Expiration date: 02/2027

Structure and Composition:

The tablets covered with a sugar coating. 1 tablet contains exemestane 25 mg

excipients: mannitol, crospovidone, polysorbate 80 hypromellose silica colloidal hydrated sodium carboxymethyl starch, magnesium stearate MCC

shell: hypromellose macrogol 6000 simetikonovaya emulsion magnesium carbonate, titanium dioxide, methyl parahydroxybenzoate polyvinyl alcohol sucrose

in blister 15 pcs. In the paper cartons 1, 2 or 6 blisters.

Description pharmaceutical form:

Round, biconvex tablets white or white with a slightly grayish tint, sugar-coated tablets, marked "7663" made of black ink on one side.

Pharmachologic effect:

Blocks estrogen and stops aromatase synthesis (without affecting the production of other steroid hormones such as cortisol and aldosterone).

Pharmacokinetics:

After intake of rapidly absorbed, mainly from the gastrointestinal tract. The absolute bioavailability of the drug has not been established. It is believed that it is limited by extensive first pass effect through the liver. For a single administration of a dose of 25 mg Cmax of 17 ng / mL in plasma and reached after 2 h. Simultaneous food intake increases the bioavailability by 40%.

Pharmacokinetic parameters are linear. The final T1 / 2 of approximately 24 hours Plasma protein binding -. 90%. Exemestane and its metabolites do not bind to red blood cells. If readmission unpredictable cumulation of exemestane was observed. Exemestane biotransformation process is carried out by oxidation of the methylene group in position 6 under the action of the isoenzyme CYP3A4 and / or reduction of the keto group at 17-aldoketoreduktazy action with subsequent conjugation. exemestane or metabolic products are inactive, or less active in the inhibition of aromatase than the parent compound.

Approximately equal amounts of exemestane (about 40%) excreted in the urine and feces for a week. From 0.1 to 1% is excreted in the urine in unchanged form. Pronounced relationship between systemic exposure of the drug and the age has been established.

In patients with severe renal failure (Cl creatinine <30 ml / min) exemestane systemic exposure 2 times higher, but the dose adjustment is required.

In patients with moderate or severe hepatic insufficiency, systemic exposure to exemestane is 2-3 times higher, but dose adjustment is required.

Description of the pharmacological actions:

Irreversible steroidal aromatase inhibitor, structurally similar to the natural substance - androstenedione.

In postmenopausal women, estrogens are produced primarily by conversion of androgens to estrogens by the enzyme aromatase in peripheral tissues. Blocking estrogen formation by inhibiting aromatase is an effective and selective treatment for hormone dependent breast cancer in postmenopausal women. The mechanism of drug action AROMASIN due to the fact that it binds irreversibly to the active fragment of the enzyme causing its inactivation. In postmenopausal women, significantly reduces AROMASIN drug concentration in serum estrogens from the dose of 5 mg, the maximum reduction (> 90%) is achieved at doses of 10-25 mg. In postmenopausal women with breast cancer who received 25 mg daily, the overall level of the enzyme aromatase in the body was reduced by 98%.

Exemestane has no progestogenic and estrogenic activity. It reveals only a slight androgenic activity, mainly at high doses.

AROMASIN drug has no effect on the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of drug action. In this regard, no need for replacement therapy mineralocorticoid and glucocorticoid.

In applying the drug even at low doses, there is a slight increase in the levels of LH and FSH in the serum, which is typical for preparations of the pharmacological groups and is probably developed as a feedback on the pituitary level: reducing the concentration of estrogen stimulates the secretion of gonadotropins by the pituitary gland also have postmenopausal women.

Dosage:

Instructions for use

OK FC MoH 16.03.2000, pr. ?1b

Description. Round, biconvex tablets with a white slightly grayish tinge, sugar-coated tablets, about 6 mm in diameter having a label numbers 7663, black ink formed on one side.

Composition. Each tablet contains:

Active ingredient: 25 mg exemestane

Excipients: mannitol, hypromellose, polysorbate 80, crospovidone, silica-, colloidal, hydrated, MCC, sodium starch glikolevokisly magnesium stearate shell: hypromellose, simethicone, macrogol 6000, sucrose, magnesium carbonate, titanium dioxide, methyl n-hydroxybenzoate, polyvinyl alcohol.

Pharmacological properties. AROMASIN is an irreversible steroidal aromatase inhibitor, structurally similar to the natural substance androstenedione.

Pharmacodynamics. In postmenopausal women, estrogens are produced primarily by conversion of androgens to estrogens by the enzyme aromatase in peripheral tissues. Blocking estrogen formation by inhibiting aromatase is an effective and selective treatment for hormone dependent breast cancer in postmenopausal women. The mechanism of drug action AROMASIN due to the fact that it binds irreversibly to the active fragment of the enzyme causing its inactivation. In postmenopausal women, AROMASIN significantly reduces the concentration of estrogens in serum, starting from a dose of 5 mg of maximum reduction (> 90%) is achieved at a dose of 10-25 mg. In postmenopausal women with breast cancer who received 25 mg daily, the overall level of the aromatase enzyme in the organism was reduced by 98%.

