Gg18a anastrozole pi (kalarex) 14_05_10_fr.ai

HIGHLIGHTS OF PRESCRIBING INFORMATION
10 OVERDOSAGE
receiving tamoxifen (9% versus 3.5%, respectively).
Anastrozole
Postmenopausal women with early breast cancer scheduled to be Respiratory: Sinusitis; bronchitis; rhinitis
PATIENT INFORMATION
These highlights do not include all the information needed to use
11 DESCRIPTION
6 ADVERSE
REACTIONS
Body system and adverse
Tamoxifen
treated with anastrozole tablets should have their bone status managed Based on results from second-line therapy and the established safety Anastrozole (an as’ troe zole) Tablets
Skin and Appendages: Hair thinning (alopecia); pruritus
anastrozole tablets safely and effectively. See full prescribing information
12 CLINICAL
PHARMACOLOGY
Serious adverse reactions with anastrozole tablets occurring in less than event by COSTART†-preferred
according to treatment guidelines already available for postmenopausal profi le of tamoxifen, the incidences of 9 pre-specifi ed adverse event Read the information that comes with anastrozole tablets before you start Urogenital: Urinary tract infection; breast pain
for anastrozole tablets.
1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or (N§ = 3092)
(N§ = 3094)
women at similar risk of fragility fracture.
categories potentially causally related to one or both of the therapies taking it and each time you get a refi ll. The information may have changed. The incidences of the following adverse event groups potentially causally Anastrozole tablets for oral use
blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/ Special Senses
because of their pharmacology were statistically analyzed. No signifi cant This leafl et does not take the place of talking with your doctor about your related to one or both of the therapies because of their pharmacology, Initial U.S. Approval: 1995
or throat. This may cause diffi culty in swallowing and/or breathing; and During the ATAC trial, more patients receiving anastrozole tablets were differences were seen between treatment groups.
medical condition or treatment. Talk with your doctor about anastrozole 13 NONCLINICAL
TOXICOLOGY
were statistically analyzed: weight gain, edema, thromboembolic disease, 3) changes in blood tests of the liver function, including infl ammation of reported to have an elevated serum cholesterol compared to patients tablets when you start taking it and at regular checkups. --------------------------------RECENT MAJOR CHANGES----------------------------
Urogenital
Patients
Pre-specifi ed Adverse Reactions in
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility gastrointestinal disturbance, hot fl ushes, and vaginal dryness. These the liver with symptoms that may include a general feeling of not being receiving tamoxifen (9% versus 3.5%, respectively).
Contraindications - Premenopausal Women and Pregnancy (4.1, 8.1) 11/2008 Trials 0030 and 0027
13.2 Animal Toxicology and/or Pharmacology six groups, and the adverse reactions captured in the groups, were well, with or without jaundice, liver pain or liver swelling [see Adverse What is anastrozole tablets?
Warnings and Precautions- Ischemic Cardiovascular Events (5.1, 6.1) 11/2008 14 CLINICAL
prospectively defi ned. The results are shown in the table below.
Number (n) and Percentage of Patients
Anastrozole tablets is a prescription medicine used in women who have tablets on lipid profi le. In the primary analysis population for lipids -------------------------------INDICATIONS AND USAGE------------------------------
14.1 Adjuvant Treatment of Breast Cancer in Postmenopausal Women Adverse Reaction*
Anastrozole Tablets NOLVADEX 20 mg
Table 6- Number (n) and Percentage of Patients with Pre-specifi ed
fi nished menopause (“the change of life”) for: Common adverse reactions (occurring with an incidence of >10%) (anastrozole tablets alone), there was no clinically signifi cant change Anastrozole tablets is an aromatase inhibitor indicated for: 14.2 First-Line Therapy in Postmenopausal Women with Advanced Adverse Reactions in Trials 0004 and 0005
in women taking anastrozole tablets included: hot fl ashes, asthenia, in LDL-C from baseline to 12 months and HDL-C from baseline to 12 Adjuvant treatment of postmenopausal women with hormone receptor- arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea Anastrozole Anastrozole
Megestrol
 after surgery, with or without radiation 14.3 Second-Line Therapy in Postmenopausal Women with Advanced and vomiting, rash, osteoporosis, fractures, back pain, insomnia, pain,  in women whose breast cancer is hormone receptor-positive First-line treatment of postmenopausal women with hormone receptor- Breast Cancer who had Disease Progression following Tamoxifen In a secondary population for lipids (anastrozole tablets+risendronate), headache, bone pain, peripheral edema, increased cough, dyspnea,  fi rst treatment of locally advanced or metastatic breast cancer, in positive or hormone receptor unknown locally advanced or metastatic there also was no clinically signifi cant change in LDL-C and HDL-C from * The combination arm was discontinued due to lack of effi cacy women whose breast cancer is hormone receptor-positive or the 16 HOW SUPPLIED/STORAGE AND HANDLING
Adverse Event Group
Treatment of advanced breast cancer in postmenopausal women with In the ATAC trial, the most common reported adverse reaction (>0.1%) † COSTART Coding Symbols for Thesaurus of Adverse Reaction  treatment of advanced breast cancer, if the cancer has grown, or the disease progression following tamoxifen therapy. Patients with ER- 17 PATIENT COUNSELING INFORMATION
leading to discontinuation of therapy for both treatment groups was hot in total cholesterol (TC) or serum triglycerides (TG) at 12 months disease has spread after tamoxifen therapy. negative disease and patients who did not respond to previous tamoxifen fl ashes, although there were fewer patients who discontinued therapy as ‡ A patient may have had more than 1 adverse event, including more therapy rarely responded to anastrozole tablets. (1.3) 17.2 Allergic (Hypersensitivity) Reactions a result of hot fl ashes in the anastrozole tablets group.
