Anzol

Film-coated, white coloured, round shape, biconvex tablet with plain on both side.
Each film-coated tablet contains: Anastrozole, USP 1 mg.
Excipients/Inactive Ingredients: Colour: Titanium Dioxide.

Pharmacotherapeutic group: Enzyme inhibitors. ATC code: L02B G03.
Pharmacology: Pharmacodynamics: Mechanism of action and pharmacodynamic effects: Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. In postmenopausal women, estradiol is produced primarily from the conversion of androstenedione to estrone through the aromatase enzyme complex in peripheral tissues. Estrone is subsequently converted to estradiol. Reducing circulating estradiol levels has been shown to produce a beneficial effect in women with breast cancer. In postmenopausal women, Anastrozole at a daily dose of 1 mg produced estradiol suppression of greater than 80% using a highly sensitive assay.
Anastrozole does not possess any progestogenic, androgenic, or estrogenic activity.
Daily doses of Anastrozole up to 10 mg do not have any effect on cortisol or aldosterone secretion, measured before or after standard adrenocorticotrophic hormone (ACTH) challenge testing. Corticoid supplements are therefore not needed.
Pharmacokinetics: Absorption: Absorption of anastrozole is rapid and maximum plasma concentrations typically occur within two hours of dosing (under fasted conditions). Food slightly decreases the rate but not the extent of absorption. The small change in the rate of absorption is not expected to result in a clinically significant effect on steady-state plasma concentrations during once daily dosing of Anastrozole tablets. Approximately 90 to 95% of plasma anastrozole steady-state concentrations are attained after 7 daily doses, and accumulation is 3- to 4-fold. There is no evidence of time or dose-dependency of anastrozole pharmacokinetic parameters.
Anastrozole pharmacokinetics are independent of age in postmenopausal women.
Distribution: Anastrozole is only 40% bound to plasma proteins.
Elimination: Anastrozole is eliminated slowly with a plasma elimination half-life of 40 to 50 hours. Anastrozole is extensively metabolised by postmenopausal women with less than 10% of the dose excreted in the urine unchanged within 72 hours of dosing. Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. The metabolites are excreted primarily via the urine. Triazole, the major metabolite in plasma, does not inhibit aromatase.
Renal or hepatic impairment: The apparent clearance (CL/F) of anastrozole, following oral administration, was approximately 30% lower in volunteers with stable hepatic cirrhosis than in matched controls (Study 1033IL/0014). However, plasma anastrozole concentrations in the volunteers with hepatic cirrhosis were within the range of concentrations seen in normal subjects in other trials. Plasma anastrozole concentrations observed during long-term efficacy trials in patients with hepatic impairment were within the range of plasma anastrozole concentrations seen in patients without hepatic impairment.
The apparent clearance (CL/F) of anastrozole, following oral administration, was not altered in volunteers with severe renal impairment (GFR <30ml/min) in Study 1033IL/0018, consistent with the fact that anastrozole is eliminated primarily by metabolism. Plasma anastrozole concentrations observed during long- term efficacy trials in patients with renal impairment were within the range of plasma anastrozole concentrations seen in patients without renal impairment. In patients with severe renal impairment, administration of Anastrozole should be performed with caution (see Dosage & Administration and Precautions).
Paediatric population: In boys with pubertal gynaecomastia (10-17 years), anastrozole was rapidly absorbed, was widely distributed, and was eliminated slowly with a half-life of approximately 2 days. Clearance of anastrozole was lower in girls (3-10 years) than in the older boys and exposure higher. Anastrozole in girls was widely distributed and slowly eliminated.

Anastrozole 1mg film-coated tablet is indicated for the: Treatment of hormone receptor-positive advanced breast cancer in postmenopausal women. Efficacy has not been demonstrated in oestrogen receptor negative patients unless they had a previous positive clinical response to tamoxifen.
Adjuvant treatment of hormone receptor positive early invasive breast cancer in postmenopausal women.
Adjuvant treatment of hormone receptor positive early invasive breast cancer in postmenopausal women who have received 2 to 3 years of adjuvant tamoxifen.

Posology: The recommended dose of Anastrozole 1mg film-coated tablets for adults including the elderly is one 1 mg tablet once a day.
For postmenopausal women with hormone receptor-positive early invasive breast cancer, the recommended duration of adjuvant endocrine treatment is 5 years.
Special populations: Paediatric population: Anastrozole Tablets is not recommended for use in children and adolescents due to insufficient data on safety and efficacy.
Renal impairment: No dose change is recommended in patients with mild or moderate renal impairment. In patients with severe renal impairment, administration of Anastrozole 1mg film-coated tablets should be performed with caution (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: No dose change is recommended in patients with mild hepatic disease. Caution is advised in patients with moderate to severe hepatic impairment (see Precautions).
Method of administration: Anastrozole 1mg film-coated tablets should be taken orally.

There is limited clinical experience of accidental overdose. In animal studies, anastrozole demonstrated low acute toxicity. Clinical trials have been conducted with various dosages of Anastrozole, up to 60 mg in a single dose given to healthy male volunteers and up to 10 mg daily given to postmenopausal women with advanced breast cancer; these dosages were well tolerated. A single dose of Anastrozole that results in life-threatening symptoms has not been established. There is no specific antidote to overdosage and treatment must be symptomatic.
In the management of an overdose, consideration should be given to the possibility that multiple agents may have been taken. Vomiting may be induced if the patient is alert. Dialysis may be helpful because Anastrozole is not highly protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

Anastrozole is contraindicated in: Pregnant or breastfeeding women.
Patients with known hypersensitivity to anastrozole or to any of the excipients as listed.

