Фарестон®

General characteristics. Structure:

Active ingredient: 20,0 mg or 60,0 mg of a toremifen in the form of a toremifen of citrate.

Excipients: starch corn, lactoses monohydrate, povidone, sodium glikolit starch, cellulose microcrystallic, magnesium stearate, silicon colloid anhydrous.

The anti-oestrogenic drug which is effectively blocking growth of a tumor of a mammary gland. Besides, торемифен has ability to reduce products of prolactin that can also play a positive role at treatment of patients with cancer of a mammary gland. Has no mutagen and teratogenic properties and does not lead to development of hepatocellular cancer and endometrial cancer.

Pharmacological properties:

Pharmacodynamics. Toremifen is to nonsteroid derivatives of a-phenyl stilbene. As well as other representatives of this class, for example Tamoxifenum, clomifene, торемифен contacts receptors of estrogen and renders estrogenopodobny, anti-oestrogenic (or at the same time) effect, depending on duration of treatment, a floor, a target organ and other features.

At treatment toremifeny patients with cancer of a mammary gland in a postmenopause moderate decrease in serumal cholesterol and LPNP was revealed.

Toremifen competitively contacts estrogenretseptor and slows down estrogenoposredovanny stimulation of synthesis of DNA and cellular replication. On experimental models of cancer at use of high doses торемифен rendered estrogennezavisimy antineoplastic effect.

The antineoplastic effect of a toremifen on a breast cancer is mediated by anti-oestrogenic action, however it is impossible to exclude that other mechanisms (changes in an expression of oncogenes, secretion of growth factors, induction of apoptosis and impact on kinetics of a cellular cycle) can also exert antineoplastic effect.

Pharmacokinetics. After oral administration торемифен it is quickly absorbed. The peak of concentration in plasma is defined in 3 (2-5) hours. The food does not influence absorption duration, but can remove achievement of peak concentration for 1,5-2 hours. The changes connected with meal clinically are not significant.

Concentration in a blood plasma is described by a bieksponentsialny curve. The elimination half-life in the first phase (distribution) makes 4 (2-12) hours, in the second (elimination) – 5 (2-10) days. And V were not estimated by CL due to the lack of researches of intravenous infusions. More than 99,5% of a toremifen contact plasma proteins (albumine). The kinetics of a toremifen in plasma at intake from 11 to 680 mg a day has linear character. Average steady-state concentration of a toremifen at reception of the recommended dose of 60 mg a day makes 0,9 (0,6-1,3) mkg/ml.

Toremifen is actively metabolized. In plasma the main metabolite is N-dimetiltoremifen with an average elimination half-life of 11 (4-20) days. It has similar anti-oestrogenic effect, however a little smaller, than торемифен. More than 99,9% are connected with proteins of plasma. 3 more less significant metabolites are defined in plasma: деаминогидрокситоремифен, 4-gidroksitoremifen and N, N-didemetiltoremifen.

Toremifen eliminirutsya generally in the form of metabolites with excrements. Enterogepatichesky recirculation can be observed. About 10% of the applied dose are removed with urine in the form of metabolites. Because of slow elimination of steady-state concentration in plasma is reached within 4-6 weeks.

Data on polymorphic metabolism are absent. P450-dependent cytochrome a fermental complex is responsible for metabolism of a toremifen at people. The main way – the N-demethylation mediated by CYP 3A.

The pharmacokinetics of a toremifen was studied in an open research on 4 parallel groups with 10 subjects: normal subjects, patients with insufficient (nuclear heating plant of 57 U/l – ALT 76 U/l – scale of GT of 329 U/l) or the activated function of a liver (nuclear heating plant 25U/l – ALT 30 U/l – scale of GT of 91 U/l) – patients, the accepting anti-epileptic drugs, and also patients with a renal failure (creatinine of 176 µmol/l). In this research the kinetics of a toremifen at patients with a renal failure had no considerable differences in comparison with that at normal subjects. Elimination of a toremifen and its metabolites was considerably accelerated at patients with the activated function of a liver and slowed down at a liver failure.

Indications to use:

Fareston apply as drug of the first line to treatment of a hormonedependent metastatic breast cancer in a postmenopause and to prevention and treatment of dishormonal giperplaziya of a mammary gland.

