Letrozole

Package leaflet (information for patients)

Tradename
Letrozole

Dosage form
Tablets 2.5 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Letrozole 2.5 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Prospect of tivoopuholevoe agent, an inhibitor of estrogen synthesis.

Pharmacological properties
Antineoplastic. Competitively binds to the prosthetic part (heme) of cytochrome P450 - an aromatase subunit involved in the transformation of androgens into estrone and estradiol, inhibits the biosynthesis of estrogens in tissues and, in particular, eliminates their stimulating effect on tumor growth. After oral administration, it is completely absorbed, bioavailability approaches 100%. At moderate therapeutic doses, the equilibrium concentration is reached after 2–6 weeks. It breaks down in the liver, forming inactive derivatives. The half-life is about 48 hours. It is excreted mainly by the kidneys. Does not cumulate.

Indications for use
Adjuvant therapy for early stage hormone receptor-positive breast cancer in postmenopausal women. Continuation of adjuvant therapy for early stage hormone-dependent breast cancer in postmenopausal women who previously received standard adjuvant treatment with tamoxifen for 5 years. First-line therapy for late-stage hormone-dependent breast cancer in postmenopausal women. Advanced breast cancer in women with natural or induced menopause, after relapse or progression of the disease, who were previously treated with antiestrogens.

Method of administration and dosage
Adults and elderly patients The recommended dose of the drug is 2.5 mg once a day. No dose adjustment is required in elderly patients. If adjuvant therapy is indicated, treatment is recommended for 5 years or until tumor recurrence. For indications for adjuvant treatment, there is 2 years of clinical experience (average treatment duration 25 months). If continued adjuvant treatment is indicated, there is 4 years of clinical treatment (average treatment duration). In patients with advanced disease or a metastatic tumor, letrozole treatment should be continued until the tumor progresses. Children Not applicable. Patients with impaired renal and / or hepatic function Dose adjustments in patients with renal insufficiency with creatinine clearance greater than 30 ml / min are not required. There are not enough data for cases of renal failure with creatinine clearance less than 30 ml / min or for patients with severe hepatic impairment.

Side effects
As a rule, adverse reactions were mild to moderate and mainly associated with suppression of estrogen synthesis.
The incidence of adverse reactions is estimated as follows: occurring very often (> 10%), often (1-10%), sometimes (0.1-1%), rarely (0.01-0.1%), very rarely (<0.01%, including some messages).
From the digestive system: often - nausea, vomiting, dyspepsia, constipation, diarrhea; sometimes - abdominal pain, stomatitis, dry mouth, increased activity of liver enzymes.
From the nervous system: often - headache, dizziness, depression; sometimes - anxiety, nervousness, irritability, drowsiness, insomnia, memory impairment, dysesthesia, paresthesia, hypesthesia, impaired taste perception, episodes of cerebrovascular accident.
On the part of the hematopoietic organs: sometimes - leukopenia.
From the side of the cardiovascular system: sometimes - a feeling of palpitations, tachycardia, thrombophlebitis of superficial and deep veins, increased blood pressure, coronary heart disease (angina pectoris, 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 rash); sometimes - itchy skin, dry skin, hives; very rarely - angioedema, anaphylactic reactions.
From the musculoskeletal system: very often - arthralgia; often - myalgia, bone pain, osteoporosis, bone fractures, sometimes arthritis.
From the side of the senses: sometimes - cataracts, eye irritation, blurred vision, violation of taste.
From the urinary system: sometimes - frequent urination, urinary tract infections.
From the reproductive system: sometimes - vaginal bleeding, vaginal discharge, dryness of the vagina, pain in the mammary glands.
Others: very often - hot flashes ("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.

