Aromasin (exemestane) 25 mg, 30 tablets, Pfizer, Italy, original Order Aromasin (exemestane) 25 mg, 30 tablets, Pfizer, Italy, original. International medicine delivery within 4-5 days with storage conditions maintained. Payment on delivery. Contact +380996042415.

Interchangeable drugs with the same active ingredient:

Aromasin

Aromastan

Exemarin

Exemestane - Vista

Exemestane Grindeks

Exemestane-Teva

Exomesin

composition

active ingredient: exemestane;

1 tablet contains exemestane 25 mg

excipients: mannitol (E 421), hypromellose, polysorbate 80, crospovidone, silicon dioxide aqueous, microcrystalline cellulose, sodium starch (type A), magnesium stearate sugar shell (hypromellose, simethicone emulsion, macrogol 6000, sucrose, magnesium carbonate, titanium dioxide (E 171), methyl parahydroxybenzoate (E 218), polyvinyl alcohol, cetyl ether wax, talc, carnauba wax) ink: shellac, iron oxide (E 172), titanium oxide (E171), ethyl alcohol, isobutyl alcohol.

Dosage form

Sugar-coated tablets.

Basic physical and chemical properties: round biconvex tablets, sugar-coated, from white to slightly gray in color, about 6 mm in diameter, inscribed with the numbers 7663 in black ink on one side.

Pharmacological group

Hormon antagonists and similar agents. Enzyme inhibitors. ATC code L02B G06.

Pharmacological properties

Pharmacodynamics.

Exemestane is an irreversible steroidal aromatase inhibitor, similar in structure to the natural substance androstenedione. In postmenopausal women, estrogens are produced primarily by the conversion of androgens to estrogens by the enzyme aromatase in peripheral tissues. Blocking estrogen production by aromatase inhibition is an effective and selective treatment for hormone-dependent breast cancer in postmenopausal women. In postmenopausal women, exemestane significantly reduces the concentration of estrogen in the blood serum, starting with a dose of 5 mg, the maximum reduction (> 90%) is achieved with a dose of 10-25 mg. In postmenopausal patients diagnosed with breast cancer who received 25 mg daily, total aromatase levels decreased by 98%.

Exemestane does not have progestogenic or estrogenic activity. Minor androgenic activity, probably related to the 17-hydroderivative, was observed mainly when using the drug in high doses. In studies of long-term daily use, exemestane did not affect the biosynthesis of hormones such as cortisol or aldosterone, the levels of which changed before or after the ACTH test; This demonstrated selectivity with respect to other enzymes involved in hormonal metabolism. In this regard, there is no need for replacement therapy with GCS and mineralocorticoids.

A slight increase in the level of LH and FSH in the blood serum is observed even at low doses; this effect, however, is expected for drugs of this pharmacological group; it probably develops according to the feedback principle at the level of the pituitary gland: a decrease in the concentration of estrogen stimulates the secretion of gonadotropins by the pituitary gland (also in postmenopausal women).

Pharmacokinetics.

Absorption. After administration, exemestane is rapidly absorbed. The dose absorbed from the gastrointestinal tract is high. Absolute bioavailability has not been established, although distribution should be limited by first pass effect. With a single dose of 25 mg, the average plasma level reaches a maximum after 2:00 and is 18 ng/ml. Simultaneous use of the drug with food increases its bioavailability by 40%.

Distribution. The volume of distribution of exemestane without correction for oral bioavailability is 20000 l. The pharmacokinetics of exemestane is linear and the terminal half-life is 24 hours. Plasma protein binding is 90% and is independent of concentration. Exemestane and its metabolites bind to red blood cells. Exemestane does not accumulate directly after repeated doses.

Metabolism and excretion. Exemestane is metabolized by oxidation of the methylene group (6) using the CYP3A4 isoenzyme and/or by reduction of the 17-keto group by aldoketoreductases followed by conjugation. The clearance of exemestane is approximately 500 l/h without adjustment for oral bioavailability.

