Tamoxifen Сitrate

Package leaflet (information for patients)

Tradename
Tamoxifen Citrate

Dosage form
Tablets 10 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Tamoxifen Citrate 10 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Antiestrogens

Pharmacological properties
Tamoxifen is a non - steroidal antiestrogenic agent that also has mild estrogenic properties. Its action is based on the ability to block estrogen receptors. Tamoxifen, as well as some of its metabolites, compete with estradiol for binding sites with cytoplasmic estrogen receptors in the tissues of the breast, uterus, vagina, anterior pituitary gland, and tumors with a high content of estrogen receptors. In contrast to estrogen, tamoxifen, by binding to estrogen receptors, does not affect DNA synthesis in the nucleus, but inhibits cell division, which leads to regression of tumor cells as a result of their death. Pharmacokinetics. Oral tamoxifenwell absorbed. The maximum serum concentration is reached within 4 to 7 hours after taking a single dose. The equilibrium concentration of tamoxifen in serum is usually reached after 3-4 weeks of administration. Communication with plasma proteins - 99%. It is metabolized in the liver with the formation of several metabolites, the isoenzyme CYP2C9 is involved in the metabolism. By demethylation, tamoxifen is metabolized to N- desmethyltamoxifen, which in turn is transformed by N- demethylation into the N- desmethyl metabolite. The elimination of tamoxifen from the body is biphasic with an initial half-life of 7 to 14 hours, followed by a slow terminal half-life of 7 days. It is excreted mainly through the intestines, mainly in the form of metabolites; a small amount - by the kidneys.

Indications for use
Adjuvant therapy for early breast cancer with estrogen-positive receptors; treatment of locally advanced or metastatic breast cancer with estrogen-positive receptors; breast cancer ( including in men after castration). The drug can also be used for other solid tumors that are resistant to standard treatments, in the presence of overexpression of estrogen receptors.

Method of administration and dosage
Inside. The tablets should be taken without chewing, with a small amount of liquid, in one dose in the morning or dividing the required dose into two doses, in the morning and in the evening. The dosage regimen is usually set individually, depending on the indications. The maximum daily dose is 40 mg. The recommended dose is 20 mg of tamoxifen. When signs of disease progression appear, the drug is discontinued. The duration of treatment depends on the severity of the disease, usually long-term treatment is required. As an adjuvant therapy in women with breast cancer, the recommended duration of tamoxifen treatment is about 5 years.

Side effects
When treating with tamoxifen, the most common adverse reactions associated with its antiestrogenic effect, manifested in the form of hot flashes ("hot flashes"), vaginal bleeding or discharge, itching in the genital area, alopecia, pain in the area of the lesion, ossalgia, weight gain... Less often or rarely, the following adverse reactions were observed: fluid retention, anorexia, nausea, vomiting, constipation, fatigue, depression, confusion, headache, dizziness, drowsiness, fever, skin rash (including isolated reports of erythema multiforme, syndrome Stevens- Johnson and bullous pemphigoid ), visual impairment, including changes in the cornea, cataract and retinopathy, retrobulbar neuritis, allergic reactions, including angioedema; decreased libido in men, impotence. Interstitial pneumonitis has been reported very rarely. At the beginning of treatment, a local exacerbation of the disease is possible - an increase in the size of soft tissue formations, sometimes accompanied by severe erythema of the affected areas and adjacent areas, which usually disappears within 2 weeks. The likelihood of thrombophlebitis and thromboembolism may increase. Leg cramps are common. Transient leukopenia and thrombocytopenia, as well as an increase in the activity of "liver" enzymes, very rarely accompanied by more severe liver dysfunctions such as fatty liver, cholestasis and hepatitis, may occur infrequently. Rarely, an increase in the concentration of serum triglycerides was observed in some cases combined with pancreatitis. Some patients with bone metastases have hypercalcemia at the start of treatment. Tamoxifen causes amenorrhea or irregular menstruation in premenopausal patients, as well as the reversible occurrence of ovarian cystic tumors. With long-term treatment with tamoxifen, changes in the endometrium can be observed, including hyperplasia, polyps, the development of uterine fibroids and, in isolated cases, endometrial cancer, uterine sarcoma.

