NOLVADEX ® - Tamoxifen

NOLVADEX ® is a drug based on Tamoxifen citrate

THERAPEUTIC GROUP: Antiestrogens - hormonal antagonists and related substances

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Indications NOLVADEX ® - Tamoxifen

NOLVADEX ® is a selective anti-estrogenic drug used in the treatment of breast cancer and has recently been re-evaluated for the short-term treatment of anovulatory female infertility.

Mechanism of action NOLVADEX ® - Tamoxifen

Tamoxifen, the active ingredient of NOLVADEX ® is a derivative of triphenylethylene, a precursor of even the most widely used clomiphene citrate, characterized by an important selective pharmacological activity, which makes it one of the most widely used drugs in the treatment of estrogen-dependent breast cancer.

The aforementioned active ingredient, in fact, once taken orally and absorbed at the intestinal level, by binding to plasma albumin, reaches the various tissues competing with estrogens for binding to the estrogen receptor.

In this way tamoxifen can bind to the overexpressed estrogenic receptors during breast cancer, thus preventing estrogens from exerting their trophic and proliferative effect on the neoplastic cells of estrogen dependent breast cancer.

Recent evidence has shown that tamoxifen can reduce blood levels of total cholesterol, and in particular of LDL, while preserving the maintenance of bone mineral density, thus being protective against cardiovascular and osteoporotic diseases.

The complex biological activity of this drug is still the subject of numerous studies, whose intent is to better characterize its molecular mechanism of action.

Studies carried out and clinical efficacy

1. TAMOXIFENE: A VALID ALTERNATIVE TO CLOMIFENE IN RESISTANT WOMEN

Study demonstrating that tamoxifen may be effective at a dose of 40 mg per day in inducing ovulation in women with polycystic ovary syndrome and resistant to clomiphene citrate.

2. TAMOXIFENE AND THROMBOEMBOLIC EVENTS

Epidemiological work demonstrating how the use of tamoxifen may correlate with the increased incidence of thromboembolic episodes. These episodes were observed in 5% of women undergoing treatment under the age of 45, 7% between 45 - 54 years, 14% between 55 - 64 years, 19% between 65 - 74 years, 27% in patients older than 74 years old.

3. THE ANTIFIBROTIC EFFECTS OF TAMOXIFENE

Experimental study demonstrating how tamoxifen can inhibit renal fibrosis in nephrosclerosis models, probably by modulating the secretion of pro-fibrotic factors such as TGF beta.

Method of use and dosage

NOLVADEX ®

Film-coated tablets of 10 - 20 mg of tamoxifen citrate:

the dosage, usually between 20 and 40 mg per day, taken in one or two administrations, must necessarily be defined by your doctor, who must supervise the entire therapeutic process and the effectiveness of the treatment.

Warnings NOLVADEX ® - Tamoxifen

In order for NOLVADEX ® therapy to express the maximum therapeutic efficacy without compromising the patient's state of health, with potentially dangerous side effects, it should be preceded by a careful medical examination to evaluate the prescriptive appropriateness and absence conditions incompatible with tamoxifen.

In this regard, it is important that the doctor informs the patient of the potential side effects of the therapy and of the main signs with which these occur, so that they can be recognized promptly.

Furthermore, medical supervision becomes fundamental both to ascertain the patient's state of health and the effectiveness of tamoxifen therapy.

NOLVADEX ® contains lactose and is therefore contraindicated in patients with galactose intolerance, lactase enzyme deficiency or glucose-galactose malabsorption.

The appearance of side effects on the visual apparatus, fogginess and opacification, could make the driving of vehicles or the use of machinery dangerous.

PREGNANCY AND BREASTFEEDING

Although in the literature there are conflicting data regarding the safety profile of tamoxifen when taken during pregnancy, the numerous experimental data showing effects on the fetus similar to those induced by estrogens or clomiphene allow extending the contraindications also to tamoxifen.

These contraindications also apply to the subsequent breastfeeding phase.

Interactions

The hepatic metabolism to which tamoxifen is subjected exposes the patient to clinically relevant drug interactions.

In fact the efficacy of the treatment and the incidence of its side effects could be significantly varied by the simultaneous intake of CYP3A4 modulators, an enzyme responsible for the metabolism of tamoxifen.

Furthermore, the concomitant intake of dicumarinic anticoagulants could be accentuated by tamoxifen, thus requiring periodic supervision of coagulation indices.

Statistically, the incidence of embolic thrombus episodes was greater in patients receiving tamoxifen and cytotoxic drugs.

Contraindications NOLVADEX ® - Tamoxifen

The use of NOLVADEX ® is contraindicated in case of hypersensitivity to the active ingredient or to one of its excipients, pregnancy and lactation, as a preventive therapy for breast cancer, or in patients with ductal carcinoma in situ or with anticoagulant therapy in place.

Undesirable effects - Side effects

Long-term therapy, necessary for the treatment of breast cancer, exposes the patient to numerous side effects related to the use of tamoxifen.

More precisely, hot flashes, vaginal blood loss, skin rash, dermatitis, hydro-saline retention, dizziness, visual disturbances, lower limb cramps, volumetric increase in ovarian cysts, hepatic steatosis and liver failure are the most frequently observed adverse reactions in progress of therapy with NOLVADEX ®.

However, those that are of most concern, taking on particular importance from the clinical point of view, are linked to the greater incidence of developing embolic thrombus events and malignant pathologies concentrated mainly in the uterine and endometrial area.