Anastrozole is a selective non-steroidal aromatase inhibitor. Anastrozole is highly potent and specific for aromatase and represents the fourth generation of aromatase inhibitors. Anastrozole significantly suppresses serum estradiol levels in postmenopausal women, offering an alternative to tamoxifen. Unlike aminoglutethimide, an early aromatase inhibitor, anastrozole does not inhibit adrenal steroid synthesis. Patients taking anastrozole, therefore, do not require glucocorticoid or mineralocorticoid replacement therapy. Anastrozole causes less weight gain than megestrol and may offer a survival advantage over megestrol in women with advanced breast cancer. The results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, which compared treatment with anastrozole to tamoxifen for 5 years in women with breast cancer, indicate that anastrozole confers improved disease-free survival compared to tamoxifen; overall survival was similar. Anastrozole is indicated for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, and for the treatment of postmenopausal women with advanced breast cancer either as first-line therapy or after progression on tamoxifen therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure.
Route-Specific Administration
Oral Administration
-Administer at the same time every day with or without food.
Hot flashes (12% to 36%) were the most commonly reported adverse reaction in patients treated with anastrozole in clinical trials (n = 3,860), although the incidence was lower compared with patients receiving tamoxifen in the ATAC trial of patients with early breast cancer (n = 6,186). Most urogenital adverse reactions were less common in the ATAC trial in patients treated with anastrozole compared with tamoxifen including vaginitis (4% vs. 5%), vaginal bleeding (5% vs. 10%), vaginal hemorrhage (4% vs. 6%), vaginal discharge (4% vs. 13%), and leukorrhea (3% vs. 9%); vulvo-vaginitis was more common in the anastrozole arm (6% vs. 5%). Tumor flare (3%), leukorrhea (2%), vaginal dryness (2%), vaginal bleeding (2%), and vaginal hemorrhage (2%) were reported in patients with advanced breast cancer who received anastrozole 1 mg daily in 4 clinical trials (n = 768).
A generalized gastrointestinal disorder or disturbance was reported in 7% of patients with early breast cancer treated with anastrozole in the ATAC trial (n = 3,092) and in 29% to 38% of anastrozole-treated patients with advanced breast cancer in 4 other clinical trials (n = 768). Gastrointestinal adverse reactions reported in patients treated with anastrozole across clinical trials (n = 3,860) included nausea (11% to 19%), abdominal pain (7% to 9%), diarrhea (8% to 9%), constipation (7% to 9%), vomiting (9% or less), and dyspepsia (7% or less). A grouped term of nausea and vomiting was reported in 13% of patients with early breast cancer treated with anastrozole compared with 12% of those who received tamoxifen in the ATAC trial (n = 6,186). Anorexia (5% to 7%), xerostomia (6%), and weight loss (2% to 5%) were also reported in patients with advanced breast cancer treated with anastrozole 1 mg daily in 4 clinical trials (n = 768).
Depression (5% to 13% vs. 6% to 12%) and insomnia (2% to 10% vs. 7% to 9%) were more common in patients treated with anastrozole compared with tamoxifen in clinical trials (n = 7,718). In the ATAC trial of patients with early breast cancer (n= 6,186), mood disturbances (19% vs. 18%) and anxiety (6% vs. 6%) also occurred with a similar incidence in patients treated with anastrozole versus tamoxifen. Confusion, anxiety, and nervousness occurred in 2% to 5% of patients treated with anastrozole as second-line therapy for advanced breast cancer.
Venous thromboembolism occurred in 3% of postmenopausal patients with early breast cancer treated with anastrozole compared with 5% of those treated with tamoxifen in the ATAC trial (n = 6,186); deep vein thrombosis occurred in 2% of patients in each study arm. Thromboembolic disease, including pulmonary embolism, thrombo-phlebitis, and retinal thrombosis, occurred in 3% to 4% of anastrozole-treated patients with advanced breast cancer in 4 clinical trials (n = 768), including 1% venous thrombosis, while thrombophlebitis was reported in 2% to 5% of these patients.
