Aromasin. Aromatase inhibitors.

The Aromasin is an aromatase inhibitor and is commonly used in the adjuvant treatment of postmenopausal women with invasive breast cancer at an early stage, and estrogen receptor positive, following initial adjuvant tamoxifen therapy for 2-3 years.Aromasin – Exemestane Structural formula of exemestane, active ingredient in Aromasin.
AROMASIN is also indicated in the treatment of breast cancer at an advanced stage, in women who are post-natural or induced menopause, in which the disease has progressed following anti-estrogen therapy.
The dose commonly used for cancer therapy is 25 mg (one tablet), to be taken every day on a full stomach for a prolonged period of a few years.
Its action is very similar to the other aromatase inhibitors such as Arimidex and Femara have already seen that we will see then. By inhibiting the aromatase prevents the conversion of testosterone to estradiol, with all the pros and cons already described before and therefore I will not repeat.
At a dosage of 25mg / day, exemestane reduces by up to 85% conversion to estrogen, and this translates into a reduction up to 50% total of estradiol, resulting in increased production of endogenous testosterone.
The aromasin has its own peculiarities that is interesting to mention.  They known by the name of suicide inhibitor, by inhibiting the enzyme aromatase permanently, that is, once it is bound to the enzyme, this is no longer able to function. Instead other aromatase inhibitors, once decoupled by the enzyme, let still active. In the field andrology, Aromasin has the unique ability to increase the endogenous production of testosterone along with the natural production of IGF 1. His Arimidex and Femara counterparts can not make that claim.

That is why Aromasin is also used in the doping, during a cycle of AAS, with the aim is to obtain a hard and dry physical (thanks to the reduction of estrogen), is to get an anabolic effect (thanks IGF1) and to both support endogenous testosterone production. Aromasin is also called aromatase inhibitor  has weak androgenic effects including aggression and muscle hardening. For which it is also used illicitly .- in the field of doping – for about 7-14 days before a service or a race, solely for the purpose of obtaining a hard and dry feel. Given the suppression of estradiol due to inhibition of aromatase, the precautions relating all’Aromasin are the same as mentioned in the schedule for all Arimidex (I in fact said he has a similar mechanism of action, with the difference of the production of IGF1 mentioned).

Composition and form of release

Sugar-coated tablets 1 tab.
exemestane 25 mg
auxiliary substances: mannitol; hypromellose; polysorbate 80; crospovidone; silicon dioxide colloid hydrated; MCC ; sodium carboxymethyl starch; magnesium stearate
membrane: hypromellose; simethicone emulsion; macrogol 6000; magnesium carbonate; titanium dioxide; methyl parahydroxybenzoate; polyvinyl alcohol; sucrose

 

in the blister for 15 pcs .; in a pack of cardboard 1, 2 or 6 blisters.

Description of dosage form

Round, biconvex tablets white or white with a slightly grayish shade of color, covered with sugar shell, marked “7663”, made of black paint, on one side.

Pharmachologic effect

Pharmacological action – antitumor, inhibitory synthesis of estrogens .

It blocks aromatase and stops the synthesis of estrogens (without affecting the production of other steroid hormones, such as cortisol and aldosterone).

Pharmacodynamics

Irreversible steroidal aromatase inhibitor, similar in structure to the natural substance – androstenedione.

In postmenopausal women, estrogens are produced primarily by converting androgens to estrogens under the action of the aromatase enzyme in peripheral tissues. Blocking the formation of estrogen by inhibiting aromatase is an effective and selective method for treating hormone-dependent breast cancer in postmenopausal women. The mechanism of action of the drug Aromazin ® is due to the fact that it binds irreversibly to the active fragment of the enzyme, causing its inactivation. In postmenopausal women, Aromazine ®significantly reduces the concentration of estrogens in the blood serum, starting at a dose of 5 mg, with a maximum reduction (> 90%) achieved with doses of 10-25 mg. In postmenopausal women with breast cancer who received 25 mg of the drug every day, the total level of the aromatase enzyme in the body decreased by 98%.

Exemestane does not possess progestogen and estrogenic activity. Only minor androgenic activity is revealed, mainly with the use of high doses.

The drug Aromazin ® has 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 replacement therapy with gluco- and mineralocorticoids.

When using the drug even in low doses, a slight increase in the levels of LH and FSH in the blood serum is observed , which is characteristic for the preparations of this pharmacological group and is likely to develop on the basis of feedback at the pituitary level: a decrease in the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland also women in postmenopausal women.

Pharmacokinetics

After oral administration, it is quickly absorbed, mainly from the digestive tract . Absolute bioavailability of the drug is not established. It is assumed that it is limited to the extensive effect of the first passage through the liver. With a single dose of 25 mg C max in plasma is 17 ng / ml and is achieved after 2 hours. Simultaneous food intake increases the bioavailability of the drug by 40%.

Pharmacokinetic parameters are linear. The final T 1/2 is approximately 24 hours. Binding to plasma proteins is about 90%. Exemestane and its metabolites do not bind to erythrocytes. At repeated reception of unpredictable cumulation eksemestana it is not observed. The process of biotransformation of exemestane is carried out by oxidation of the methylene group at the 6-position under the action of the CYP3A4 isoenzyme and / or reduction of the 17-keto group under the action of aldoketoreductase followed by conjugation. Exemestane metabolism products are either inactive or less active with respect to aromatase inhibition than the parent compound.

Approximately equal amounts of exemestane (about 40%) are excreted in urine and feces within a week. From 0.1 to 1% is excreted unchanged in the urine. A marked relationship between the systemic effect of the drug and age is not established.

In patients with severe renal insufficiency ( Cl creatinine <30 ml / min) the systemic effect of exemestan is 2 times higher, however, dose adjustment is not required.

In patients with moderate or severe hepatic insufficiency, the systemic effect of exemestan is 2-3 times higher, but dose adjustment is not required.

Indications of the drug Aromazin ®

widespread breast cancer in women in natural or induced postmenopausal disease with progression of the disease against the background of anti-estrogen therapy, as well as in the progression of the disease after repeated use of various types of hormone therapy;

adjuvant therapy for early breast cancer in postmenopausal women with estrogen-positive receptors or with an unknown receptor status after the completion of 2-3 years of initial adjuvant tamoxifen therapy to reduce the risk of relapse (distant or regional) and contralateral breast cancer.

Contraindications

increased sensitivity to exemestane or to any other component of the drug;

pre-menopausal endocrine status;

pregnancy and lactation;

childhood.

With caution  – a violation of the liver or kidneys.