In this trial, treatment for 12 months with anastrozole tablets alone had Anastrozole tablets does not work in women with breast cancer who have than 1 adverse event in the same body system.
---------------------------DOSAGE AND ADMINISTRATION--------------------------
a neutral effect on lipid profi le. Combination treatment with anastrozole not fi nished menopause (premenopausal women). § N=Number of patients receiving the treatment.
adverse reaction rates observed in the clinical trials of a drug cannot be tablets and risedronate also had a neutral effect on lipid profi le.
Who should not take anastrozole tablets?
directly compared to rates in the clinical trials of another drug and may Vaginal Hemorrhage without further diagnosis.
-------------------------DOSAGE FORMS AND STRENGTHS-------------------------
not refl ect the rates observed in practice.
breast cancer scheduled to be treated with anastrozole tablets should  are pregnant, think you may be pregnant, or plan to get pregnant. ------------------------------------CONTRAINDICATIONS-----------------------------
6.1 Clinical Trial Experience
prospectively specifi ed for analysis, based on the known pharmacologic be managed using the current National Cholesterol Education Program 6.2 Post-Marketing
Experience
Anastrozole tablets may harm your unborn child. If you become *Sections or subsections omitted from the full prescribing information are not Women of premenopausal endocrine status, including pregnant women Adjuvant
properties and side effect profi les of the two drugs (see Table 2).
guidelines for cardiovascular risk-based management of individual Hepatobiliary events including increases in alkaline phosphatase, alanine pregnant while taking anastrozole tablets, tell your doctor right away. Adverse reaction data for adjuvant therapy are based on the ATAC trial * A patient may have had more than 1 adverse event.
aminotransferase, aspartate aminotransferase have been reported (1% Patients
Pre-specifi ed Adverse Event in ATAC
have not fi nished menopause (are premenopausal) Patients with demonstrated hypersensitivity to anastrozole tablets or any [see Clinical Studies (14.1)]. The median duration of adjuvant treatment Includes pulmonary embolus, thrombophlebitis, retinal vein and <10%) and gamma-GT, bilirubin and hepatitis have been reported  are allergic to any of the ingredients in anastrozole tablets. See the end FULL PRESCRIBING INFORMATION
for safety evaluation was 59.8 months and 59.6 months for patients Patients receiving anastrozole tablets had an increase in joint disorders (0.1% and <1%) in patients receiving anastrozole tablets. receiving anastrozole tablets 1 mg and tamoxifen 20 mg, respectively. of this leafl et for a list of the ingredients in anastrozole tablets. ---------------------------WARNINGS AND PRECAUTIONS---------------------------
INDICATIONS AND USAGE
Anastrozole
(including arthritis, arthrosis and arthralgia) compared with patients Includes myocardial infarction, myocardial ischemia, angina Anastrozole tablets may also be associated with rash including cases of In women with pre-existing ischemic heart disease, an increased incidence Adverse reactions occurring with an incidence of at least 5% in either 1.1 Adjuvant
Treatment
Tamoxifen
receiving tamoxifen. Patients receiving anastrozole tablets had an pectoris, cerebrovascular accident, cerebral ischemia and cerebral mucocutaneous disorders such as erythema multiforme and Stevens- of ischemic cardiovascular events occurred with anastrozole tablets use treatment group during treatment or within 14 days of the end of Anastrozole tablets is indicated for adjuvant treatment of postmenopausal increase in the incidence of all fractures (specifi cally fractures of spine, What is the most important information I should know about anastrozole
compared to tamoxifen use. Consider risks and benefi ts. (5.1, 6.1) hip and wrist) [315 (10%)] compared with patients receiving tamoxifen Second-Line Therapy
tablets?
women with hormone receptor-positive early breast cancer. Decreases in bone mineral density may occur. Consider bone mineral Anastrozole tablets may cause serious side effects including: 1.2 First-Line
Treatment
Table 1- Adverse reactions occurring with an incidence of at least 5%
anaphylaxis have been reported in patients receiving anastrozole tablets in either treatment group during treatment, or within 14 days of
Trials 0004 and 0005), with less than 3.3% of the anastrozole tablets-  Heart disease. Women with early breast cancer, who have a history
Anastrozole tablets is indicated for the fi rst-line treatment of Patients receiving anastrozole tablets had a higher incidence of carpal [see Contraindications (4.2)].
