Products
Aromatase inhibitors are commercially available in the form of film-coated tablets and coated tablets. The first third-generation agent to be approved in many countries was anastrozole in 1996 (Arimidex, USA 1995). Other drugs are available today. The active ingredients available today all belong to the third generation. Earlier agents such as aminoglutethimide and formestane are not registered in many countries.
Structure and properties
Anastrozole and letrozole have a nonsteroidal structure and are triazole derivatives. Exemestane has a steroidal structure and is related to the natural substrate androstenedione.
Effects
Aromatase inhibitors (ATC L02BG) have antiestrogenic, antiproliferative, and antitumor properties. The effects are due to reversible or irreversible inhibition of aromatase. This enzyme of the cytochrome family (CYP19A1) is responsible for the biosynthesis of endogenous estrogens (estrone, estradiol) from androgens (androstenedione, testosterone). Inhibition lowers circulating estrogen levels, leaving fewer hormones available for tumor cells to grow.
Indications
For the treatment of breast cancer in postmenopausal women.
Abuse
Aromatase inhibitors are abused in bodybuilding and as doping agents. They inhibit the conversion of anabolic steroids to estrogens and are thought to prevent the development of gynecomastia (breasts in men).
Dosage
According to the SmPC. The drugs can be taken once a day because of their long half-life. They are always administered at the same time of day.
Active ingredients
Nonsteroidal aromatase inhibitors bind reversibly to the enzyme:
- Anastrozole (Arimidex, generics).
- Letrozole (Femara, generic).
Steroidal aromatase inhibitors irreversibly bind to aromatase. They are suicide inhibitors:
- Exemestane (Aromasin, generic).
Contraindications
Contraindications include:
- Hypersensitivity
- Premenopausal hormone status
- Pregnancy, lactation
Full precautions can be found in the drug label.
Interactions
Letrozole and exemestane are substrates of CYP450 isozymes and corresponding interactions are possible. Estrogens may reverse the effects of anastrozole and should not be administered concomitantly.
Adverse Effects
Adverse effects are largely a result of reduced estrogen levels and resemble menopausal symptoms. The most common possible adverse effects include:
- Hot flashes
- Skin rash
- Headache
- Muscle and joint pain
- Fatigue
- Sleep disturbances
- Sweating
- Mood swings
- Nausea