Contraindication
Hypersensitivity, pregnancy, during lactation.
With care. Diseases of the eye (in incl. Cataracts ), hyperlipidemia, leukopenia, thrombocytopenia, hypercalcemia, expressed thrombosis, thromboembolic disease (in incl. A history ).
Category of action on the fetus. D

Overdose
Acute overdose of tamoxifen in humans has not been observed. In case of an overdose, neurotoxicity may develop (tremor, hyperreflexia, unsteadiness of gait, dizziness). No specific antidote is known. Treatment is symptomatic.

Precautions
Before starting treatment, women should undergo a thorough gynecological (exclusion of pregnancy) and therapeutic examination.
Tamoxifen induces ovulation, which increases the risk of pregnancy, therefore, women of reproductive age need to use reliable methods of contraception (non-hormonal) during treatment and within 3 months after the end of treatment.
During the period of therapy, it is necessary to periodically monitor blood clotting indicators, the concentration of Ca2 + in the blood, the blood picture (leukocytes, platelets), liver function indicators, blood pressure, conduct an examination with an ophthalmologist - every 3 months, a gynecological examination (with the appearance of bloody discharge from the vagina or vaginal bleeding the drug should be discontinued).
In patients with bone metastases, the concentration of Ca2 + in the blood serum should be determined periodically during the initial period of treatment (in case of severe hypercalcemia, tamoxifen should be temporarily discontinued). It is ineffective in the treatment of patients with metastases (especially in the liver).
If signs of venous thrombosis of the lower extremities appear (pain in the legs or their swelling), thromboembolism of the branches of the pulmonary artery (shortness of breath), the drug should be discontinued.
In patients with hyperlipidemia, during treatment, it is necessary to control the concentration of cholesterol and TG in the blood serum. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Interaction with other medicinal products
With the simultaneous use of tamoxifen and cytostatics, the risk of thrombus formation increases. There are reports of an increase in tamoxifen of the anticoagulant effect of indirect anticoagulants - coumarin derivatives (for example, warfarin ). Drugs that reduce calcium excretion (eg, thiazide diuretics) may increase the risk of hypercalcemia. The combined use of tamoxifen and tegafur can contribute to the development of active chronic hepatitis and liver cirrhosis. The simultaneous use of tamoxifen with other hormonal drugs (especially, estrogen-containing contraceptives) leads to a weakening of the specific effect of both drugs. With the simultaneous use of tamoxifen and bromocriptine, an increase in the concentration of tamoxifen and N- desmethyltamoxifen in blood plasma is observed. Tamoxifen should not be used concomitantly with aromatase inhibitors ( anastrozole, letrozole ).

Special instructions
Carefully. Diseases of the eyes ( including cataract), severe thrombophlebitis, thromboembolic disease ( including history), hyperlipidemia, leukopenia, thrombocytopenia, hypercalcemia, liver disease; hereditary lactose intolerance, lactase deficiency or impaired absorption of glucose and galactose (the drug contains lactose). Application during pregnancy and during breastfeeding: It is a contraindication for the use of the drug. Women receiving tamoxifen should have regular gynecological examinations (once every 3 months). If you experience bleeding from the vagina or vaginal bleeding, the drug should be discontinued. Tamoxifen can cause ovulation, which increases the risk of pregnancy, and therefore women of reproductive age need to use reliable methods of contraception (non-hormonal) during treatment and for 3 months after the end of treatment. In patients with bone metastases, the concentration of calcium in the blood serum should be determined periodically during the initial period of treatment. In case of severe disorders ( hypercalcemia ), tamoxifen should be temporarily discontinued. If signs of venous thrombosis of the lower extremities appear (pain in the legs or their swelling), pulmonary embolism (shortness of breath), the drug should be discontinued. During the period of therapy, it is necessary to periodically monitor the blood coagulation indicators, the calcium content in the blood, the blood picture (leukocytes, platelets), liver function indicators, blood pressure, and an ophthalmologist's examination every 3 months. In patients with hyperlipidemia, during treatment, it is necessary to control the concentration of cholesterol and triglycerides in the blood serum. During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Pregnancy and elbowing
This drug should not be used during pregnancy and lactation.
In accordance with the adverse reactions that may occur in infants, it is necessary to decide whether to stop breastfeeding or stop taking the drug.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
On prescription.

Packaging
Tamoxifen Сitrate 10 mg Tablets. There are 25 tablets in a blister. 4 blisters are packed in a cardboard box together with an enclosed leaflet.