Increases in total cholesterol may occur. Consider cholesterol monitoring. treated patients and 4.0% of the megestrol acetate-treated patients of blockages in heart arteries (ischemic heart disease) and who take postmenopausal women with hormone receptor-positive or hormone the end of treatment in the ATAC Trial*
tunnel syndrome [78 (2.5%)] compared with patients receiving tamoxifen fi nger has been reported (0.1% and <1%) in patients receiving anastrozole tablets may have a slight increase in this type of heart receptor unknown locally advanced or metastatic breast cancer. Anastrozole
--------------------------------ADVERSE REACTIONS---------------------------------
The principal adverse reaction more common with anastrozole tablets disease compared to similar patients who take tamoxifen. 1.3 Second-Line
Treatment
Body system and adverse
Tamoxifen
INTERACTIONS
In the early breast cancer (ATAC) study, the most common (occurring with than megestrol acetate was diarrhea. Adverse reactions reported in  Stop taking anastrozole tablets and call your doctor right away if you Anastrozole tablets is indicated for the treatment of advanced breast event by COSTART†-preferred
patients versus the anastrozole tablets-treated patients 317 (10%) versus 7.1 Tamoxifen
an incidence of >10%) side effects occurring in women taking anastrozole greater than 5% of the patients in any of the treatment groups in these have chest pain or shortness of breath. These can be symptoms of cancer in postmenopausal women with disease progression following (N§ = 3092)
(N§ = 3094)
tablets included: hot fl ashes, asthenia, arthritis, pain, arthralgia, pharyngitis, two controlled clinical trials, regardless of causality, are presented below: tamoxifen therapy. Patients with ER-negative disease and patients who Body as a whole
patients reduced anastrozole plasma concentration by 27%. However, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, did not respond to previous tamoxifen therapy rarely responded to Osteoporosis (bone softening and weakening). Anastrozole tablets
fl ashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous Table 5- Number (N) and Percentage of Patients with Adverse Reactions in
the coadministration of anastrozole and tamoxifen did not affect the back pain, insomnia, headache, peripheral edema and lymphedema, regardless lowers estrogen in your body, which may cause your bones to thromboembolic events and ischemic cerebrovascular events compared Trials 0004 and 0005
pharmacokinetics of tamoxifen or N-desmethyltamoxifen. At a median become softer and weaker. This can increase your chance of fractures, ADMINISTRATION
Anastrozole
Megesterol
follow-up of 33 months, the combination of anastrozole tablets and specifi cally of the spine, hip and wrist. Your doctor may order a test In the advanced breast cancer studies, the most common (occurring with an 2.1 Recommended
First-Line
Anastrozole
tamoxifen did not demonstrate any effi cacy benefi t when compared incidence of >10%) side effects occurring in women taking anastrozole tablets for you called a bone mineral density study before you start taking The dose of anastrozole tablets is one 1 mg tablet taken once a day. Adverse reactions occurring with an incidence of at least 5% in either Tablets 10 mg
with tamoxifen in all patients as well as in the hormone receptor-positive included: hot fl ashes, nausea, asthenia, pain, headache, back pain, bone pain, anastrozole tablets and during treatment with anastrozole tablets as For patients with advanced breast cancer, anastrozole tablets should be subpopulation. This treatment arm was discontinued from the trial treatment group of trials 0030 and 0027 during or within 2 weeks of the Adverse Reaction*
increased cough, dyspnea, pharyngitis and peripheral edema. (6.1) continued until tumor progression. Anastrozole tablets can be taken with [see Clinical Studies (14.1)]. Based on clinical and pharmacokinetic end of treatment are shown in Table 3.
To report SUSPECTED ADVERSE REACTIONS, contact Karalex Pharma, LLC
results from the ATAC trial, tamoxifen should not be administered with What should I tell my doctor before taking anastrozole tablets?
Table 3- Adverse Reactions Occurring With an Incidence of at Least 5% in
at 1-866-306-0240 or FDA at 1-800-FDA-1088 or www. fda.gov/medwatch
For adjuvant treatment of early breast cancer in postmenopausal women, Anastrozole tablets may not be right for you. Before taking anastrozole
Trials 0030 and 0027
-------------------------------DRUG INTERACTIONS----------------------------------
the optimal duration of therapy is unknown. In the ATAC trial anastrozole 7.2 Estrogen
tablets, tell your doctor about all your medical conditions, including if
Tamoxifen: Do not use in combination with anastrozole tablets. No tablets was administered for fi ve years [see Clinical Studies (14.1)]. Number (%) of Subjects
Estrogen-containing therapies should not be used with anastrozole additional benefi t seen over tamoxifen monotherapy (7.1, 14.1) Body System
Anastrozole Tablets
Tamoxifen
tablets as they may diminish its pharmacological action.  have not fi nished menopause. Talk to your doctor if you are not sure. No dosage adjustment is necessary for patients with renal impairment or Cardiovascular
Estrogen-containing products: Combination use may diminish activity of Adverse Reaction*
for elderly patients [see Use in Speci c Populations (8.6)]. 7.3 Warfarin
See “Who should not take anastrozole tablets?” Whole body
 have had a previous heart problem 2.2 Patients with Hepatic Impairment
---------------------------USE IN SPECIFIC POPULATIONS---------------------------
and AUC) and anticoagulant activity (as  have a condition called osteoporosis Digestive
Pediatric patients: Effi cacy has not been demonstrated for pubertal boys of measured by prothrombin time, activated partial thromboplastin time, hepatic impairment. Anastrozole tablets has not been studied in patients * Patients with multiple events in the same category are counted only adolescent age with gynecomastia or girls with McCune-Albright Syndrome and thrombin time) of both R- and S-warfarin. with severe hepatic impairment [see Use in Speci c Populations (8.7)]. are pregnant, planning to become pregnant, or breast feeding. See 7.4 Cytochrome
DOSAGE FORMS AND STRENGTHS
“Who should not take anastrozole tablets?” † Refers to joint symptoms, including joint disorder, arthritis, See 17 for PATIENT COUNSELING INFORMATION and FDA-approved
in vitro and in vivo results, it is unlikely that co-administration  are nursing a baby. It is not known if anastrozole tablets passes of anastrozole tablets 1 mg will affect other drugs as a result inhibition of Patient Labeling.
