Products
Tamoxifen is commercially available in the form of film-coated tablets (Nolvadex, generic). It was synthesized in 1962 and tested as a contraceptive (“morning-after pill”) but was not suitable for this purpose. It was first used as a breast cancer drug in the early 1970s. It has been approved in many countries since 1976.
Structure and properties
Tamoxifen (C26H29NO, Mr = 371.5 g/mol) is present in drugs as tamoxifen citrate, a white crystalline powder that is sparingly soluble in water. The -triphenylethylene derivative has a nonsteroidal structure and carries a dimethylaminoethoxy side chain (cf. diethylstilbestrol).
Effects
Tamoxifen (ATC L02BA01) has antiproliferative and antitumor properties. It is either estrogen antagonistic or estrogen agonistic, depending on the tissue. It acts as an antagonist on breast tissue, but as an agonist on the endometrium, bone, and blood lipids. Tamoxifen is therefore also known as SERM (Selective Estrogen Receptor Modulator). The effects are based on competitive binding to intracellular estrogen receptors. Tamoxifen or its metabolites have a long half-life of up to 14 days.
Indications
For the treatment of breast cancer (adjuvant therapy, palliative therapy). In some countries, tamoxifen is also approved for breast cancer prevention in high-risk patients.
Dosage
According to the SmPC. Tablets are taken once daily at the same time of day, independent of meals. A treatment duration of five or ten years is recommended for adjuvant therapy.
Abuse
Tamoxifen can be abused as a doping agent. For competitive athletes, it is banned during and out of competition.
Contraindications
- Hypersensitivity
- Children and adolescents
- Pregnancy and lactation (harmful to fertility).
Full precautions can be found in the drug label.
Interactions
Tamoxifen is a prodrug that itself is only weakly effective and is metabolized by CYP2D6 and others to active metabolites. CYP2D6 inhibitors such as paroxetine may reduce efficacy by decreasing the formation of active metabolites. Appropriate combinations must be avoided. Other interactions have been described with CYP3A4 inducers, cytostatic agents, aromatase inhibitors, hormonal preparations (estrogens), vitamin K antagonists, and antiplatelet agents, among others.
Pharmacogenetics
Slow metabolizers of CYP2D6 form the active metabolites to a lesser extent and therefore may be less responsive to the drug.
Adverse effects
Potential adverse effects arise primarily because of estrogenic and antiestrogenic effects. The most common possible adverse effects include fatigue, tiredness, fluid retention, skin rashes, hot flashes, nausea, vaginal bleeding, and vaginal discharge. Possible serious side effects include:
- Endometrial cancer
- Blood count disorders such as anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis
- Thromboembolic events
- Visual disturbances
- Liver disease
- Severe skin rashes
