Femara pills 2.5mg, 30pcs

Composition

1 tablet contains:

Active ingredients:

letrozole 2.5 mg.

Auxiliary substances:

lactose monohydrate,

microcrystalline cellulose,

corn starch,

sodium carboxymethyl starch,

colloidal silicon dioxide,

magnesium stearate,

hypromellose,

talc,

macrogol 8000,

iron oxide yellow (17268) dye,

titanium dioxide.

The blister contains 10 tablets.

There are 3 blisters in a cardboard box.

Pharmacological action

Pharmacodynamics

Antitumor drug. It has an anti-estrogenic effect, selectively inhibits aromatase (an enzyme of estrogen synthesis) by highly specific competitive binding to the subunit of this enzyme – the cytochrome P450 heme. Blocks the synthesis of estrogens in both peripheral and tumor tissues.

In postmenopausal women, estrogens are formed mainly with the participation of the aromatase enzyme, which converts androgens synthesized in the adrenal glands (primarily androstenedione and testosterone) into estrone and estradiol.

Daily intake of letrozole in a daily dose of 0.1-5 mg leads to a decrease in the concentration of estradiol, estrone and estrone sulfate in blood plasma by 75-95% of the initial content. Suppression of estrogen synthesis is maintained throughout treatment.

When using Femara® in the dose range from 0.1 to 5 mg, there is no violation of the synthesis of steroid hormones in the adrenal glands, the ACTH test does not detect violations of the synthesis of aldosterone or cortisol. Additional use of glucocorticoids and mineralocorticoids is not required.

The blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are precursors of estrogens. While taking Femara, there were no changes in the concentrations of luteinizing and follicle-stimulating hormones in blood plasma, changes in thyroid function, changes in the lipid profile, and an increase in the frequency of myocardial infarction and stroke.

With Femara treatment, the incidence of osteoporosis is slightly increased (6.9% compared to 5.5% in the placebo group). However, the incidence of bone fractures in patients receiving Femara® does not differ from that in healthy people of the same age.

Adjuvant Femara therapy for early-stage breast cancer reduces the risk of progression, increases the survival rate without signs of the disease for 5 years, and reduces the risk of developing a tumor of another breast.

Prolonged adjuvant Femara therapy reduces the risk of progression by 42%. A significant advantage in disease-free survival in the Femara group was observed regardless of the involvement of lymph nodes. Treatment with Femara ® reduces mortality among patients with lymph node involvement by 40%.

Pharmacokinetics

Suction

Letrozole is rapidly and completely absorbed from the gastrointestinal tract (the average bioavailability is 99.9%). Food intake slightly reduces the rate of absorption. The average value of T_max of letrozole in blood within 1 h when taking Femara fasting and 2 h when taken with food; the average value of C_max is 129±20,3 nmol/l in the fasting and 98,7±18,6 nmol/l when taken with food, but the degree of absorption of letrozole (measured on AUC) is not altered. Small changes in the rate of absorption are considered not clinically relevant, so letrozole can be taken regardless of food intake.

Distribution

The binding of letrozole to plasma proteins is approximately 60% (mainly with albumin-55%). The concentration of letrozole in red blood cells is about 80% of its level in blood plasma. The apparent _{Vd during the}equilibrium period is about 1.87±0.47 l / kg. C_ss is achieved within 2-6 weeks of taking a daily dose of 2.5 mg. The pharmacokinetics are non-linear. Accumulation with prolonged use was not observed.

Metabolism

Letrozole is largely metabolized by the CYP3A4 and CYP2A6 isoenzymes to form a pharmacologically inactive carbinol compound.

Deduction

It is mainly excreted by the kidneys in the form of metabolites, to a lesser extent-through the intestines. The final T_1/2 is 48 h

. Pharmacokinetics in special clinical cases

, the pharmacokinetic parameters of letrozole do not depend on the patient’s age.

In patients with renal insufficiency, the pharmacokinetic parameters do not change.

With moderate hepatic impairment (Child-Pugh class B), the average AUC values, although higher by 37%, remain within the range of values observed in individuals without impaired liver function. In patients with cirrhosis of the liver and severe liver dysfunction (Child-Pugh class C), AUC increases by 95% and T_1/2 by 187%. However, given the good tolerability of high doses of the drug (5-10 mg/day) in these cases, there is no need to change the dose of letrozole.

Indications

• Early-stage breast cancer, whose cells have hormone receptors, in postmenopausal women, as adjuvant therapy.
• Early-stage breast cancer in postmenopausal women after completion of standard adjuvant tamoxifen therapy as extended adjuvant therapy.
• Common hormone-dependent forms of breast cancer in postmenopausal women (first-line therapy).
• Common forms of breast cancer in postmenopausal women (natural or artificially induced) who received previous antiestrogen therapy.

Use during pregnancy and lactation

Femara® is contraindicated for use during pregnancy and lactation.

