Anastrozole 1 mg film -coated tablets - summary of the product properties (SMPC) (2023)

Each film -coated tablet contains 1 mg anastrozole.

Auxiliary substances with a known effect:

Each film-coated tablet contains 93 mg lactose monohydrate (see section 4.4).

You can find the full list of auxiliary substances in section 6.1.

Film -coated tablet.

White film-coated round Biconvex tablets, designated on one page with "Ana" and "1".

Anastrozole is given for the:

• Treatment of hormone receptor-positive advanced breast cancer in women after menopause.

• Adjuvant treatment of hormone receptor-positive early invasive breast cancer in women after menopause.

• Adjuvant treatment of hormone receptor-positive early invasive breast cancer in women after menopause who have received 2 to 3 years of adjuvant tamoxifen.

Dosage

The recommended dose of anastrozole for adults, including older people, is a 1 mg tablet once a day.

In women after menopause with hormone receptor -positive early invasive breast cancer, the recommended duration of adjuvant endocrine treatment is 5 years.

Special populations

Children's population

Anastrozole is not recommended for use in children and adolescents due to insufficient data on security and effectiveness (see sections 4.4 and 5.1).

Kidney dysfunction

In patients with light or moderate kidney impairment, no dose change is recommended. In patients with severe kidney impairment, anastrozole should be administered with caution (see section 4.4 and 5.2).

Liver dysfunction

In patients with a slight liver disease, no dose change is recommended. Caution is required for patients with moderate to serious liver impairment (see section 4.4).

Advocation method

Anastrozole should be taken orally.

Anastrozole is in:

• Pregnant or breastfeeding women.

• hypersensitivity to the active substance or to one of the auxiliary substances listed in Section 6.1.

Generally

Anastrozol should not be used in women before menopause.there is no data to support the use of anastrozole with LHRH analoga.

The simultaneous administration of tamoxifen or estrogen-containing therapies with anastrozole should be avoided, since this can reduce its pharmacological effect (see section 4.5 and 5.1).

Effect on the bone mineral density

If Anastrozole lowers the circulating estrogen level, this can lead to a reduction in bone mineral density, with a possible increased risk of fracture (see section 4.8).

Women with osteoporosis or a risk of osteoporosis should have formally assessed their bone mineral density at the beginning of treatment and at regular intervals.B. bisphosphonates can stop another bone mineral loss caused by anastrozole in women after menopause, and could be taken into account (see section 4.8).

Liver dysfunction

Anastrozole was not examined in breast cancer patients with moderate or severe liver impairment. The exposure to anastrozol can be increased in subjects with liver impairment (see section 5.2); the administration of anastrozol in patients with moderate and serious liver impairment should be carried out with caution (see section 4.2)The treatment should be based on an evaluation of the benefit risk for the individual patient.

Kidney dysfunction

Anastrozole was not examined for breast cancer patients with severe kidney impairment. The exposure to anastrozole is not increased in subjects with severe kidney impairment (size <30 ml/min, see section 5.2); in patients with severe kidney impairment, the administration of anastrozole should be carried out (caution (see section 4.2).

Children's population

Anastrozole is not recommended for use in children and adolescents, since security and effectiveness has not been determined in this patient group (see section 5.1).

Anastrozole should not be used in boys with growth hormone deficiency in addition to the treatment of growth hormone. In the central clinical study, the central clinical study has not been proven and security has not been determined (see section 5.1). Since Anastrozol reduces the estradiol level, anastrozol may be able to use growth hormone in girlsGrowth hormone deficiency are not used. Long -term safety data in children and adolescents are not available.

Auxiliary substances with a known effect

Lactose

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the entire Lactas deficiency or the glucose-galactose malabsorption should not take this medicine.

Sodium

This drug contains less than 1 mmol sodium (23 mg) per tablet, ie essentially "sodium -free".

Anastrozol inhibits Cyps 1A2, 2C8/9 and 3A4 in vitro.klinic studies with anti-pyrin and warfarin that anastrozol did not significantly inhibit the metabolism of antipyrine and R and S-warfarin with a 1 mg dose, which pointed out to be indicated by CYP-Enzymes.

