AROMAZIN

Active material: jeksemestan
When ATH: L02BG06
CCF: Anticancer drug. Aromatase inhibitor
ICD-10 codes (testimony): C50
When CSF: 15.13.04.01
Manufacturer: PHARMACIA ITALIA S.p.A. (Italy)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, sugar-coated white or white with serovatam brown color, round, lenticular; labeled “7663” on one side, executed in black ink.

Excipients: mannyt, gipromelloza, polysorbate 80, krospovydon, silicon dioxide colloidal, hydrated, microcrystalline cellulose, sodium carboxymethyl, magnesium stearate.

Ingredients sugar shell: gipromelloza, simetikonovaja emulsion, macrogol 6000, magnesium carbonate, Titanium dioxide, methyl-n-gidroksibenzoat, polyvinyl alcohol, sucrose.

15 PC. – blisters (1) – packs cardboard.
15 PC. – blisters (2) – packs cardboard.
15 PC. – blisters (6) – packs cardboard.

Pharmacological action

Irreversible steroid aromatase inhibitor, similar in structure to the natural substance androstendionom.

Among women postmenopause estrogens are produced primarily by making androgens into estrogen by the action of the aromatase enzyme in peripheral tissues. Blocking estrogen formation by inhibiting the aromatase is an effective and selective treatment of hormone-dependent breast cancer in postmenopausal women. The mechanism of action of the preparation Aromazin^® due to the fact, that it irreversibly binds to the active enzyme fragment, causing its inactivation. In postmenopausal women Aromazin^® reliably reduces the concentration of estrogen in the blood serum, starting dose 5 mg, with maximum reduction (>90%) achieved in the application of doses 10-25 mg. In patients with postmenopausal women diagnosed with breast cancer, receiving 25 mg daily, the overall level of the enzyme aromatase in the body fell 98%.

Jeksemestan has no progestogenic and estrogenic activity. Taped little androgenic activity, mainly when used in high doses.

Aromazin^® has no effect on the biosynthesis of cortisol and aldosterone in the adrenal glands, that confirms the selectivity of drug action. In this regard, there is no need for replacement therapy glukokortikoidami and mineralokortikoidami.

In applying the drug even in low doses, there had been a slight increase of LH and FSH in serum, What is characteristic for this pharmacological groups and, probably, develops the principle of feedback on level of pituitary: reduction of the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland also in postmenopausal women.

Pharmacokinetics

Absorption

After intake of rapidly absorbed jeksemestan, primarily, from the gastrointestinal tract. The absolute bioavailability is not installed. Suggest, that it's limited to extensive effect of the first passage through the liver. In single dose of the drug at a dose of 25 mg C_max Plasma is 17 ng / ml achieved after 2 no. Simultaneous eating increases bioavailability at 40%.

Pharmacokinetic parameters mg of exemestane are linear in nature.

Distribution

Relationship to plasma proteins – about 90%. Jeksemestan and its metabolites are not associated with erythrocytes. The readmission unpredictable cumulation is not observed mg of exemestane.

Metabolism

Biotransformation process mg of exemestane is performed by oxidation of methylene groups in 6 position under the influence of izofermenta SYR3A4 and/or restoring 17-ketogroup under action al'doketoreduktazy followed kongugaciei. Products of metabolism mg of exemestane or inactive, or less active against aromatase inhibition, than the original connection.

Deduction

The final T_1/2 approximately 24 no. Approximately equal number of mg of exemestane (about 40%) excreted in the urine and feces for a week. From 0.1 to 1% return with urine in unchanged form.

Pharmacokinetics in special clinical situations

Expressed the relationship between systemic effects of the drug and age is not installed.

Patients with severe renal insufficiency (CC < 30 ml / min) systemic effects mg of exemestane in 2 times higher, However, dose adjustment is not required.

In patients with moderate or severe hepatic insufficiency systemic effects mg of exemestane in 2-3 times higher, However, dose adjustment is not required.

