Anastrozole is an aromatase inhibitor indicated for:
Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer ( 1.1 )
First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer ( 1.2 )
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 ( 1.3 )
1.1Adjuvant Treatment
Anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
1.2First-Line Treatment
Anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
1.3Second-Line Treatment
Anastrozole tablets are 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 tablets.
Contraindications
Women of premenopausal endocrine status, including pregnant women ( 4.1 , 8.1 )
Patients with demonstrated hypersensitivity to anastrozole or any excipient ( 4.2 )
4.1Pregnancy and Premenopausal Women
Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies in pregnant women using anastrozole. If anastrozole is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus or potential risk for loss of the pregnancy [see Use in Specific Populations ( 8.1 )].
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 Adverse Reactions ( 6.2 )].
Warnings and precautions
In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with anastrozole use compared to tamoxifen use. Consider risks and benefits. ( 5.1 , 6.1 )
Decreases in bone mineral density may occur. Consider bone mineral density monitoring. ( 5.2 , 6.1 )
Increases in total cholesterol may occur. Consider cholesterol monitoring. ( 5.3 , 6.1 )
5.1Ischemic Cardiovascular Events
In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with anastrozole in the ATAC trial (17% of patients on anastrozole and 10% of patients on tamoxifen). Consider risk and benefits of anastrozole therapy in patients with pre-existing ischemic heart disease [see Adverse Reactions ( 6.1 )].
5.2 Bone Effects Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Consider bone mineral density monitoring in patients treated with anastrozole [see Adverse Reactions ( 6.1 )] .
5.3 Cholesterol During the ATAC trial, more patients receiving anastrozole were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions ( 6.1 )].
Interactions
Tamoxifen: Do not use in combination with anastrozole. No additional benefit seen over tamoxifen monotherapy ( 7.1 , 14.1 ).
Estrogen-containing products: Combination use may diminish activity of anastrozole ( 7.2 ).
7.1Tamoxifen 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 Clinical Studies ( 14.1 )] . Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole.
7.2Estrogen
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 C max 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 Clinical Pharmacology ( 12.3 )].
Pregnancy and breastfeeding
8.1Pregnancy PREGNANCY CATEGORY
X [see Contraindications ( 4.1 )] Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. In animal studies, anastrozole caused pregnancy failure, increased pregnancy loss, and signs of delayed fetal development. There are no studies of anastrozole use in pregnant women.
If anastrozole is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus and potential risk for pregnancy loss. In animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 1 (rats) and 1/3 (rabbits) the recommended human dose on a mg/m 2 basis. 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. Fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (AUC 0-24hr 9 times higher). In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m 2 basis [see Animal Toxicology and/or Pharmacology ( 13.2 )].
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 Adverse Reactions ( 6.2 )].
Common adverse reactions (occurring with an incidence of ≥10%) in women taking anastrozole included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, pain, 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 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. ( 6.1 )
In the advanced breast cancer studies, the most common (occurring with an incidence of >10%) side effects occurring in women taking anastrozole included: hot flashes, nausea, asthenia, pain, headache, back pain, bone pain, increased cough, dyspnea, pharyngitis and peripheral edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Adjuvant Therapy
Adverse reaction data for adjuvant therapy are based on the ATAC trial [see Clinical Studies (14.1)]. 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 The combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up. Body system and adverse reactions by COSTART COSTART Coding Symbols for Thesaurus of Adverse Reaction Terms. preferred term A patient may have had more than 1 adverse reaction, including more than 1 adverse reaction in the same body system.
Table 2 — Number of Patients with Pre-specified Adverse Reactions in ATAC Trial Patients with multiple events in the same category are counted only once in that category. Anastrozole N=3092 (%) Tamoxifen N=3094 (%) Odds-ratio 95% CI Hot Flashes 1104 (36) 1264 (41) 0.80 0.73 to
0.89Musculoskeletal Events Refers
to joint symptoms, including joint disorder, arthritis, arthrosis and arthralgia. 1100 (36) 911 (29) 1.32 1.19 to
1.47 Fatigue/Asthenia 575 (19) 544 (18) 1.07 0.94 to
1.22 Mood Disturbances 597 (19) 554 (18) 1.10 0.97 to
1.25 Nausea and Vomiting 393 (13) 384 (12) 1.03 0.88 to
1.19 All Fractures 315 (10) 209 (7) 1.57 1.30 to
1.88 Fractures of Spine, Hip, or Wrist 133 (4) 91 (3) 1.48 1.13 to
Percentages calculated based upon the numbers of patients with an intact uterus at baseline 4 (0.2) 13 (0.6) 0.31 0.10 to
0.94Ischemic Cardiovascular Events
Between treatment arms in the overall population of 6186 patients, there was no statistical difference in ischemic cardiovascular events (4% anastrozole vs. 3% tamoxifen). In the overall population, angina pectoris was reported in 71/3092 (2.3%) patients in the anastrozole arm and 51/3094 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37/3092 (1.2%) patients in the anastrozole arm and 34/3094 (1.1%) patients in the tamoxifen arm.
In women with pre-existing ischemic heart disease 465/6186 (7.5%), the incidence of ischemic cardiovascular events was 17% in patients on anastrozole and 10% in patients on tamoxifen. In this patient population, angina pectoris was reported in 25/216 (11.6%) patients receiving anastrozole and 13/249 (5.2%) patients receiving tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients receiving anastrozole and 8/249 (3.2%) patients receiving tamoxifen.
Bone Mineral Density Findings Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Because anastrozole lowers circulating estrogen levels it ma
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Composition
Active ingredients
ANASTROZOLE 1MG
Strengths and forms
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