Vero-Tamoxifen (Tablets) Instructions for Use

ATC Code

L02BA01 (Tamoxifen)

Active Substance

Tamoxifen (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiestrogenic drug with antitumor action

Pharmacotherapeutic Group

Antineoplastic agent, antiestrogen

Pharmacological Action

Antineoplastic agent. Tamoxifen has a combined spectrum of pharmacological action – acting as both an antagonist and an agonist of estrogen in various tissues.

In patients with breast cancer, in tumor cells, Tamoxifen primarily exhibits an antiestrogenic effect, preventing the binding of estrogens to 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 lobe, and tumors with high estrogen content.

In contrast to the estrogen receptor complex, the tamoxifen receptor complex does not stimulate DNA synthesis in the nucleus but inhibits cell division, leading to regression and death of tumor cells.

Pharmacokinetics

After oral administration, Tamoxifen is well absorbed from the gastrointestinal tract.

The maximum serum concentration (C_max) is reached within 4 to 7 hours after a single dose.

Steady-state concentration (C_ss) in the blood serum is usually achieved after 3-4 weeks.

Plasma protein binding is 99%.

It is metabolized in the liver to form several metabolites.

The elimination of tamoxifen from the body is biphasic with an initial half-life (T_1/2) of 7 to 14 hours and a subsequent slow terminal half-life (T_1/2) over 7 days.

It is excreted mainly as conjugates, primarily in the feces; small amounts are excreted in the urine.

Indications

Breast cancer in postmenopausal women, breast cancer in men after castration, kidney cancer, melanoma (containing estrogen receptors), ovarian cancer; prostate cancer with resistance to other drugs.

ICD codes

Dosage Regimen

The dosage regimen is set individually by the treating physician based on the specific indication, disease stage, and the patient’s overall condition.

For adjuvant treatment of breast cancer and metastatic breast cancer in postmenopausal women, the usual adult dose is 20 mg once daily.

For metastatic breast cancer in men, the recommended dose is 20 mg daily.

For reduction of breast cancer incidence in high-risk women, the recommended dose is 20 mg daily for five years.

In the treatment of advanced renal carcinoma and metastatic melanoma, doses of 20 mg to 40 mg daily may be used, administered in one or two divided doses.

For advanced ovarian cancer and androgen-independent prostate cancer, doses of 20 mg to 40 mg daily are commonly employed.

Doses exceeding 20 mg daily should be administered in divided doses (morning and evening).

Swallow the tablet whole with water, with or without food. Do not crush or chew the tablet.

Adhere strictly to the prescribed schedule. If a dose is missed, take it as soon as remembered unless it is almost time for the next dose. Do not double the dose to make up for a missed one.

Continue therapy for the duration prescribed by your physician, even if you feel well. Do not discontinue therapy without consulting your doctor.

Regular monitoring, including blood tests, liver function tests, and gynecological examinations, is essential during long-term treatment.

Adverse Reactions

From the immune system hypersensitivity reactions.

From the hematopoietic system often – anemia; infrequently – leukopenia, thrombocytopenia; rarely – agranulocytosis, neutropenia; very rarely – pancytopenia.

From the endocrine system: often – hypercalcemia (especially in patients with bone metastases at the start of therapy).

From metabolism very often – fluid retention in the body; often – increased plasma triglyceride concentration; very rarely – significant increase in plasma triglyceride concentration, sometimes in combination with pancreatitis; frequency unknown – increased body weight, anorexia.

From the nervous system often – headache, dizziness; frequency unknown – depression, confusion, photophobia, drowsiness.

From the organ of vision often – visual impairment (sometimes reversible, including cataract, retinopathy, corneal changes); rarely – optic neuropathy, optic neuritis (including with the development of blindness).

From the cardiovascular system often – leg cramps, transient ischemic attacks, thromboembolism, including pulmonary embolism (the risk of thromboembolic complications increases with combination therapy with other cytotoxic drugs), deep vein thrombosis of the lower extremities; infrequently – stroke.

From the respiratory system infrequently – interstitial pneumonitis.

From the digestive system very often – nausea; often – vomiting, diarrhea, constipation.

From the liver and biliary tract often – increased activity of hepatic transaminases, fatty liver degeneration; infrequently – liver cirrhosis; very rarely – cholestasis, hepatitis, jaundice, liver cell necrosis, liver failure (including fatal outcome).