Chest pain (unspecified) was reported in 5% to 7% of patients treated with anastrozole in clinical trials. In the ATAC trial of postmenopausal patients with early breast cancer (n = 6,186), there was no statistical difference in ischemic cardiovascular events in the overall population of postmenopausal women treated with anastrozole (4%) compared with tamoxifen (3%); angina occurred in 2.3% and myocardial infarction in 1.2% of patients in the anastrozole arm. The incidence of ischemic cardiovascular events in anastrozole-treated patients in the ATAC trial increased to 17% in women with pre-existing ischemic heart disease; angina occurred in 11.6% of these patients and myocardial infarction in 0.9%. Ischemic cerebrovascular events occurred in 2% of patients treated with anastrozole and 2% of patients treated with tamoxifen in the ATAC trial. In two other clinical trials of postmenopausal women with advanced breast cancer (n = 1,017), coronary and cerebral events occurred in 2.5% of patients treated with anastrozole, including myocardial infarction, myocardial ischemia, angina pectoris, cerebrovascular accident (stroke), cerebral ischemia, and cerebral infarct.
Hypercholesterolemia has been reported in patients treated with anastrozole in clinical trials. During the ATAC trial (n = 6,186), elevated serum cholesterol levels occurred in 9% of postmenopausal women with early breast cancer treated with anastrozole compared with 3.5% of those receiving tamoxifen. Mean serum total cholesterol levels increased by 0.5 mmol/L in patients with advanced breast cancer treated with anastrozole 1 mg daily in two clinical trials (n = 262). In a postmarketing trial, anastrozole had a neutral effect on lipid profile, with no clinically significant change in LDL-C or HDL-C from baseline to 12 months in patients treated with anastrozole, as well as in a secondary population for lipids treated with anastrozole plus risedronate. In both populations for lipids, there was no clinically significant difference in total cholesterol or serum triglycerides at 12 months compared with baseline. Postmenopausal women with early breast cancer who develop hypercholesterolemia should be managed according to current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations.
Musculoskeletal events, including joint symptoms, arthritis, arthrosis, and arthralgia, occurred in 36% of patients with early breast cancer treated with anastrozole in the ATAC trial (n = 3,860) compared with 29% of those who received tamoxifen (n = 3,094) in the ATAC trial (HR 1.32; 95% CI, 1.19 to 1.47). Specifically, pain (17% vs. 16%), arthritis (17% vs. 14%), arthralgia (15% vs. 11%), back pain (10% vs. 10%), breast pain (8% vs. 6%), bone pain (7% vs. 6%), arthrosis (7% vs. 5%), joint disorder (6% vs. 5%), and myalgia (6% vs. 5%) were reported in the ATAC trial. In 4 smaller clinical trials of patients with advanced disease who received anastrozole 1 mg daily (n = 768), myalgia and arthralgia were each reported in 2% to 5% of patients. Reports of pain at various locations were similar to patients with early disease, including generalized pain (11% to 14%), back pain (11% to 12%), bone pain (6% to 11%), pelvic pain (5%), neck pain (less than 5%), and breast pain (less than 5%). Accidental injury has also been reported in 2% to 10% of patients treated with anastrozole in clinical trials.
Because anastrozole lowers circulating estrogen levels, it may cause a reduction in bone mineral density (BMD). Patients treated with anastrozole experienced a mean decrease in both lumbar spine and total hip BMD at 12 and 24 months compared to baseline in the ATAC trial bone substudy; patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Osteoporosis was reported in 11% of patients treated with anastrozole compared with 7% of those who received tamoxifen in the ATAC trial (n = 6,186). Bone fractures were also more common in the anastrozole arm (10% vs. 7%), although the incidence of wrist/Colles' fractures (2% vs. 2%), spine fractures (1% vs. 1%), and hip fractures (1% vs. 1%) were the same in the anastrozole versus tamoxifen arms. Similarly, after a median follow-up of 36 months in the combined analysis of the ABCSG trial 8 and the ARNO 95 trials, the odds of bone fractures in patients taking anastrozole were significantly increased compared with tamoxifen (2% vs. 1%). At the 10-year follow-up on safety results from the ATAC trial, the cumulative incidence of all first fractures (serious and non-serious; occurring both during or after treatment) was 15% in patients treated with anastrozole compared with 11% for those who received tamoxifen. The increased first fracture rate during treatment did not continue in the post-treatment follow-up period. Pathological fracture was reported in 2% to 5% of patients with advanced breast cancer treated with anastrozole 1 mg daily in 2 clinical trials (n = 262). In a postmarketing trial, bisphosphonate treatment during anastrozole therapy preserved bone density in most patients at risk of fracture.
