Anastrozole Tablets

FDA Drug Information • Also known as: Anastrozole

Brand Names: Anastrozole
Drug Class: Aromatase Inhibitor [EPC]
Route: ORAL
Dosage Form: TABLET
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Anastrozole Tablets，USP for oral administration contain 1 mg of anastrozole, a non-steroidal aromatase inhibitor. It is chemically described as 1,3-Benzenediacetonitrile, a, a, a', a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl). Its molecular formula is C 17 H 19 N 5 and its structural formula is: Anastrozole, USP is an off-white powder with a molecular weight of 293.4. Anastrozole, USP has moderate aqueous solubility (0.5 mg/mL at 25°C); solubility is independent of pH in the physiological range. Anastrozole, USP is freely soluble in methanol, acetone, ethanol, and tetrahydrofuran, and very soluble in acetonitrile. Each tablet contains as inactive ingredients: colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol/macrogol sodium starch glycolate, and titanium dioxide . Chemical Structure for anastrozole

What Is Anastrozole Tablets Used For?

1 INDICATIONS AND USAGE Anastrozole is an aromatase inhibitor indicated for:

Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer ( Error! Hyperlink reference not valid. )

First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer ( Error! Hyperlink reference not valid. )

Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to Anastrozole ( Error! Hyperlink reference not valid. ) 1.1 Adjuvant Treatment Anastrozole is indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. 1.2 First-Line Treatment Anastrozole is indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. 1.3 Second-Line Treatment Anastrozole is indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION One 1 mg tablet taken once daily ( 2.1 ) 2.1 Recommended Dose The dose of anastrozole is one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression.Anastrozole tablets can be taken with or without food. For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial, anastrozole was administered for five years [see Error! Hyperlink reference not valid. ]. No dosage adjustment is necessary for patients with renal impairment or for elderly patients [see Error! Hyperlink reference not valid. ]. 2.2 Patients with Hepatic Impairment No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. Anastrozole tablets have not been studied in patients with severe hepatic impairment [see Error! Hyperlink reference not valid. ].

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Serious adverse reactions with anastrozole occurring in less than 1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling [ see Error! Hyperlink reference not valid. ]. Common adverse reactions (occurring with an incidence of ≥10%) in women taking anastrozole included: hot flashes, asthenia, arthritis, pain, arthralgia, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, bone pain, peripheral edema, increased cough, dyspnea, pharyngitis and lymphedema. In the ATAC trial, the most common reported adverse reaction (>0.1%) leading to discontinuation of therapy for both treatment groups was hot flashes, although there were fewer patients who discontinued therapy as a result of hot flashes in the anastrozole group. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In the early breast cancer (ATAC) study, the most common (occurring with an incidence of ≥10%) side effects occurring in women taking anastrozole tablets included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema and lymphedema, regardless of causality. ( Error! Hyperlink reference not valid. ) In the advanced breast cancer studies, the most common (occurring with an incidence of >10%) side effects occurring in women taking anastrozole tablets included: hot flashes, nausea, asthenia, pain, headache, back pain, bone pain, increased cough, dyspnea, pharyngitis and peripheral edema. ( Error! Hyperlink reference not valid. ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Adjuvant Therapy Adverse reaction data for adjuvant therapy are based on the ATAC trial [ see Error! Hyperlink reference not valid. ]. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole 1 mg and tamoxifen 20 mg, respectively. Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in Table 1. Table 1 — Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment, or within 14 days of the end of treatment in the ATAC trial * Body system and adverse reactions by COSTART † preferred term † Anastrozole 1 mg (N § = 3,092) Tamoxifen 20 mg (N § = 3,094) Body as a whole Asthenia 575 (19) 544 (18) Pain 533 (17) 485 (16) Back pain 321 (10) 309 (10) Headache 314 (10) 249 (8) Abdominal pain 271 (9) 276 (9) Infection 285 (9) 276 (9) Accidental injury 311 (10) 303 (10) Flu syndrome 175 (6) 195 (6) Chest pain 200 (7) 150 (5) Neoplasm 162 (5) 144 (5) Cyst 138 (5) 162 (5) Cardiovascular Vasodilatation 1,104 (36) 1,264 (41) Hypertension 402 (13) 349 (11) Digestive Nausea 343 (11) 335 (11) Constipation 249 (8) 252 (8) Diarrhea 265 (9) 216 (7) Dyspepsia 206 (7) 169 (6) Gastrointestinal disorder 210 (7) 158 (5) Hemic and lymphatic Lymphedema 304 (10) 341 (11) Anemia 113 (4) 159 (5) Metabolic and nutritional Peripheral edema 311 (10) 343 (11) Weight gain 285 (9) 274 (9) Hypercholesterolemia 278 (9) 108 (3.5) Musculoskeletal Arthritis 512 (17) 445 (14) Arthralgia 467 (15) 344 (11)...

Drug Interactions

7 DRUG INTERACTIONS

Tamoxifen: Do not use in combination with anastrozole tablets. No additional benefit seen over tamoxifen monotherapy. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. )

Estrogen-containing products: Combination use may diminish activity of Anastrozole Tablets. ( Error! Hyperlink reference not valid. ) 7.1 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 anastrozole 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 [ see Error! Hyperlink reference not valid. ]. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole. 7.2 Estrogen Estrogen-containing therapies should not be used with anastrozole as they may diminish its pharmacological action. 7.3 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. 7.4 Cytochrome P450 Based on in vitro and in vivo results, it is unlikely that co-administration of anastrozole 1 mg will affect other drugs as a result of inhibition of cytochrome P450 [see Error! Hyperlink reference not valid. ].

Contraindications

4 CONTRAINDICATIONS

Patients with demonstrated hypersensitivity to anastrozole tablets or any excipient ( Error! Hyperlink reference not valid. ) Hypersensitivity Anastrozole is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria [see Error! Hyperlink reference not valid. ].

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, anastrozole may cause fetal harm when administered to a pregnant woman [ see Error! Hyperlink reference not valid. ]. There are no studies of anastrozole use in pregnant women. Anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (AUC). In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m2 basis. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively, (about 1 and 1/3 the recommended human dose on a mg/m 2 basis, respectively). In both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses). In rats, these effects were dose related, and placental weights were significantly increased at doses equal to or greater than 0.1 mg/kg/day. Fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses of 1 mg/kg/day that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (AUC 0-24 hr 9 times higher). In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m 2...

8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiation of anastrozole. Contraception Females Based on animal studies, anastrozole can cause fetal harm when administered to a pregnant woman [ see Error! Hyperlink reference not valid. ]. Advise females of reproductive potential to use effective contraception during treatment with anastrozole tablets and for at least 3 weeks after the last dose. Infertility Females Based on studies in female animals, anastrozole may impair fertility in females of reproductive potential [ see Error! Hyperlink reference not valid. ].

Overdosage

10 OVERDOSAGE Clinical trials have been conducted with 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 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, consider 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Anastrozole Tablets, USP 1 mg are supplied in bottles of 30 tablets (NDC 82804-162-30) and 90 tablets (82804-162-90). Storage Store at 20°to 25°C (68°to 77°F) [see USP Controlled Room Temperature].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.