Fareston tablets 20mg, No. 30

Estrogen-dependent metastatic breast cancer in postmenopausal women (first-line therapy).

Fareston is not recommended for use in patients with a tumor not associated with estrogen receptors.

By mouth during meals or not associated with them.

The recommended daily dose is 60 mg.

Use in patients with renal impairment

No dose adjustment is required for patients with renal impairment.

Use in patients with hepatic impairment

Toremifene should be used with caution in patients with impaired liver function (see section 'Pharmacokinetics').

Application in children

In pediatrics, Fareston is usually not prescribed.

Each tablet contains:

Active substance :

Toremifene 20.0 mg

Excipients : corn starch, lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, povidone, magnesium stearate, colloidal silicon dioxide.

Hypersensitivity to toremifene and / or any other ingredient in the drug.

- A history of indications of endometrial hyperplasia and severe hepatic failure are contraindications for long-term use of toremifene.

- A history of thromboembolic events is a contraindication for the use of toremifene.

- Pregnancy and the period of breastfeeding.

- Congenital or acquired documented lengthening of the QT interval.

- Electrolyte imbalance, especially uncorrected hypokalemia.

- Clinically significant bradycardia.

- Clinically significant heart failure with reduced left ventricular ejection fraction.

- A history of symptomatic arrhythmia.

- Simultaneous administration of drugs that lengthen the QT interval.

- Childhood (efficacy and safety have not been studied).

Carefully:

Leukopenia thrombocytopenia hypercalcemia (including against the background of bone metastasis) decompensated heart failure severe angina proarrhythmogenic conditions (acute myocardial ischemia prolongation of the QT interval) elderly lactase deficiency lactose intolerance lactose intolerance syndrome of glucose-galactose malabsorption with CYP3 inhibitors.

Trade name of the drug

Fareston

International non-proprietary name

Toremifen

Dosage form

pills

Composition

Each tablet contains:

Active substance :

Toremifene 20.0 mg or 60.0 mg (as toremifene citrate);

Excipients : corn starch, lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, povidone, magnesium stearate, colloidal silicon dioxide.

Description

Tablets with a dosage of 20 mg: white round, flat with beveled edges, with TO20 code on one side.

60 mg tablets: white round, flat with beveled edges, with TO60 code on one side.

Pharmacotherapeutic group

Antineoplastic, antiestrogen

ATX code

L02BA

Pharmacodynamics:

Toremifene is a non-steroidal anti-estrogenic agent. derivative of triphenylethylene. Like other members of this class (for example, tamoxifen and clomiphene), toremifene binds to estrogen receptors and can cause estrogenic anti-estrogenic or both effects, depending on the duration of therapy for the animal species of the target organ and the selected parameter. In general, however, nonsteroidal triphenylethylene derivatives are predominantly anti-estrogenic in humans.

In postmenopausal breast cancer patients, toremifene treatment leads to a moderate decrease in both total cholesterol and low-density lipoprotein (LDL) serum levels.

Toremifene specifically binds to estrogen receptors and competes with estradiol to inhibit estrogen-induced DNA synthesis and cell replication. In high doses, toremifene may have anticancer effects unrelated to estrogen.

The antitumor effect of toremifene in breast cancer patients is mainly associated with its antiestrogenic activity, although other mechanisms cannot be excluded (regulation of expression of the oncogene, secretion of growth factor, induction of apoptosis, influence on the kinetics of the cell cycle) that may be involved in the development of the antitumor effect.

Pharmacokinetics:

Suction

Toremifene is rapidly absorbed when taken orally. The maximum concentration in the blood serum occurs within 3 hours (2-5 hours). Food intake has no effect on absorption but may delay the time to reach maximum concentration by 15 - 2 hours. Food intake changes are clinically insignificant.

Distribution

The serum concentration curve can be described by a biexponential equation. The fast distribution phase with an average elimination half-life of about 4 hours (range 2-12 hours) is followed by a slow elimination phase with an average half-life of about 5 days (range 2-10 days). Toremifene binds intensively (> 995%) to blood plasma proteins, mainly albumin. Toremifene obeys linear serum pharmacokinetics at daily oral doses ranging from 11 to 680 mg. The average concentration of toremifene at steady state is 09 ?g / ml (range 06-13 ?g / ml) with a recommended dose of 60 mg per day.

Metabolism

Toremifene is actively metabolized in the liver. Major metabolic pathway. N-demethylation is mediated mainly by CYP 3A. In serum, the main metabolite is N-demethyltoremifene with an average elimination half-life of 11 days (range 4-20 days). Its equilibrium concentration is approximately twice that of the parent compound. It has a similar antiestrogenic effect. although weaker antitumor activity than the parent compound.