Peripheral vasodilation occurred in 25% to 36% of patients treated with anastrozole in clinical trials (n = 3,860). Hypertension has also been reported in 2% to 13% of anastrozole-treated patients.
Rash occurred in 6% to 11% of breast cancer patients treated with anastrozole in clinical trials (n = 3,860). Skin reactions such as lesions, skin ulcer, or blisters occurred in less than 1 in 10,000 patients treated with anastrozole in clinical trials, while cases of mucocutaneous disorders such as erythema multiforme and Stevens-Johnson syndrome have been reported in postmarketing experience with anastrozole. Additional dermatologic adverse reactions include sweating (hyperhidrosis), alopecia, and pruritus, each occurring in 2% to 5% of patients treated with anastrozole. Cysts occurred in 5% of patients with early breast cancer who received anastrozole in the ATAC trial (n = 3,092) compared with 5% of those who received tamoxifen (n = 3,090).
In the ATAC trial of patients with early breast cancer (n = 6,186), infection occurred with the same incidence in patients treated with anastrozole compared with tamoxifen (9% vs. 9%). Pharyngitis (14% vs. 14%), urinary tract infection (8% vs. 10%), influenza syndrome (6% vs. 6%), sinusitis (6% vs. 5%), and bronchitis (5% vs. 5%) were individually reported. In 4 clinical trials of patients with advanced breast cancer treated with anastrozole 1 mg daily (n = 768), infection was reported in 2% to 5% of patients, with the following individually reported: pharyngitis (6% to 10%), flu syndrome (2% to 7%), sinusitis (2% to 5%), bronchitis (2% to 5%), rhinitis (2% to 5%), and urinary tract infection (2% to 5%); fever was also reported in 2% to 5% of these patients.
Anemia was reported in 4% of patients with early breast cancer treated with anastrozole in the ATAC trial (n = 3,092) compared with 5% of those who received tamoxifen. In 2 clinical trials, both anemia and leukopenia occurred in 2% to 5% of patients with advanced breast cancer receiving anastrozole 1 mg daily (n = 262).
Cataracts occurred in 6% of patients with early breast cancer treated with anastrozole in the ATAC trial (n = 3,860) compared with 7% of those who received tamoxifen (HR 0.85; 95% CI, 0.69 to 1.04).
Hypercalcemia (with or without an increase in parathyroid hormone) has been reported in postmarketing experience with anastrozole.
Peripheral edema occurred in 5% to 10% of patients with early or advanced breast cancer treated with anastrozole in clinical trials (n = 3,860); weight gain was reported in 2% to 9% of these patients. Lymphedema occurred in 10% of patients with early breast cancer treated with anastrozole compared with 11% of those who received tamoxifen in the ATAC trial (n = 6,186). Generalized edema was also reported in 7% of patients with advanced breast cancer who received anastrozole 1 mg daily in 2 controlled trials of second-line therapy (n = 262).
The incidence of fatigue/asthenia (16% to 19% vs. 16 to 18%), headache (9% to 13% vs. 8%), and dizziness (6% to 8% vs. 4% to 8%) did not differ greatly between anastrozole and tamoxifen arms in clinical trials (n = 6,186). Malaise (2% to 5%), somnolence (2% to 5%), and lethargy (1% or less) and were additionally reported in patients with advanced breast cancer treated with anastrozole 1 mg daily in clinical trials (n = 768).
Elevated hepatic enzymes, including increased gamma GT, increased SGOT, increased SGPT, and increased alkaline phosphatase, were reported in 2% to 5% of patients with advanced breast cancer treated with anastrozole 1 mg daily in 2 clinical trials (n = 262). Changes in liver function with symptoms of malaise, jaundice, liver pain, and inflammation of the liver occurred in less than 1 in 10,000 patients treated with anastrozole in clinical trials. Increased alkaline phosphatase, increased ALT, increased AST, increased gamma-GT, hyperbilirubinemia, and hepatitis were reported in postmarketing experience with anastrozole.
Tumor flare was reported in 3% of patients with advanced breast cancer who received anastrozole 1 mg daily in 4 clinical trials (n = 768).