AROMASIN has no progestogenic and estrogenic activity. It reveals only a slight androgenic activity, mainly at high doses. During tests with multiple dosing during a day AROMASIN no effect on the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of action of this drug.

In this regard, there is no need for replacement therapy with glucocorticoids and mineralocorticoids. The slight increase in levels of LH and FSH in the serum observed even at low doses for this effect, however, is expected for the formulations of this pharmacological group he probably develops as a feedback on the pituitary level: reducing the concentration of estrogen stimulates the secretion of gonadotropins by the pituitary gland also have postmenopausal women.

Pharmacokinetics. Suction. After oral administration, AROMASIN rapidly and extensively absorbed. For a single administration of a dose of 25 mg postprandial mean peak plasma level of 18 ng / ml is achieved within 2 hours. It was established that the food improve absorption achieved with 40% higher plasma levels than patients treated with medication on an empty stomach.

Distribution. After reaching the maximum level of the drug in plasma AROMASIN reduced, and the final T1 / 2 of approximately 24 h. AROMASIN widely distributed in tissues, as indicated by the large volume of distribution. AROMASIN drug binding to plasma proteins is approximately 90%, with the extent of binding is independent of total concentration.

Metabolism and excretion. After repeated receptions of 25 mg / day, the concentration in plasma unchanged drug was similar to that measured after a single dose. After oral administration of a single dose of radiolabeled drug AROMASIN been found that the elimination of the drug and its metabolites generally complete within 1 week, with approximately equal parts dose excreted in the urine and feces. The amount of drug excreted in the urine in unchanged form, is less than 1% of the administered dose. AROMASIN is characterized by a high ground clearance, mainly due to metabolism. biotransformation process is carried out by oxidation of the methylene group in position 6 involving CYP 3A4 isoenzyme and / or by reducing the 17-keto involving aldoketoreduktaz. As a result, numerous secondary metabolites are formed, but the number of each of them is very small compared to the administered dose. The inhibition of aromatase, or of these metabolites are inactive, or less active than the parent compound.

Indications for use. AROMASIN is indicated for the treatment of advanced breast cancer in women with natural or induced postmenopausal women who showed progression of the disease on the background of anti-estrogen therapy.

Aromasin is also indicated as a hormone replacement therapy of the third row in advanced breast cancer in women with natural or induced postmenopausal women who showed progression of the disease on the background of anti-estrogen therapy, and therapy or non-steroidal aromatase inhibitors or progestins.

Dosage. Adults and elderly patients

AROMASIN recommended to take 25 mg daily one time a day, preferably after the meal. Treatment should be continued until signs of progression of tumor diseases.

In patients with hepatic or renal insufficiency of dose adjustment is not required.

Children. Not recommended for use in children.

Side effect. In clinical trials, Aromasin drug, there are side effects were mild or moderate in intensity. The most common side effects are associated with the drug, and arose at an unidentified reason, were hot flashes (hot flushes), nausea, fatigue, sweating, and dizziness. Less frequently observed headache, insomnia, skin rash, abdominal pain, anorexia, depression, alopecia, peripheral edema (swelling of feet, legs), constipation or indigestion.

Episodes lymphocyte levels decline observed in approximately 20% of patients receiving Aromasin, particularly in patients with an initial lymphopenia but the average count for quite a long time in these patients was not significantly changed, and not observed concomitant increase in the incidence of viral infections.

Also, in rare cases revealed thrombocytopenia and leukopenia.

Occasionally recorded an increase in liver function test parameters in serum, as well as increased levels of alkaline phosphatase. Such an increase in enzyme levels observed predominantly in patients with liver metastases and bone, as well as the presence of other liver lesions. These changes could be related to a drug Aromasin, and not associated with it.

Contraindications. AROMASIN contraindicated in patients with known hypersensitivity to the drug or any of the excipients, as well as pregnancy and breastfeeding child.

Interaction with other drugs and other forms of interaction. Preparations containing estrogens while the use of AROMASIN completely negate the pharmacological effect of the latter.

To date, no studies of interactions with other drugs. in vitro studies have shown that the drug is metabolized under the influence of cytochrome P450 (CYP) 3A4 and aldoketoreduktaz and does not inhibit any of the major CYP-isozymes. During clinical pharmacokinetic study it has been found that specific inhibition of CYP 3A4 ketoconazole had no significant effect on the pharmacokinetics of the drug AROMASIN. However, we can not exclude a possible reduction in the concentration of drug in plasma Aromasin under the influence of substances known as inducers of CYP 3A4.

