ANASTROZOLE RATIOPHARM 1 mg film-coated tablet is indicated in the treatment of advanced breast cancer in hormone receptors positive in menopausal women


The recommended dosage of ANASTROZOLE RATIOPHARM in adults, including the elderly, is one tablet at 1 mg once daily.

Pediatric populations

ANASTROZOLE RATIOPHARM is not recommended for use in children and adolescents because of insufficient tolerance and efficacy data (see sections 4.4 and 4.4). >

Renal insufficiency

No dosage adjustment is recommended in patients with mild or moderate renal impairment. In patients with severe renal impairment, administration of ANASTROZOLE RATIOPHARM should be carried out with caution (see sections 4.4 and 4.4),

Anastrozole is devoid of any progestational, androgenic or estrogenic activity.
Daily doses of anastrozole up to 10 mg per day had no effect on the secretion of cortisol or aldosterone measured before or after a standard adrenocorticotropic hormone (ACTH). Corticosteroid supplementation is therefore not necessary.

Efficacy and clinical safety

Breast cancer, advanced

First-line treatment of advanced breast cancer in postmenopausal women

Two randomized, double-blind, controlled trials of similar regimen (Study 1033IL / 0030 and Study 1033IL / 0027) were conducted to compare the efficacy of anastrozole with tamoxifen in first-line treatment Menopausal women with locally advanced or metastatic breast cancer, hormone receptors positive or unknown. A total of 1,021 patients were randomized to receive 1 mg of anastrozole once daily or 20 mg of tamoxifen once daily. The main criteria of the two trials were time to progression, tumor, tumor response rate and tolerance.
For the main criteria, study 1033IL / 0030 showed an advantage, statistically significant for anastrozole compared to tamoxifen in terms of time to progression tumor (Hazard ratio [HR]: 1.42, interval of; 95% CI: [1.11 to 1.82], median time to progression of 11.1, and 5.6 months for anastrozole and tamoxifen respectively, p '= 0.006) , The tumor response rates were similar, for anastrozole and tamoxifen. In the study, 1033IL / 0027, tumor-specific response rates and tumor progression times were similar for anastrozole and tamoxifen. The results on the secondary endpoints confirmed the results on the main efficacy criteria. The number of deaths in all treatment groups in the two trials was too low to allow conclusions about a difference in overall survival.
Second-line treatment of advanced breast cancer in postmenopausal women

Anastrozole was studied in two controlled clinical trials (Study 0004 and Study 0005), postmenopausal women with advanced breast cancer having progressed, following treatment with tamoxifen for Early or early breast cancer A total of 764 patients were randomized to receive a single daily dose of 1 mg or 10 mg of anastrozole or 40 mg of megestrol acetate four times day. The main criteria for effectiveness were time, progress and objective response rate, prolonged stable disease rate (over 24 weeks), progression rate and survival were also calculated. In both studies, there was no significant difference between treatment arms regardless of the parameters of efficacy.

In the Phase III / IV SABER study, 234 postmenopausal women with early breast cancer with hormone receptor positive and eligible for treatment with anastrozole 1 mg per day , Were stratified in low, moderate, and high risk groups according to their existing risk of fracture fracture The primary endpoint of efficacy analyzed was the bone mineral density of the lumbar spine determined by DEXA scan. All patients were treated with vitamin D and calcium, patients in the low-risk group received anastrozole alone (N '= 42), those in the moderate risk group were randomized to receive Anastrozole plus risedronate 35 mg once a week (N '= 77) or anastrozole plus placebo (N' = 77), and those in the high-risk group received anastrozole plus risedronate; 35 mg once weekly (N '= 38). The main criterion was the change in bone mineral density of the lumbar spine at 12 months by comparison with that at entry into the study. Code>
The main analysis at 12 months showed that patients who were already at moderate to high risk of fracture showed no decrease in bone mineral density (measured at the lumbar spine by DEXA scan) Treated with anastrozole 1 mg / day in combination with risedronate 35 mg once weekly. In addition, a non-statistically significant decrease in BMD was observed in the low-risk group treated with anastrozole 1 mg / day alone. The change in total hip BMD at twelve months by comparison with inclusion in the study (secondary efficacy endpoint) was consistent with these results.

