Nolvadex

General information

Nolvadex is a drug with antitumor and anti-estrogenic properties, used for the treatment and prevention of hormone-dependent neoplasms. The drug effectively blocks the effect of estrogens on tissues, which makes it an important tool in the therapy of certain types of cancer and other pathologies associated with hormonal imbalance.

Trade name

Nolvadex

International Nonproprietary Name (INN)

Tamoxifen

Form of release

The drug is available in the following form:

• Film-coated tablets: dosages of 10 mg, 20 mg, 30 mg and 40 mg.

Composition

Acting substance

Tamoxifen (in the form of tamoxifen citrate).

Auxiliary components

The composition includes the following additional substances:

• Lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose (as part of the shell), titanium dioxide, polyethylene glycol.

Pharmacologic properties

Pharmacodynamics

Nolvadex, containing tamoxifen, has anti-estrogenic action, which is based on competitive binding to estrogen receptors in target tissues such as breast, uterus and tumor cells. The drug blocks estrogen-dependent stimulation of cell growth, which is particularly important in the treatment of hormone-dependent forms of breast cancer. Tamoxifen acts as a selective estrogen receptor modulator (SERM): in some tissues it exhibits anti-estrogenic properties, inhibiting cell proliferation, and in others (e.g., in bone tissue and endometrium) it may have a partial estrogen-like effect, which affects bone density and blood lipid levels.

The mechanism of action involves inhibiting the transcription of estrogen-dependent genes, which disrupts the cell cycle and leads to the arrest of tumor cell division in the G1 phase. The drug also decreases the secretion of growth factors such as TGF-α and increases the production of inhibitory factors such as TGF-β. Its therapeutic effect occurs gradually and peaks with prolonged use, making it suitable for both treatment and prevention of recurrence.

Pharmacokinetics

Tamoxifen is well absorbed from the gastrointestinal tract after oral administration, reaching maximum plasma concentrations after 4-7 hours. Bioavailability is about 90%, and food intake insignificantly affects the rate of absorption. The drug undergoes a first-pass effect through the liver, where its metabolism begins, but this does not reduce its efficacy due to the formation of active metabolites.

Binding to plasma proteins (mainly albumin) reaches 99%, and the volume of distribution is about 50-60 liters, indicating a wide penetration into tissues. Metabolism is carried out in the liver with the participation of enzymes of the cytochrome P450 system, mainly CYP2D6 and CYP3A4. The main active metabolites, N-desmethyltamoxifen and 4-hydroxytamoxifen, have comparable or even greater activity than the parent substance and contribute significantly to the therapeutic effect.

The elimination half-life of tamoxifen is about 5-7 days, and of its metabolites - up to 14 days, which provides prolonged action after a single dose. Excretion occurs mainly through the intestine with bile (about 65% in the form of conjugates), and only a small part (about 30%) is excreted by kidneys. In patients with impaired liver function, metabolism may be slowed down, which requires an individual approach to dosage.

Indications for use

Diseases and conditions for which the drug is prescribed

Nolvadex is used for the following conditions and diseases:

• Breast cancer in women and men with estrogen receptor positive breast cancer (as adjuvant therapy after surgery or primary treatment).
• Metastatic breast cancer in patients with hormone-dependent tumors.
• Prevention of breast cancer in high-risk women (e.g., with a family history or identified precancerous conditions).
• Treatment of infertility in women associated with anovulation by stimulation of ovulation (as prescribed by a physician in certain cases).
• Endometrial cancer (in rare cases, as part of a complex therapy).

Contraindications

Conditions under which the use of the drug is prohibited

The use of Nolvadex is prohibited in the following conditions:

• Individual hypersensitivity to tamoxifen or any auxiliary components of the drug.
• Pregnancy and breastfeeding period (due to high risk of teratogenic effects on the fetus).
• Severe thrombocytopenia, leukopenia, or hypercalcemia unrelated to the underlying disease.
• Thromboembolic diseases in the active phase (deep vein thrombosis, pulmonary embolism) or their presence in the anamnesis without adequate control.
• Severe hepatic insufficiency with impaired metabolism of the drug.
• Simultaneous use with potent CYP2D6 inhibitors (e.g., paroxetine) without dose adjustment, if it significantly reduces efficacy.

How to use and dosage

How to take

Nolvadex is taken orally, regardless of meals. Tablets should be swallowed whole, drinking enough water (100-200 ml) to ensure normal passage through the digestive tract. It is recommended to take the drug at the same time of day to maintain a stable concentration in the body.