Revised: [05/10]
anastrozole. The tablets are impressed on one side with “3RP” and on the into breast milk. You and your doctor should decide if you will take Percentages calculated based upon the numbers of patients with an cytochrome P450 [see Clinical Pharmacology (12.3)].
anastrozole tablets or breast feed. You should not do both. FULL PRESCRIBING INFORMATION: CONTENTS*
Hemic and lymphatic
USE IN SPECIFIC POPULATIONS
4 CONTRAINDICATIONS
Tell your doctor about all the medicines you take, including prescription and INDICATIONS AND USAGE
Cardiovascular
8.1 Pregnancy
non-prescription medicines, vitamins, and herbal supplements. Especially tell 4.1 Pregnancy and Premenopausal Women
Between treatment arms in the overall population of 6186 patients, Anastrozole tablets may cause fetal harm when administered to a Metabolic and nutritional
there was no statistical difference in ischemic cardiovascular events Anastrozole tablets may cause fetal harm when administered to a  Tamoxifen. You should not take anastrozole tablets with tamoxifen.
pregnant woman and offers no clinical benefi t to premenopausal women (4% anastrozole tablets vs. 3% tamoxifen). In the overall population, Digestive
pregnant woman and offers no clinical benefi t to premenopausal women Taking tamoxifen with anastrozole tablets may lower the amount of DOSAGE AND ADMINISTRATION
with breast cancer. Anastrozole tablets are contraindicated in women who angina pectoris was reported in 71/3092 (2.3%) patients in the with breast cancer. Anastrozole tablets are contraindicated in women are or may become pregnant. There are no adequate and well- controlled anastrozole tablets arm and 51/3094 (1.6%) patients in the tamoxifen anastrozole tablets in your blood and may cause anastrozole tablets who are or may become pregnant. In animal studies, anastrozole caused studies in pregnant women using anastrozole tablets. If anastrozole arm; myocardial infarction was reported in 37/3092 (1.2%) patients in pregnancy failure, increased pregnancy loss, and signs of delayed fetal DOSAGE FORMS AND STRENGTHS
tablets are used during pregnancy, or if the patient becomes pregnant Musculoskeletal
the anastrozole tablets arm and 34/3094 (1.1%) patients in the tamoxifen  Medicines containing estrogen. Anastrozole tablets may not work if
development. There are no studies of anastrozole tablets use in pregnant 4 CONTRAINDICATIONS
while taking this drug, the patient should be apprised of the potential women. If anastrozole tablets are used during pregnancy, or if the hazard to a fetus or potential risk for loss of the pregnancy [see Use in In women with pre-existing ischemic heart disease 465/6186 (7.5%), patient becomes pregnant while receiving this drug, the patient should the incidence of ischemic cardiovascular events was 17% in patients Metabolic and Nutritional
be apprised of the potential hazard to the fetus and potential risk for WARNINGS AND PRECAUTIONS
4.2 Hypersensitivity
on anastrozole tablets and 10% in patients on tamoxifen. In this patient Anastrozole tablets are contraindicated in any patient who has shown a population, angina pectoris was reported in 25/216 (11.6%) patients Musculoskeletal
hypersensitivity reaction to the drug or to any of the excipients. Observed In animal reproduction studies, pregnant rats and rabbits received receiving anastrozole tablets and 13/249 (5.2%) patients receiving reactions include anaphylaxis, angioedema, and urticaria [see Adverse anastrozole during organogenesis at doses equal to or greater than tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients * A patient may have more than one adverse reaction.
6 ADVERSE
REACTIONS
1 (rats) and 1/3 (rabbits) the recommended human dose on a mg/m2 Know the medicines you take. Keep a list of them and show it to your doctor receiving anastrozole tablets and 8/249 (3.2%) patients receiving Other less frequent (2% to 5%) adverse reactions reported in patients basis. In both species, anastrozole crossed the placenta, and there was and pharmacist each time you get a new medicine. WARNINGS AND PRECAUTIONS
Nervous system
receiving Anastrozole tablets 1 mg in either Trial 0004 or Trial 0005 are increased pregnancy loss (increased pre-and/or post-implantation loss, 5.1 Ischemic Cardiovascular Events
How should I take anastrozole tablets?
listed below. These adverse experiences are listed by body system and increased resorption, and decreased numbers of live fetuses). In rats, In women with pre-existing ischemic heart disease, an increased incidence Results from the ATAC trial bone substudy at 12 and 24 months Take anastrozole tablets exactly as prescribed by your doctor. Keep taking are in order of decreasing frequency within each body system regardless these effects were dose related, and placental weights were signifi cantly of ischemic cardiovascular events was observed with anastrozole tablets demonstrated that patients receiving anastrozole tablets had a mean anastrozole tablets for as along as your doctor prescribes it for you. increased. Fetotoxicity, including delayed fetal development (i.e., in the ATAC trial (17% of patients on anastrozole tablets and 10% of decrease in both lumbar spine and total hip bone mineral density (BMD) Respiratory
 Take one anastrozole tablet each day. INTERACTIONS
incomplete ossifi cation and depressed fetal body weights), occurred in patients on tamoxifen). Consider risk and benefi ts of anastrozole tablets Whole: Flu syndrome; fever; neck pain; malaise; accidental
compared to baseline. Patients receiving tamoxifen had a mean increase  Anastrozole tablets can be taken with or without food. rats at anastrozole doses that produced peak plasma levels 19 times therapy in patients with pre-existing ischemic heart disease [see Adverse in both lumbar spine and total hip BMD compared to baseline. higher than serum levels in humans at the therapeutic dose (AUC If you miss a dose, take it as soon as you remember. If it is almost Respiratory
Cardiovascular: Hypertension; thrombophlebitis
Because anastrozole tablets lowers circulating estrogen levels it may times higher). In rabbits, anastrozole caused pregnancy failure at doses time for your next dose, skip the missed dose. Take your next regularly Hepatic: Gamma GT increased; SGOT increased; SGPT increased
cause a reduction in bone mineral density.
Skin and Appendages
equal to or greater than 16 times the recommended human dose on a mg/ scheduled dose. Do not take two doses at the same time. Results from the ATAC trial bone substudy at 12 and 24 months USE IN SPECIFIC POPULATIONS
Hematologic: Anemia; leucopenia
m2 basis [see Animal Toxicology and/or Pharmacology (13.2)].