N-demethyltoremifene binds to plasma proteins more intensively than toremifene, the protein-bound fraction is> 999%. Three minor metabolites were found in blood serum: (deaminohydroxy) toremifene 4-hydroxytoremifene. and N N-didemethyltoremifene. Although they cause theoretically interesting hormonal effects, their concentration during toremifene therapy is too low to assess significant biological significance.

Withdrawal

Toremifene is excreted mainly as metabolites through the intestines. Enterohepatic circulation can be expected. Approximately 10% of the dose taken is excreted through the kidneys as metabolites. Due to the slow elimination, the equilibrium serum concentration is reached within 4 to 6 weeks.

Separate patient groups

Clinical antitumor efficacy and serum concentration are not positively correlated at a recommended daily dose of 60 mg.

No information is available regarding polymorphic metabolism. The enzyme complex responsible for the metabolism of toremifene in humans is a cytochrome P450-dependent mixed-function hepatic oxidase.

The pharmacokinetics of toremifene was studied in an open-label study with four parallel groups of ten people each: healthy volunteers, patients with impaired liver function, patients receiving anticonvulsants, and patients with impaired renal function. The pharmacokinetics of toremifene in patients with impaired renal function did not differ significantly from that in healthy volunteers. The excretion of toremifene and its metabolites was significantly higher in patients receiving anticonvulsants and lower in patients with impaired liver function.

Indications:

Estrogen-dependent metastatic breast cancer in postmenopausal women (first-line therapy).

Fareston is not recommended for use in patients with a tumor not associated with estrogen receptors.

Contraindications:

- Hypersensitivity to toremifene and / or any other ingredient in the drug.

- A history of indications of endometrial hyperplasia and severe hepatic failure are contraindications for long-term use of toremifene.

- A history of thromboembolic events is a contraindication for the use of toremifene.

- Pregnancy and the period of breastfeeding.

- Congenital or acquired documented lengthening of the QT interval.

- Electrolyte imbalance, especially uncorrected hypokalemia.

- Clinically significant bradycardia.

- Clinically significant heart failure with reduced left ventricular ejection fraction.

- A history of symptomatic arrhythmia.

- Simultaneous administration of drugs that lengthen the QT interval.

- Childhood (efficacy and safety have not been studied).

Carefully:

Leukopenia thrombocytopenia hypercalcemia (including against the background of bone metastasis) decompensated heart failure severe angina proarrhythmogenic conditions (acute myocardial ischemia prolongation of the QT interval) elderly lactase deficiency lactose intolerance lactose intolerance syndrome of glucose-galactose malabsorption with CYP3 inhibitors.

Pregnancy and lactation:

Torimifen is recommended for postmenopausal patients.

The drug is contraindicated for use during pregnancy. Animal studies have demonstrated reproductive toxicity and the potential risk to humans is not known. Toremifene should not be used during breastfeeding.

Method of administration and dosage:

By mouth during meals or not associated with them.

The recommended daily dose is 60 mg.

Use in patients with renal impairment

No dose adjustment is required for patients with renal impairment.

Use in patients with hepatic impairment

Toremifene should be used with caution in patients with impaired liver function (see section 'Pharmacokinetics').

Application in children

In pediatrics, Fareston is usually not prescribed.

Side effect

From the reproductive system: often - hot flushes, uterine bleeding, vaginal discharge; rarely - endometrial hypertrophy, endometrial polyps; very rarely - endometrial hyperplasia, endometrial cancer.

From the nervous system: often - increased fatigue, dizziness, edema, nausea, vomiting, increased sweating, rash, itching, depression; rarely - disorientation in space, insomnia, headache.

From the side of the digestive system: rarely - loss of appetite, increased activity of transaminases, constipation; very rarely - jaundice.

From the side of the cardiovascular system: rarely - thromboembolic episodes (deep vein thrombosis, thrombophlebitis and pulmonary embolism).

From the side of metabolism: rarely - increased body weight, hypercalcemia, especially in patients with bone metastases.

Others: rarely - dyspnea; very rarely - short-term corneal opacity, alopecia.

Overdose:

Symptoms: vertigo dizziness, headache, nausea and / or vomiting were observed at daily doses of 680 mg. Consideration should be given to the possibility of a dose-dependent prolongation of the QT interval. No specific antidote has been found. Treatment: symptomatic therapy.

Interaction:

Drugs that reduce renal calcium excretion (including thiazide diuretics) may increase the risk of hypercalcemia.

Drugs that stimulate the intensity of microsomal oxidation (for example, phenobarbital phenytoin or carbamazepine) can accelerate the metabolism of toremifene. thus reducing its equilibrium serum concentration. In such cases, it may be necessary to double the daily dose.