Route of administration and doses:

Dishormonal hyperplasia of a mammary gland. The recommended dose – 20 mg a day.
Estrogenozavisimy breast cancer.

The mode of dosing is set individually. As the standard dose for the first line of hormonal therapy is recommended reception of 60 mg orally daily, is long. At Fareston's appointment as the second line of hormonal treatment the dose of drug can be increased to 240 mg a day (on 120 mg 2 times a day).

Renal failure. At a renal failure dose adjustment is not required.

Liver failure. At a liver failure торемифен it has to be appointed with care.

Features of use:

Before an initiation of treatment the patient has to undergo inspection at the gynecologist. Special attention has to be paid to a condition of a mucous membrane of an endometria. Then gynecologic inspections have to repeat not less once a year. Patients who have arterial hypertension, a diabetes mellitus the body weights having the high level of an index (> 30), or those which received long replacement hormonal therapy are in risk group on endometrial cancer and therefore need careful monitoring.

Toremifen is not recommended for treatment of patients who in the anamnesis had cases of a serious clotting disease.

Patients with dekompensirovanny heart failure or patients with heavy stenocardia need careful monitoring.

As at patients with metastasises the hypercalcemia can develop in bones in an initiation of treatment with drug, these patients need careful monitoring.

Toremifen is recommended for use at post-menopausal age. As specific data are absent or are insufficient, торемифен it is not necessary to apply during pregnancy and a lactation.

During the researches on animals торемифен interfered with implantation, caused weakness of patrimonial activity and reduced perinatal survival. Besides, use in the period of an organogenesis led to disturbances of ossification, anomalies of development of edges, development of hypostases in a fruit.

Does not influence ability to manage motor transport and work with mechanisms.

Side effects:

Often or less often (<1/100) the found side effects: pristupoobrazny feeling of heat (inflows), the increased perspiration, vulval bleedings or allocations, increased fatigue, nausea, rash, an itch in genitals, a liquid delay, dizziness and a depression. These side effects are expressed usually benign and caused by anti-oestrogenic action of a toremifen.

Less often or seldom (<1/1 000, <1/100) the following side reactions were observed: increase in body weight, anorexia, vomiting, a lock, short wind, a headache, sleeplessness, skin rash, a vision disorder, including changes of a cornea, a cataract, a deep vein thrombosis, an embolism of a pulmonary artery, an alopecia, change of level of liver enzymes (increase in level of transaminases) and is very rare – the including single messages (<1/10 000) about severe defeats of function of a liver (jaundice).

At patients with metastasises in a bone cases of development of a hypercalcemia in the initiation of treatment were noted.

The risk of emergence of changes of an endometria, such as hyperplasia, polyposes and cancer, increases. It can be caused by the main pharmacological property of drug - oestrogenic stimulation.

Interaction with other medicines:

Specific researches of medicinal interaction were not conducted.
At simultaneous use of the drugs reducing renal excretion of calcium (thiazide diuretics) development of a hypercalcemia is possible.

Inductors of fermental systems of a liver (for example phenobarbital, carbamazepine), can accelerate metabolism of a toremifen in a liver and lead to decrease in equilibrium concentration in a blood plasma. In such cases there can be a need to double a daily dose.

The concomitant use of anti-estrogen and varfarinopodobny anticoagulants can increase a bleeding time considerably. It is necessary to avoid their simultaneous use.

Theoretically some drugs inhibiting the fermental CYP3A4-6 system can slow down metabolism of a toremifen. At simultaneous use of such drugs (for example a ketokonazola, erythromycin, a troleandomitsin) it is necessary to consider this fact.

Contraindications:

Endometria hyperplasia in the anamnesis and the expressed liver failure are contraindications to prolonged use of a toremifen.

Overdose:

Cases of overdose were not noted. Dizziness, a headache, nausea and/or vomiting were noted at doses 680 mg a day. Theoretically the overdose can be shown by strengthening of anti-oestrogenic effects (inflows) or oestrogenic effects (vaginal bleedings). Treatment: symptomatic therapy.

Storage conditions:

To store at the room temperature (15-25 °C), in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 30 tablets in a bottle; in a cardboard box.