Testimony

is a common breast cancer among women in the natural or induced postmenopausal women with the progression of diseases amid antiestrogenic therapy, as well as the progression of the disease after repeated use of different types of hormone therapy;

— adjuvant therapy of early breast cancer in postmenopausal women with estrogen receptor-positive or unknown receptor status, After the completion of 2-3 years of initial adjuvant therapy with tamoxifen, in order to reduce the risk of recurrence (remote or regional), as well as the contralateral breast cancer.

Dosage regimen

Assign inside. To adults and elderly patients The recommended dose is 25 mg 1 once per day, preferably after meals.

Early breast cancer treatment should continue until the, total duration of sequential adjuvant hormone therapy does not reach 5 years. Treatment of breast cancer for a long. When signs of progression of the tumor disease or when the contralateral breast cancer treatment Aromazinom^® discontinue.

At hepatic or renal failure dose adjustment is required.

It is not recommended to use the drug in children.

Side effect

Unwanted effects in the application of the drug in a dose 25 mg/day are minor or moderately expressed.

Listed below are the unwanted reactions, distributed over the body's systems and frequency: Often (>10%), often (>1%, <10%), infrequently (>0.1%, <1%), rarely (>0.01%, <0,1%).

From the digestive system: Often – nausea; often – anorexia, abdominal pain, vomiting, constipation, dyspepsia, diarrhea.

Part of the central and peripheral nervous system: Often – insomnia, headache; often – depression, dizziness, carpal tunnel syndrome.

Cardio-vascular system: Often – tides.

Dermatological reactions: Often – Sweating; often – rash, alopecia.

On the part of the musculoskeletal system: Often – Joint and Musculoskeletal pain.

Other: Often – fatigue; often – unspecified pain localization, peripheral edema or swelling of the legs.

Approximately 20% patients (especially in patients with baseline limfopeniej) observed periodic decrease in the number of lymphocytes. However, the average number of lymphocytes in these patients have not significantly changed over time, and the concomitant increase in the incidence of viral infections have been observed.

Sometimes observed increase in liver enzymes and AP, mainly in patients with liver metastases and bone, and in the presence of other liver disease (not installed, whether these changes are associated with taking the drug or not).

Contraindications

— premenopauznyj endocrine status;

- Pregnancy;

- Lactation (breast-feeding);

-hypersensitivity to jeksemestanu or to any other component of the drug.

FROM caution use in patients with abnormal liver function or kidney.

Pregnancy and lactation

Aromazin^® contraindicated during pregnancy and lactation.

Cautions

Aromazin^® nor should appoint women with premenopauznym endocrine status, so, where, When it is clinically justified, postmenopausny status should certify the level of LH, FSH and estradiol.

Aromazin^® should not be administered concomitantly with drugs, containing estrogens.

Effects on ability to drive vehicles and management mechanisms

Patients should be warned about the possibility of the emergence during treatment Aromazinom^® drowsiness, fatigue and dizziness. If you experience these symptoms, patients are advised to abstain from driving and other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

A single dose of the drug, that could cause life-threatening symptoms, not installed. Application of mg of exemestane in one dose to 800 mg in healthy women and in the daily dose of up to 600 mg in postmenopausal women with advanced breast cancer good postponed.

Treatment: No specific antidotes. If necessary spend symptomatic therapy, as well as regular monitoring of vital signs and close observation.

Drug Interactions

Preparations, containing estrogen, together with the application Aromazinom^® completely negate its pharmacological action.

Jeksemestan metabolizmu influenced by CYP3A4 and al'doketoreduktaz and not inhibited none of the major CYP Isoenzymes. Specific inhibition of CYP3A4 ketoconazole has no reliable impact on farmakokinetiku mg of exemestane. Despite the established pharmacokinetic interaction of rifampicin mg of exemestane, strong CYP3A4 inducer, pharmacological activity of Aromazina^® (Suppression of estrogen) remains unchanged, Therefore, dose adjustment is not required.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored at a temperature of no higher than 30° c, out of reach of children. Shelf life – 3 year. The drug should not be used after the expiry date, on the package.