By aromatase inhibition, these metabolites are either inactive or less active than the parent compound. The amount of unchanged drug excreted in the urine is 1% of the dose. The same amount (40%) of exemestane, labeled with the 14 C isotope, was excreted in urine and feces for a week.

Special groups. Age. There was no significant correlation between the systemic exposure of the drug Aromasin and the age of the patients.

Patients with impaired renal and liver function - see “Peculiarities of use.”

indications

Adjuvant therapy in women with invasive breast cancer of early stages with a positive test for estrogen receptors during the postmenopausal period after 2-3 years of initial adjuvant therapy with tamoxifen.

Treatment of advanced breast cancer in women with natural or induced postmenopausal status in whom disease progression has been detected after antiestrogens therapy. No effectiveness has been demonstrated in patients with a negative test for estrogen receptors.

Contraindications

Aromasin Contraindicated in patients with hypersensitivity to the active ingredient of the drug or to any other component of the drug. The drug is also contraindicated in the premenopausal period, women during pregnancy and breastfeeding.

Interaction with other drugs and other types of interactions

The results of in vitro studies showed that this drug is metabolized under the influence of cytochrome P450 3A4 (CYPZA4) and aldoketoreductases and does not block any of the main CYP isoenzymes. In a clinical pharmacokinetic study, specific inhibition of CYP3A4 by ketoconazole was found to have no effect on the pharmacokinetics of exemestane.

Although pharmacokinetic effects were observed in pharmacokinetic studies with rifampicin, a potent inhibitor of CYP3A4, the drug's pharmacological activity (i.e., estrogen suppression) was not observed and no correction was observed. no dose required.

Aromasin do not use with medications containing estrogen, since when used simultaneously they have a negative pharmacological effect.

features of use

Before starting treatment with aromatase inhibitors, it is necessary to evaluate the levels of 25-hydroxy vitamin D in the body, since severe deficiency often occurs associated with the early stages of breast cancer. Women with vitamin D deficiency need to receive additional vitamin D.

Given the mechanism of action, Aromasin should not be prescribed to women with premenopausal endocrine status. Therefore, in acceptable clinical cases, it is necessary to establish postmenopausal status by assessing the levels of LH, FSH and estradiol.

Given that Aromasin is a drug that strongly reduces estrogen levels, a decrease in bone mineral density can be expected. During adjuvant therapy with the drug, women suffering from osteoporosis or at risk of developing it should have their bone mineral density parameters assessed using densitometry at the beginning of treatment. Patients who use Aromasin should be observed and, if necessary, osteoporosis therapy should be started.

Aromasin tablets contain sucrose and should not be prescribed to patients with rare congenital defects of fructose metabolism, malabsorption of glucose and galactose, or sucrose isomaltase deficiency.

Aromasin tablets contain methylparaben, which may cause allergic reactions (possibly delayed).

Patients with renal failure.

In patients with severe kidney damage (CL with r

Patients with liver failure.

In patients with moderate or severe liver damage the level exemestane exposure is 2-3 times higher compared to healthy volunteers. No dose adjustment is required.

Use during pregnancy or breastfeeding.

Pregnancy. Animal studies have shown reproductive toxicity, therefore Aromasin is contraindicated in pregnant women.

Feeding Aromasin should also not be used by women who are breastfeeding.

Women who are perimenopausal or have the potential to give birth.

With women who have the potential to become pregnant, the physician should discuss the need for appropriate contraception, as well as with women who are perimenopausal or have recently become postmenopausal until their postmenopausal status is established. will become fully studied.

The ability to influence the speed of reaction when driving vehicles or other mechanisms.

During the use of the drug, drowsiness, somnolence, asthenia and dizziness have been reported, so patients should refrain from driving vehicles or operating other mechanisms.

Dosage and administration

Adults and elderly patients

Aromasin is recommended to take 25 mg 1 time per day daily, preferably after food.

In patients with early-stage breast cancer, treatment with Aromasin should be continued until completion of five years of sequential adjuvant hormonal therapy (continuation of Aromasin therapy after use of tamoxifen) or tumor relapse occurs.