General: Anastrozole should not be used in premenopausal women. The menopause should be defined biochemically (luteinizing-hormone [LH], follicle stimulating hormone [FSH], and/or estradiol levels) in any patient where there is doubt about menopausal status. There are no data to support the use of Anastrozole with LHRH analogues.
Co-administration of tamoxifen or estrogen-containing therapies with Anastrozole should be avoided as this may diminish its pharmacological action.
Effect on bone mineral density: As Anastrozole lowers circulating estrogen levels it may cause a reduction in bone mineral density with a possible consequent increased risk of fracture.
Women with osteoporosis or at risk of osteoporosis, should have their bone mineral density formally assessed at the commencement of treatment and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis should be initiated as appropriate and carefully monitored. The use of specific treatments, e.g., bisphosphonates, may stop further bone mineral loss caused by Anastrozole in postmenopausal women and could be considered.
Hepatic impairment: Anastrozole has not been investigated in breast cancer patients with moderate or severe hepatic impairment. Exposure to anastrozole can be increased in subjects with hepatic impairment; administration of Anastrozole in patients with moderate and severe hepatic impairment should be performed with caution. Treatment should be based on a benefit-risk evaluation for the individual patient.
Renal impairment: Anastrozole has not been investigated in breast cancer patients with severe renal impairment. Exposure to anastrozole is not increased in subjects with severe renal impairment (GRF<30ml/min); in patients with severe renal impairment, administration of Anastrozole should be performed with caution.
Hypersensitivity to lactose: This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use in Children: Anastrozole is not recommended for use in children and adolescents as safety and efficacy have not been established in this group of patients.
Anastrozole should not be used in boys with growth hormone deficiency in addition to growth hormone treatment. In the pivotal clinical trial, efficacy was not demonstrated and safety was not established. Since anastrozole reduces estradiol levels, anastrozole must not be used in girls with growth hormone deficiency in addition to growth hormone treatment. Long-term safety data in children and adolescents are not available.

Pregnancy: There are no data from the use of Anastrozole in pregnant women. Studies in animals have shown reproductive toxicity. Anastrozole is contraindicated during pregnancy.
Breast-feeding: There are no data on the use of Anastrozole during lactation. Anastrozole is contraindicated during breast-feeding.
Fertility: The effects of Anastrozole on fertility in humans have not been studied. Studies in animals have shown reproductive toxicity.

The following table presents adverse reactions from clinical trials, post-marketing studies or spontaneous reports. Unless specified, the frequency categories were calculated from the number of adverse events reported in a large phase III study conducted in 9,366 postmenopausal women with operable breast cancer given adjuvant treatment for five years (the Anastrozole, Tamoxifen, Alone or in Combination [ATAC] study).
Adverse reactions listed as follows are classified according to frequency and System Organ Class (SOC). Frequency groupings are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000). The most frequently reported adverse reactions were headache, hot flushes, nausea, rash, arthralgia, joint stiffness, arthritis, and asthenia. (See Table 1.)

Click on icon to see table/diagram/image

The table as follows presents the frequency of pre-specified adverse events in the ATAC study after a median follow-up of 68 months, irrespective of causality, reported in patients receiving trial therapy and up to 14 days after cessation of trial therapy. (See Table 2.)

Click on icon to see table/diagram/image

Fracture rates of 22 per 1,000 patient-years and 15 per 1,000 patient-years were observed for the Anastrozole and tamoxifen groups, respectively, after a median follow-up of 68 months. The observed fracture rate for Anastrozole is similar to the range reported in age-matched postmenopausal populations. The incidence of osteoporosis was 10.5% in patients treated with Anastrozole and 7.3% in patients treated with tamoxifen.
It has not been determined whether the rates of fracture and osteoporosis seen in ATAC in patients on Anastrozole treatment reflect a protective effect of tamoxifen, a specific effect of Anastrozole, or both.

Anastrozole inhibits CYPs 1A2, 2C8/9 and 3A4 in vitro. Clinical studies with antipyrine and warfarin showed that anastrozole at a 1 mg dose did not significantly inhibit the metabolism of antipyrine and R- and S-warfarin indicating the co-administration of Anastrozole with other medicinal products is unlikely to result in clinically significant medicinal product interactions mediated by CYP enzymes.
The enzymes mediating metabolism of anastrozole have not been identified. Cimetidine, a weak, unspecific inhibitor of CYP enzymes, did not affect the plasma concentrations of anastrozole. The effect of potent CYP inhibitors is unknown.
A review of the clinical trial safety database did not reveal evidence of clinically significant interaction in patients treated with Anastrozole who also received other commonly prescribed medicinal products. There were no clinically significant interactions with bisphosphonates.
Co-administration of tamoxifen or estrogen-containing therapies with Anastrozole should be avoided as this may diminish its pharmacological action.

Instructions and Special Precautions for Handling and Disposal: Any unused product or waste material should be disposed of in accordance with local requirements.

Store at temperatures not exceeding 30°C.

Cancer Hormone Therapy

L02BG03 - anastrozole ; Belongs to the class of enzyme inhibitors. Used in treatment of neoplastic diseases.

Rx