Aromeston (Tablets) Instructions for Use

Marketing Authorization Holder

Veropharm, JSC (Russia)

ATC Code

L02BG06 (Exemestane)

Active Substance

Exemestane (Rec.INN registered by WHO)

Dosage Form

Aromeston

Film-coated tablets, 25 mg: 30 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (1) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antitumor drug. Aromatase inhibitor

Pharmacotherapeutic Group

Antineoplastic agent, estrogen synthesis inhibitor

Pharmacological Action

Antitumor drug, aromatase inhibitor, structurally similar to the natural steroid hormone androstenedione.

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

Exemestane has no progestogenic or estrogenic activity. When used in high doses, only slight androgenic activity is manifested. It does not affect the biosynthesis of cortisol and aldosterone in the adrenal glands.

A slight increase in serum LH and FSH levels is noted even at low doses of exemestane. This effect, however, is not typical for drugs of this pharmacological group. It probably develops by a feedback principle at the pituitary level: a decrease in estrogen concentration stimulates the secretion of gonadotropins in the pituitary gland even in postmenopausal women.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. After a single 25 mg dose with food, C_max is 18 ng/ml and is achieved within 2 hours. Food improves absorption: the plasma level of exemestane achieved in this case is 40% higher than after administration on an empty stomach.

After reaching C_max, the plasma level of the active substance decreases; the terminal T_1/2 is approximately 24 hours. Exemestane is widely distributed in tissues. Plasma protein binding is about 90%, and the degree of binding does not depend on the total concentration.

After repeated doses 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. It is 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. As a result, numerous secondary metabolites are formed, but the amount of each of them is very small compared to the administered dose. Regarding aromatase inhibition, these metabolites are either inactive or less active than the unchanged substance.

Excreted in urine and feces. The elimination of exemestane and its metabolites from the body is mainly completed within 1 week. Less than 1% is excreted unchanged in the urine.

Indications

Treatment of advanced breast cancer in women with natural or induced postmenopause in whom disease progression has been detected during antiestrogen therapy.

Hormonal therapy for advanced breast cancer in women with natural or induced postmenopause in whom disease progression has been detected during therapy with either non-steroidal aromatase inhibitors or progestins.

ICD codes

Dosage Regimen

Administer the recommended dose of 25 mg as a single daily oral intake.

Take the tablet once daily, preferably after a meal to enhance absorption.

Continue treatment until tumor progression is observed.

Do not adjust the dose for patients with mild to moderate hepatic impairment.

Do not adjust the dose for patients with renal impairment.

Confirm postmenopausal status prior to initiating therapy.

Monitor lymphocyte counts in patients with pre-existing lymphopenia.

Monitor liver function tests in patients with liver metastases or pre-existing liver disease.

Adverse Reactions

From the central nervous system frequent – fatigue, dizziness; sometimes – headache, insomnia, depression, asthenia.

From the digestive system frequent – nausea; sometimes – abdominal pain, anorexia, constipation, dyspepsia; rare – increased serum liver function test values, increased alkaline phosphatase level.

From the endocrine system frequent – hot flashes.

Dermatological reactions possible – skin rash, alopecia.

From the hematopoietic system frequent – decreased lymphocyte level; rare – thrombocytopenia, leukopenia.

From metabolism possible – peripheral edema (edema of the feet, legs).

Other frequent – increased sweating.

Contraindications

Pregnancy, lactation (breastfeeding), hypersensitivity to exemestane.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

No dose adjustment is required in case of hepatic impairment.

Use in Renal Impairment

No dose adjustment is required in case of renal impairment.

Pediatric Use

Not recommended for use in children.

Special Precautions

Should not be used in women with premenopausal endocrine status, as the efficacy and safety of the drug in this category of patients has not been evaluated. In cases where the need for use is clinically justified, postmenopausal status should be confirmed by determining the levels of LH, FSH and estradiol.

In patients with baseline lymphopenia, there is an increased risk of decreased lymphocyte count. Increased serum liver function test values and increased alkaline phosphatase levels were observed mainly in patients with liver and bone metastases, as well as in the presence of other liver lesions.

Not recommended for use in children.

Effect on ability to drive vehicles and operate machinery

When performing work requiring concentration and high speed of psychomotor reactions, patients should be aware that drowsiness and dizziness may occur when using exemestane.

Drug Interactions

Drugs containing estrogens, when used concomitantly with exemestane, completely negate its pharmacological action.

No studies of the interaction of exemestane with other drugs have been conducted to date. 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. A clinical pharmacokinetic study found that specific inhibition of the CYP3A4 isoenzyme by ketoconazole did not cause significant changes in the pharmacokinetic parameters of exemestane. However, a possible decrease in exemestane plasma concentration under the influence of drugs that are inducers of the CYP3A4 isoenzyme cannot be ruled out.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.