Celana, 1 mg 30 pcs

Pharmacotherapeutic group:

Antitumor drug, estrogen synthesis inhibitor.

The ATC code: L02BG03

Pharmacological properties

Pharmacodynamics

The Anastrozole is a highly selective nonsteroidal aromatase inhibitor. Aromatase is an enzyme by which, in postmenopausal women, androstenedione is converted in peripheral tissues to estrone and then to estradiol. Anastrozole has antitumor activity against estrogen-dependent breast tumors in postmenopausal women. In postmenopausal period the drug in daily dose of 1 mg causes decrease of concentration of estradiol by 80%.

Anastrozole has no progestogenic, androgenic or estrogenic activity.

Anastrozole at a daily dose of up to 10 mg has no effect on cortisol and aldosterone secretion (therefore, no corticosteroid replacement is required with the use of the drug).

Pharmacokinetics

Intake

After oral administration, anastrozole is rapidly absorbed from the gastrointestinal tract. Maximum concentration (Cmax) in plasma is reached within 2 hours (fasting). Food slightly reduces the rate of absorption, but not its degree and does not lead to a clinically significant effect on the equilibrium plasma concentration of the drug in a single daily dose.

Distribution

Anastrozole binds to plasma proteins by 40%. Approximately 90% to 95% of the equilibrium plasma concentration of anastrozole is reached after 7 days of administration. No pharmacokinetic parameters are known to be time and dose dependent.

Metabolism

Anastrozole is metabolized by N-dealkylation, hydroxylation, and glucuronidation. Triazole, the main metabolite determined in plasma, does not inhibit aromatase.

Elimation

Anastrozole is excreted slowly with a half-life (T1/2) of 40 to 50 hours.

Anastrozole and its metabolites are excreted mainly in the urine. Less than 10% of the dose is excreted unchanged in the urine within 72 hours after drug administration. Pharmacokinetics in Special Clinical Cases

The determined clearance of anastrozole after oral administration in patients with cirrhosis or impaired renal function does not differ from that determined in healthy subjects.

The pharmacokinetics of anastrozole are independent of age in postmenopausal women.

Indications

Active ingredient

Composition

(1 tablet):

How to take, the dosage

The tablet should be swallowed whole and drunk with water. It is recommended to take the drug at the same time of the day.

In adults, including elderly patients, the drug is prescribed 1 mg orally 1 time per day, long-term. If there are signs of disease progression, the drug should be discontinued. As adjuvant therapy, the recommended duration of treatment is 5 years.

Patients with mild to moderate renal insufficiency do not require dose adjustment.

Patients with mild hepatic impairment do not require dose adjustment.

Interaction

Drug interactions with phenazone (Antipyrine) and cimetidine indicate that co-administration of anastrozole with other drugs is unlikely to result in clinically significant cytochrome P450 interactions.

There are no data on clinically significant drug interactions when anastrozole is coadministered with other commonly used drugs.

There are currently no data on the use of anastrozole in combination with other anticancer drugs.

The drugs containing estrogens should not be used concomitantly with anastrozole, because they reduce the pharmacological effect of the latter.

Tamoxifen should not be used at the same time as anastrozole, because it may decrease the pharmacological action of the latter.

Special Instructions

The patient’s menopausal hormonal status must be confirmed by determination of serum sex hormones.

The efficacy of anastrozole in women with estrogen receptor-negative tumors has not been noted unless there has been a previous positive clinical response to tamoxifen.

There are no data on the safety of anastrozole in patients with significant hepatic impairment or in patients with severe renal impairment (creatinine clearance less than 20 ml/min).

In case of persistent uterine bleeding during anastrozole administration, a gynecologist should be consulted and monitored.

Oestrogen-containing medications should not be administered concomitantly with anastrozole. By reducing the concentration of circulating estradiol, anastrozole may cause a decrease in bone mineral density.

