2010/09/21

Aromasin

Composition, structure and packing

Tablets are coated with sugar coat white or white with a grayish tint, round, biconvex, marked "7663" on one side, executed in black paint.

1 tab. eksemestan 25 mg.

Excipients: mannitol, gipromelloza, polysorbate 80, krospovidon, silicon dioxide colloidal hydrated, microcrystalline cellulose, sodium karboksimetilkrahmal, magnesium stearate. Composition of sugar-shell: gipromelloza, simetikonovaya emulsion, macrogol 6000, magnesium carbonate, titanium dioxide, methyl-p-hydroxybenzoate, polyvinyl alcohol, sucrose.

Clinico-pharmacological group: The antitumor drug. Aromatase inhibitors.

Pharmacological action

The irreversible steroidal aromatase inhibitor, similar in structure to the natural substance androstenedione. In postmenopausal women estrogens are produced mainly by converting androgens to estrogens under the action of the enzyme aromatase in peripheral tissues.

Blocking formation of estrogens by inhibiting aromatase is an effective and selective treatment for hormone breast cancer in postmenopausal women. The mechanism of action of the drug Aromazin due to the fact that it irreversibly binds to the active fragment of the enzyme, causing its inactivation.

In postmenopausal women Aromazin significantly reduces the concentration of estrogen in the blood serum, starting with a dose of 5 mg, with the maximum reduction (> 90%) is achieved at doses of 10-25 mg. Patients diagnosed with postmenopausal breast cancer, treated with 25 mg of the drug on a daily basis, the overall level of the enzyme aromatase in the body decreased by 98%. Eksemestan not possess progestogenic and estrogenic activity. Showed only a slight androgenic activity, mainly when used in high doses. Aromazin no effect on the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of the drug.

In this regard, there is no need for substitution treatment of glucocorticoid and mineralocorticoid. In applying the drug, even at low doses there is a slight increase in levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum, which is characteristic of drugs of this pharmacological group, and probably developed on the basis of feedback at the level of the pituitary: decrease the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland and also in postmenopausal women.

Pharmacokinetics

Absorption

Once inside eksemestan rapidly absorbed, mainly from the gastrointestinal tract. Absolute bioavailability is not installed. It is believed that it is limited by extensive first-pass effect through the liver. In single dose of the drug in a dose of 25 mg Cmax in plasma was 17 ng / ml achieved after 2 h. Simultaneous ingestion increases bioavailability by 40%. Pharmacokinetic parameters eksemestana are linear.

Distribution

Relationship to plasma proteins - approximately 90%. Eksemestan and its metabolites do not bind to erythrocytes. If readmission unpredictable cumulation eksemestana not observed.

Metabolism

The process of biotransformation eksemestana effected by oxidation of methylene groups in position 6 under the action of isoenzyme SYR3A4 and / or restoration of 17-keto group under the action of aldoketoreduktazy with subsequent conjugation. Products of metabolism eksemestana either inactive or less active in respect of inhibition of aromatase than the parent compound.

Withdrawal

Final T1 / 2 approximately 24 hours approximately equal amounts of eksemestana (40%) excreted in the urine and feces for a week. From 0.1 to 1% excreted in the urine in unchanged form.

Pharmacokinetics in special clinical situations

Relation between the systemic impact of the drug and the age is not established. In patients with renal failure severe (CC <30 ml / min) systemic exposure eksemestana 2 times higher, but dose adjustment is required. In patients with moderate or severe hepatic insufficiency systemic exposure eksemestana 2-3 times higher, but dose adjustment is required.

Statement
common breast cancer in women with natural or induced postmenopausal women with disease progression on a background Antiestrogenic therapy, as well as with the progression of the disease after repeated application of different types of hormone replacement therapy;
adjuvant therapy for early breast cancer in postmenopausal women with estrogen-receptor positive or unknown receptor status, after 2 or 3 years of initial adjuvant therapy with tamoxifen, to reduce the risk of recurrence (distant or regional), as well as contralateral breast cancer .