The enzymes that convey the metabolism of Anastrozole have not been identified. Cimetidine, a weak, unspecific inhibitor of CYP enzymes, did not influence the plasma concentrations of anastrozole. The effect of strong CYP inhibitors is unknown.

A review of the safety database for clinical studies showed no indications of a clinically significant interaction in patients treated with anastrazole and also received other frequently prescribed medicines. There were no clinically significant interactions with bisphosphonates (see section 5.1).

The simultaneous administration of tamoxifen or estrogen-containing therapies with anastrozole should be avoided, since this can reduce its pharmacological effect (see section 4.4 and 5.1).

pregnancy

There is no data from the use of anastrozol in pregnant women. Studies on animals showed reproduction stoxicity (see section 5.3). Anastrozol is contraindicated during pregnancy (see section 4.3).

Breastfeed

There is no data for using anastrozol during the lactation. Anastrozol is contraindicated during breastfeeding (see section 4.3).

fertility

The effects of anastrozole on fertility in humans have not been examined.

In the following table, undesirable reactions from clinical studies, re -market studies or spontaneous reports are presented.

The side effects listed below are classified in accordance with the frequency and system organization classes (SOC)./1,000 to <1/100), rare (≥ 1 // 10,000 to <1/1,000) and very rare (<1/10,000).Joint stiffness, arthritis and asthenia.

Table 1 Side effects according to system organization and frequency

*Events of the carpal tunnel syndrome have been reported in patients who receive anastrozole treatment in a larger number in clinical studies than patients treated with tamoxifen, but the majority of these events occurred in patients with identifiable risk factors for the development of the disease.

** Since skin vasculitis and Henoch-Schönlein-Purpura were not observed in ATAC, the frequency category for these events can be regarded as "rare" (≥ 0.01% and <0.1%) based on the worst value of the puncture.

*** Vaginal bleeding was often reported, mainly in patients with advanced breast cancer in the first few weeks after changing from the existing hormonal therapy for treatment with anastrozol.

The following table shows the frequency of predetermined undesirable events in the ATAC study after a medium follow-up of 68 months, regardless of causality, reported in patients who received study therapy, and up to 14 days after the end of experiments.

Table 2 ATAC study specified undesirable events

For the anastrozole and tamoxifen groups, a fracture rate of 22 per 1,000 patient years and 15 per 1,000 patient years were observed after a medium follow-up of 68 months.Osteoporosis was 10.5% in patients treated with anastrozole and in patients treated with tamoxifen, 7.3%.

It was not determined whether the fracture and osteoporosis observed in patients on anastrozole treatment reflect a protective effect of tamoxifen, a specific effect of anastrozole or both.

Reporting on suspected side effects

It is important to report suspected disadvantageous reactions after approval of the healing product.UK/Yellowcard or search or search for Mhra Yellow Card in the Google Play or Apple App Store.

There is only limited clinical experience with accidental overdose.

Anastrozol showed little acute toxicity in animal studies.

Clinical studies were carried out with various doses of anastrozole, up to 60 mg in a single dose of healthy male volunteers and up to 10 mg daily on women after menopause with advanced breast cancer.Leading life -threatening symptoms was not found.

There is no specific antidote against overdose and the treatment must be symptomatic.

When managing an overdose, it should be taken into account that several agents may have been taken.

Vomiting can be induced when the patient is vigilant.

Dialysis can be helpful because Anastrozole is not strongly protected.

The general supportive care, including the frequent monitoring of vital functions and close observation of the patient, is given.

Pharmacotherapeutic group: hormone antagonists and related active ingredients aromatase inhibitors

ATC -Code: L02B G03

Mechanism of action and pharmacodynamic effects

Anastrozole is a strong and highly selective non -steroidal aromata chimmer. After menopause, Oestradiol is mainly produced by converting AndrostEdion into the estrons into peripheral tissue.Circulating estradiol levels in women with breast cancer causes an advantageous effect.

In women after menopause, a daily dose of 1 mg anastrozole used to be oppressed by more than 80%using a highly sensitive assay.

Anastrozol has no testogenic, androgens or Austrian activity.

The daily doses of Anastrozole up to 10 mg have no influence on cortisol or aldosterone secretion, measured before or according to the standard adrophotrophic hormone (ACTH) test tests.

