FEMARA
Active material: Letrozole
When ATH: L02BG04
CCF: Anticancer drug. Aromatase inhibitor
ICD-10 codes (testimony): C50
When CSF: 15.13.04.01
Manufacturer: NOVARTIS PHARMA AG (Switzerland)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Pills, Film-coated dark yellow, round, slightly biconcave, with beveled edges, on one side printed “FV”, another – “CG”.
| 1 tab. | |
| letrozole | 2.5 mg |
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate, gipromelloza, talc, macrogol 8000, dye iron oxide yellow (17268), Titanium dioxide.
10 PC. – blisters (3) – packs cardboard.
Pharmacological action
Anticancer drug. Provides antiestrogennoe action, selectively inhibits aromatase (enzyme synthesis of estrogen) by vysokospecifichnogo competitive binding subunit of this enzyme – haemom cytochrome P450. Blocks the synthesis of estrogens in both peripheral, and in tumor tissues.
Among women postmenopauzne period estrogens are produced mostly with the participation of the aromatase enzyme, formed in the adrenal glands which converts androgens (Firstly, androstenedione and testosterone) estron and estradiol.
Daily intake of letrozole in daily dose 0.1-5 mg leads to a decrease in the concentration of estradiol, estrone and estrone sulfate in the blood plasma in 75-95% from the original content. Suppression of estrogen synthesis is maintained throughout the treatment.
In applying the drug Femara® in the range of doses from 0.1 to 5 mg violation of synthesis of steroid hormones in the adrenal glands are not observed, ACTH test does not detect violations of synthesis of aldosterone or cortisol. An additional appointment of glucocorticoids and mineralokortikoidov not required.
Blockade of estrogen biosynthesis does not lead to the accumulation of androgens, are precursors to estrogen. Against the backdrop of the admission of Femary changes in the concentrations of luteinizing and follicle-stimulating hormone in plasma, changes of thyroid function, changes in lipid profile, increasing the frequency of myocardial infarctions and strokes has been observed.
Against the backdrop of increased frequency of weak Femaroj treatment of osteoporosis (6.9% compared with 5.5% placebo). However, the frequency of bone fractures in patients, receiving the drug Femara®, is no different from that of healthy people of the same age.
Adjuvant therapy Femaroj early stages of breast cancer reduces the risk of progression, disease-free survival increases during 5 years, reduces the risk of another tumor of the breast.
Extended adjuvant therapy Femaroj reduces the risk of progression to 42%. A significant advantage for survival without signs of disease in Femary Group noted regardless of the involvement of lymph nodes. Treatment with Femara® reduces mortality among patients with involvement of lymph nodes on the 40%.
Pharmacokinetics
Absorption
Letrozole is rapidly and completely absorbed from the digestive tract (average bioavailability is 99.9%). Eating slightly reduces speed removals. The average value of Tmax Letrozole in the blood is 1 h when taken on an empty stomach and Femary 2 no – when taken with food; the average value of Cmax is 129 ± 20.3 nmol/l to prandial and 98.7 ± 18.6 nmol/l – when taken with food, However, the extent of absorption of letrozole (in the evaluation of the AUC) not changed. Small changes in the speed of absorption are seen as having no clinical significance, therefore letrozole may be taken regardless of mealtimes.
Distribution
The binding of letrozole with blood plasma proteins is approximately 60% (mostly to albumin – 55%). Concentration of letrozole in erythrocytes is about 80% from its level in the blood plasma. In Кажущийсяd during the period of equilibrium is about 1.87 ± 0.47 l/kg.. Css It reached within 2-6 weeks of daily reception daily intake 2.5 mg. Pharmacokinetics is nonlinear. Cumulation with long-term use not stated.
Metabolism
Letrozole is heavily under the influence of metabolizmu isoenzymes CYP3A4 and CYP2A6 with formation of pharmacologically inactive karbinolovogo connections.
Deduction
Write mainly by the kidneys as metabolites, less – through the intestine. The final T1/2 is 48 no.
Pharmacokinetics in special clinical situations
Pharmacokinetic parameters letrozole does not depend on the age of the patient.
When kidney failure pharmacokinetic parameters do not change.
With moderately expressed liver (Class B of Child-Pugh) average AUC although and above 37%, but they remain within that range of values, which shall be observed in individuals without violations of the liver. In patients with liver cirrhosis and severe violations of its functions (class C on the scale of Child-Pugh) AUC is increased by 95% and T1/2 on 187%. But, given the good tolerability of high doses of the drug (5-10 mg / day) in these cases, the need to change the dose of letrozole no.
Testimony
— early stage breast cancer, cells that have receptors for hormones, in postmenopausal women, as an adjuvant therapy;
-early stage breast cancer in postmenopausal women after completion of standard adjuvant therapy with tamoxifen as extended adjuvant therapy;
— common gormonozawisimae breast cancer in postmenopausal women (first-line therapy);
-common forms of breast cancer in postmenopausal women (natural or artificially induced), prior to receiving therapy antiestrogenami.
