Anastrozole (hormone inhibitor)
Mechanism:
Selective non-steroidal aromatase inhibitor, which inhibits the conversion of androstenedione to oestrone, through the aromatase enzyme complex in peripheral tissue where oesrone is subsequently converted to oestradiol.In post-menopausal women, a daily dose of 1mg produced oestradiol suspension of greater than 80%.
Does not possess any progestogenic, androgenic or oestrogenic activity.
Does not have any effect on cortisol or aldosterone secretion, measured before or after standard ACTH challenge testing.
Indications:
Treatment of advanced breast cancer in post-menopausal women.
Efficacy has not been demonstrated in oestrogen receptor negative patients unless they have had a previous positive clinical response to tamoxifen.
Contra-Indications:
Hypersensitive patients.
Pre-menopausal women.
Pregnant/lactating women.
Patients with severe renal impairment (creatinine clearance less than 20ml/min.
Patients with moderate or severe hepatic disease.
Dosage:
Management of overdose:
Symptoms: There is no clinical experience of acxcidental overdosage. In animal studies, anastrozole demonstrated low acute toxicity Clinical trials have been conducted with various dosages of Arimidex* up to 60mg in a single dose given to healthy male volunteers and up to 10mg daily given to post-menopausal women with advanced breast cancer, these dosages were well tolerated. A single dose of Arimidex* that results in life-threatening symptoms has not been established.
Rx: There is no specific antidote to overdose and treatment must be symptomatic.In management of 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 the drug is not highly protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the patient is indicated.
Kinetics: Absorption of anastrozole is rapid and maximum plasma concentrations occur after two hours of dosing under fasted conditions.Anastrozole is eliinated slowly with plasma elimination half life of 40 - 50 hours.Food decreases the rate but not the extent of absorption.Approximately 90 - 95% of plasma anastrozole steady-state concentrations are attained after 7 daily doses.There is no evidence of time or dose dependency of anastrozole on pharmacokinetic parameters. Anastrozole pharmacokinetics are independant of age in post- menopausal women. Pharmacokinetics have not been studied in children. Anastrozole is only 40% bound to plasma proteins. Anastrozole is extensively metabolised by post-menopausal women with less than 10% of the d se excreted in urine unchanged within 72 hours of dosing.Metabolism occurs by N-dealkylation, hydroxylation and glucuronidation. The metabolites are excreted primarily via the urine.Triazole, a major metabolite in plasma and urine, does not inhibit aromatase.The apparent iral clearance of anastrozole in volunteers with mild, stable hepatic cirrhosis or mild renal impairment was in the range observed in healthy volunteers.
Dose:
1mg orally, daily.
Side-Effects:
Expected effects include: Hot flushes, vaginal dryness, hair thinning.
May also be associated with: Anorexia, nausea, vomiting, diarrhoea, asthenia, somnolence, headache or rash.
Hepatic changes (elevated gamma-GT or alkaline phosphatase) have been reported in patients with advanced breast cancer, many of whom had liver or bone metastases. A casual relationship for these events has not been established.
Thromboembolism, fluid retention, dizziness, vaginal haemorrhage and slight increases in total cholesterol have been observed in clinical trials with Arimidex*.
Precautions:
Not recommended for use in children as safety and efficacy have not been established.
The menopause should be defined biochemically in any patient where there is doubt about hormonal status.
There is no data to support the safe use in patients with moderate to severe hepatic impairment, or in patients with severe impairment of renal function. (creatinine clearance less than 20ml/min).
Contra-indicated in pregnancy and lactation.
Asthenia and somnolence has been reported and caution should be observed when driving or operating machinery while such symptoms persist.
Contra-indicated in pregnancy and lactation.
Safety and efficacy in children has not been established and is as such not recommended.
Information source:
Arimidex Package Insert
I went through more than a dozen studies, with only mention of a slight elevation in blood cholesterol as a possible side effect. More common is water gain and dizzyness.
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