This study provided evidence that the use of bisphosphonates could be considered in the management of possible bone mineral loss in postmenopausal women with early stage breast cancer who are eligible for treatment with Anastrozole.

Pediatric population

Anastrozole is not indicated for use in children and adolescents Effectiveness has not been established in the pediatric populations studied (see below). The number of children being treated was too limited to allow reliable conclusions about the security of employment. No data on the potential effects of long-term anastrozole therapy in children and adolescents is available (see also section Preclinical safety data). >

The European Medicines Agency has granted a derogation from the obligation to submit the results of studies of anastrozole in one or more subgroups of children, small in size due to a deficit, Growth hormone, testotoxicosis, gynecomastia or McCune-Albright syndrome (see Posology and method of administration).
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Small size due to growth hormone deficiency

A multicenter, randomized, double-blind study evaluated 52 pubescent boys (ages 11 to 16 years inclusive) with growth hormone deficiency treated with 1 mg / day of anastrozole or placebo, for 12 to 36 Month in combination with growth hormone. Only 14 subjects under anastrozole completed 36 months of treatment.
No statistically significant differences were observed from placebo on growth-related parameters (predicted adult size, size, size, SDS [standard deviation score] and velocity; growth). Final size data were not available. Although the number of children treated is too limited to allow for reliable findings on safety, employment, increased fracture rates and a tendency to decrease bone mineral density, Observed in children treated with anastrozole compared with placebo.


An open-label, multicenter, non-comparative study evaluated 14 male children (ages 2 to 9 years) with familial precocious puberty limited to boys, also known as testotoxicosis, treated with the combination of anastrozole and Bicalutamide. The main objective of this study was to evaluate the efficacy and safety of this association for 12 months. Of the 14 patients included in the study, 13 completed the 12-month treatment with the combination (1 patient was lost to follow-up) .; After 12 months of treatment, no significant difference in growth rate Was observed in comparison with the 6 months preceding the inclusion in the study

Studies on gynecomastia

Trial 0006 was a randomized, double-blind multicenter study of 82 pubescent boys (ages 11 to 18 inclusive) with gynecomastia present for at least 12 months receiving either anastrozole 1 mg per day or one; Placebo for at least 6 months. No significant difference was observed between the group treated with anastrozole 1 mg and the placebo group in terms of number of patients with a reduction in total breast volume greater than or equal to 50% after 6 months of treatment .

Test 001 was an open-label pharmacokinetic study with repeated doses of anastrozole 1 mg / day in 36 pubescent boys with gynecomastia for less than 12 months. The secondary objectives were to evaluate the proportion of patients with a reduction of at least 50% of the combined volume of the two breasts calculated between the first day of inclusion and the sixth month of treatment and to determine Tolerance and safe use of this treatment. A decrease of 50% or more of the total breast volume was observed in 56% (20/36) of boys after 6 months.
Study in the McCune Albright syndrome

Test 0046 was an open-label, open-label, international, exploratory trial in 28 girls with a McCune Albright syndrome (SMA) treated with anastrozole. The primary objective was to evaluate the safety and efficacy of anastrozole 1 mg / day in patients with SMA. The efficacy of the treatment of the study was determined on the basis of the proportion of patients meeting predefined criteria for vaginal bleeding, bone age and growth rate. >

No statistically significant changes in the frequency of days of vaginal bleeding were observed under treatment. No clinically significant changes in the Tanner stage, mean ovarian volume, or mean uterine volume were observed. No statistically significant change in the rate of increase in age, bone under treatment compared to the initial period was observed. The growth rate (in cm / year) decreased significantly (p