During Femara therapy, given the potential for pregnancy, women in the perimenopausal and early postmenopausal period should use reliable methods of contraception until stable postmenopausal hormone levels are established.

Contraindications

• Endocrine status characteristic of the reproductive period;
• pregnancy;
• lactation (breastfeeding);
• children and adolescents under 18 years of age;
• hypersensitivity to letrozole or any other component of the drug.
• There are no data on the use of Femara® in patients with a creatinine clearance of less than 10 ml/min. Before prescribing Femara to such patients, the ratio between the potential risk and the expected effect of treatment should be carefully weighed.

Side effects

The frequency of side effects is estimated as follows:

• occurring very frequently (≥10%);
• frequently (≥1, < 10%);
• sometimes (≥0,1%, < 1%);
• rare (≥0.01, < 0.1%);
• very rare (

As a rule, adverse reactions were mild or moderate and mainly associated with suppression of estrogen synthesis.

From the digestive system: often – nausea, vomiting, dyspepsia, constipation, diarrhea; sometimes-abdominal pain, stomatitis, dry mouth, increased activity of liver enzymes.

From the central nervous system and peripheral nervous system: often-headache, dizziness, depression; sometimes – anxiety, nervousness, irritability, drowsiness, insomnia, memory loss, dysesthesia, paresthesia, hypesthesia, taste perception disorders, episodes of cerebral circulation disorders.

From the hematopoietic system: sometimes-leukopenia.

From the cardiovascular system: sometimes-palpitation, tachycardia, superficial and deep vein thrombophlebitis, increased blood pressure, IHD (angina, myocardial infarction, heart failure), thromboembolism; rarely – pulmonary embolism, arterial thrombosis, stroke.

From the respiratory system: sometimes-shortness of breath, cough.

Dermatological reactions: often-alopecia, excessive sweating, skin rash (including erythematous, maculopapular, vesicular rash, psoriasis-like rashes); sometimes-pruritus, dry skin, urticaria; very rarely-angioedema, anaphylactic reactions.

From the musculoskeletal system: very often – arthralgia; often-myalgia, bone pain, osteoporosis, bone fractures; sometimes-arthritis.

From the sensory organs: sometimes-cataracts, eye irritation, blurred vision, impaired taste sensations.

From the urinary system: sometimes-frequent urination, urinary tract infections.

From the reproductive system: sometimes-vaginal bleeding, vaginal discharge, vaginal dryness, pain in the mammary glands.

Other: very often – paroxysmal sensations of heat (hot flashes); often – increased fatigue, asthenia, malaise, peripheral edema, weight gain, hypercholesterolemia, anorexia, increased appetite; sometimes – weight loss, thirst, hyperthermia (pyrexia), dry mucous membranes, generalized edema, pain in tumor foci.

Interaction

No clinically significant interaction was observed when letrozole was co-administered with cimetidine and warfarin.

There is currently no clinical experience with the use of letrozole in combination with other antitumor agents.

According to the results of in vitro studies, letrozole suppresses the activity of cytochrome P isoenzymes%^%450-2%^%A%^%6 and 2%^%C%^%19 (the latter – moderately). When deciding on the significance of these data for the clinic, it should be taken into account that the CYP2A6 isoenzyme does not play a significant role in drug metabolism.

In vitro experiments have shown that letrozole, used at concentrations 100 times higher than the equilibrium plasma values, does not significantly inhibit the metabolism of diazepam (a substrate for CYP2C19).

Thus, clinically significant interactions with the CYP2C19 isoenzyme are unlikely. However, caution should be exercised when concomitantly using letrozole and drugs that are primarily metabolized with the participation of the above-mentioned isoenzymes and have a narrow therapeutic index.

How to take, course of use and dosage

For adults, the recommended dose of Femara® is 2.5 mg 1 time/day, daily for a long time.

As an extended adjuvant therapy, treatment should be continued for 5 years (no longer than 5 years).

If signs of disease progression appear, Femara should be discontinued.

In elderly patients, no dose adjustment of Femara is required.

In patients with impaired liver and/or kidney function (creatinine clearance ≥ 10 ml/min), no dose adjustment is required. However, patients with severe hepatic impairment (Child-Pugh class C) should be constantly monitored.

Tablets are taken orally, regardless of food intake.

Overdose

There are isolated reports of overdose of Femara®.

Treatment: No specific treatments for overdose are known.

Symptomatic and supportive therapy is indicated. Letrozole is eliminated from the plasma by hemodialysis.

Special instructions

Patients with severe hepatic impairment should be constantly monitored.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Some side effects of the drug, such as general weakness and dizziness, may affect the ability to perform potentially dangerous activities that require concentration and rapid reactions.

In this regard, care should be taken when driving vehicles and mechanisms.

Form of production

Film-coated tablets

Storage conditions

In a dry place, at a temperature not exceeding 30 °C

Shelf life

5 years

Active ingredient

Letrozole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Cancer, Breast Cancer