Instructions for administration
Common International Name of the Active Substance: Anastrozolum
1 tablet contains: the active substance: anastrozole 0.25 mg or 1.0 mg;
Excipients: magnesium stearate, Kollidon CL (crospovidone), coloring agent FD & C Yellow 5, Ludipress (lactose, polyvidone, crospovidone).
DESCRIPTION OF THE MEDICINAL PRODUCT
0.25 mg tablets
Yellow tablets, square shape, compact structure and homogeneous, split line and “BP” inscription on one side of the tablet, with tight edges, rounded edge side. Marble is permitted on the surface of the tablets.
1 mg tablets
Yellow tablets, square shape, compact structure and homogeneous, split line and the “BP” inscription on one side of the tablet and with the inscription “1” – on the other side of the tablet, with sharp edges, flat side with rounded edges. Marble is permitted on the surface tablets.
THE PHARMACOTERAPEUTICAL GROUP and the ATC Code
Hormonal antagonist and related substances. Aromatase inhibitor, L02BG03.
Anastrozole refers to a new generation of aromatase-selective nonsteroidal inhibitors, used in the treatment of disseminated breast cancer in postmenopausal women. Under the action of anastrozole, inhibition occurs multiplication and growth of mammary gland cells, endogenous estrogen dependent. The mechanism of action of anastrozole is reduced to the selective inhibition of aromatase activity, the cytochrome P450 enzyme. The main source of estrogens in menopausal women are androgens in main androatendione and testosterone. Aromatase provides for their multiple hydroxylation by transformation into estrone and then estradiol into adipose and muscle tissue, adrenal and tumor tissue.
Anastrozole selectively inhibits aromatase by interacting with the iron of the citrochrome hem P-450. Thus, the preparation provides an inhibition marked activity of the enzyme, which contributes to the maximal reduction of estrogen levels in both the peripheral and tumor the therapeutic effect in women with breast cancer. In postmenopausal anastrozole at the dose of 1 mg / day causes a decrease in estradiol levels with 80%. Anastrozole does not show progestative, androgenic or estrogen activity. The preparation does not influence the secretion of cortisol and aldosterone. Therefore, no corticosteroid supplementation is required.
Absorption of anastrozole is rapid and maximum plasma concentrations are usually reached within the first two hours after administration (under the conditions fasting). Foods slightly decrease speed but not absorption. It is not expected that the minor change in the absorption rate to determine a clinical signaling effect on plasma concentration at steady state, when given as a single daily dose of 1 mg anastrozole tablets.
Approximately 90 to 95% of steady-state anastrozole is reached after 7 days of daily administration. There is no evidence of time or dose dependence of the pharmacokinetic parameters of anastrozole. The pharmacokinetics of anastrozole are age-independent for postmenopausal women.
Anastrozole binds only 40% to plasma proteins. Anastrozole is slowly eliminated with a half-life of plasma by elimination of 40 to 50 hours. It is metabolized extensively in postmenopausal women, less than 10% of the dose being excreted unchanged in urine within 72 hours of administration.
The metabolism of anastrozole occurs through N-dealkylation, hydroxylation and glucuronidation. Metabolites are mainly excreted via the urinary tract. Triazole, the major metabolite present in plasma, does not have the effect of aromatase inhibition.
Renal or hepatic impairment
Clearance (Cl / F) of anastrozole after oral administration a was approximately 30% lower in volunteers with stable liver cirrhosis compared to the control group (Study 1033IL / 0014).
However, the plasma concentrations of anastrozole recorded in volunteers with cirrhosis were within the range of concentration values observed in normal subjects in other studies clinical. The plasma concentrations of anastrozole observed in during the long-term efficacy studies performed in patients with hepatic impairment were within the range of plasma concentrations observed in patients without hepatic impairment.
The apparent clearance (Cl / F) of anastrozole was not altered in volunteers with severe renal impairment (GFR <30 ml / min) in study 1033IL / 0018, which is consistent with the fact that anastrozole is mainly eliminated by metabolism. The plasma concentrations of anastrozole observed during long-term efficacy studies in patients with renal impairment were within the observed plasma concentrations observed in patients without renal impairment. In patients with severe renal insufficiency, anastrozole should be administered with caution.
Treatment of advanced breast cancer with receptors estrogen present in postmenopausal women.
Adjuvant treatment for incipient invasive breast cancer with estrogen receptors in postmenopausal women.
Adjuvant treatment for early invasive breast cancer with estrogen receptors in postmenopausal women they received adjuvant treatment with tamoxifen for 2 to 3 years.
DOSES AND METHOD OF ADMINISTRATION
The tablets are administered internally with water without chewing. It is recommended that the preparation be given at one and the same time. Postmenopausal women, including the elderly, indicate 1 mg once per day for a long time. In the progression of the disease, it’s interrupted. Dosage adjustment in patients with mild and moderate liver and kidney function disorder is unnecessary.