Clinical effectiveness and security

Advanced breast cancer

First line therapy for women after menopause with advanced breast cancer

Two double -blind, controlled clinical studies with a similar design (study 1033il/0030 and study 1033il/0027) were carried out or metastatic breast cancer in women after the menopause. 1,021 patients were randomized once a day 1 mg of anastrozol or 20 mg TamoxifenThe primary endpoints for both studies were time for the progression of the tumor, the objective tumor response rate and security.

For the primary endpoints, study 1033il/0030 showed that anastrozol has a statistically significant advantage over Tamoxifen for the time up to tumor progression (Hazard ratio (HR) 1.42, 95% confidence interval (CI) [1.11, 1.82], mean time until progression 11.111.11 and 5.6 months for anastrozol or tamoxifen, p = 0.006); the objective tumor response rates were similar for anastrozole and tamoxifen.Tumor reaction rates and time until the tumor progression.

Second line therapy in women after menopause with advanced breast cancer

Anastrozole was examined in two controlled clinical studies (study 0004 and study 0005) after menopause with advanced breast cancer, which after tamoxifen therapy either for advanced or early breast cancer had a disease progression.1 mg or 10 mg of anastrozole or megelol acetate 40 mg four times a day. The primary effectiveness variables for progress and objective response rates. The rate of the longer (more than 24 weeks) stable illness, the progression rate and the survival rate were also calculated.There were no significant differences between the treatment arms in relation to the effectiveness parameters.

Additional treatment of early invasive breast cancer in hormone receptor-positive patients

In a large phase -III study, which was carried out in 9366 postmenopausal women with surgical breast cancer, which was treated for 5 years, it was shown that anastrozole tamoxifen in the disease -free survival is statistically superior.A greater extent of the benefit was observed for tamoxifen for the prospectively defined hormone receptor-positive population.Table 3 ATAC final overview: 5-year closing analysis of the treatment

^AThe disease -free survival encompasses all reciprocities and is defined as the first occurrence of local regional recurrence, contralateral new breast cancer, removed or death (for any reason).

^BDistant disease -free survival is defined as the first occurrence of removed or death (for any reason).

^CThe time of recurrence is defined as the first occurrence of local regional recurrence, contralateral new breast cancer, removed recurrence or death due to breast cancer.

^DThe time to the removed recurrence is defined as the first occurrence of remote recurrence or death by breast cancer.

^eNumber (%) of the died patients.

The combination of anastrozole and tamoxifen showed no effectiveness advantages compared to tamoxifen in all patients and in the hormone receptor-positive population.

With an updated follow-up in a median of 10 years, it was shown that the long-term comparison of the treatment effects of anastrozole matches tamoxifen with previous analyzes.

Adjuvant treatment of early breast cancer in patients treated with adjuvant tamoxifen

In a phase -III study (Austrian breast and intestinal cancer group [ABCSG 8]), which was carried out in 2579 women with hormone receptor positive early breast cancer postmenopausal women who were operated on with or without radiation therapy, with tamoxifen was statistically supervision in the disease -free survivalCompared to tamoxifen after a medium follow -up of 24 months.

Table 4 ABCSG 8 -study endpoint and results Summary without radiation therapy and without chemotherapy (see below)

Two other similar studies (GABG/Arno 95 and ITA), in which a patient had received surgery and chemotherapy as well as a combined analysis of the Austrian breast and colon cancer group (ABCSG 8) and GABG/Arno 95, supported these results.

The anastrozole security profile in these 3 studies matched the well -known security profile in postmenopausal women with hormone receptor positive early breast cancer.

Bone mineral density (BMD)

In the phase III/IV study (study by anastrozol with the bisphosphonate Risedronat [Sabre]), 234 postmenopausal women with hormone receptor-positive early breast cancer, which were planned for treatment with anastrozole 1 mg/day, were milder until low,Risk groups layered and high risk of their existing risk of a fragility fracture. The primary effectiveness parameter was the analysis of the bone mass density of the lumbar spine using dexa -scanning. All patients were treated with vitamin D and calcium.42), those in the moderate group were once a week (n = 77) or anastrozol plus placebo (n = 77) and in the wedding on anastrozol plus starter the risk group received anastrozol plus Riedronat 35 mg once a week (n = 38).The primary endpoint was the change from the initial line in the bone mass density of the lumbar spine after 12 months.