Dosage regimen

Assign inside. For adults and elderly patients the recommended dose is 25 mg 1 time / day, preferably after a meal. In early breast cancer treatment drug is recommended to continue for as long as the total duration of sequential adjuvant hormonal therapy did not reach 5 years.

Treatment of patients with advanced cancer of the breast long. If signs of progression of a tumor or when the contralateral breast cancer treatment Aromazinom should be discontinued. When hepatic or renal failure dose adjustment is required. Do not use the drug in children.

Side effect

Adverse effects associated with use of the drug in a dose of 25 mg / day were minor to moderate. The following adverse reactions, divided by the body's systems and frequency: very frequent (> 10%), frequent (> 1%, <10%),> 0.1%, <1%),> 0.01%, <0 , 1%).

On the part of the digestive system: very often - nausea, often - anorexia, abdominal pain, vomiting, constipation, indigestion and diarrhea.

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

Since the cardiovascular system: very often - the tides. Dermatological reactions: very often - sweating, often - a rash, alopecia.

On the part of the musculoskeletal system: very often - articular and musculoskeletal pain.

Other: very often - fatigue, often - the pain of unspecified location, peripheral edema, or swelling feet. Approximately 20% of patients (especially patients with an initial lymphopenia) were observed periodically reduce the number of lymphocytes.

However, the average number of lymphocytes in these patients over time has not significantly changed, and the concomitant increase in the incidence of viral infections were observed. Sometimes the observed increase in liver enzymes and alkaline phosphatase, primarily in patients with liver metastases and the bone, as well as the presence of other hepatic lesions (not determined whether these changes to the drug intake or not).

Contraindications
premenopauzny endocrine status;
Pregnancy
Lactation (breastfeeding);
Hypersensitivity to eksemestanu or to any other component of the drug.

With care use in patients with abnormal liver function or kidney.

Pregnancy and lactation

Aromazin contraindicated during pregnancy and lactation.

Application for violations of liver function

When liver failure dose adjustment is required. With care use in patients with abnormal liver function.

Application for violations of renal function

In renal insufficiency, dose adjustment is required. Precautions should be used drug in violation of renal function.

Cautions

Aromazin should not be given to women with premenopauznym endocrine status, therefore, in those cases where it is clinically justified, postmenopauzny status should be acknowledged definition of the level of LH, FSH and estradiol. Aromazin should not be given concurrently with any medication containing estrogen.

Effects on ability to drive vehicles and management mechanisms

Patients should be warned of the emergence during treatment Aromazinom somnolence, asthenia and dizziness. If you experience these symptoms for patients to refrain from driving lessons and other potentially hazardous activities that require high concentration and speed of psychomotor reactions.

Overdose

A single dose of the drug, which could cause a life-threatening symptoms that are not installed. Application eksemestana a single dose of 800 mg in healthy women and in a daily dose of 600 mg in postmenopausal women with advanced breast cancer is well tolerated.

Treatment: No specific antidotes. If necessary, carry out palliative care, as well as regular monitoring of vital functions and closely monitored.

Drug Interactions

Preparations containing estrogens, while the use of Aromazinom completely negate its pharmacological action. Eksemestan undergoes metabolism under the influence of CYP3A4 and aldoketoreduktaz and did not inhibit any of the major isoenzymes of CYP.

Specific inhibition of CYP3A4 ketoconazole had no significant effect on the pharmacokinetics eksemestana. Despite the established pharmacokinetic interaction eksemestana with rifampicin, a strong inducer of CYP3A4, pharmacological activity Aromazina (suppression of estrogen) remains unchanged, so dose adjustment is required.

Terms and Conditions of storage

List B. The drug should be stored at temperatures not above 30 ° C in the reach of children. Shelf life - 3 years. The drug should not be used beyond the expiration date indicated on the package.