Antiestrogen drug with antitumor activity
Tamoxifen is a nonsteroidal anti-estrogen agent having also weak estrogenic properties. Its action is based on the ability to block estrogen receptors. Tamoxifen, as well as some of its metabolites, estradiol compete for binding sites with cytoplasmic estrogen receptors in breast tissue, uterus, vagina, pituitary gland tumor and with a high content of estrogen receptors. In contrast to estrogen receptor complex receptor complex tamoxifen does not stimulate DNA synthesis in the nucleus and inhibits cell division that leads to tumor regression and cell death.
After oral administration, tamoxifen is well absorbed. Serum Cmax achieved in the range of 4 to 7 h after administration of a single dose. Tamoxifen equilibrium concentration in serum is usually achieved after 3-4 weeks of administration. Relationship to plasma proteins – 99%.
It is metabolized in the liver with the formation of metabolites.
Tamoxifen excretion from the body has a biphasic pattern with an initial T1 / 2 of 7 to 14 hours followed by a slow and a terminal T1 / 2 for 7 days. It provided mainly as conjugates, mainly with faeces and only a small amount excreted in urine. Read more
The dosage regimen is generally determined individually depending on the evidence. The daily dose is 20-40 mg. As a standard dose is recommended to take 20 mg of tamoxifen daily for a long time inside. If signs of progression of the disease reception cancel preparation.
Tablets should be taken with liquid, squeezed small amounts of liquid, at once in the morning, or by separating the required dose into two doses, morning and evening.
Acute overdose of tamoxifen in humans has not been observed. It is expected that an overdose can cause amplification of the above adverse reactions. There is no specific antidote, treatment should be symptomatic.
When concomitant administration of tamoxifen and cytotoxic drugs increases the risk of thrombosis.
Antacids, histamine H2-blockers of receptors and other drugs of similar action by raising pH in the stomach can cause premature dissolution and loss of protective effect of enteric tablets. The interval between tamoxifen and these drugs should be 1-2 hours.
There are reports on the strengthening of the anticoagulant effect of drugs tamoxifen coumarin (eg warfarin).
Drugs that reduce the excretion of calcium (eg, thiazide diuretics number) may increase the risk of hypercalcemia.
The combined use of tamoxifen and tegafur can contribute to the development of chronic active hepatitis and cirrhosis.
Concomitant use of tamoxifen with other hormonal drugs (especially estrogensoderjath contraceptives) leads to a weakening of the specific actions of both drugs.
Pregnancy and lactation
Tamoxifen can cause ovulation, which increases the risk of pregnancy, in connection with which women who are sexually active, during (and for about 3 months after) treatment with tamoxifen is recommended to use a mechanical or non-hormonal contraceptive.
When tamoxifen most common adverse reactions associated with its anti-estrogenic activity, manifested in the form of hot flashes (hot flushes), vaginal bleeding or discharge, itching in the genital area, alopecia, pain in the area of ??the lesion, ossalgia, weight gain.
Less frequently or infrequently observed the following side effects: water retention, anorexia, nausea, vomiting, constipation, fatigue, depression, confusion, headache, dizziness, drowsiness, fever, skin rash, visual disturbances, including corneal changes, cataracts , retinopathy and optic neuritis.
At the beginning of the treatment capacity of local worsening of the disease – an increase in the size of soft tissue structures, sometimes accompanied by severe erythema lesions and surrounding areas – which usually resolves within 2 weeks. It may increase the risk of thrombophlebitis and thromboembolism. Sometimes there may be transient leukopenia and thrombocytopenia, as well as an increase in liver enzymes, rarely accompanied by a severely impaired liver function, such as fatty liver, cholestasis and hepatitis.
In some patients with bone metastases at the beginning of the treatment of hypercalcemia observed.
Tamoxifen causes amenorrhea or irregular menstruation in women in pre-menopausal, as well as the development of reversible cystic ovarian tumors.
With long-term treatment with tamoxifen may experience endometrial changes including hyperplasia, polyps, and in rare cases – endometrial cancer, and the development of uterine fibroids.
Terms and Conditions of storage
List B. In a dry place at temperatures no higher than 25 ° C. Shelf life – 3 years.
– Estrogen-dependent breast cancer in women (especially in menopause) and male breasts.
The drug can be used to treat ovarian cancer, endometrial cancer, kidney cancer, melanoma, soft tissue sarcomas in the presence of estrogen receptor in the tumor, as well as for the treatment of prostate cancer with resistance to other drugs.
– Hypersensitivity to tamoxifen and / or any other ingredients of the formulation.
Precautions: renal failure, diabetes, eye diseases (including cataracts), deep vein thrombosis and thromboembolic disease (including history), hyperlipidemia, leukopenia, thrombocytopenia, hypercalcemia, concomitant therapy with indirect anticoagulants.
Women taking tamoxifen should undergo regular gynecological examination. When bleeding from the vagina, or vaginal bleeding should stop taking the drug.
In patients with bone metastases periodically during the initial period of treatment should be determined the concentration of calcium in blood serum. In case of apparent violations of tamoxifen should be suspended.
If signs of thrombosis of the lower extremities (leg pain or swelling), pulmonary embolism (shortness of breath), the drug should be discontinued.
During therapy should be periodically monitored blood coagulation indices, blood calcium, blood count (leukocytes and platelets), liver function, blood pressure, inspect an ophthalmologist.
Patients with hyperlipidemia in the treatment necessary to control the concentration of cholesterol and triglycerides in the blood serum.
Effects on ability to drive vehicles and management mechanisms
In the period of treatment should refrain from activities potenialno hazardous activities that require high concentration and psychomotor speed reactions.