The side effects listed below are classified by frequency, system and organ. Frequency groups according to the convention MedDRA: very common (≥1 / 10), common (≥ 1/100 and <1/10), less (≥ 1/1000 to <1/100), rare (≥1 / 10000 and <1/1000) and very rare (<1/10000).
The most commonly reported side effects were headache, hot flushes, nausea, rash, arthralgia, joint stiffness, arthritis and asthenia.
Metabolic and nutritional disorders
Common: anorexia, hypercholesterolemia.
Nervous system disorders
Very common: headache.
Common: somnolence, carpal tunnel syndrome.
Very common: hot flushes.
Very common: Heavy.
Common: diarrhea, vomiting.
Common: increases in serum alkaline phosphatase, AST and ALT.
Uncommon: increase in plasma levels of γ-GT and bilirubin, hepatitis.
Skin and subcutaneous tissue disorders
Very common: rash.
Common: thinning of the hair / alopecia, allergic reactions.
Rare: polymorphic erythema, anaphylactoid reactions, cutaneous vasculitis (including
some reports of purple Henoch-Schönlein).
Very rare: Stevens-Johnson syndrome, angioedema.
Musculoskeletal and connective tissue disorders
Very common: arthralgia / joint redness, arthritis, osteoporosis.
Common: bone pain.
Uncommon: digital tenosynovitis.
Reproductive system and breast disorders
Common: dryness of the vaginal mucosa, vaginal bleeding.
General disorders and administration site conditions
Very common: asthenia.
Hypersensitivity to anastrozole or any of the other ingredients of the preparation.
Severe renal insufficiency (creatinine clearance below 20 ml / min.)
Moderate or severe hepatic impairment (harmlessness and efficacy are not confirmed).
Pregnancy and breastfeeding.
Cases of overdose have not been reported.
ATTENTION AND SPECIAL PRECAUTIONS FOR USE
It is not recommended for use in women of childbearing potential. In the case of women with hormone status unknown, it is recommended to confirm its menopause status by hormonal methods.
There is insufficient data on the safety of anastrozole in patients with moderate and marked liver function disorder or with severe renal impairment (creatinine clearance below 20 ml / min.).
Anastrozole is not recommended for use in children, as harmlessness and efficacy are not established.
If metrorrhagia persists on the background of anastrozole, it is consultation with the gynecologist.
Anastrozole, by decreasing the circulating estradiol level, can reduce the bone mineral density. In patients suffering from osteoporosis or at risk of developing osteoporosis, it is recommended to determine the bone mineral density at the start of the treatment and through it by the densimetric method (DEXA scan). If necessary, treatment or prophylaxis of osteoporosis will be performed under monitoring medical.
This medicine contains lactose. Patients with rare hereditary conditions galactose intolerance, lactase (Lapp) or glucose-galactose malabsorption should not take this medicine.
Contains FD & C Yellow dye Nr. 5 (E102). May cause allergic reactions.
Administration during pregnancy or lactation
Anastrozole is contraindicated in pregnancy and lactation.
Influence on the ability to drive or use machines
Due to the adverse drug reaction profile, the ability of driving vehicles and using machinery can be affected.
INTERACTIONS WITH OTHER MEDICINES,
OTHER TYPES OF INTERACTION
In vitro, anastrozole inhibits the CYP 1A2, 2C8 / 9 and 3A4 isoenzymes. Studies clinical trials with antipyrine and warfarin have shown that anastrozole given at a dose of 1 mg, does not significantly inhibit metabolism anti-RNA and R- and S-warfarin, thus, administration is unlikely concomitant anastrozole with other drugs to produce interactions clinically meaningful, mediated by to CYP enzymes.
Enzymes that mediate the metabolism of anastraozole have not been identified. Cimentidine, a weak, non-specific inhibitor of CYP enzymes, does not influence plasma concentrations of anastrozole. Effect of strong inhibitors CYP is unknown.
There were no clinically significant interactions at patients treated with anastrozole receiving concomitant therapy with other medicines. There were no significant clinical interactions with bisphosphonates.
Co-administration with tamoxifen or medicines containing it estrogens should be avoided, as action may diminish pharmacology.
0.25 mg and 1 mg tablets.
Twenty (20) tablets in the blister.
Three blister packs with the instruction for administration in a carton.
Keep at temperatures below 25 ° C.
Keep out of the reach and sight of children!
TERMS OF VALIDITY
3 years. Do not use after the expiry date stated on the pack.
CERTIFICATE OF REGISTRATION
SC Balkan Pharmaceuticals SRL N. Grădescu str., 4, MD-2002, or. Chisinau, Republic of Moldova.
SC Balkan Pharmaceuticals SRL Industrial Street, 7 / A, MD-2091, or. Singera, Republic of Moldova.
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