Anastrozole

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

Crystals from ethyl acetate/cyclohexane

Off-white powder

Freely soluble in methanol, acetone, ethanol, tetrahydrofuran; very soluble in acetonitrile.

In water, 0.5 mg/mL at 25 °C; solubility is dependent of pH in the physiological range.

6.61e-02 g/L

Breast Feeding; Lactation; Milk, Human; Antineoplastic Agents, Hormonal; Aromatase Inhibitors

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

Hormones and antihormones

81-82 °C

130.14 °C

Danger

H301 (38.7%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P280, P301+P316, P301+P317, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 75 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl anastrozole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/

For more Disposal Methods (Complete) data for ANASTROZOLE (8 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/

For more Preventive Measures (Complete) data for ANASTROZOLE (19 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

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. Based on these in vitro and in vivo results, it is unlikely that co-administration of anastrozole 1 mg with other drugs will result in clinically significant inhibition of cytochrome P450 mediated metabolism.

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

Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27% compared to those achieved with anastrozole alone; however, the coadministration did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen.

Serum enzymes are reported to be elevated in 2% to 4% of women treated with anastrozole, but these elevations are usually mild, asymptomatic and self-limited, rarely requiring dose modification. There have been rare instances of clinically apparent liver injury associated with anastrozole therapy, typically arising within 1 to 4 months of starting treatment and having variable presentations but generally with a hepatocellular or mixed serum enzyme pattern (Case 1). Too few instances have been described in the literature to provide specific characteristics or clinical phenotype. Immunoallergic features (fever, rash, eosinophilia) were not mentioned in published cases, but low levels of autoantibodies were sometimes found. Recovery is usually rapid once anastrozole is stopped. There have been no cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome attributed to anastrozole use. Unlike tamoxifen, anastrozole has not been associated with development of fatty liver disease, although some degree of steatosis and steatohepatitis have been mentioned in descriptions of liver biopsies from acute cases. According to the product label, anastrozole has been linked to cases of hypersensitivity reactions and Stevens-Johnson syndrome as well as cases of hepatitis with jaundice.

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. Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

/SIGNS AND SYMPTOMS/ Systemic allergic reactions, including angioedema, urticaria, and anaphylaxis, have been reported rarely in patients receiving anastrozole.

/SIGNS AND SYMPTOMS/ Anemia and leukopenia each were reported in 2-5% of patients receiving anastrozole as second-line therapy, which was similar to experience in those receiving the drug as first-line therapy.

/SIGNS AND SYMPTOMS/ Mucocutaneous disorders, including erythema multiforme and Stevens-Johnson syndrome, have been reported rarely in patients receiving anastrozole.

/SIGNS AND SYMPTOMS/ Among patients receiving anastrozole as first-line therapy, thromboembolic disease was reported in 18 patients (4%), with 5 patients experiencing venous thrombosis (including pulmonary embolus, thrombophlebitis, and retinal vein thrombosis) and 13 patients experiencing coronary and/or cerebral thrombosis (including myocardial infarction, myocardial ischemia, angina pectoris, cerebrovascular accident, cerebral ischemia, and cerebral infarct). Despite its lack of estrogenic activity, there was no evidence of an increased incidence of myocardial infarction in patients receiving anastrozole compared with those receiving tamoxifen.

/CASE REPORTS/ /Investigators/ report here our experience with two cases of gynecomastia in men undergoing TRT who were successfully treated with the aromatase inhibitor anastrozole.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Anastrozole

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ In an oral acute toxicity study in the dog the median lethal dose was greater than 45 mg/kg/day.

