Exemestane - instructions for use, dose, side effects, contraindications

In postmenopausal women, estrogens are produced primarily by converting androgens to estrogens under the action of the aromatase enzyme in peripheral tissues. The mechanism of action of exemestane is due to irreversible binding to the active fragment of aromatase, which leads to inactivation of the enzyme.

Exemestane does not possess progestagenic and estrogenic activity. When used in high doses, only a slight androgenic activity appears. Has no effect on the biosynthesis of cortisol and aldosterone in the adrenal glands.

A slight increase in the levels of LH and FSH in serum is observed even at low doses of exemestane. This effect, however, is uncharacteristic for the drugs of this pharmacological group.It probably develops on the principle of feedback at the level of the pituitary: a decrease in the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland also in postmenopausal women.

Pharmacokinetics:

After oral intake quickly absorbed (the food improves absorption, the plasma level achieved in this case is 40% higher than when taken on an empty stomach). With a single application of 25 mg after meals, the maximum concentration (18 ng / ml) is achieved within 2 hours. Binding to plasma proteins is 90% and is independent of the total concentration. Well distributed in tissues. Metabolized by oxidation of the methylene group at position 6 with the participation of the CYP3A4 isoenzyme and / or by reduction of the 17-keto group with the participation of aldoketoreductases to form inactive or inactive metabolites. The elimination half-life is 24 hours. It is excreted in urine (less than 1% unchanged) and with faeces in approximately equal parts within 1 week.

Indications:

Treatment of advanced breast cancer in women in natural or induced postmenopausal women who have progression of the disease on the background of anti-estrogen therapy.

Hormonal therapy for advanced breast cancer in women in natural or induced postmenopausal women who have progressed to treatment with either non-steroid aromatase inhibitors or progestins.

ICD-10

II.C50.C50 Malignant neoplasm of breast

Contraindications:

Pregnancy, lactation (breastfeeding), children's age, hypersensitivity to exemestan.

Carefully:

Dysfunction of the liver and kidneys, despite an increase in the concentration of the drug in the blood plasma with moderate and severe hepatic and renal insufficiency, dose adjustment is not required. The safety of prolonged administration of exemestane in such patients has not been studied.

Pregnancy and lactation:

Action category for the fetus by FDA - D. Contraindicated in pregnancy.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

If administered orally, the recommended dose for adults and elderly patients is 25 mg once daily, preferably after meals. Treatment should continue until signs of progression of the tumor, after which it is recommended to adjust the medical tactics.

With hepatic or renal failure, dose adjustment is not required.

Side effects:

From the side CNS: often fatigue, dizziness; sometimes - headache, insomnia, depression, asthenia.

From the side digestive system: often - nausea; sometimes - abdominal pain, anorexia, constipation, dyspepsia; rarely - an increase in the indicators of functional hepatic tests in the serum, an increase in the level of alkaline phosphatase.

From the side endocrine system: often - paroxysmal sensations of heat (hot flashes).

Dermatological reactions: possible - skin rash, alopecia.

From the side hematopoiesis system: often - a decrease in the level of lymphocytes; rarely - thrombocytopenia, leukopenia.

From the side metabolism: possible - peripheral edema (edema of the feet, shins).

Other: often - increased sweating.

Overdose:

Symptoms: Acute leukocytosis (chills, cough, eye pain, fever, feeling of weakness, sore throat, unusual weakness).

There is no specific antidote.

Treatment symptomatic: gastric lavage, hemodialysis, control of vital body functions.

Interaction:

Preparations containing estrogens, when used simultaneously with eksemestanom completely level its pharmacological effect.

Inductors of cytochrome P450 (for example, carbamazepine, phenobarbital, phenytoin, rifampicin, preparations of St. John's wort) - it is possible to reduce the concentration of exemestane in blood plasma; a dose modification is necessary.

Special instructions:

It should not be used in women with premenopausal endocrine status, as the effectiveness and safety of the drug in this category of patients was not evaluated. In those cases when the need for application is clinically justified, postmenopausal status should be confirmed by determining the level of LH, FSH and estradiol.

In patients with initial lymphopenia, the risk of a decrease in the number of lymphocytes is increased. An increase in the parameters of functional hepatic tests in the serum and an increase in the level of alkaline phosphatase was noted mainly in patients with liver and bone metastases, as well as in the presence of other liver lesions.

It is not recommended for use in children.

When performing work related to the need for concentration of attention and high speed of psychomotor reactions, patients should be kept in mind,that the use of exemetan may cause drowsiness and dizziness.

Instructions

Exemestan (Exemestanum)