A new primary malignancy has been reported in patients treated with anastrozole. However, in the ATAC trial (n = 6,186), patients treated with anastrozole had a lower incidence of endometrial cancer compared with patients receiving tamoxifen (0.2% vs. 0.6%; HR 0.6; 95% CI, 0.1 to 094). Neoplasm (5% vs. 5%) and breast neoplasm (5% vs. 5%) were also reported in the ATAC trial. The cumulative incidence of new primary cancers was similar in the anastrozole group compared to the tamoxifen group at the 10-year follow-up of safety results from ATAC (13.7% vs. 13.9%); the incidence of endometrial cancer remained higher in the tamoxifen group, consistent with the previous analysis (0.2% vs. 0.8%).
Patients with early breast cancer treated with anastrozole in the ATAC trial (n = 3,860) had a higher incidence of carpal tunnel syndrome compared with patients receiving tamoxifen (n = 3,890) (2.5% vs. 0.7%). In 2 clinical trials of patients with advanced breast cancer (n = 1,017), hypertonia occurred in 3% of patients receiving anastrozole 1 mg daily compared with 5% of those treated with tamoxifen. Trigger finger has also been reported in postmarketing experience with anastrozole.
Cases of allergic reactions including angioedema, urticaria, and anaphylaxis (anaphylactoid reactions) have been reported in postmarketing experience with anastrozole. In clinical trials, allergic reactions with swelling of the face, lips, tongue, and/or throat occurred in less than 1 in 10,000 patients treated with anastrozole.
Cough (8% to 11%) and dyspnea (8% to 10%) were reported across clinical trials of patients with breast cancer treated with anastrozole (n = 3,860).
Paresthesias were reported in 5% of patients with advanced breast cancer treated with anastrozole 1 mg daily in 2 clinical trials (n = 262).
Use anastrozole with caution in patients with pre-existing hypercholesterolemia. During the ATAC trial, postmenopausal women receiving anastrozole had increased serum cholesterol compared to patients receiving tamoxifen (9% vs. 3.5%). Postmenopausal women with early breast cancer who develop hypercholesterolemia during anastrozole treatment should be managed according to current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations.
Consider bone mineral density (BMD) monitoring in patients treated with anastrozole. Use anastrozole with caution in patients with pre-existing osteoporosis. In the ATAC trial bone substudy, patients receiving anastrozole had a mean decrease in both lumbar spine and total hip BMD at 12 and 24 months compared to baseline. After a median follow-up of 68 months, significantly more bone fractures occurred in patients taking anastrozole compared with tamoxifen (11% vs. 7.7%). Significantly more bone fractures also occurred in patients treated with anastrozole compared with tamoxifen in a combined analysis of 2 other clinical trials (ABCSG 8 and ARNO 95) (2% vs. 1%).
Use anastrozole with caution in patients with pre-existing ischemic cardiac disease. In the ATAC trial, postmenopausal women with pre-existing ischemic heart disease had an increased incidence of ischemic cardiovascular events compared with tamoxifen (17% vs. 10%).
The efficacy of anastrozole in children for the treatment of pubertal gynecomastia in adolescent boys and precocious puberty in girls with McCune-Albright Syndrome has not been demonstrated. In a multicenter, randomized clinical trial of boys with pubertal gynecomastia (n = 80), there was not a significant difference in the percentage of patients experiencing a 50% or greater reduction in gynecomastia after 6 months of treatment with anastrozole compared with placebo; secondary efficacy analyses (absolute change in breast volume, reduced calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. Serum estradiol concentrations at 6 months were reduced by 15.4% in the anastrozole group compared with 4.5% in the placebo arm. In another multicenter, single-arm clinical trial in girls with McCune-Albright Syndrome and progressive precocious puberty, there were no on-treatment significant reductions in the frequency of vaginal bleeding days or the rate of increased bone age. There were also no clinically significant changes in Tanner staging, mean ovarian volume, mean uterine volume, or mean predicted adult height.