In patients with osteoporosis or at risk of osteoporosis, bone mineral density should be evaluated by densitometry (e.g., a DEXA scan) at the start of treatment and over time. If necessary, treatment or prophylaxis for osteoporosis should be initiated under close medical supervision. There are no data on concomitant use of anastrozole and gonadotropin-releasing hormone (GnRH) analogues. It is not known whether anastrozole improves treatment outcomes when used together with chemotherapy.

Safety data on long-term treatment with anastrozole are not yet available.

The efficacy and safety of anastrozole and tamoxifen when used concomitantly, regardless of hormone receptor status, is comparable to that of tamoxifen alone. The exact mechanism of this phenomenon is not yet known.

Impact on driving and operating machinery

Cautious driving and operating machinery should be observed because some side effects of the drug, such as asthenia, headache, dizziness and sleep disturbances, may adversely affect the ability to perform work requiring increased concentration and rapid psychomotor reactions. If these side effects occur, you should refrain from performing the specified activities.

Contraindications

With caution

Osteoporosis, hypercholesterolemia, lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the drug form contains lactose), coronary heart disease, liver function disorders.

Side effects

The side effects reported more frequently than sporadic observations are listed below by organ and system with the frequency of occurrence.

Defining the frequency of adverse reactions: very common (> 10%); common (1-10%); infrequent (0.1 – 1%); rare (0.01 – 0.1%); very rare (< 0.01%).

Cardiovascular system disorders: very common – “hot flashes” of fever, increased blood pressure; common – vasodilation, ischemic cardiovascular disease.

Muscular system disorders: very common – arthralgia, joint stiffness, arthritis, back pain, decreased bone mineral density, osteoporosis and bone fractures; common – bone pain, myalgia; infrequent – “trigger finger” or “clicking finger” (impaired ability to straighten a finger, usually the middle or ring finger).

Reproductive and genitourinary system disorders: Frequent – vaginal mucosal dryness, vaginal bleeding (mostly during the first weeks after withdrawal or change from prior hormone therapy to anastrozole preparations), vulvovaginitis, vaginitis, pelvic pain; infrequent – mucous vaginal discharge, urinary tract infections, breast pain; rare – endometrial cancer, breast neoplasms.

With the blood and lymphatic system: very common – lymphedema; infrequent – anemia.

The digestive system: very frequently – nausea, vomiting; frequently – diarrhea, constipation, dyspepsia, increased activity of alkaline phosphatase, alaniaminotransferase, aspartate transferase; infrequently – abdominal pain, increased activity of gamma-glutamintransferase and bilirubin concentration, hepatitis, dry mouth.

Nervous system disorders: very frequently – headache, dizziness, sleep disturbances, depression; frequently – carpal tunnel syndrome (mostly observed in patients with risk factors for this disease), anxiety, paresthesias.

Senses: infrequent – cataracts.

Respiratory system: very often – pharyngitis, increased cough, shortness of breath; infrequently – chest pain, sinusitis, bronchitis.

Mechanical system disorders: very common – peripheral edema; common – anorexia, hypercholesterolemia, hypercalcemia (with or without increase of parathormone concentration), weight gain.

Skin and appendages: very common – skin rash; common – thinning of hair, alopecia; infrequent – erythema multiforme (Stevens-Johnson syndrome), cutaneous vasculitis (including single cases of purpura (Schoenlein-Genoch syndrome)).

Allergic reactions: common – allergic reactions; infrequent – urticaria; rare – anaphylactoid reaction; very rare – angioedema.

Others: very common – asthenia.

If you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Single clinical cases of anastrozole overdose have been described. The single dose of anastrozole at which life-threatening symptoms develop has not been established.

Treatment: There is no specific antidote. If necessary, symptomatic therapy is carried out. Vomiting shall be initiated (if the patient is conscious), general supportive therapy and observation of the patient, control of functions of vital organs and systems shall be performed. Dialysis may be performed.