Dosages for adults and children

Adults

Dosage depends on the indication:

• Breast cancer (treatment and adjuvant therapy): 20 mg once daily, in some cases an increase to 40 mg daily (divided into two 20 mg doses) is possible.
• Breast cancer prophylaxis: 20 mg once daily for 5 years or according to the regimen prescribed by a physician.
• Metastatic breast cancer: 20-40 mg per day, divided into 1-2 doses depending on tolerability.
• Infertility (anovulation): 20 mg per day from the 2nd to the 5th day of the menstrual cycle, if necessary, the dose can be increased to 40 mg.

Children

The use of Nolvadex in children is not recommended, as the safety and efficacy of the drug in this age group are not sufficiently studied. Use is possible only in exceptional cases for strict indications (for example, in rare hormone-dependent tumors) and under the supervision of a specialist.

Dose adjustment for certain conditions

Dose adjustment is usually not required in renal insufficiency, as excretion of the drug through the kidneys is minimal. However, in severe hepatic insufficiency (e.g., cirrhosis), the metabolism of tamoxifen slows down, which may lead to accumulation of active substances. In such cases, the initial dose is reduced to 10 mg per day with subsequent observation of the patient's condition. In elderly people the dosage is not adjusted, but monitoring of liver function and blood coagulation system is required.

Side effects

Possible adverse reactions of the body

The following adverse reactions may occur during the use of Nolvadex:

• From the side of the reproductive system: hot flashes, menstrual disorders, vaginal discharge, itching in the genital area.
• Side of the digestive system: nausea, vomiting, decreased appetite, discomfort in the abdominal region.
• Nervous system: headache, dizziness, fatigue, depression or mood swings.
• Skin and hair: hair loss, skin rash, dry skin.
• Cardiovascular system: edema of the lower extremities, increased risk of thromboembolic complications.
• Side of the organs of vision: changes in the ocular fundus, cataracts, decreased visual acuity (with prolonged use).
• Other: increase in blood calcium levels, bone pain or tumors, temporary increase in liver enzyme activity.

Overdose

Symptoms of overdose

The following symptoms may occur if the recommended dose of Nolvadex is exceeded:

• Exacerbation of side effects: marked hot flashes, nausea, dizziness.
• Neurologic disorders: tremor, confusion, seizures (in rare cases).
• Cardiovascular disorders: palpitations, fluctuations in blood pressure.
• Hypercalcemia: weakness, thirst, confusion (especially in patients with bone metastases).

First aid measures

In case of suspected overdose it is necessary:

1. Stop taking the drug immediately.
2. Seek medical attention.
3. Rinse the stomach if ingestion has occurred recently (within 1-2 hours).
4. Give the patient activated charcoal (1 g/kg body weight) to reduce absorption.
5. Provide symptomatic support: control of calcium levels, hydration, observation of the condition until the arrival of a doctor.

Interaction with other drugs

Influence on the effects of other drugs

Nolvadex may affect the effectiveness of other medicines:

• Exacerbates the effects of anticoagulants (e.g., warfarin), increasing the risk of bleeding, which requires monitoring of blood clotting parameters.
• Decreases the effectiveness of drugs metabolized by CYP2D6 (e.g., some antidepressants such as fluoxetine) due to competition for enzymes.
• Coadministration with CYP3A4 inhibitors (e.g., ketoconazole) may increase tamoxifen blood concentrations.
• CYP3A4 inducers (e.g., rifampicin) accelerate the metabolism of the drug, reducing its efficacy.
• Combined use with other hormonal agents (estrogens) may weaken the therapeutic effect of Nolvadex.

Compatibility with alcohol and food

Alcohol consumption during treatment with Nolvadex is not recommended, as it may increase side effects such as nausea and dizziness, as well as increase the load on the liver, where the drug is metabolized. Food does not significantly affect the absorption of tamoxifen, but taking it after a meal may reduce stomach irritation in some patients.

Special Instructions

Use in pregnancy and breastfeeding

Nolvadex is contraindicated during pregnancy because tamoxifen has teratogenic potential and may cause fetal malformations, including genital and skeletal abnormalities. Women of reproductive age should use reliable contraceptive methods during treatment and for 2 months after its completion. The drug penetrates into breast milk, therefore its use during lactation is prohibited; if treatment is necessary, breastfeeding should be discontinued.

Effect on driving and mechanisms

The drug may cause side effects such as dizziness, fatigue and visual disturbances, especially at the beginning of treatment or when changing the dosage. Patients are recommended to refrain from driving vehicles and working with mechanisms until individual tolerability of Nolvadex is established and influence on concentration is excluded.

Particulars of use in the elderly and children

In elderly patients Nolvadex is used in standard doses, but regular monitoring of liver function and blood coagulation system is required due to increased risk of thromboembolic complications and metabolic changes. In children, the use of the drug is limited to rare cases of hormone-dependent tumors; dosage and duration of therapy are determined individually, taking into account the potential impact on growth and development of the endocrine system.