Pregnancy should be avoided by females of reproductive potential during anastrozole treatment and for at least 3 weeks after the last dose. Although there are no adequately controlled studies in pregnant animals or women, anastrozole can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving anastrozole should be apprised of the potential hazard to the fetus. In animal reproduction studies, anastrozole crossed the placenta and caused increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased live fetuses) when administered to pregnant rats and rabbits during organogenesis at doses approximately 1/3 and 1 times the recommended human dose on a mg/m2 basis. These effects were dose-related in rats, and placental weights were significantly increased at doses greater than or equal to the dose comparable to the recommended human dose on a mg/m2 basis. Fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights) occurred in rats at doses that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose. In rabbits, pregnancy failure occurred at doses about 16 times the recommended human dose on a mg/m2 basis.
Counsel patients about the reproductive risk and contraception requirements during anastrozole treatment. Anastrozole can be fetotoxic and teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 3 weeks after treatment with anastrozole. Females of reproductive potential should undergo pregnancy testing prior to initiation of anastrozole. Women who become pregnant while receiving anastrozole should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of anastrozole on human fertility, female infertility has been observed in animal studies.
Due to the potential for serious adverse reactions in nursing infants from anastrozole, advise women to discontinue breast-feeding during treatment and for 2 weeks after the final dose. It is not known whether anastrozole is present in human milk, although many drugs are excreted in human milk.
For the treatment of breast cancer:
-for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer:
Oral dosage:
Postmenopausal females: 1 mg PO once daily. The optimal duration of the therapy is not known, although in the ATAC trial anastrozole was administered for 5 years. After a median of 10 years follow-up, adjuvant treatment with 5 years of anastrozole (n = 3,125) significantly improved disease-free survival in the intent-to-treat population (HR 0.91) as well as the hormone receptor-positive population (HR 0.86) compared with tamoxifen (n = 3,116) in a multicenter, double-blind clinical trial (ATAC) in postmenopausal women. Overall survival was not significantly different.
-for adjuvant treatment of estrogen receptor-positive early breast cancer in postmenopausal women who have received 2 to 3 years of tamoxifen therapy, to complete a total of 5 consecutive years of adjuvant hormonal therapy*:
Oral dosage:
Postmenopausal females: 1 mg PO once daily to complete a total of 5 years of adjuvant hormonal therapy. Compared with 5 consecutive years of tamoxifen, patients switched to anastrozole after 2 to 3 years of tamoxifen experienced significantly improved disease-free survival (DFS; HR 0.35) and event-free survival (EFS; HR 0.15) after a median of 36 months of follow-up. When measured after a median follow-up of 64 months, EFS was still improved by anastrozole. Adverse gastrointestinal symptoms and lipid metabolism disorders were reported more commonly in patients taking anastrozole, while gynecological complaints including endometrial carcinoma were reported more commonly in patients taking tamoxifen; bone fracture rates were similar in the 2 groups. In another phase 3 clinical trial (n = 979), treatment with anastrozole after 2 years of tamoxifen therapy to complete 5 years total significantly improved DFS (HR 0.66) and overall survival (HR 0.53) compared with tamoxifen alone. Furthermore, in a combined analysis of this trial and another phase 3 trial (n = 2,262), EFS was significantly improved by switching to anastrozole after 2 to 3 years of tamoxifen compared to continuing tamoxifen for 5 years. There were significantly more fractures and fewer thromboses in patients who received anastrozole compared with tamoxifen. In a meta-analysis of these 3 studies (data from the above studies), patients randomized to anastrozole after 2 to 3 years of tamoxifen (n = 2,009) had improved DFS (HR 0.59), EFS (HR 0.55), and overall survival (HR 0.71) compared with patients taking 5 years of tamoxifen (n = 1,997) after a median follow-up of 30 months.
-for the first-line treatment of hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer, in postmenopausal women:
Oral dosage:
Postmenopausal females: 1 mg PO once daily until tumor progression is noted. In a double-blind clinical trial, first-line treatment of hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer in postmenopausal women with anastrozole (n = 171) significantly improved median time to progression (TTP) compared with tamoxifen (n = 182) (11.1 months vs. 5.6 months); best objective response rate (ORR) was 21.1% versus 17%, respectively. In another double-blind clinical study with similar trial design, median TTP (8.2 months vs. 8.3 months) and ORR (32.9% vs. 32.6%) were similar between the anastrozole (n = 340) and tamoxifen (n = 328) arms.
-for the first-line treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women, in combination with fulvestrant*:
Oral dosage:
Postmenopausal females: 1 mg PO once daily in combination with fulvestrant 500 mg IM as two 5 mL injections (one in each buttock) on day 1, followed by 250 mg IM every 2 weeks for 2 doses then 250 mg IM every 4 weeks thereafter was evaluated in 2 randomized, open label, phase III trials. Treatment was continued until disease progression.