Dosage regimen
To Adult the recommended dose of the drug Femara® is 2.5 mg 1 time / day, daily long-.
As extended adjuvant therapy treatment should continue for 5 years (no longer 5 years).
When signs of disease progression reception Femary should stop.
In elderly patients dose adjustment is not required Femary.
In patients with human liver and/or kidney disease (CC ≥ 10 ml / min) correction dose is not required. Nonetheless, at severe hepatic dysfunction (class C Child-Pugh) patients must be under the constant supervision of.
The tablets are taken orally, regardless of the meal.
Side effect
The incidence of side effects is estimated as follows:: arise very often (≥10%), often (≥1, <10%), sometimes (≥0.1%, <1%), rarely (≥ 0.01, <0.1%), rarely (<0.01%, including isolated reports).
Usually, adverse reactions were weakly or moderately expressed and are mostly related to the Suppression of estrogen synthesis.
From the digestive system: often – nausea, vomiting, dyspepsia, constipation, diarrhea; sometimes – stomach ache, stomatitis, dry mouth, increase in liver enzymes.
From the central and peripheral nervous system: often – headache, dizziness, depression; sometimes – alarm, nervousness, irritability, drowsiness, insomnia, memory impairment, dysesthesia, paraesthesia, gipesteziya, breach of taste perception, episodes of cerebral circulation.
From the hematopoietic system: sometimes – leukopenia.
Cardio-vascular system: sometimes palpitations, tachycardia, thrombophlebitis of superficial and deep veins, increased blood pressure, CHD (angina, myocardial infarction, heart failure), thromboembolism; rarely – pulmonary embolism, coronary arteries, stroke.
The respiratory system: sometimes – breathlessness, cough.
Dermatological reactions: often – alopecia, increased sweating, skin rash (including jeritematoznuju, makulopapuleznuju, vezikuliarnuu rash, psoriasiform rash); sometimes – itching, xerosis, hives; rarely – angioedema, anaphylactic reactions.
On the part of the musculoskeletal system: Often – arthralgia; often – myalgia, ostealgias, osteoporosis, fractures; sometimes – arthritis.
From the senses: sometimes – Cataract, eye irritation, blurred vision, dysgeusia.
From the urinary system: sometimes – frequent urination, urinary tract infection.
Reproductive system: sometimes – vaginal bleeding, vaginal discharge, vaginal dryness, pain in the milk glands.
Other: Often – hot flashes (tides); often – fatigue, asthenia, malaise, peripheral edema, weight gain, hypercholesterolemia, anorexia, increased appetite; sometimes – weight loss, thirst, hyperthermia (pyrexia), dryness of mucous membranes, generalized edema, pain in tumor foci.
Contraindications
— endocrine status, characteristic of the reproductive period;
- Pregnancy;
- Lactation (breast-feeding);
- Childhood and adolescence up 18 years;
-hypersensitivity to letrozolu or any other component of the drug.
No data on the use of the drug Femara® ground clearance in patients with creatinine less than 10 ml / min. Before assigning this Femary patients should carefully weigh the ratio between potential risk and expected effect of treatment.
Pregnancy and lactation
The Drug Femara® contraindicated during pregnancy and lactation.
During therapy Femaroj, given the potential for pregnancy, women in the perimenopauznom and early postmenopauzne period should use reliable methods of contraception prior to the establishment of a stable postmenopauznogo hormone level.
Cautions
Patients with severely impaired hepatic function should be monitored on a continuous basis.
Effects on ability to drive vehicles and management mechanisms
Some side effects of the drug, such as weakness and dizziness, may affect the ability to perform potentially hazardous activities, requiring concentration and fast reactions. In this context, caution must be exercised in the management of vehicles and mechanisms.
Overdose
There are sporadic reports of cases of drug overdose Femara®.
Treatment: any specific methods of treatment of overdose are unknown. Shown symptomatic and supportive therapy. Letrozole is derived from plasma at hemodialysis.
Drug Interactions
While appointing letrozole with cimetidine and warfarin clinically meaningful interaction is not observed.
Clinical experience on the use of letrozole in combination with other protivoopujolevami means is currently not available.
According to the results of in vitro studies, letrozole inhibits the activity of isoenzymes of cytochrome p 450 – 2A6 and 2s19 (the last is moderately). In determining the meaning of these data for clinics must take into account the, What CYP CYP2A6 does not play a significant role in the metabolism of drugs. In in vitro experiments, it was shown, that letrozole, used in concentrations, in 100 times higher than equilibrium plasma values, not have the ability to significantly inhibit the metabolism of diazepam (substrate for CYP2S19). Thus, clinically meaningful interaction with izofermentom CYP2S19 is unlikely. Nonetheless, caution must be exercised in the use of letrozole and preparations, mainly with the participation of the above-mentioned metaboliziruthan isoenzymes and have a narrow therapeutic index.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored in a dry, inaccessible to children at temperature not exceeding 30 ° C. Shelf life – 5 years.
The drug should not be used after the expiration date.
