Aromasin (exemestane) 25 mg. 30 tab. PFIZER, Italy

Interchangeable drugs with the same active ingredient:

Aromasin

Aromastan

Exemine

Exemestane - Vista

Exemestane Grindeks

Exemestane-Teva

Exomesin

compound

active ingredient: exemestane;

1 tablet contains exemestane 25 mg

excipients: mannitol (E 421), hypromellose, polysorbate 80, crospovidone, aqueous silicon dioxide, 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 waxes, 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 sugar-coated tablets, 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

Hormone antagonists and similar agents. enzyme inhibitors. ATX 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 predominantly by the conversion of androgens to estrogens by the action of the aromatase enzyme in peripheral tissues. Blocking estrogen production by inhibiting aromatase 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 decrease (> 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 were reduced by 98%.

Exemestane has no progestogenic and estrogenic activity. A small androgenic activity, probably associated with 17-hydroderivative, was observed mainly with the use of 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 for other enzymes involved in hormonal metabolism. In this regard, there is no need for replacement therapy with corticosteroids and mineralocorticoids.

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

Pharmacokinetics.

Absorption. After administration, exemestane is rapidly absorbed. The dose is absorbed from the gastrointestinal tract, high. Absolute bioavailability has not been established, although distribution should be limited by the 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 20,000 liters. The pharmacokinetics of exemestane is linear and the terminal half-life is 24 hours. Plasma protein binding is 90% and does not depend on concentration. Exemestane and its metabolites bind to red blood cells. Exemestane does not accumulate in a nonpermissible way after repeated doses.

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

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

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

Patients with impaired renal and hepatic function - see "Peculiarities of use".

testimony

Adjuvant therapy in postmenopausal women with estrogen receptor-positive early-stage invasive breast cancer after 2-3 years of initial adjuvant therapy with tamoxifen.

Treatment of advanced breast cancer in women with natural or induced postmenopausal status, in which disease progression has been detected after antiestrogen therapy. Neither has been shown to be effective in estrogen receptor negative patients.

Contraindications

Aromasin is 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 lactation.

Interaction with other medicinal products and other forms of interaction

The results of in vitro studies have shown that this drug is metabolized under the influence of cytochrome P450 3A4 (CYP3A4) and aldoketoreductases and does not block any of the main CYP isoenzymes. During a clinical pharmacokinetic study, it was found that the specific inhibition of CYP3A4 by ketoconazole does not affect the pharmacokinetics of exemestane.

Although pharmacokinetic interaction studies with rifampicin, a potent inhibitor of CYP3A4, have shown pharmacokinetic effects, the drug's pharmacological activity (i.e. estrogen suppression) was not aroused and dose adjustment is not required.

Aromasin should not be used with drugs containing estrogen, since they have a negative pharmacological effect when used simultaneously.

application features

25-hydroxyvitamin D levels in the body should be assessed prior to initiating treatment with aromatase inhibitors, as severe deficiency is often associated with early-stage breast cancer. Women with vitamin D deficiency need to get extra 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.

Considering that Aromasin is a drug that strongly lowers estrogen levels, a decrease in bone mineral density can be expected. For adjuvant therapy with the drug, women suffering from or at risk of osteoporosis should evaluate bone mineral density parameters using densitometry at the beginning of treatment. Patients who use Aromasin should be monitored and, if necessary, treated for osteoporosis.

Aromasin tablets contain sucrose and should not be administered to patients with rare congenital defects in 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 insufficiency.

In patients with severe renal impairment (CL with r

Patients with liver failure.

In patients with moderate or severe liver damage, the level of exemestane exposure is 2-3 times higher compared to healthy volunteers. Dose adjustment is not required.

Use during pregnancy or lactation.

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

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

Women in the perimenopausal period or with 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 transitioned to postmenopausal, until their postmenopausal status is fully understood.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms.

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

Dosage and administration

Adults and elderly patients

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

In patients with early breast cancer, treatment with Aromasin should be continued until completion of five years of consecutive adjuvant hormone therapy (continuation of Aromasin after tamoxifen) or tumor recurrence.

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

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

Children.

The drug is not recommended for children.

Overdose

Data on the use of Aromasin in single doses of 600-800 mg indicate that these doses are well tolerated. The dose of Aromasin, which may lead to life-threatening symptoms, has not been established. In animal experiments, lethality was recorded after administration of a single dose equivalent to 2000 and 4000, respectively, of the recommended human dose in mg/m 2 . There are no specific antidotes for overdose; symptomatic treatment should be carried out.

adverse reactions

Aromasin was generally well tolerated in all studies at the 25 mg/day dose, adverse events were generally mild to moderate in severity.

The rate of discontinuation due to adverse events was 7.4% in patients with early-stage breast cancer 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 estrogen blockage (eg, hot flashes).

The following are adverse reactions of various organs and systems of the body. Very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000) ).

On the part of metabolism and metabolism: often - anorexia.

On the part of the psyche: very often - depression, insomnia.

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

From the side of the vessels: very often - hot flashes.

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

From the digestive system: very often - an increase in the level of liver enzymes, an increase in the level of bilirubin in the blood, an increase in the level of alkaline phosphatase in the blood.

From 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 extremities, in the back, osteoarthritis, arthritis, myalgia, stiffness in the joints) often - fractures, osteoporosis.

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

From the blood and lymphatic system: in patients with advanced breast cancer, thrombocytopenia and leukopenia have rarely been reported. 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, however, the average number of lymphocytes for a fairly long time in these patients did not change significantly; there was also no increase in the incidence of viral infections. These effects were not observed in patients with early-stage breast cancer.

In a study of early stage breast cancer, the incidence of ischemic cardiac events 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 events, including hypertension (9.9% vs. 8.4%), myocardial infarction (0.6% vs. 0.2%), and heart failure (1.1% vs. 0.7%). There were also vaginal hemorrhages (4% vs. 5.3%), early-stage cancers of other organs (3.6% vs. 5.3%), thromboembolism (0.7% vs. 0.8%) .

Exemestane was associated with more cases of hypercholesterolemia compared to tamoxifen (3.7% versus 2.1%).

In a study of early stage breast cancer, gastric ulcers were observed at slightly higher rates in the exemestane group than in the tamoxifen group (0.7% versus <0.1%). The majority of patients who had gastric ulcers were taking concomitant treatment with non-steroidal anti-inflammatory drugs concomitantly with exemestane therapy and/or had a history of ulcers.

Post-marketing experience

From the immune system: infrequently - hypersensitivity.

From the nervous system: often - paresthesia.

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

On the part of the skin and subcutaneous tissue: often - urticaria, itching; rarely - acute generalized exanthematous pustulosis.

best before date

3 years.

storage conditions

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.