/LABORATORY ANIMALS: Acute Exposure/ In rats, lethality was observed after single oral doses that were greater than 100 mg/kg and was associated with severe irritation to the stomach (necrosis, gastritis, ulceration, and hemorrhage).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In mice, oral doses of anastrozole 5-50 mg/kg daily for up to 2 years resulted in an increased incidence of benign ovarian stromal, epithelial, and granulosa cell tumors in female mice at all dosage levels and an increased incidence of lymphosarcoma in male and female mice at the high dose. In female mice, a dose-related increase in the incidence of ovarian hyperplasia also was observed; the ovarian changes observed are considered to be rodent-specific effects of aromatase inhibition...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In rats administered anastrozole 1-25 mg/kg daily by oral gavage for up to 2 years, an increase in the incidence of hepatocellular adenoma and carcinoma and uterine stromal polyps was observed in females and an increased incidence of thyroid adenoma was observed in males receiving the high dose. In female rats, a dose-related increase in the incidence of ovarian and uterine hyperplasia was observed.

For more Non-Human Toxicity Excerpts (Complete) data for ANASTROZOLE (10 total), please visit the HSDB record page.

There is no known specific antidote for anastrozole overdosage. Management of overdosage should consist of symptomatic treatment and general supportive care, including frequent monitoring of vital signs and close observation of the patient. The possibility that multiple agents may have been taken should be considered. ... Because anastrozole is not highly bound to plasma proteins, dialysis may be helpful.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl anastrozole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

L02BG03

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

L02BG03

Anastrozole prevents the conversion of adrenal androgens (e.g. [testosterone]) to estrogen in peripheral and tumour tissues. As the growth of many breast cancers is stimulated and/or maintained by the presence of estrogen, anastrozole helps to treat these cancers by decreasing the levels of circulating estrogens. Anastrozole has a relatively long duration of action allowing for once daily dosing - serum estradiol is reduced by approximately 70% within 24 hours of beginning therapy with 1mg once daily, and levels remain suppressed for up to 6 days following cessation of therapy. The incidence of ischemic cardiovascular events was increased during anastrozole therapy and patients with pre-existing ischemic heart disease should consider the risks and benefits of anastrozole before beginning therapy. Anastrozole has also been reported to decrease spine and hip bone mineral density (BMD), so consideration should be given to monitoring of BMD in patients receiving long-term therapy.

Anastrazole exerts its anti-estrogenic effects via selective and competitive inhibition of the aromatase enzyme found predominantly in the adrenal glands, liver, and fatty tissues. Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone. In postmenopausal women, estrogen is primarily derived from the conversion of adrenally-produced androgens into estrogens by the aromatase enzyme - by competitively inhibiting the biosynthesis of estrogen at these enzymes, anastrozole effectively suppresses circulating estrogen levels and, subsequently, the growth of hormone receptor-positive tumours.

Anastrozole is a nonsteroidal aromatase inhibitor that interferes with estradiol production in peripheral tissues. Adrenally generated androstenedione, the chief source of circulating estrogen in postmenopausal women, is converted by aromatase to estrone, which is further converted to estradiol. Growth of many breast cancer tumors containing estrogen receptors and aromatase can be promoted by estrogen.

Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.

Because estrogen acts as a growth factor for hormone-dependent breast cancer cells, anastrozole-induced reduction of serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression. Anastrozole selectively inhibits the conversion of androgens to estrogens. In postmenopausal women, ovarian secretion of estrogen declines and conversion of adrenal androgens (mainly androstenedione and testosterone) to estrone and estradiol in peripheral tissues (adipose, muscle, and liver), catalyzed by the aromatase enzyme, is the principal source of estrogens. Anastrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P-450 unit of the enzyme; suppression of estrogen biosynthesis in all tissues reduces serum concentrations of circulating estrogens, including estrone, estradiol, and estrone sulfate. Anastrozole selectively inhibits synthesis of estrogens and does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone. In animals, anastrozole has not been shown to possess direct progestogenic, androgenic, or estrogenic activity, but alterations in the circulating concentrations of progesterone, androgens, and estrogens have been observed.

The elimination half-life of anastrozole is approximately 50 hours.