-for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy:
NOTE: Patients with estrogen receptor-negative disease and patients who did not respond to previous tamoxifen therapy rarely respond to anastrozole.
Oral dosage:
Postmenopausal females: 1 mg PO once daily until disease progression. In 2 controlled clinical trials, treatment with anastrozole after progression following tamoxifen therapy resulted in similar median time to progression (4.4 to 5.7 months vs. 3.9 to 5.1 months), median time to death (24.3 to 29.6 months vs. 19.8 to 26.7 months), and objective response rate (12.5% to 12.6% vs. 10.2% to 14.4%) compared with megestrol 160 mg once daily in postmenopausal women with advanced breast cancer.
-for the treatment of HER2-positive, hormone receptor-positive metastatic breast cancer in combination with trastuzumab*:
Oral dosage:
Adults: 1 mg PO once daily in combination with trastuzumab (4 mg/kg IV over 90 minutes on week 1 followed by 2 mg/kg IV over 30 minutes once weekly starting week 2). Treatment should be continued until disease progression or unacceptable toxicity. In a phase III trial, 207 patients were randomized to receive anastrozole with or without trastuzumab. The primary endpoint, progression-free survival, was significantly improved with the addition of trastuzumab (4.8 months vs. 2.4 months, p = 0.0016). Overall survival was not significantly different between the treatment groups (28.5 months vs. 23.9 months, p = 0.325). Of note, 70% of patients in the anastrozole alone arm received a trastuzumab-containing regimen after developing progressive disease on anastrozole. Cardiac events occurred more frequently in the trastuzumab arm (14 events vs. 2 events); however, the incidence of grade 3 or 4 events was similar between the groups (2 events each).
For the treatment of uterine leiomyomata*:
Oral dosage:
Premenopausal adult females: Preliminary data indicate that 1 mg PO once daily may be effective in reducing uterine leiomyomata size and improving patient symptoms. In a study of 41 premenopausal women, anastrozole 1 mg/day PO for three 28-day cycles decreased leiomyomata volumes by 55.7%. Women with larger leiomyomata at baseline (i.e., > 50 mm) tended to experience the greatest reduction in leiomyomata volume; additionally, only women > 40 years of age experienced a reduction in leiomyomata volume. Symptoms such as vaginal bleeding and pelvic pain/pressure were less, and hematocrit concentrations increased indicating an improvement in menstrual irregularities.
For the treatment of endometriosis* refractory to other medical or surgical treatments:
Oral dosage:
Adults: 1 mg/day PO for up to 6 months, with or without other hormonal therapies, has been studied. For patients with endometriosis-associated pain refractory to other medical or surgical treatment, aromatase inhibitors may be considered, as they reduce endometriosis-associated pain. Aromatase inhibitors may be prescribed in combination with oral contraceptives, progestins, GnRH agonists or GnRH antagonists.
Maximum Dosage Limits:
-Adults
1 mg per day PO.
-Geriatric
1 mg per day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
-Mild to moderate hepatic impairment: No dosage adjustments are recommended.
-Severe hepatic impairment: Anastrozole has not been studied in this patient population.
Patients with Renal Impairment Dosing
No dosage adjustment needed.
*non-FDA-approved indication
Conjugated Estrogens: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Conjugated Estrogens; Bazedoxifene: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Conjugated Estrogens; Medroxyprogesterone: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Desogestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Dienogest; Estradiol valerate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Drospirenone; Estetrol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Drospirenone; Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Drospirenone; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Esterified Estrogens: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Esterified Estrogens; Methyltestosterone: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estradiol; Levonorgestrel: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estradiol; Norethindrone: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estradiol; Norgestimate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estradiol; Progesterone: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estrogens: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Estropipate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Ethinyl Estradiol; Norelgestromin: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Ethinyl Estradiol; Norgestrel: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Etonogestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Levonorgestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Norethindrone; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Norgestimate; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Segesterone Acetate; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and anastrozole. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as anastrozole.
