Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
The antitumor agent, the aromatase inhibitor, is similar in structure to the natural steroid hormone androstenedione.
In postmenopausal women, estrogens are primarily produced 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 administration, it is rapidly absorbed from the digestive tract. With a single dose of 25 mg after meals, Cmax is 18 ng / ml and is reached within 2 hours. The food improves absorption: the level of exemestane obtained in plasma is 40% higher than after fasting.
After reaching C max, the level of the active substance in the plasma decreases; while the final T 1/2 is approximately 24 hours. Exemestane is widely distributed in tissues. Binding to plasma proteins is about 90%, the degree of binding does not depend on the total concentration.
After repeated administration at a dose of 25 mg / day, the plasma concentration of the unchanged substance was similar to that after a single dose.
Exemestane is characterized by high clearance, mainly due to metabolism. 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 aldokode-reductase. As a result, numerous secondary metabolites are formed, but the amount of each is very small compared to the administered dose. With regard to the inhibition of aromatase, these metabolites are either inactive or less active than the unaltered substance.
It is excreted in the urine and with feces. Excretin and its metabolites are excreted from the body mainly within 1 week. Less than 1% is excreted in the urine unchanged.
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.
DOSING MODE
If administered orally, the recommended dose for adults and elderly patients is 25 mg 1 time / day 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 EFFECT
From the side of the central nervous system: often - fatigue, dizziness; sometimes - headache, insomnia, depression, asthenia.
From the 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.
On the part of the endocrine system: often - paroxysmal sensations of heat (hot flashes).
Dermatological reactions: possible - skin rash, alopecia.
On the part of the hematopoiesis system: often - decrease in the level of lymphocytes; rarely - thrombocytopenia, leukopenia.
From the metabolism: possible - peripheral edema (edema of the feet, shins).
Other: often - increased sweating.
CONTRAINDICATIONS
Pregnancy, lactation (breastfeeding), increased sensitivity to eksemestanu.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With renal failure, dose adjustment is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With hepatic failure, dose adjustment is not required.
APPLICATION FOR CHILDREN
It is not recommended for use in children.
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 indices of functional hepatic tests in the serum and an increase in the level of AF was noted mainly in patients with metastases to the liver and bone, as well as in the presence of other liver lesions.
It is not recommended for use in children.
Impact on the ability to drive vehicles and manage mechanisms
When performing work related to the need for concentration of attention and high speed of psychomotor reactions, patients should be aware that the use of exemetan may cause drowsiness and dizziness.
DRUG INTERACTION
Preparations containing estrogens, when used simultaneously with eksemestanom completely level its pharmacological effect.
Until now, there have been no studies of the interaction of exemestane with other drugs. The results of in vitro studies have shown that exemestane is metabolized under the influence of the CYP3A4 isoenzyme and aldoketoreductases and does not inhibit any of the major CYP isoenzymes. In a clinical pharmacokinetic study, it was found that specific inhibition of the CYP3A4 isoenzyme by ketoconazole does not cause significant changes in the pharmacokinetic parameters of exemestane. However, it is impossible to exclude a possible decrease in the concentration of exemestane in plasma under the influence of preparations that are inducers of the isoenzyme CYP3A4.