 If you have taken more anastrozole tablets than your doctor has demonstrated that patients receiving anastrozole tablets had a mean tablets and the bisphosphonate risendronate on changes from baseline in Urogenital
Metabolic
Nutritional: Alkaline phosphatase increased; weight loss
prescribed, contact your doctor right away. Do not take any additional 8.3 Nursing
decrease in both lumbar spine and total hip bone mineral density (BMD) BMD and markers of bone resorption and formation in postmenopausal anastrozole tablets until instructed to do so by your doctor. It is not known if anastrozole is excreted in human milk. Because many compared to baseline. Patients receiving tamoxifen had a mean increase Mean serum total cholesterol levels increased by 0.5 mmol/L among women with hormone receptor-positive early breast cancer. All patients drugs are excreted in human milk and because of the tumorigenicity in both lumbar spine and total hip BMD compared to baseline.
* A patient may have had more than 1 adverse event.
patients receiving anastrozole tablets. Increases in LDL cholesterol have Talk with your doctor about any health changes you have while taking Skin and appendages
received calcium and vitamin D supplementation. At 12 months, small shown for anastrozole in animal studies, or the potential for serious been shown to contribute to these changes. 5.3 Cholesterol
reductions in lumbar spine bone mineral density were noted in patients adverse reactions in nursing infants, a decision should be made whether anastrozole tablets 1 mg in either Trial 0030 or Trial 0027 were similar to Musculoskeletal: Myalgia; arthralgia; pathological fracture
During the ATAC trial, more patients receiving anastrozole tablets were not receiving bisphosphonates. Bisphosphonate treatment preserved to discontinue nursing or to discontinue the drug, taking into account the reported to have elevated serum cholesterol compared to patients bone density in most patients at risk of fracture.
Nervous:
Somnolence; confusion; insomnia; anxiety; nervousness importance of the drug to the mother.
Leafl et size: 680x300 mm Folded size: 36x38mm Ph_code: 172_std Date: 14/05/2010
What are possible side effects of anastrozole tablets?
8.4 Pediatric
12.2 Pharmacodynamics
not studied. No dose adjustment is necessary for stable hepatic cirrhosis Table 7- Demographic and Baseline Characteristics for ATAC Trial
The survival data with 68 months follow-up is presented in Table 9.
trial. Patients in the 0005 trial had responded better to prior tamoxifen Anastrozole tablets can cause serious side effects including: effi cacy of anastrozole in the treatment of pubertal gynecomastia in [see Dosage and Administration (2.2) and Use in Speci c Populations Anastrozole
In the group of patients who had previous adjuvant chemotherapy (N=698 a statistically signifi cant advantage over tamoxifen (p=0.006) for time treatment. Of the patients entered who had prior tamoxifen therapy  See “What is the most important information I should know about
adolescent boys and in the treatment of precocious puberty in girls with Mean serum concentrations of estradiol were evaluated in multiple to tumor progression; objective tumor response rates were similar for for advanced disease (58% in Trial 0004; 57% in Trial 0005), 18% of for anastrozole tablets and N=647 for tamoxifen), the hazard ratio for McCune-Albright Syndrome has not been demonstrated.
daily dosing trials with 0.5, 1, 3, 5, and 10 mg of anastrozole tablets anastrozole tablets?”
13 NONCLINICAL
TOXICOLOGY
anastrozole tablets and tamoxifen. Trial 0027 showed that anastrozole these patients in Trial 0004 and 42% in Trial 0005 were reported by the Anastrozole
disease-free survival was 0.91 (95% CI: 0.73 to 1.13) in the anastrozole  increased blood cholesterol (fat in the blood). You doctor may check
in postmenopausal women with advanced breast cancer. Clinically 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
tablets arm compared to the tamoxifen arm. The frequency of individual tablets and tamoxifen had similar objective tumor response rates and time primary investigator to have responded. In Trial 0004, 81% of patients Tamoxifen
Tamoxifen
your cholesterol while you take anastrozole tablets therapy. anastrozole in pubertal boys of adolescent age with gynecomastia and signifi cant suppression of serum estradiol was seen with all doses. A conv entional carcinogenesis study in rats at doses of 1.0 to 25 mg/kg/ events in the intent-to-treat population and the hormone receptor-positive to tumor progression (see Table 11 and Figure 3 and 4). were ER-positive, 13% were ER-unknown, and 6% were ER-negative. In Demographic
in girls with McCune-Albright Syndrome and progressive precocious Doses of 1 mg and higher resulted in suppression of mean serum Trial 0005, 58% of patients were ER-positive, 37% were ER-unknown, skin reactions. Stop taking anastrozole tablets and call your doctor
day (about 10 to 243 times the daily maximum recommended human subpopulation are described in Table 8.