The interaction between antiestrogens and anticoagulants of the warfarin series can lead to a pronounced increase in blood coagulation time (the simultaneous use of toremifene and drugs of this group should be avoided).

Theoretically, the metabolism of toremifene can be inhibited by drugs that inhibit the cytochrome CYP 3A enzyme system, which is responsible for the main metabolic pathways. Examples of such drugs are antifungal drugs derived from imidazole (ketoconazole); other antifungal drugs (itraconazole voriconazole posaconazole); protease inhibitors (ritonavir nelfinavir) macrolides (claritomycin erythromycin telithromycin). Caution is advised when these medicines are used concomitantly with toremifene.

An additive effect on prolongation of the QT interval between toremifene and the following drugs cannot be ruled out, which may lead to an increased risk of ventricular arrhythmias including ventricular arrhythmias 'pirouette-type' (see section 'Contraindications'):

- class IA antiarrhythmic drugs (for example, quinidine hydroquinidine disopyramide);

- Class III antiarrhythmic drugs (for example, amiodarone sotalol dofetilide, ibutilide);

- antipsychotics (for example, phenothiazine pimozide, sertindole haloperidol sultopride);

- certain antimicrobial agents (moxifloxacin erythromycin pentamidine antimalarial agents, especially halofantrine);

- certain antihistamines (terfenadine astemizole mizolastine);

- others (cisapride. vincamine intravenously bepridil. diphemanil).

Simultaneous administration of toremifene with these drugs is contraindicated.

Special instructions:

Before starting treatment, the patient must be examined by a gynecologist. Particular attention should be paid to the condition of the endometrium. Then gynecological examinations should be repeated at least once a year. Patients with diseases such as arterial hypertension, diabetes mellitus, having a high level of body mass index (> 30) or receiving long-term hormone replacement therapy are at risk of developing endometrial cancer and therefore need careful monitoring (see the 'Side effects' section).

Toremifene is not recommended for patients with a history of severe thromboembolic complications (see the 'Side Effects' section).

Patients with decompensated heart failure or severe angina need close monitoring. Hypercalcemia can develop in patients with bone metastases at the beginning of treatment with the drug, they need to be closely monitored.

On the electrocardiograms of some patients, a dose-dependent lengthening of the QT interval was observed while taking toremifene (see section 'Contraindications').

Toremifene should be used with caution in patients with proarrhythmic conditions (especially in elderly patients) such as acute myocardial ischemia or prolonged QT interval as this can lead to an increased risk of ventricular arrhythmias (including ventricular pirouette arrhythmias) and cardiac arrest ( see section 'Contraindications').

?сли во врем¤ лечени¤ торемифеном про¤вл¤ютс¤ симптомы или признаки которые могут говорить об аритмии следует отменить терапию и сделать Ё v.

?сли интервал QT > 500 мс. не следует принимать торемифен.

ќтсутствуют систематические данные по пациентам с лабильным диабетом пациентам в т¤желом состо¤нии или пациентам с сердечной недостаточностью.

“аблетки ‘арестон содержат лактозу. ѕациентам с редкой наследственной непереносимостью галактозы недостаточностью лактазы или синдромом глюкозо-галактозной мальабсорбции не следует принимать данное средство.

ќтмечались анеми¤ лейкопени¤ и тромбоцитопени¤. ѕри приеме торемифена следует контролировать число эритроцитов лейкоцитов или тромбоцитов.

ќтмечались случаи печеночной недостаточности в том числе повышение уровн¤ печеночных ферментов (более чем в 10 раз выше верхней границы нормы) гепатита и желтухи при приеме торемифена. Ѕольшинство из них возникали в первые мес¤цы применени¤. —труктура повреждени¤ печени была преимущественно гепатоцеллюл¤рной.

¬ли¤ние на способность управл¤ть трансп. ср. и мех.:

“оремифен не оказывает вли¤ни¤ на способность управл¤ть автомобилем и прочими механизмами.

‘орма выпуска/дозировка:

“аблетки по 20 мг или 60 мг.

”паковка:

ѕо 30 60 или 100 таблеток во флаконе из ѕЁ¬ѕ с завинчивающейс¤ крышкой из ѕЁ¬ѕ с контролем первого вскрыти¤. ѕо 1 флакону в картонной пачке вместе с инструкцией по применению.

”слови¤ хранени¤:

’ранить при температуре от 15 до 25?C.

’ранить в недоступном дл¤ детей месте.

—рок годности:

5 лет.

Do not use after the expiration date indicated on the package.

Vacation conditions

On prescription