tension / tenderness, and back pain.

Studies of drug interactions were not conducted.

Efficacy of estrogen and progestogen may be impaired.

• The metabolism of estrogens and progestogens can be enhanced by the simultaneous use of substances with a known ability to induce enzymes involved in drug metabolism, especially enzymes 2B6, ZA4, ZA5, ZA7 of the cytochrome P450 system. These substances include anticonvulsant drugs (for example, phenobarbital, Carbamazepine, phenytoin) and antimicrobial agents (for example rifampicin, rifabutin, nevirapine, efavirenz).
• Despite the fact that ritonavir and nelfinavir are known as potent inhibitors of CYP450, ZA4, A5, A7, while being used with steroid hormones, they, on the contrary, activate these enzymes.
• Herbal preparations, a component of which is perforated St. John's wort (Hypericum perforatum), can enhance the metabolism of estrogens and progestogens due to the effects on CYP450, ZA4.
• It has been clinically proven that increased metabolism of estrogens and progestogens can lead to a weakening of their effect and a change in the profile of uterine bleeding.

Estrogens may interfere with the metabolism of other drugs.

Estrogens can inhibit CYP450 enzymes involved in drug metabolism by competitive inhibition. This should especially be considered in relation to drugs with a narrow therapeutic index, such as:

• tacrolimus and cyclosporin A (CYP450 3A4, 3A3);
• fentanyl (CYP450 3A4);
• theophylline (CYP450 1A2).

Clinically, this may lead to an increase in plasma levels of such substances in toxic concentrations. Thus, careful monitoring of the drug over a long period may be required, as well as a reduction in the dose of tacrolimus, fentanyl, cyclosporin A and theophylline.

Overdose

Both estradiol and didrogesterone are substances with low toxicity. Overdose can cause symptoms such as nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness / fatigue, and withdrawal bleeding. It is unlikely that overdose will require any specific symptomatic treatment. This also applies to cases of overdose in children.

Storage conditions

Store at a temperature not higher than 25 ° С.

Keep out of the reach of children.