Characteristic
(N=3125)
(N=3116)
(N=3125)
puberty is approved for AstraZeneca Pharmaceuticals LP’s Arimidex®. concentrations of estradiol to the lower limit of detection (3.7 pmol/L). dose on a mg/m2 basis) administered by oral gavage for up to 2 years and 5% were ER-negative. In Trial 0004, 62% of patients had measurable right away if you get any skin lesions, ulcers, or blisters. Table 8- All Recurrence and Death Events*
However, due to AstraZeneca Pharmaceuticals LP’s marketing exclusivity The recommended daily dose, anastrozole tablets 1 mg, reduced estradiol revealed an increase in the incidence of hepatocellular adenoma and disease compared to 79% in Trial 0005. The sites of metastatic disease severe allergic reactions. Get medical help right away if you have:
Table 11- Effi cacy Results of First-line Treatment
by approximately 70% within 24 hours and by approximately 80% after rights, a description of those trials and studies is not approved for this carcinoma and uterine stromal polyps in females and thyroid adenoma were similar among treatment groups for each trial. On average, 40% of  swelling of the face, lips, tongue, or throat. 14 days of daily dosing. Suppression of serum estradiol was maintained Age Distribution (%)
Intent-To-Treat
Receptor-Positive
in males at the high dose. A dose related increase was observed in the the patients had soft tissue metastases; 60% had bone metastases; and Trial 0030
Trial 0027
for up to 6 days after cessation of daily dosing with anastrozole tablets 1 Population‡
Subpopulation‡
40% had visceral (15% liver) metastases. 8.5 Geriatric
incidence of ovarian and uterine hyperplasia in females. At 25 mg/kg/day, Anastrozole
Anastrozole
levels in rats were 110 to 125 times higher than the level Anastrozole Tamoxifen
Tamoxifen
Effi cacy results from the two studies were similar as presented in  liver problems. Anastrozole tablets can cause infl ammation of the
Anastrozole Tamoxifen
Tamoxifen
65 years of age had moderately better tumor response and time to tumor The effect of anastrozole tablets in premenopausal women with early or exhibited in postmenopausal volunteers at the recommended dose. A Tablets 1 mg
Table 12. In both studies there were no signifi cant differences between liver and changes in blood tests of the liver function. Your doctor may Tablets 1 mg
progression than patients <65 years of age regardless of randomized advanced breast cancer has not been studied. Because aromatization separate carcinogenicity study in mice at oral doses of 5 to 50 mg/kg/day End point
treatment arms with respect to any of the effi cacy parameters listed in the monitor you for this. Stop taking Anastrozole tablets and call your of adrenal androgens is not a signifi cant source of estradiol in (N†=3125)
(N†=3116) (N†=2618) (N†=2598)
treatment. In studies 0004 and 0005 50% of patients were 65 or older. (about 24 to 243 times the daily maximum recommended human dose doctor right away if you have any of these signs or symptoms of a liver premenopausal women, anastrozole tablets would not be expected to on a mg/m2 basis) for up to 2 years produced an increase in the incidence Response rates and time to progression were similar for the over 65 and Receptor Status (%)
Table 12- Effi cacy Results of Second-line Treatment
lower estradiol levels in premenopausal women. of benign ovarian stromal, epithelial and granulosa cell tumors at all dose levels. A dose related increase in the incidence of ovarian hyperplasia was Anastrozole Anastrozole Megestrol
In the ATAC study 45% of patients were 65 years of age or older. The  yellowing of the skin or whites of the eyes In multiple daily dosing trials with 3, 5, and 10 mg, the selectivity also observed in female mice. These ovarian changes are considered to effi cacy of Anastrozole tablets compared to tamoxifen in patients who  pain on the right side of your abdomen of anastrozole was assessed by examining effects on corticosteroid be rodent-specifi c effects of aromatase inhibition and are of questionable 119 (3.8)
149 (4.8)
101 (3.9)
were 65 years or older (N=1413 for anastrozole tablets and N=1410 for Other Treatment (%)
Common side effects in women taking anastrozole tablets include: synthesis. For all doses, anastrozole did not affect cortisol or aldosterone signifi cance to humans. The incidence of lymphosarcoma was increased tamoxifen, the hazard ratio for disease-free survival was 0.93 (95% CI: prior to Randomization
secretion at baseline or in response to ACTH. No glucocorticoid or in males and females at the high dose. At 50 mg/kg/day, plasma AUC 0.80, 1.08)) was less than effi cacy observed in patients who were less levels in mice were 35 to 40 times higher than the level exhibited in than 65 years of age (N=1712 for anastrozole tablets and N=1706 for mineralocorticoid replacement therapy is necessary with anastrozole. postmenopausal volunteers at the recommended dose. tamoxifen, the hazard ratio for disease-free survival was 0.79 (95% CI:  carpal tunnel syndrome (tingling, pain, coldness, weakness in parts of Anastrozole tablets has not been shown to be mutagenic in in vitro hormone (TSH) was measured; there was no increase in TSH during tests (Ames and E. coli bacterial tests, CHO-K1 gene mutation assay) The pharmacokinetics of anastrozole are not affected by age.
the administration of anastrozole tablets. Anastrozole tablets does or clastogenic either in vitro (chromosome aberrations in human 8.6 Renal Impairment
not possess direct progestogenic, androgenic, or estrogenic activity lymphocytes) or in vivo (micronucleus test in rats). 324 (10.4) 375 (12.0)
226 (8.6)
Since only about 10% of anastrozole is excreted unchanged in the urine, in animals, but does perturb the circulating levels of progesterone, Oral administration of anastrozole to female rats (from 2 weeks before Primary Tumor Size (%)
the renal impairment does not infl uence the total body clearance. Dosage mating to pregnancy day 7) produced signifi cant incidence of infertility 411 (13.2) 420 (13.5) 296 (11.3)
adjustment in patients with renal impairment is not necessary [see 12.3 Pharmacokinetics
and reduced numbers of viable pregnancies at 1 mg/kg/day (about 10 Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
times the recommended human dose on a mg/m2 basis and 9 times 8.7 Hepatic Impairment
Inhibition of aromatase activity is primarily due to anastrozole, the found in postmenopausal volunteers at the Nodal Status (%)
The plasma anastrozole concentrations in the subjects with hepatic parent drug. Absorption of anastrozole is rapid and maximum plasma recommended dose). Pre-implantation loss of ova or fetus was increased cirrhosis were within the range of concentrations seen in normal subjects concentrations typically occur within 2 hours of dosing under fasted at doses equal to or greater than 0.02 mg/kg/day (about one-fi fth the across all clinical trials. Therefore, dosage adjustment is also not conditions. Studies with radiolabeled drug have demonstrated that orally recommended human dose on a mg/m2 basis). Recovery of fertility was necessary in patients with stable hepatic cirrhosis. Anastrozole tablets has administered anastrozole is well absorbed into the systemic circulation. observed following a 5-week non-dosing period which followed 3 weeks * The combination arm was discontinued due to lack of effi cacy not been studied in patients with severe hepatic impairment [see Dosage Food reduces the rate but not the overall extent of anastrozole absorption. of dosing. It is not known whether these effects observed in female rats Tumor Grade (%)
and Administration (2.2) and Clinical Pharmacology (12.3)].
