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Arimidex (anastrozole) tablets

Summary about Arimidex

Arimidex (anastrozole) 1 mg tablets is a prescription hormonal treatment that helps fight breast cancer by lowering the amount of estrogen in the body. Arimidex is a selective, non-steroidal aromatase inhibitor, which signifcantly lowers serum estradiol (estrogen) concentrations, without interfering with the formation of adrenal corticosteroids or aldosterone.

It is FDA approved for the following 3 conditions:

  • As an adjuvant treatment for postmenopausal women with hormone receptor-positive early breast cancer
  • For the initial treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer
  • For the treatment of postmenopausal women with advanced breast cancer that has progressed following treatment with tamoxifen

If you’ve been diagnosed with hormone receptor-positive (HR+) early breast cancer, you and your doctor may be discussing treatment options for reducing the risk of recurrence. Only your doctor can decide if Arimidex is right for you.

Arimidex is supplied in bottles of 30 1-mg tablets and should be taken daily.

Important Safety Information About Arimidex:

  • Prescription Arimidex is only for postmenopausal women. It should not be taken if you are pregnant because it may harm your unborn child. Do not take Arimidex if you are allergic to any of its ingredients
  • Based on information from a study in patients with early breast cancer, women with a history of blockages in heart arteries (ischemic heart disease) who take Arimidex may have a slight increase in this type of heart disease compared to similar patients who take tamoxifen
  • Arimidex can cause bone softening/weakening (osteoporosis) increasing the chance of fractures. In a clinical study in early breast cancer, there were more fractures (including fractures of the spine, hip, and wrist) with Arimidex (10%) than with tamoxifen (7%)
  • In a clinical study in early breast cancer, some patients taking Arimidex had an increase in cholesterol. Skin reactions, allergic reactions, and changes in blood tests of liver function have also been reported
  • In the early breast cancer clinical trial, the most common side effects seen with Arimidex include hot flashes, joint symptoms (including arthritis and arthralgia), weakness, mood changes, pain, back pain, sore throat, nausea and vomiting, rash, depression, high blood pressure, osteoporosis, fractures, swelling of arms/legs, insomnia, and headache
  • In advanced breast cancer trials, the most common side effects seen with Arimidexversus tamoxifen include hot flashes, nausea, decreased energy and weakness, pain, back pain, headache, bone pain, increased cough, shortness of breath, sore throat, and swelling of arms and legs. Joint pain/stiffness has been reported in association with the use of Arimidex.
  • Arimidex should not be taken with tamoxifen or estrogen-containing therapies

 

 

Arimidex (anastrozole)

Active Ingredient

Anastrozole

Administration Route

Tablets for oral use

Alcohol Warning

Drinking of alcohol (in small amounts) does not appear to affect the safety or efficacy of anastrozole.

Available Strength

Tablets 1mg

Breastfeeding Warning

In Australia and United Kingdom use is contraindicated during breastfeeding.
In the United States a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.Excreted into human milk: Unknown
Excreted into animal milk: Data not available

Clinical Pharmacology

Pharmacodynamics

Effect on Estradiol

Mean serum concentrations of estradiol were evaluated in multiple daily dosing trials with 0.5, 1, 3, 5, and 10 mg of ARIMIDEX in postmenopausal women with advanced breast cancer. Clinically significant suppression of serum estradiol was seen with all doses. Doses of 1 mg and higher resulted in suppression of mean serum concentrations of estradiol to the lower limit of detection (3.7 pmol/L). The recommended daily dose, ARIMIDEX 1 mg, reduced estradiol by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing. Suppression of serum estradiol was maintained for up to 6 days after cessation of daily dosing with ARIMIDEX 1 mg.

The effect of ARIMIDEX in premenopausal women with early or advanced breast cancer has not been studied. Because aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women, ARIMIDEX would not be expected to lower estradiol levels in premenopausal women.

Effect on Corticosteroids

In multiple daily dosing trials with 3, 5, and 10 mg, the selectivity of anastrozole was assessed by examining effects on corticosteroid synthesis. For all doses, anastrozole did not affect cortisol or aldosterone secretion at baseline or in response to ACTH. No glucocorticoid or mineralocorticoid replacement therapy is necessary with anastrozole.

Other Endocrine Effects

In multiple daily dosing trials with 5 and 10 mg, thyroid stimulating hormone (TSH) was measured; there was no increase in TSH during the administration of ARIMIDEX. ARIMIDEX does not possess direct progestogenic, androgenic, or estrogenic activity in animals, but does perturb the circulating levels of progesterone, androgens, and estrogens.

Pharmacokinetics

Absorption

Inhibition of aromatase activity is primarily due to anastrozole, the parent drug. Absorption of anastrozole is rapid and maximum plasma concentrations typically occur within 2 hours of dosing under fasted conditions. Studies with radiolabeled drug have demonstrated that orally administered anastrozole is well absorbed into the systemic circulation. Food reduces the rate but not the overall extent of anastrozole absorption. The mean Cmax of anastrozole decreased by 16% and the median Tmax was delayed from 2 to 5 hours when anastrozole was administered 30 minutes after food. The pharmacokinetics of anastrozole are linear over the dose range of 1 to 20 mg, and do not change with repeated dosing. The pharmacokinetics of anastrozole were similar in patients and healthy volunteers.

Distribution

Steady-state plasma levels are approximately 3- to 4-fold higher than levels observed after a single dose of ARIMIDEX. Plasma concentrations approach steady-state levels at about 7 days of once daily dosing. Anastrozole is 40% bound to plasma proteins in the therapeutic range.