Tamoxifen: (Major) Avoid coadministration of tamoxifen with anastrozole, as there is no benefit when compared to tamoxifen alone. Additionally, in the ATAC trial, coadministration of anastrozole and tamoxifen in breast cancer patients reduced the anastrozole plasma concentration by 27% compared to that achieved with anastrozole alone; the tamoxifen concentration was not altered.
Anastrozole is a selective non-steroidal aromatase inhibitor. In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. Suppression of estrogen biosynthesis in peripheral tissues and in cancer cells can be achieved by specifically inhibiting the aromatase enzyme. Anastrozole significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone. Anastrozole doses of 1mg or more suppressed mean serum concentrations of estradiol in postmenopausal women with advanced breast cancer to the lower limit of detection (3.7 pmol/L) in multiple daily dosing trials (range, 0.5 mg to 10 mg). The recommended dose of 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 of anastrozole 1 mg. The effect of anastrozole in premenopausal women with early or advanced breast cancer has not been studied. However, because aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women, anastrozole would not be expected to lower estradiol levels in premenopausal women.
Anastrozole did not affect cortisol or aldosterone secretion at baseline or in response to ACTH in multiple daily dosing trials (range, 3 mg to 10 mg). Similarly, there was no increase in TSH during administration of anastrozole 5 mg or 10 mg daily.
Anastrozole is administered orally. It is 40% bound to plasma proteins in the therapeutic range. Steady-state plasma concentrations are approximately 3- to 4-fold higher than levels observed after a single dose of anastrozole. The mean elimination half-life of anastrozole is 50 hours; steady-state concentrations are reached after approximately 7 days of daily dosing. The pharmacokinetics of anastrozole are linear over the dose range of 1 mg to 20 mg, and do not change with repeated dosing. Hepatic metabolism by N-dealkylation, hydroxylation, and glucuronidation accounts for approximately 85% of elimination. Three metabolites have been identified in human plasma and urine (triazole, a glucuronide conjugate of anastrozole, and a glucuronide conjugate of hydroxy-anastrozole). The major circulating metabolite, triazole, lacks pharmacologic activity. Eighty-five percent of radiolabeled anastrozole was recovered in feces and urine. Renal elimination accounts for approximately 10% of total clearance.
Affected cytochrome P450 isoenzymes: None
Anastrozole inhibits CYP1A2, CYP2C8/9, and CYP3A4 in vitro with Ki values approximately 30 times higher than the mean steady-state Cmax values observed following a 1 mg daily dose.
-Route-Specific Pharmacokinetics
Oral Route
Absorption of anastrozole is rapid, with maximum plasma concentrations occurring within 2 hours of dosing (Tmax) under fasting conditions. Studies with radiolabeled drug show that it is well absorbed into the systemic circulation, with 85% bioavailability.
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.
-Special Populations
Hepatic Impairment
Plasma concentrations of anastrozole in patients with hepatic cirrhosis were within the range of concentrations seen in subjects with normal hepatic function across clinical trials. Anastrozole has not been studied in patients with severe hepatic impairment.
Renal Impairment
Renal impairment does not influence the total body clearance of anastrozole, although renal clearance decreased proportionally with creatinine clearance and was approximately 50% lower in volunteers with severe renal impairment (CrCL less than 30 mL/min/1.73 m2) compared to controls.
Pediatrics
The mean time to reach the maximum anastrozole concentration (Tmax) was 1 hour in pediatric patients following multiple daily doses of anastrozole 1 mg. The mean clearance (CL/F) was 1.54 L/hour (range, 0.77 to 4.53 L/hour) and the mean volume of distribution (V/F) was 98.4 liters (range, 50.7 to 330 liters). The terminal elimination half-life was 46.8 hours in pediatric patients, which was similar to that observed in postmenopausal women treated with anastrozole for breast cancer. Based on a population pharmacokinetic analysis, the pharmacokinetics of anastrozole were similar in boys with pubertal gynecomastia and girls with McCune-Albright Syndrome.
Geriatric
No age-related effects on the pharmacokinetics of anastrozole were seen in postmenopausal females over the range of less than 50 years to greater than 80 years.
Ethnic Differences
Estradiol and estrone sulfate serum levels were similar between Japanese and Caucasian postmenopausal women who received anastrozole 1 mg daily for 16 days. Anastrozole mean steady-state minimum plasma concentrations were 30.4 ng/mL and 25.7 ng/mL, respectively.