of anastrozole decreased by 16% and the median T are indicative of impaired fertility in humans. 10 OVERDOSAGE
was delayed from 2 to 5 hours when anastrozole was administered 30 Multiple-dose studies in rats administered anastrozole for 6 months at Figure 3- Kaplan-Meier probability of time to disease progression for
Clinical trials have been conducted with anastrozole tablets, up to 60 minutes after food. The pharmacokinetics of anastrozole are linear over doses equal to or greater than 1 mg/kg/day (which produced plasma Patients may fall into more than one category.
all randomized patients (intent-to-treat) in Trial 0030
mg in a single dose given to healthy male volunteers and up to 10 mg the dose range of 1 to 20 mg, and do not change with repeated dosing. A summary of the study effi cacy results is provided in Table 9.
daily given to postmenopausal women with advanced breast cancer; The pharmacokinetics of anastrozole were similar in patients and healthy the respective values found in postmenopausal volunteers at the  lymphedema (build up of lymph fl uid in the tissues of your affected arm) Table 9-ATAC Effi cacy Summary*
these dosages were tolerated. A single dose of anastrozole tablets that recommended dose) resulted in hypertrophy of the ovaries and the N=Number of patients randomized to the treatment.
 trigger fi nger (a condition in which one of your fi ngers or your thumb results in life-threatening symptoms has not been established. There is presence of follicular cysts. In addition, hyperplastic uteri were observed The combination arm was discontinued due to lack of effi cacy benefi t Intent-To-Treat
Hormone Receptor-
no specifi c antidote to overdosage and treatment must be symptomatic. When data from the two controlled trials are pooled, the objective Steady-state plasma levels are approximately 3- to 4-fold higher than in 6-month studies in female dogs administered doses equal to or greater Population
Positive Subpopulation
Call your doctor for medical advice about side effects. You may report side In the management of an overdose, consider that multiple agents may response rates and median times to progression and death were similar levels observed after a single dose of anastrozole tablets. Plasma than 1 mg/kg/day (which produced plasma anastrozole C Includes patients who were estrogen receptor (ER) positive or Anastrozole
Anastrozole
have been taken. Vomiting may be induced if the patient is alert. Dialysis for patients randomized to anastrozole tablets 1 mg and megestrol concentrations approach steady-state levels at about 7 days of once daily that were 22 times and 16 times higher than the respective values progesterone receptor (PgR) positive, or both positive Tablets 1 Tamoxifen
Tablets 1
Tamoxifen
HOW SHOULD I STORE ANASTROZOLE TABLETS?
may be helpful because anastrozole tablets are not highly protein bound. acetate. There is, in this data, no indication that anastrozole tablets 10 mg dosing. Anastrozole is 40% bound to plasma proteins in the therapeutic found in postmenopausal women at the recommended dose). It is not § Includes patients with both ER negative and PgR negative receptor status General supportive care, including frequent monitoring of vital signs and is superior to anastrozole tablets 1 mg.
Store anastrozole tablets at 68°F to 77°F (20°C to 25°C). known whether these effects on the reproductive organs of animals are ¶ Includes all other combinations of ER and PgR receptor status unknown (N=3125)
(N=3116)
(N=2618)
(N=2598)
close observation of the patient, is indicated.
associated with impaired fertility in premenopausal women.
# Among the patients who had breast conservation, radiotherapy was Table 13- Pooled Effi cacy Results of Second-line Treatment
Keep anastrozole tablets and all medicines out of the reach of children. Number of Events
Number of Events
11 DESCRIPTION
Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and 13.2 Animal Toxicology and/or Pharmacology
administered to 95.0% of patients in the anastrozole tablets arm, Disease-free
General information about anastrozole tablets.