The 12-month main analysis has shown that patients who are already with a moderate to high fragility fracture with a moderate to high fragility fracture. 35 mg once a week.Watched with anastrozole 1 mg/day treated low risk group.

This study provides indications that the use of bisphosphonates in the treatment of a possible bone mineral loss in women after menopause could be treated with early breast cancer with anastrozole.

Children's population

Anastrozol is not indicated for use in children and adolescents. The effectiveness was not determined in the examined pediatric populations (see below). The number of children treated was too limited to draw reliable conclusions for safety.Potential long -term effects of anastrozole treatment available in children and adolescents (see also section 5.3).

The European Medicines Agency has given up the obligation to present the results of studies with anastrozole in one or more sub-groups of the pediatric population in a short stature due to a growth hormone deficiency (GHD), testotoxicosis, gynecomastia and McCune-Albright syndrome (see section 4.2).

Short stature due to the growth hormone lack

A randomized, double -blind, multicenter study evaluated 52 puberty boys (11 to 16 years included) with GHD, which were treated for 12 to 36 months with anastrozole 1 mg/day or placebo in combination with growth hormone..

No statistically significant difference to placebo was observed for the growing parameters of the predicted height, height, height, heights, heights (standard deviation evaluation) and height speed. The final height data was not available.To draw conclusions for safety, there was an increased fracture rate and a trend towards a reduced bone mineral density in the anastrozol arm compared to placebo.

Test

An open, non -comparative, multicenter study examined 14 male patients (at the age of 2 to 9) with family -limited early puberty, also known as testotoxicosis, treated with the combination of anastrozole and bicalutamide.to evaluate this combination program over 12 months. Thirty of the 14 enrolled patients completed 12 months of combination treatment (one patient was lost by follow-up). There was no significant difference in the growth rate after 12 months of treatment, compared to the growth rate during the 6 months beforeEntry into the study.

GynaeComastia -Studies

The study 0006 was a randomized, double-blind, multicenter study of 82 pubescent boys (11-18 years at the age of 11 to 18 years) with gynaecoma of more than 12 months, which with Anastrozole 1 mg/day or placebo daily for up to 6Months were treated. There was no significant difference in the number of patients with a reduction in the entire breast volume by 50% or more between the anastrozole -1 -mg group and the placebo group.

The study 0001 was an open pharmacokinetic examination of anastrozole 1 mg/day in 36 pubertal boys with gynacoma of less than 12 months.% between day 1 and after 6 months of study treatment as well as the compatibility and security of patients.

McCune-Albright-Syndromstudie

The study 0046 was an international, multicenter, open exploratory study with anastrozole in 28 girls (2 to ≤ 10 years) with the McCune-Albright syndrome (MAS).to be evaluated in patients with MAS.The effectiveness of the study treatment was based on the proportion of patients who met defined criteria in relation to vaginal bleeding, bone age and growth speed.

There was no statistically significant change in the frequency of vaginal blood days during treatment. There were no clinically significant changes in the Tanner -Sating, in the middle ovarian volume or in the middle uterine volume.observed for the rate during the baseline.0.05).

Absorption

The absorption of anastrozole is quick and maximum plasma concentrations typically occur within two hours after dosage (under fast conditions). The food easily reduces the speed, but not the extent of the absorption is not expected that the low change in the absorption rate is not expectedTo a clinically significant effect on the plasma concentrations of stationary state during the daily dosage of anastrozole tablets.-Fach. There is no evidence of time or dose dependency of anastrozole pharmacokinetic parameters.

The anastrozole pharmacokinetics are independent of age in women after menopause.

distribution

Anastrozole is only bound 40% of plasma proteins.

Anastrozole is slowly eliminated with a half -life of plasma of 40 to 50 hours. Anastrozole is metabolized by women after menopause, with less than 10% of the dose excreted in the urine within 72 hours after dosage.By N-Dealkylation, hydroxylation and glucuronidation. The metabolites are mainly excreted via the urine.

Elimination

Kidney or liver impairment

The apparent clearance (CL/F) of anastrozol after oral administration was about 30% lower in volunteers with stable liver cirrhosis than in the case of unanimous controls (study 1033il/0014) .plasmaanastrozole concentrations in volunteers with liver cirrhosis, however, within the concentration area in normal subjects in other studies.Plasma anastrozole concentrations, which were observed in long -term efficacy studies in patients with liver impairment, were in the area of plasma anastrozole concentrations in patients without liver impairment.