In patients with advanced breast cancer, treatment with Aromasin should be continued until tumor progression is evident.

Patients with insufficient liver or kidney function do not require dose adjustment.

Children.

The drug is not recommended for use in children.

Overdose

Data on the use of Aromasin in single doses of 600-800 mg indicate good tolerability of these doses. The dose of Aromasin that may cause life-threatening symptoms has not been established. In animal studies, mortality was recorded after a single dose equivalent to 2000 and 4000 mg/m2 of the recommended human dose, respectively. There are no specific antidotes for overdose; symptomatic treatment should be carried out.

adverse reactions

Aromasin was generally well tolerated in all studies when using a dose of 25 mg / day; adverse events were usually mild to moderate in severity.

The rate of treatment interruptions due to adverse events was 7,4% in patients with breast cancer at an early stage, treated with Aromasin after initial adjuvant therapy with tamoxifen. The most common adverse events were hot flashes (22%), arthralgia (18%), and fatigue (16%).

The rate of treatment discontinuation due to adverse events was 2,8% in the general population of patients with advanced breast cancer. The most common adverse events were hot flashes (14%) and nausea (12%).

Most adverse events can be explained by the normal pharmacological consequences of blocking estrogen (eg, hot flashes).

The following are adverse reactions of various organs and systems of the body. Very often (≥ 1/10), often (from ≥ 1/100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely (from ≥ 1/10 000 to <1/1000).

Metabolism and metabolism: often - anorexia.

From the psyche: very often - depression, insomnia.

From the nervous system: very often - headache, dizziness, often - carpal tunnel syndrome infrequently - drowsiness.

From the blood vessels: very often - hot flashes.

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

On the part of the digestive system: very often - increased levels of liver enzymes, increased levels of bilirubin in the blood, increased levels of alkaline phosphatase in the blood.

On the part of the skin and subcutaneous tissue: very often - increased sweating; often - alopecia, rash.

From the musculoskeletal system: very often - pain in the joints and muscles (including arthralgia and to a lesser extent - pain in the limbs, back, osteoarthritis, arthritis, myalgia, stiffness in the joints) often - fractures, osteoporosis.

General disorders: very often - pain, increased fatigue; often - peripheral edema; infrequently - asthenia.

On the part of the blood and lymphatic system: thrombocytopenia and leukopenia have rarely been reported in patients with advanced breast cancer. Episodes of a decrease in the number of lymphocytes were noted in approximately 20% of patients taking Aromasin, in particular in patients with pre-existing lymphopenia, but the average number of lymphocytes did not change significantly for quite a long time in these patients; There was also no increase in the incidence of viral infections. These effects were not observed in patients with early stages of breast cancer.

In a study of early stage breast cancer, the incidence of ischemic cardiac complications in the exemestane and tamoxifen treatment groups was 4,5% and 4,2%, respectively. No significant difference was seen for any of the individual cardiovascular complications, including hypertension (9,9% versus 8,4%), myocardial infarction (0,6% versus 0,2%), and heart failure (1,1% versus 0,7%). Vaginal hemorrhage (4% compared to 5,3%), early stage cancer of other organs (3,6% compared to 5,3%), thromboembolism (0,7% compared to 0,8%) also occurred.

Exemestane was associated with a higher incidence of hypercholesterolemia compared with tamoxifen (3,7% versus 2,1%).

In a study of early breast cancer, gastric ulcers were observed at a slightly higher rate in the exemestane group compared with the tamoxifen group (0,7% versus <0,1%). Most patients who had a gastric ulcer, simultaneously with exemestane therapy, took concomitant treatment with non-steroidal anti-inflammatory drugs and / or had a history of ulcers.

Post-marketing experience

On the part of the immune system: uncommon - hypersensitivity.

On the part of the nervous system: often - paresthesia.

From the digestive system: rarely - hepatitis, cholestatic hepatitis.

From the skin and subcutaneous tissue: often - urticaria, itching rarely - acute generalized exanthematous pustulosis

expiration date

3 year.

storage conditions

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.