Letrozole (femara)

Description

Information about the drug

Letrozole (Femara) is an effective inhibitor of aromatase, an enzyme that is responsible for the synthesis of estrogen in the body. The drug blocks the action of the enzyme, thereby preventing the conversion of testosterone to estrogens.

This drug is approved by the FDA for use in the treatment of breast cancer on its early stages in women.

Thanks to the ability to suppress estrogenic activity, this drug is widely used in sports. Its main users are athletes who apply aromatized Androgenic Anabolic Steroids (AAS).

The drug is different from other similar, it is extremely powerful, and leaves its competitors far behind. The principle of action is significantly different from competitors, it does not act on the estrogens themselves, it prevents their production in the organism. The effect of this drug is so effective that the decreasing of estrogen in the blood occurs to a level of 15%.

The drug is present on the market since 1999 and available in tablets for oral using in a dosage of 25 mg.

Pharmacology

Letrozole is a non-steroidal aromatase inhibitor (estrogen biosynthesis inhibitor); antitumor drug.

In cases where the growth of tumor tissue depends on the presence of estrogens, the elimination of mediated stimulating effects is a prerequisite for inhibiting tumor growth. In postmenopausal women, estrogens are formed mainly by the participation of the aromatase enzyme, which converts androgens synthesized in the adrenal glands (primarily androstenedione and testosterone), to estrone (E1) and estradiol (E2). Therefore, inhibition of estrogen biosynthesis in peripheral tissues can be achieved by specific inhibition of the aromatase enzyme.

Letrozole inhibits aromatase through competitive binding to the subunit of this enzyme, the cytochrome P450 hem, which leads to a decrease in estrogen biosynthesis in all tissues.

A single dose of 0.1 mg, 0.5 mg and 2.5 mg of letrozole reduced serum estrone and estradiol levels (compared to baseline) by 75-78% and 78%, respectively. The maximum reduction is reached in 48-78 hours.

Letrozole is a highly specific aromatase inhibitor. Violation of steroid hormone synthesis in the adrenal glands was not detected.

Letrozole is rapidly and completely absorbed from the gastrointestinal tract (mean bioavailability is 99.9%). Food slightly reduces the rate of absorption (mean time to reach maximum concentration of letrozole in blood (Tmax) is 1 hour when taking letrozole on an empty stomach and 2 hours – when taken with food; average value of maximum concentration of letrozole in blood (Cmax) is 129 ± 20, 3 nmol / l when fasted and 98.7 ± 18.6 nmol / l when taken with food), but the degree of absorption of letrozole does not change. Minor changes in the rate of absorption are regarded as having no clinical significance, so letrozole can be used regardless of food intake.

Distribution. The binding of letrozole to plasma proteins is approximately 60% (preferably albumin is 55%). The concentration of letrozole in erythrocytes is almost 80% of its level in blood plasma. The systemic effect of letrozole metabolites is negligible. Letrozole is rapidly and widely distributed in tissues.

Metabolism and excretion. Letrozole is largely metabolized to form a pharmacologically inactive carbinol compound, the major route of elimination. Metabolic clearance of letrozole is less than hepatic blood flow. It was found that the conversion of letrozole to its metabolite is carried out under the influence of CYP3A4 and CYP2A6 isoenzymes of cytochrome P450.

The half-life from plasma is approximately 2 days. After daily administration of 2.5 mg of the drug, the equilibrium concentration of letrozole is reached within 2-6 weeks, at which it is approximately 7 times higher than after a single dose. As the equilibrium concentration of letrozole is maintained during treatment for a long time, it can be concluded that letrozole accumulation does not occur.

The pharmacokinetic effects of letrozole are independent of age.

Applying

For regular AAS users there are 2 ways of applying:

1. Adding the drug to the AAS course.
2. Using during the post-course therapy.

Applying on the course. The dosage is 12.5 mg (a half of the tablet) after the meal in a day.

Applying during the PCT. The drug is also used every other day but at a higher dosage, 25 mg for 10 days, after that the dosage is reduced twice and the drug is taken for another two weeks. After the course of Letrozole, you should make a pause.

The total time of application should not exceed 4 weeks.

Side effects

This drug will help you effectively deal with estrogenic side effects if it is used correctly. Letrozole relieves athletes of such disorders as: Gynecomastia (unnatural growth of the mammary glands in men); the accumulation of body fat on the female type (on the abdomen, waist and hips); Excessive accumulation of water in the body; High blood pressure.

Following the recommendations of this medicine using you will not feel any extraneous symptoms.

If you violate the dosage or period of using, you may feel the following symptoms:

• Individual allergic reaction;
• Headache;
• Nausea and vomiting;
• Disorders in the gastrointestinal tract;
• Pain in the joints;
• Mood changes;
• Low level of energy.

There is no clinical experience of overdose. In animal studies, letrozole is known to show only a small degree of acute toxicity. There is no clinical data on a specific dose of letrozole, which may cause life-threatening symptoms.

Warning!

This drug is medical product and requires following recommendations of using and storing. It should be stored in the cool dark place, avoiding direct sunlight. It’s also necessary to prevent applying this drug by children.

You MUST consult with your attending physician before you start using this drug. We also ask you to take into account that this drug may cause some side effects, some of them can be life-threatening. If you notice any disturbing symptoms you should to contact with your physician. In some cases, it is necessary to stop taking the drug for a while. Also you must inform your doctor if you taking this drugs with other medicines. So physician can prescribe proper treatment and help to avoid any unpleasant adverse effects.