The apparent clearance (CL/F) of anastrozol after oral administration was not changed in volunteers with severe kidney impairment (GFR <30 ml/min) in study 1033il/0018, which corresponds to the fact that Anastrozol is primarily eliminated by metabolism.Plasmaanastrozole concentrations, which were observed in long -term efficacy studies in patients with kidney impairment, were within the area of plasma anastrozole concentrations in patients without kidney impairment. In the case of patients with severe kidney impairment, the administering of anastrozole should be carried out with caution (see section 4.2 and 4.4).

Children's population

In boys with a puberty of gynecomastia (10-17 years), Anastrozole was quickly absorbed, widespread and slowly eliminated with a half-life of about 2 days.Higher. Anastrozole in girls was widespread and slowly removed.

Non -clinical data does not show any special dangers for people based on conventional studies on security pharmacological, repeated dosient oxicity, genotoxicity, cancer -generating potential and toxicity for reproduction for the specified population.

acute toxicity

In animal studies, the toxicity was only observed at high doses. In acute toxicity studies in rodents, the median dose of anastrozol was more than 100 mg/kg/day on the oral route and on the intraperitoneal route more than 50 mg/kg/day.An oral acute toxicity study in the dog was the middle fatal dose greater than 45 mg/kg/day.

Chronic toxicity

In animal studies, undesirable effects were only observed at high doses. Several dose-toxicity studies used rats and dogs. In the toxicity studies, no no-effect levels for anastrozol were determined, but those effects that at low doses (1 mg/kg/day)and medium -sized doses (dog 3 mg/kg/day; rat 5 mg/kg/kg/were observed; day) were either related to the pharmacological or the enzyme that induce the properties of anastrozol and of significant toxic or degenerativeChanges were unfounded.

Mutagicity

Genetic toxicological studies with Anastrozol show that it is not a mutagen or a clastogenic.

Reproduction oxicology

In a fertility study, the male rats were dosed orally with 50 or 400 mg/l anastrozole for 10 weeks.Mating indices were disadvantageous in both dose groups, while a reduction in fertility was only visible at 400 mg/l dose level. The reduction was temporary, since all mating and fertility parameters were similar to the control group values after a 9-week treatment-free recovery phase.

The oral administration of anastrozole compared to female rats led to a high incidence of infertility at 1 mg/kg/day and increased the pre -implantation loss at 0.02 mg/kg/day. This effect occurred in clinically relevant doses.are not excluded. This effects were with the pharmacology of the connection and were completely reversed after a 5-week connection acceptance period.

The oral administration of anastrozole compared to pregnant rats and rabbits did not cause teratogenic effects in doses of up to 1.0 or 0.2 mg/kg/day.related to the pharmacology of the connection.

The survival of sausages that were born the rats at 0.02 mg/kg/day and higher (from day 17 of pregnancy until day 22 after the birth) were administered.Connection to the party.

Carcinogenicity

A two-year study on the oncogenicity of rats led to an increase in the incidence of liver opplasms and uterine current polyps in women and thyroid adenomes in men with high dose (25 mg/kg/day).than with human therapeutic doses and are considered not clinically relevant to the treatment of patients with anastrozole.

A two-year study on mouse-oncogenicity led to the induction of benign ovarian tumors and a disturbance of the incidence of lymphoretic neoplasms (less histiocytic sarcomas in women and more deaths as a result of lymphomas).not clinically relevant with Anastrozole.

Tablet -Kern

Lactose monohydrate

Sodium -strengthening lycolate (type A)

Povidone (K31) (E1201)

Magnesiumstearat (E572)

Film coating

Macrogol 400

Hypromellose (E464)

Titandioxide (E171)

Cardon boxes with PVC/PE/PVDC/aluminum blisters from 10, 14, 20, 28, 30, 50, 56, 60, 84, 90, 98, 100 or 300 tablets and hospital bubbles (PVC/PVDC/aluminum) with 28,50, 84, 98, 300 or 500 tablets.

Not all pack sizes can be marketed.

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