Metabolism

Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. Three metabolites of anastrozole (triazole, a glucuronide conjugate of hydroxy-anastrozole, and a glucuronide conjugate of anastrozole itself) have been identified in human plasma and urine. The major circulating metabolite of anastrozole, triazole, lacks pharmacologic activity.

Anastrozole inhibited reactions catalyzed by cytochrome P450 1A2, 2C8/9, and 3A4 in vitro with Ki values which were approximately 30 times higher than the mean steady-state Cmax values observed following a 1 mg daily dose. Anastrozole had no inhibitory effect on reactions catalyzed by cytochrome P450 2A6 or 2D6 in vitro. Administration of a single 30 mg/kg or multiple 10 mg/kg doses of anastrozole to healthy subjects had no effect on the clearance of antipyrine or urinary recovery of antipyrine metabolites.

Excretion

Eighty-five percent of radiolabeled anastrozole was recovered in feces and urine. Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance. The mean elimination half-life of anastrozole is 50 hours.

Effect of Gender and Age

Anastrozole pharmacokinetics have been investigated in postmenopausal female volunteers and patients with breast cancer. No age-related effects were seen over the range <50 to >80 years.

Effect of Race

Estradiol and estrone sulfate serum levels were similar between Japanese and Caucasian postmenopausal women who received 1 mg of anastrozole daily for 16 days. Anastrozole mean steady-state minimum plasma concentrations in Caucasian and Japanese postmenopausal women were 25.7 and 30.4 ng/mL, respectively.

Effect of Renal Impairment

Anastrozole pharmacokinetics have been investigated in subjects with renal impairment. Anastrozole renal clearance decreased proportionally with creatinine clearance and was approximately 50% lower in volunteers with severe renal impairment (creatinine clearance < 30 mL/min/1.73m2) compared to controls. Total clearance was only reduced 10%. No dosage adjustment is needed for renal.

Effect of Hepatic Impairment

Anastrozole pharmacokinetics have been investigated in subjects with hepatic cirrhosis related to alcohol abuse. The apparent oral clearance (CL/F) of anastrozole was approximately 30% lower in subjects with stable hepatic cirrhosis than in control subjects with normal liver function. However, these plasma concentrations were still with the range of values observed in normal subjects. The effect of severe hepatic impairment was not studied. No dose adjustment is necessary for stable hepatic cirrhosis

Cost

Approximate Price

from  https://www.drugs.com/price-guide/anastrozole

oral tablet:

1 mg (6 ea): from $16.05

Dosage Form

Oral tablet

Dose Schedule

One 1 mg tablet taken once daily.

Drug Class

L02BG — Aromatase inhibitors

Drug Unit

mg

Food Warning

There are no specific foods that you must exclude from your diet when receiving Arimidex.

Included In
Health Insurance Plan

Yes.

100% of Medicare Part D and Medicare Advantage plans cover this drug.

Interacting Drugs

Tamoxifen

Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. However, the co-administration of anastrozole and tamoxifen did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen. At a median follow-up of 33 months, the combination of ARIMIDEX and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole.

Estrogen

Estrogen-containing therapies should not be used with ARIMIDEX as they may diminish its pharmacological action.

Warfarin

In a study conducted in 16 male volunteers, anastrozole did not alter the exposure (as measured by Cmax and AUC) and anticoagulant activity (as measured by prothrombin time, activated partial thromboplastin time, and thrombin time) of both R- and S-warfarin.

Cytochrome P450

Based on in vitro and in vivo results, it is unlikely that co-administration of ARIMIDEX 1 mg will affect other drugs as a result of inhibition of cytochrome P450

Is Available Generically

Yes. There is a therapeutically equivalent version of Arimidex available under the generic name anastrozole.

Is Proprietary

Yes

Label Details

https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf

Legal Status

Legal.

Is not subject to the Controlled Substances Act.

Manufacturer

ANI PHARMS INC

Maximum Intake

1mg

Mechanism of Action

Anastrozole selectively inhibits aromatase. The principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues. Therefore, aromatase inhibition leads to a decrease in serum and tumor concentration of estrogen, leading to a decreased tumor mass or delayed progression of tumor growth in some women. Anastrozole has no detectable effect on synthesis of adrenal corticosteroids, aldosterone, and thyroid hormone.

Non Proprietary Name

Anastrozole

Overdosage

Clinical trials have been conducted with ARIMIDEX, 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 tolerated. A single dose of ARIMIDEX 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, consider that multiple agents may have been taken. Vomiting may be induced if the patient is alert. Dialysis may be helpful because ARIMIDEX is not highly protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

Pregnancy Category


AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Pregnancy Warning

Use is contraindicated in women who are or may become pregnant.

Animal studies have revealed pregnancy failures, increased pregnancy loss, signs of delayed fetal development, significant incidences of infertility, and adverse effects on reproductive organs. However, there was no evidence of teratogenicity in animal data. There are no controlled data in human pregnancy.

Prescribing Info

https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf

Prescription Status

Prescription drug

Proprietary Name

Arimidex

Related Drugs

Vorozole, Letrozole, Formestane, Aminoglutethimide

RxCUI

262485

Warning


In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with ARIMIDEX use compared to tamoxifen use. Consider risks and benefits.Decreases in bone mineral density may occur. Consider bone mineral density monitoring.Increases in total cholesterol may occur. Consider cholesterol monitoring.

 

Links:

https://www.arimidex.com/
https://www.drugs.com/cons/Arimidex.html
https://www.drugbank.ca/drugs/DB01217
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=acbfaaa9-503c-4691-9828-76a7146ed6de

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