Included in the formulation
АТХ:L.02.B.A Antiestrogens
L.02.B.A.02 Toremifene
Pharmacodynamics:Antineoplastic anti-estrogenic non-steroidal drug, a derivative of triphenylethylene. Refers to selective modulators of estrogen receptors. Toremifene high affinity binds to estrogen receptors, competes with estradiol, inhibits estrogen-induced DNA synthesis and cell replication. In high doses toremifene can have an antitumor effect that is not associated with an estrogen-dependent effect.
Pharmacokinetics:Absorption is high, regardless of food intake. The volume of distribution is 8.28 l / kg. The connection with plasma proteins is more than 99.5% (very high), mainly with albumin. Biotransformation in the liver (CYP3A4) to form N-demethyltoremifene, which also has an antiestrogenic effect, but shows a weak antitumor activity in vivo. The distribution period is about 4 hours. The half-life period is about 5 days. Elimination with feces and kidneys (about 10%) for 1 week. The slow elimination of toremifene is caused by intestinal hepatic recirculation.
Indications:Estrogen-dependent breast cancer in postmenopausal women.
II.C50.C50 Malignant neoplasm of breast
Contraindications:- Hypersensitivity.
- Pregnancy, breast-feeding.
- Thromboembolic conditions in the anamnesis.
Carefully:Hypersensitivity.
Pregnancy and lactation:Studies in humans have not been conducted. Women of reproductive age who receive toremifene, should be instructed about the need to use contraceptives during the period of taking the drug. There is no evidence of penetration into human milk, but excreted in breast milk of rats. In view of the potential risk of adverse effects on the child (side effects) during treatment with toremifene, breastfeeding is recommended to be discontinued.
Recommendations FDA category D.
Dosing and Administration:Assign inside. As a standard dose for the first line of hormone therapy, taking a dose of 60 mg daily for a long time is recommended.
When the appointment of toremifene as the second line of hormonal treatment, the dose of the drug can be increased to 240 mg per day (120 mg twice a day).
When there are signs of progression of the disease, taking the drug is canceled.
Side effects:From the side endocrine system: rarely - an increase in body weight.
From the side digestive system: rarely anorexia, vomiting, constipation.
From the side CNS: rarely - headache, insomnia, increased levels of transaminases; in some cases - severe violations of the liver (jaundice).
From the side organ of vision: rarely - visual impairment, including changes in the cornea, cataracts.
From the side of cardio-vascular system: rarely - deep vein thrombosis, pulmonary embolism.
Dermatological reactions: rarely - skin rash, alopecia.
Other: rarely - shortness of breath.
Overdose:Symptoms: dizziness, headache, nausea, vomiting. Perhaps the appearance of symptoms, probably due to anti-estrogenic (hot flashes) and pro-estrogenic (uterine bleeding, dizziness, ataxia, nausea) effects. There is no specific antidote.
Treatment symptomatic.
Interaction:Drugs that reduce renal calcium excretion (including thiazide diuretics) may increase the risk of hypercalcemia.
Microsomal oxidation inductors (for example, phenobarbital, phenytoin or carbamazepine), can accelerate the metabolism of toremifene, reducing its concentration in the serum. In such cases, the daily dose should be doubled.
The interaction between antiestrogens and warfarin can lead to a marked increase in bleeding time (simultaneous use of toremifene and drugs of this group should be avoided).
Theoretically, the metabolism of toremifene can be slowed down by the effect of preparations inhibiting the isoenzyme CYP3A4, with the participation of which the metabolism of toremifene is realized. These drugs include ketoconazole and other such antifungal agents, as well as erythromycin, oleandomycin.
Special instructions:The treatment should be managed by specialists who have experience in carrying out endocrine therapy for malignant tumors. Before starting treatment, women should undergo thorough gynecological (pregnancy exclusion) and therapeutic examination.
The potential risk and benefit of using toremifene in bone metastasis should be correlated (careful monitoring of hypercalcaemia during the first weeks of taking toremifene), endometrial hyperplasia before treatment (long-term use of toremifene is not recommended), leukopenia,thrombocytopenia, ischemic heart disease, heart failure.