Treatment of hormone-dependent metastatic breast cancer in postmenopause as a first-line drug. Prevention and treatment of dishormonal hyperplasia of the breast. Fareston is not recommended for patients with estrogen receptor negative tumors.
Fareston 20 mg Storage
active substance: 1 tablet contains toremifene citrate, equivalent to 20 mg or 60 mg of toremifene;
Excipients: corn starch, lactose monohydrate, povidone, sodium starch glycolate (type A), magnesium stearate, microcrystalline cellulose, colloidal anhydrous silica.
Fareston 20 mg Dosage form
Basic physical and chemical properties:
tablets of 20 mg: white, almost white, round, flat, with beveled edges, marked TO 20 on one side;
tablets of 60 mg: white, almost white, round, flat, with beveled edges, marked TO 60 on one side.
Fareston 20 mg Pharmacotherapeutic group
ATX code L02B A02.
Toremifene is a non-steroidal derivative of triphenylethylene. Like other members of this class (eg, tamoxifen and clomiphene), toremifene binds to estrogen receptors and has an estrogen-like and / or antiestrogenic effect, depending on the duration of treatment, sex, target organ, and other characteristics.
Treatment of toremifene in postmenopausal breast cancer patients showed a moderate decrease in serum cholesterol and LDL.
Toremifene binds competitively to estrogen receptors and inhibits estrogen-mediated stimulation of DNA synthesis and cell replication. In experimental cancer models, high-dose toremifene had an estrogen-independent antitumor effect.
The antitumor effect of toremifene on breast cancer is mediated by antiestrogenic effects, but it cannot be ruled out that other mechanisms (changes in oncogene expression, secretion of growth factors, induction of apoptosis and effects on cell cycle kinetics) may also have an antitumor effect.
Absorption. After oral administration, toremifene is rapidly absorbed. The peak concentration in blood plasma is determined on average after 3 (within 2-5) hours. Food does not affect the duration of absorption, but may delay the acquisition of peak concentrations for 1.5-2 hours. Changes in dietary intake are clinically insignificant.
Distribution. The concentration in blood plasma is described by a biexponential curve. The half-life in the first phase (distribution) is 4 (2-12) hours, in the second (elimination) – 5 (2-10) days. Apparent clearance (CL) and volume of distribution (V) were not evaluated due to the lack of intravenous infusion studies. More than 99.5% of toremifene is bound to plasma proteins (albumins). The kinetics of toremifene in blood plasma when taken orally from 11 to 680 mg per day is linear. The mean steady-state concentration of toremifene at the recommended dose of 60 mg per day is 0.9 (0.6–1.3) μg / ml.
Metabolism. Toremifene is actively metabolized. The major metabolite in plasma is N-dimethyltoremifene with a mean half-life of 11 (4–20) days. It has a similar antiestrogenic effect, but slightly less than toremifene. More than 99.9% are associated with plasma proteins. Another 3 less significant metabolites are detected in blood plasma: deaminohydroxytoremifene, 4-hydroxytoremifene and N, N-didemethyltoremifene.
Elimination. Toremifene is eliminated mainly as metabolites in the faeces. Enterohepatic recirculation may occur. More than 10% of the administered dose is excreted in the urine as metabolites. Due to slow elimination, steady-state plasma concentrations are reached within 4-6 weeks.
Treatment of hormone-dependent metastatic breast cancer in postmenopause as a first-line drug.
Fareston is not recommended for patients with estrogen receptor-negative tumors.
History of endometrial hyperplasia and severe hepatic insufficiency are contraindications to long-term use of toremifene.
Hypersensitivity to toremifene or to any of the excipients.
With the use of toremifene there were changes in cardiac conductivity, namely – prolongation of the QT interval, so the drug is contraindicated in patients with:
congenital or acquired prolongation of the QT interval;
electrolyte imbalance, especially with uncorrected hypokalemia;
clinically significant bradycardia;
clinically significant heart failure with decreased left ventricular ejection fraction;
symptomatic arrhythmias in the anamnesis.
Toremifene is not recommended for use with drugs that prolong the QT interval.