Overdose. Data on the use of AROMASIN in single doses of 600-800 mg indicate a good tolerability of doses. A single dose of the drug Aromasin, which can cause life-threatening symptoms has not been established. No specific antidote for an overdose does not exist, should be symptomatic treatment. It shows the general supportive therapy, as well as regular monitoring of vital signs and careful observation.

Special warnings and precautions for use. Aromasin should not be administered to women with premenopauznom endocrine status, as efficacy and safety of the drug in this group of patients has not been evaluated. Therefore, in cases where it is clinically justified, postmenopausal status should be confirmed determination of the level of LH, FSH and estradiol.

It is unlikely that AROMASIN impairs the ability of patients to drive or operate machinery moving or accurate. However, when using this drug observed symptoms such as somnolence, asthenia and dizziness. Patients should be warned that the appearance of these phenomena, their physical and / or mental capabilities required for the job, requiring special attention and fast reactions can be violated.

Product form. 25 mg tablets, sugar-coated tablets, in blisters to 15 pcs., In a carton box 1, 2 or 6 boxes.

Storage conditions. Store at a temperature not exceeding 30 & ° C, out of reach of children.

Shelf life. 3 years.

Testimony:

• common breast cancer among women in natural or induced postmenopausal women with disease progression on a background of antiestrogen therapy and disease progression after repeated use of various types of hormone replacement therapy
  
• adjuvant treatment of early breast cancer in postmenopausal women with receptor-estrogenpolozhitelnymi or unknown receptor status, after the completion of 2-3 years of initial adjuvant tamoxifen therapy in order to reduce the risk of recurrence (distant or regional) and contralateral breast cancer.
  

Contraindications:

• Hypersensitivity to eksemestanu or to any other component of the drug
  
• premenopauznom endocrine status
  
• pregnancy and lactation
  
• childhood.
  

With care - abnormal liver or renal function.

Side effect:

In general tolerability of the drug Aromasin good undesirable effects when using the drug at a dose of 25 mg / day are minor to moderate.

The following are adverse reactions, distributed by body system and frequency: very common -> 10% frequently -> 1 <10% sometimes -> 0.1 to <1% of rare -> 0.01 <0.1%.

From the digestive system: very often - nausea often - anorexia, abdominal pain, vomiting, constipation, dyspepsia, diarrhea.

On the part of the central and peripheral nervous system: very often - insomnia, headache often - depression, dizziness, carpal tunnel syndrome.

From the circulatory system: very often - flushing.

Skin and skin appendages: very often - sweating often - rash, alopecia.

From the musculoskeletal system: very often - joint and musculoskeletal pain.

Other: often - fatigue often - unspecified pain, peripheral edema or swelling of the feet.

Approximately 20% of patients (especially in patients with initial lymphopenia) were observed periodically reducing the number of lymphocytes. However, the average number of lymphocytes in these patients over time did not change significantly, and the concomitant increase in the incidence of viral infections was observed.

Sometimes there is an increase in liver enzymes and alkaline phosphatase, especially in patients with liver metastases and bone, as well as the presence of other liver damage (not revealed whether these changes taking this medication or not).

Drug Interactions:

Preparations containing estrogens, completely negate the pharmacological effect of exemestane.

The drug is metabolized by the action of cytochrome P450 (CYP) 3A4 and aldoketoreduktaz and does not inhibit any of the major CYP-isozymes.

Specific inhibition of CYP3A4 by ketoconazole had no significant effect on the pharmacokinetics of exemestane. Although exemestane set pharmacokinetic interaction with rifampicin, a potent inducer of CYP3A4, the pharmacological activity of the drug Aromasin (estrogen suppression) remains unchanged, so dose adjustment is required.

Dosage and administration:

Inside, preferably after meals. Adults and elderly patients - 25 mg 1 time per day.

In patients with early breast cancer drug treatment is recommended to continue until a consistent overall length of adjuvant hormonal therapy did not reach 5 years. Treatment of patients with breast cancer a long common. If signs of disease progression of tumor or when the contralateral breast cancer, treatment with Aromasin should be discontinued.

Patients with hepatic or renal insufficiency dose adjustment is required.

Do not use in children.

Overdose:

A single dose of the drug, which could cause a life-threatening symptoms has not been established. Use of exemestane in a single dose up to 800 mg in healthy women at a daily dose of 600 mg in postmenopausal women with breast cancer is well tolerated common.

Treatment: symptomatic, under regular supervision of vital signs and careful observation. No specific antidote.

Special instructions:

The drug Aromasin should not be administered to women with premenopauznom endocrine status, so in those cases where it is clinically justified postmenopausal status should be confirmed determination of the level of LH, FSH and estradiol.

The drug Aromasin should not be administered concurrently with medications containing estrogen.

Patients should be warned of the possibility of occurrence during treatment with Aromasin somnolence, asthenia and dizziness. If you have these symptoms, patients are advised to refrain from driving and other activities potentially hazardous activities that require high concentration and psychomotor speed reactions.