From the skin and subcutaneous tissues: very often – rash; often – urticaria, alopecia, hypersensitivity reactions (including angioedema); rarely – vasculitis; very rarely – systemic lupus erythematosus, erythema multiforme, Stevens-Johnson syndrome, bullous pemphigoid.

From the musculoskeletal and connective tissue: often – myalgia; very rarely – bone pain.

From the reproductive system: very often – vaginal bleeding, vaginal discharge, menstrual cycle disorders (including amenorrhea in premenopausal women); often – genital itching, increase in uterine fibroids, proliferative changes of the endometrium (neoplasia, hyperplasia, polyps, rarely endometriosis); infrequently – endometrial cancer; rarely – polycystic ovaries, uterine sarcoma (more often malignant mixed Mullerian tumor), vaginal polyposis, decreased libido in men, impotence in men.

Other very often – hot flashes (due to the antiestrogenic effect of tamoxifen); rarely – pain in the area of affected tissues (especially at the beginning of therapy); very rarely – late cutaneous porphyria; frequency unknown – increased body temperature, increased fatigue. 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 pronounced erythema of the affected areas and adjacent regions (usually resolves within 2 weeks).

Contraindications

Hypersensitivity to tamoxifen; pregnancy, lactation (breastfeeding); childhood – depending on the dosage form.

With caution renal failure, diabetes mellitus, eye diseases (including cataract), deep vein thrombosis and thromboembolic disease (including in history), hyperlipidemia, leukopenia, thrombocytopenia, hypercalcemia, concomitant therapy with indirect anticoagulants.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding). If it is necessary to use during lactation, breastfeeding should be discontinued.

There are reports of spontaneous abortions, congenital malformations, and fetal death in women taking Tamoxifen during pregnancy, although a causal relationship has not been established.

Tamoxifen inhibits lactation.

Use in Renal Impairment

Should be used with caution in renal failure.

Pediatric Use

Can be used in children according to indications, in recommended doses and dosage forms. It is necessary to strictly follow the instructions in the tamoxifen drug leaflets regarding contraindications for the use of specific tamoxifen dosage forms in children of different ages.

Special Precautions

During therapy, it is necessary to periodically monitor blood clotting parameters, blood calcium levels, blood picture (leukocytes, platelets), liver function parameters, blood pressure, and to undergo an ophthalmological examination.

Women receiving tamoxifen therapy should regularly undergo gynecological examination.

In patients with hyperlipidemia, serum cholesterol and triglyceride concentrations should be monitored during treatment.

Tamoxifen should not be used in combination with drugs containing hormones, especially estrogens.

With simultaneous use with drugs that affect the blood coagulation system, dose adjustment of tamoxifen is necessary.

Effect on ability to drive vehicles and machinery

During the use of tamoxifen, patients should exercise caution when driving vehicles and machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with coumarin derivative anticoagulants, the risk of enhancing the anticoagulant effect increases; with cytostatics – an increase in the risk of thrombosis is possible.

With simultaneous use with allopurinol, hepatotoxic effects are possible; with aminoglutethimide – a decrease in the plasma concentration of tamoxifen, apparently due to increased metabolism.

In patients receiving Tamoxifen, prolongation of neuromuscular blockade caused by atracurium is possible.

With simultaneous use, bromocriptine may enhance the dopaminergic effect of bromocriptine.

In patients receiving Tamoxifen, when using warfarin, there is a risk of developing a threatening clinical situation: prolongation of prothrombin time, hematuria, hematoma are possible.

With simultaneous use with mitomycin, the risk of developing hemolytic-uremic syndrome increases.

Estrogens may reduce the therapeutic effect of tamoxifen.

Drugs that reduce calcium excretion (for example, thiazide diuretics) may increase the risk of hypercalcemia.

Concomitant use of tamoxifen and tegafur may contribute to the development of active chronic hepatitis and liver cirrhosis.

Simultaneous use of tamoxifen with other hormonal drugs (especially estrogen-containing contraceptives) leads to a weakening of the specific action of both drugs.

A decrease in the plasma concentration and clinical effect of tamoxifen is possible with simultaneous use with potent inhibitors of the CYP2D6 isoenzyme (for example, paroxetine, fluoxetine, quinidine, cinacalcet, bupropion, antidepressants from the group of selective serotonin reuptake inhibitors).

Tamoxifen should not be used simultaneously with anastrozole, as it may weaken the pharmacological action of the latter.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.