Fareston, tablets 20 mg 30 pcs

Pharmacodynamics

The anti-tumor anti-estrogenic non-steroidal drug, a triphenylethylene derivative.

Toremifene specifically binds to estrogen receptors, competing with estradiol, inhibits estrogen-induced DNA synthesis and cell replication. At high doses, toremifene can have an antitumor effect unrelated to estrogen-dependent action.

In breast cancer patients the antitumor effect of toremifene is mainly related to its anti-estrogen activity, although other mechanisms (regulation of oncogene expression, growth factor secretion, apoptosis induction, influence on cell cycle kinetics) cannot be excluded.

Pharmacokinetics

Absorption

Toremifene is completely absorbed after oral administration. Cmax in blood plasma is reached after 3 h (2-5 h). Food intake has no effect on the completeness of absorption, but may increase the time to reach Cmax by 1.5-2 hours. These changes have no clinical significance.

Distribution

The binding to plasma proteins (mainly to albumin) is 99.5%. Css in plasma is established within 3-4 weeks (at a dose of 60 mg/day).

Metabolism and excretion

The rapid phase of distribution with a mean T1/2 of about 4 h (2-12 h) is followed by a slow phase of excretion with a mean T1/2 of about 5 days (2-10 days).

Toremifene is metabolized in the liver by hydroxylation and demethylation with the participation of CYP3A4 isoenzyme to form the active metabolite, N-demethyltoremifene. Average T1/2 of N-demethyltremifene is 11 days (4-20 days). In blood serum we found 3 more metabolites: deaminohydroxytoremifene, 4-hydroxytoremifene and N,N-didemethyltoremifene. Total clearance is 5 l/h.

Extracted through the intestine, mainly as metabolites; about 10% – by the kidneys.

Indications

Estrogen-dependent breast cancer in postmenopausal women.

Active ingredient

Composition

1 tablet contains:

Active substances:

Toremifene (in citrate form) 20 mg.

Associates:

Corn starch,

lactose,

How to take, the dosage

Prescribe orally. The dosing regimen is set on an individual basis.

As a standard dose for first-line hormone therapy, a daily dose of 60 mg is recommended for the long term.

If Fareston is prescribed as a second-line hormone treatment, the dose can be increased to 240 mg/day (120 mg twice daily).

The drug should be stopped if there are signs of disease progression.

Interaction

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

Microsomal oxidation inducers (e.g., phenobarbital, phenytoin or carbamazepine) may accelerate the metabolism of toremifene, reducing its concentration in serum. In such cases, the daily dose should be doubled.

The interaction between anti-estrogens and warfarin may lead to a marked increase in bleeding time (concomitant use of toremifene and drugs of this group should be avoided).

Theoretically metabolism of toremifene can be slowed by the drugs that inhibit CYP3A4 isoenzyme, which metabolizes toremifene. These drugs include ketoconazole and other similar antifungal drugs, as well as erythromycin and oleandomycin.

Special Instructions

Before starting treatment, the patient should be examined by a gynecologist. Particular attention should be paid to the condition of the endometrial mucosa. Then gynecological examinations should be repeated at least once a year.

Patients with conditions such as hypertension, diabetes, high body mass index (>30), or who have been on long-term OST are at risk for endometrial cancer and therefore should be monitored closely.

Toremifene is not recommended in patients with a history of severe thromboembolic disease.

Patients with decompensated heart failure or severe angina require close monitoring.

Because patients with bone metastases may develop hypercalcemia at the start of treatment with the drug, these patients need close monitoring.

Contraindications

With caution: the drug is prescribed in case of leukopenia, thrombocytopenia, hypercalcemia (including in case of metastases in bone tissue).

Side effects

The effects due to anti-estrogenic action: the most common are hot flashes (hot flashes), increased sweating, vaginal bleeding or discharge, increased fatigue, nausea, rash, genital itching, fluid retention, dizziness, depression. These effects are usually mild.

Endocrine system disorders: rarely – weight gain.

The digestive system: rarely – anorexia, vomiting, constipation.

CNS disorders: rarely – headache, insomnia, increased level of transaminases; in some cases – severe liver function disorders (jaundice).

An organ of vision: rare – visual impairment, including changes of the cornea, cataracts.

Cardiovascular system disorders: rare – deep vein thrombosis, pulmonary embolism.

Dermatological reactions: rarely – skin rash, alopecia.

Others: rarely – shortness of breath.

In patients with bone metastases there have been cases of hypercalcemia at the beginning of treatment.

The risk of endometrial changes such as hyperplasia, polyposis, and cancer is increased. This can be caused by the main pharmacological property of the drug – estrogen stimulation.

Overdose

Symptoms: Dizziness, headaches, nausea and/or vomiting have been observed at a daily dose of Fareston 680 mg. Theoretically, an overdose can manifest as an increase in anti-estrogenic effects (hot flashes) or estrogenic effects (vaginal bleeding).

Treatment: conducting symptomatic therapy.

Pregnancy use

Fareston is contraindicated in pregnancy and during lactation (breastfeeding).