Anastro-cell

Each film-coated tablet contains 1 mg of Anastrozole.
Excipients: Lactose monohydrate, Sodium starch glycollate, Povidone K-25, Magnesium stearate.

Pharmacotherapeutic group: Enzyme inhibitors. ATC Code: L02BG03.
Pharmacological Properties: Pharmacodynamic Properties: 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 method.
Anastrozole does not possess any progestogenic, androgenic or oestrogenic activity.
Daily doses of Anastrozole up to 10 mg do not have any effect on cortisol or aldosterone secretion, measured before or after standard ACTH (adrenocorticotropic hormone) challenge testing. Corticoid supplements are therefore not needed.
Primary adjuvant treatment of early breast cancer: As with all treatment decisions, women with breast cancer and their physician, should assess the relative benefits and risks of the treatment.
When Anastrozole and tamoxifen were co-administered, the efficacy and safety were similar to tamoxifen when given alone, irrespective of hormone receptor status. The exact mechanism of this is not yet clear. It is not believed to be due to a reduction in the degree of estradiol suppression produced by Anastrozole.
Pediatrics: Anastrozole is not indicated for use in children. Efficacy has not been established in the pediatric populations studied (see as follows). The number of children treated was too limited to draw any reliable conclusions on safety. No data on the potential long-term effects of anastrozole treatment in children are available.
Pharmacokinetic Properties: 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. There is no evidence of time or dose-dependency of Anastrozole pharmacokinetic parameters.
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.
Metabolism: 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.
The apparent oral clearance of Anastrozole in volunteers with stable hepatic cirrhosis or renal impairment was in the range observed in healthy volunteers.
Age dependency of pharmacokinetics: Anastrozole pharmacokinetics is independent of age in postmenopausal women.
Pharmacokinetics in children and adolescents: In boys with pubertal gynecomastia, 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 than in boys and exposure higher, Anastrozole in girls was widely distributed and slowly eliminated, with an estimated half-life of approximately 0.8 days.

Treatment of 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 postmenopausal women with hormone receptor positive early invasive breast cancer.
Adjuvant treatment of early breast cancer in hormone receptor positive postmenopausal women who have received 2 to 3 years of adjuvant tamoxifen.

Adults including the elderly: One film-coated tablet (1 mg) to be taken orally once a day.
Children and adolescents: Anastrozole is not recommended for use in children.
Renal and hepatic impairment: No dose change is recommended in patients with mild or moderate renal impairment.
No dose change is recommended in patients with mild hepatic disease.
For early disease, the recommended duration of treatment should be 5 years.
Or as prescribed by the physician.

There is limited clinical experience of accidental overdose. In animal studies, Anastrozole demonstrated low acute toxicity.
In the management of an overdose, consideration should be given to the possibility that multiple agents may have been taken. Absorption can be lowered by gastric lavage followed by administration of activated charcoal or charcoal. 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: premenopausal women; pregnant or lactating women; patients with severe renal impairment (creatinine clearance less than 20 mL/min); patients with moderate or severe hepatic disease; patients with known hypersensitivity to Anastrozole or to any of the excipients.
Oestrogen-containing therapies should not be co-administered with Anastrozole as they would negate its pharmacological action.
Tamoxifen should not be co-administered with Anastrozole, as this may diminish its pharmacological action.

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.
The menopause should be defined biochemically in any patient where there is doubt about hormonal status.
There are no data to support the safe use of Anastrozole in patients with moderate or severe hepatic impairment, or patients with severe impairment of renal function (creatinine clearance less than 20 mL/min).
Women with osteoporosis or at risk of osteoporosis, should have their bone mineral density formally assessed by bone densitometry e.g. DEXA (dual energy x-ray absorptiometry) scanning at the commencement of treatment and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis should be initiated as appropriate and carefully monitored.
There are no data available for the use of Anastrozole with LHRH (luteinizing hormone-releasing hormone) analogues. This combination should not be used outside clinical trials.
As Anastrozole lowers circulating oestrogen levels, it may cause a reduction in bone mineral density with a possible consequent increased risk of fracture. The use of bisphosphonates may stop further bone mineral loss caused by Anastrozole in postmenopausal women and could be considered.
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Anastrozole is unlikely to impair the ability of patients to drive and operate machinery. However, asthenia and somnolence have been reported with the use of Anastrozole and caution should be observed when driving or operating machinery while such symptoms persist.

Anastrozole is contraindicated in pregnant and lactating women.
Pregnancy: There are no data on the use of Anastrozole in pregnant patients. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Anastrozole is contraindicated in pregnant women.
Lactation: It is unknown whether Anastrozole is excreted in human milk Anastrozole is contraindicated in lactating women.

Rates of incidence: Very common (>1/10): Headache (mild to moderate), hot flushes, nausea, rash, joint pain/stiffness and asthenia.
Common (≥/100, <1/10): Anorexia (mainly mild), hypercholesterolemia (mainly mild), somnolence (mainly mild), carpal tunnel syndrome, diarrhea, vomiting, increase in alkaline phosphatase/alanine aminotransferase/aspartate aminotransferase; alopecia, allergic reaction, bone pain and vaginal dryness.
Uncommon (≥1/1,000, <1/100): Increase in gamma-GT and bilirubin, hepatitis and urticaria.
Rare (≥1/10,000, <1/1,000): Erythema multiforme and anaphylactoid reactions.
Very rare (≤1/10,000).
Not known (cannot be estimated from the available data): Stevens-Johnson syndrome and angioedema.

Anastrozole inhibited cytochrome P450 1A2, 2C8/9 and 3A4 in vitro, but a clinical interaction study with warfarin indicated that Anastrozole at a 1 mg dose does not significantly inhibit the metabolism of substances that are metabolised via cytochrome P450.
No clinically significant interactions between Anastrozole and bisphosphonates have been identified.

Use only as directed by the physician. Notify the physician if the patient experienced any of the adverse effects.

Store at temperatures not exceeding 25°C.
Shelf life: 36 months.

Cancer Hormone Therapy

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

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