Following oral administration of anastrozole in postmenopausal women, a mean terminal elimination half-life of approximately 50 hours has been reported.

Anastrozole is primarily metabolized in the liver via oxidation and glucuronidation to a number of inactive metabolites, including hydroxyanastrozole (both free and glucuronidated) and anastrozole glucuronide. Oxidation to hydroxyanastrozole is catalyzed predominantly by CYP3A4 (as well as CYP3A5 and CYP2C8, to a lesser extent) and the direct glucuronidation of anastrozole appears to be catalyzed mainly by UGT1A4. Anastrozole may also undergo N-dealkylation to form triazole and 3,5-Bis-(2-methylpropiononitrile)-benzoic acid. Labels for anastrozole state the main metabolite found in plasma following administration is triazole, but a recent pharmacokinetic study was unable to detect any products of N-dealkylation _in vitro_.

Anastrozole is extensively metabolized in the liver. Metabolism of anastrozole occurs via N-dealkylation, hydroxylation, and glucuronidation. Three metabolites of anastrozole have been identified in human plasma and urine: triazole, a glucuronide conjugate of anastrozole, and a glucuronide conjugate of hydroxyanastrozole. Triazole, the major circulating metabolite of anastrozole, lacks pharmacologic activity, and the aromatase inhibiting activity of anastrozole results principally from the parent drug. In addition, there are several minor metabolites of anastrozole, accounting for less than 5% of an administered dose, which have not been identified.

Hepatic. Metabolized mainly by N-dealkylation, hydroxylation, and glucuronidation to inactive metabolites. Primary metabolite is an inactive triazole. Route of Elimination: Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance. Half Life: 50 hours

2Z07MYW1AZ

ANASTROZOLE

Established Pharmacologic Class [EPC] - Aromatase Inhibitor

Mechanisms of Action [MoA] - Aromatase Inhibitors

Anastrozole is an Aromatase Inhibitor. The mechanism of action of anastrozole is as an Aromatase Inhibitor.

ANASTROZOLE

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)

Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.

Anastrozole is rapidly absorbed and Tmax is typically reached within 2 hours of dosing under fasted conditions. Coadministration with food reduces the rate but not the overall extent of absorption - mean Cmax decreased by 16% and the median Tmax was extended to 5 hours when anastrozole was administered 30 minutes after ingestion of food, though this relatively minor alteration in absorption kinetics is not expected to result in clinically significant effects.

Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Approximately 10% of the administered dosage is eliminated unchanged in the urine.

The volume of distribution of anastrozole into brain tissue in mice is 3.19 mL/g. Distribution into the CNS is limited due to the activity of P-gp efflux pumps at the blood brain barrier, of which anastrozole is a substrate.

Anastrozole's clearance is mainly via hepatic metabolism and can therefore be altered in patients with hepatic impairment - patients with stable hepatic cirrhosis exhibit an apparent oral clearance approximately 30% lower compared with patients with normal liver function. Conversely, renal impairment has a negligible effect on total drug clearance as the renal route is a relatively minor clearance pathway for anastrozole. In volunteers with severe renal impairment, renal clearance was reduced by 50% while total clearance was only reduced by approximately 10%.

Anastrozole is well absorbed into systemic circulation following oral administration. Plasma concentrations approach steady-state at about 7 days of once-daily dosing, and steady-state concentrations are approximately 3-4 times higher than concentrations achieved after a single dose of the drug. Food does not affect the extent of oral absorption of anastrozole.

Within the therapeutic plasma concentration range, anastrozole is 40% bound to plasma proteins.

Non-steroidal aromatase inhibitor

THERAP CAT: Antineoplastic

Use (kg; approx.) in Germany (2009): >25

For adjuvant treatment of hormone receptor positive breast cancer , as well as hormonal treatment of advanced breast cancer in post-menopausal women. Has also been used to treat pubertal gynecomastia and McCune-Albright syndrome; however, manufacturer states that efficacy for these indications have not been established.