In osteoporotic women or at a risk of osteoporosis, the bone mineral density must be rigorously evaluated at the beginning of treatment and then at regular intervals. Appropriate treatment or prevention of osteoporosis should be instituted and monitored carefully.
Hepatic impairment

ANASTROZOLE RATIOPHARM has not been evaluated in patients with breast cancer and with moderate to severe hepatic impairment. Exposure to anastrozole may be increased in subjects with hepatic impairment (see section: Pharmacokinetic properties), administration of anastrozole in patients with moderate and severe hepatic impairment should be performed with; Precautions (see Dosage and Mode of Administration). Treatment should be based on an assessment of the benefit-risk ratio for each patient individually

Renal insufficiency

ANASTROZOLE RATIOPHARM has not been evaluated in patients with breast cancer and with severe renal impairment. Exposure to anastrozole in subjects with severe renal insufficiency is not increased (filtration rate, glomerularity
Hypersensitivity to lactose

This product contains lactose. Patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency or glucose / galactose malabsorption syndrome should not take this drug
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In vitro, anastrozole inhibits CYP 1A2, 2C8 / 9 and 3A4. Clinical studies with antipyrin and warfarin showed that anastrozole at a dose of 1 mg did not significantly inhibit the metabolism of antipyrin and warfarin (R and S), indicating that It is unlikely that the administration of anastrozole with other drugs will result in clinically significant drug interactions originating in cytochromes CYP. The enzymes responsible for the metabolism of anastrozole have not been identified.

Cimetidine, a weak and non-specific inhibitor of cytochrome CYP, has not altered plasma concentrations of anastrozole The effect of potent cytochrome CYP inhibitors is unknown.

A review of the tolerance database from clinical studies did not reveal any clinically significant interaction in patients receiving anastrozole and also other frequently prescribed medications. There was no clinically significant interaction with bisphosphonates (see section 5.1 Pharmacodynamic properties).
The concomitant administration of ANASTROZOLE RATIOPHARM with tamoxifen or estrogen-containing therapies should be avoided as it may diminish its pharmacological action (see sections 4.4 and 4.4) .

Not applicable.

Clinical experience related to accidental overdose is limited. In animal studies, anastrozole has demonstrated low acute toxicity. Clinical trials were conducted with different dosages from anastrozole up to a maximum dose of 60 mg in single administration to healthy male and male volunteers up to a maximum daily dose of 10 mg administered to Women with postmenopausal breast cancer at an advanced stage these doses were well tolerated. No single dose of anastrozole causing life-threatening symptoms has been identified. There is no specific antidote for overdose and treatment should be symptomatic.

The action to be taken in the face of overdosage must take account of the possibility of simultaneous ingestion of several products. If the patient is conscious, vomiting may be induced. Dialysis may be useful as anastrozole is not strongly related to proteins. The usual measures of management, including the monitoring of the vital functions and the careful monitoring of the patient are indicated.


There are no data on the use of anastrozole in pregnant women. Studies in animals have shown reproductive toxicity (see section Preclinical safety data). Anastrozole is contraindicated during pregnancy (see section Contraindications).

There are no data on the use of anastrozole during breastfeeding. Anastrozole is contraindicated during breast-feeding (see section Contraindications).

The effects of anastrozole on fertility in the human species have not been studied. Studies in animals have shown reproductive toxicity (see section Preclinical safety data).

The following table shows the adverse effects from clinical trials, post-marketing studies or spontaneous declarations. Unless specified, frequency groups were calculated from the number of adverse events reported in a large Phase III clinical study conducted in 9,366 postmenopausal patients with operable breast cancer receiving treatment Adjuvant for 5 years (study, ATAC: Anastrozole, Tamoxifen, Alone or in Combination, study).
The adverse reactions listed below are categorized by frequency, and by organ system class (SOC). Frequency groups are defined according to the following convention: very common (≥1 / 10), frequent (≥ 1/100, to