Contraindication
Hypersensitivity to letrozole or any other component of the drug. Hormonal reproductive status, including premenopause. Pregnancy, breastfeeding period. Age under 18. Precautions: Care should be taken when using letrozole in patients with severe liver dysfunction (class C according to Child- Pugh classification), severe renal dysfunction (creatinine clearance less than 10 ml / min). Use during pregnancy and during breastfeeding: In animal studies, letrozole has demonstrated embio - and fetotoxicity, as well as teratogenic properties. Patients with preserved reproductive potential, including patients in the perimenonausal period and in the early postmenopausal period, should be informed about the need for adequate contraception until a stable postmenopausal hormonal status is established. The use of the drug during breastfeeding is contraindicated. The patient should be informed about the potential risk of using the drug during breastfeeding.

Overdose
There are isolated reports of letrozole overdose.
No specific treatments for overdose are known. Symptomatic and supportive therapy is indicated. Letrozole is cleared from plasma by hemodialysis.

Precautions
Patients with severe impaired function of the liver must find sya under constant supervision.
Clinical experience on the use of letrozole in combination with other anticancer agents in the present Bp emya not available.
Influence on the ability to manage the transport means and mechanisms.
Some side effects of the drug, such as the general weakness and dizziness, may affect on the ability to perform potentially dangerous kinds of activity, requiring concentration of attention and fast reaction. In this regard, should observe caution when managing transport means and mechanisms.

Interaction with other medicinal products
Clinical interaction studies with cimetidine and warfarin have shown that the combined use of letrozole with these drugs does not cause clinically significant interactions. A review of the database of clinical trials showed no evidence of other clinically significant interactions with other commonly prescribed drugs. To date, there is no clinical experience with the use of letrozole in combination with other anticancer drugs. In vitro letrozole inhibits cytochrome P450 isoenzymes 2A6 and, to a small extent, 2C19. CYP2A6 and CYP3A4 do not play an important role in drug metabolism. Thus, precaution is required during the concomitant use of drugs, the availability of which is largely dependent on these isoenzymes, and which have a low therapeutic index.

Special instructions
Renal impairment: There is no data on the use of letrozole in patients with creatinine clearance less than 10 ml / min. Before starting the use of the drug letrozole in such patients, the ratio of the expected benefit to the possible risk should be carefully evaluated. Liver dysfunction: In patients with severe liver dysfunction (Child-Pyo class C), the systemic exposure of letrozole and the terminal elimination half-life are approximately 2 times higher than those in healthy volunteers. In connection with the above, patients of this category should be carefully observed. Effect on bone tissue: There is evidence of the development of osteoporosis and / or the occurrence of bone fractures during the use of Femara (see "Adverse reactions from the musculoskeletal system and connective tissue"), and therefore it is recommended to carefully monitor the state of bone tissue in during the entire period of drug use. Hormonal status: In patients with unspecified hormonal status, the concentration of LH, FSH and / or estradiol should be determined before starting drug therapy. The use of the drug is possible only in patients with confirmed stable postmenopausal hormonal status. Fertility The pharmacological consequence of the drug is a decrease in estrogen secretion by inhibiting aromatase. In premenopausal patients, a response increase in the concentration of gonadotropic hormones (LH, FSH) is possible. An increase in FSH concentration in turn can stimulate follicular growth and induce ovulation. Thus, there is a potential for pregnancy in perimenopausal and early postmenopausal patients. In such cases, reliable methods of contraception should be used until a stable postmenopausal hormonal status is established in this category of patients. Drug interactions. It is recommended to avoid the simultaneous use of the drug letrozole with tamoxifen, other anti-estrogenic and estrogen - containing drugs, since these drugs can weaken the pharmacological effect of letrozole (see “Interaction with other drugs). The mechanism of this interaction has not been studied. The drug is not indicated for the treatment of breast cancer that does not contain receptors for steroid hormones (estrogen or progesterone).

Pregnancy and elbowing
Prescription of the drug during pregnancy and lactation is contraindicated.
During letrozole therapy, given the potential for pregnancy, women in the perimenopausal and early postmenopausal period should use reliable methods of contraception until a stable postmenopausal hormonal level is established.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
On prescription.

Packaging
Letrozole 2.5 mg Tablets. There are 25 tablets in a blister. 4 blisters are packed in a cardboard box together with an enclosed leaflet.