Anastrozole Anastrozole Megestrol
Anastrozole tablets for oral administration contain 1 mg of anastrozole, glucuronidation. Three metabolites of anastrozole (triazole, a glucuronide 94.1% in the tamoxifen arm and 94.5% in the anastrozole tablets plus Survival
Medicines are sometimes prescribed for conditions that are not mentioned a non-steroidal aromatase inhibitor. It is chemically described as conjugate of hydroxy-anastrozole, and a glucuronide conjugate of Anastrozole has been found to cross the placenta following oral in patient information leafl ets. Do not take anastrozole tablets for a condition Trials 0004 & 0005
1,3-Benzenediacetonitrile, a, a, a’, a’-tetramethyl-5-(1H-1,2,4-triazol-1- anastrozole itself) have been identifi ed in human plasma and urine. The administration of 0.1 mg/kg in rats and rabbits (about 1 and 1.9 times for which it was not prescribed. Do not give anastrozole tablets to other Patients in the two monotherapy arms of the ATAC trial were treated for a Figure 4- Kaplan-Meier probability of time to progression for all
(Pooled Data)
ylmethyl). Its molecular formula is C H N and its structural formula is: the recommended human dose, respectively, on a mg/m2 basis). major circulating metabolite of anastrozole, triazole, lacks pharmacologic people, even if they have the same symptoms you have. It may harm them. median of 60 months (5 years) and followed for a median of 68 months. randomized patients (intent-to-treat) in Trial 0027
Studies in both rats and rabbits at doses equal to or greater than 0.1 Disease-free survival in the intent-to-treat population was statistically Distant Disease-
This patient information leafl et summarizes the most important information and 0.02 mg/kg/day, respectively (about 1 and 1/3, respectively, the Anastrozole inhibited reactions catalyzed by cytochrome P450 1A2, signifi cantly improved [Hazard Ratio (HR) = 0.87, 95% CI: 0.78, 0.97, free Survival
about anastrozole tablets. If you would like more information, talk with recommended human dose on a mg/m2 basis), administered during the 2C8/9, and 3A4 in vitro with Ki values which were approximately 30 times p=0.0127 in the anastrozole tablets arm compared to the tamoxifen arm. your doctor. You can ask your pharmacist or doctor for information about period of organogenesis showed that anastrozole increased pregnancy In the hormone receptor-positive subpopulation representing about anastrozole tablets that is written for health professionals. For more loss (increased pre- and/or post-implantation loss, increased resorption, daily dose. Anastrozole had no inhibitory effect on reactions catalyzed by 84% of the trial patients, disease-free survival was also statistically and decreased numbers of live fetuses); effects were dose related in rats. Overall Survival
cytochrome P450 2A6 or 2D6 in vitro. Administration of a single 30 mg/ signifi cantly improved (HR =0.83, 95% CI: 0.73, 0.94, p=0.0049) in the Placental weights were signifi cantly increased in rats at doses of 0.1 mg/ What are the ingredients in anastrozole tablets?
kg or multiple 10 mg/kg doses of anastrozole to healthy subjects had anastrozole tablets arm compared to the tamoxifen arm.
no effect on the clearance of antipyrine or urinary recovery of antipyrine 16 HOW SUPPLIED/STORAGE AND HANDLING
Figure 1- Disease-free Survival Kaplan-Meier Survival Curve for all
Anastrozole is an off-white powder with a molecular weight of 293.4. Evidence of fetotoxicity, including delayed fetal development (i.e., * The combination arm was discontinued due to lack of effi cacy Inactive ingredients: lactose monohydrate, lactose anhydrous, sodium starch These tablets are supplied in bottles of 30 tablets (NDC 42043-180-03). Patients Randomized to Anastrozole Tablet or Tamoxifen Monotherapy
Anastrozole has moderate aqueous solubility (0.5 mg/mL at 25°C); incomplete ossifi cation and depressed fetal body weights), was observed glycolate, microcrystalline cellulose, colloidal silicon dioxide, magnesium in the ATAC trial (Intent-to-treat)
solubility is independent of pH in the physiological range. Anastrozole in rats administered doses of 1 mg/kg/day (which produced plasma stearate, titanium dioxide, hypromellose, and polyethylene glycol.
Eighty-fi ve percent of radiolabeled anastrozole was recovered in feces 14.2 First-Line Therapy in Postmenopausal Women with Advanced Breast
Storage: Store at controlled room temperature, 20-25°C (68-77°F) [see
is freely soluble in methanol, acetone, ethanol, and tetrahydrofuran, and and urine. Hepatic metabolism accounts for approximately 85% of than the respective values found in postmenopausal volunteers at the anastrozole elimination. Renal elimination accounts for approximately Two double-blind, controlled clinical studies of similar design (0030, a 17 PATIENT COUNSELING INFORMATION
recommended dose). There was no evidence of teratogenicity in rats 10% of total clearance. The mean elimination half-life of anastrozole is 50 North American study and 0027, a predominately European study) were 17.1 Pregnancy
administered doses up to 1.0 mg/kg/day. In rabbits, anastrozole caused anastrozole. The tablets are impressed on one side with “3RP” and on the conducted to assess the effi cacy of anastrozole tablets compared with pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about tamoxifen as fi rst-line therapy for hormone receptor positive or hormone They should also be advised that anastrozole tablets are not for use in 16 times the recommended human dose on a mg/m2 basis); there was no Results from the secondary endpoints were supportive of the results receptor unknown locally advanced or metastatic breast cancer in premenopausal women; therefore, if they become pregnant they should evidence of teratogenicity in rabbits administered 0.2 mg/kg/day (about 3 of the primary effi cacy endpoints. There were too few deaths occurring postmenopausal women. A total of 1021 patients between the ages of 30 anhydrous, sodium starch glycolate, microcrystalline cellulose, colloidal female volunteers and patients with breast cancer. No age related effects stop taking anastrozole tablets and immediately contact their doctor. times the recommended human dose on a mg/m2 basis).
across treatment groups of both trials to draw conclusions on overall and 92 years old were randomized to receive trial treatment. Patients were silicon dioxide, magnesium stearate, titanium dioxide, hypromellose, and were seen over the range <50 to >80 years. 17.2 Allergic (Hypersensitivity) Reactions
14 CLINICAL
randomized to receive 1 mg of anastrozole tablets once daily or 20 mg of Patients should be informed of the possibility of serious allergic reactions 14.1 Adjuvant Treatment of Breast Cancer in Postmenopausal Women
14.3 Second-Line Therapy in Postmenopausal Women with Advanced Breast
12 18 24 30 36 42 48 54 60 66 72 78 84 90 tamoxifen once daily. The primary end points for both trials were time to 12 CLINICAL
PHARMACOLOGY
Estradiol and estrone sulfate serum levels were similar between Japanese with swelling of the face, lips, tongue and/or throat (angioedema) which Cancer who had Disease Progression following Tamoxifen Therapy
tumor progression, objective tumor response rate, and safety.
may cause diffi culty in swallowing and/or breathing and to immediately 12.1 Mechanism of Action
and Caucasian postmenopausal women who received 1 mg of anastrozole postmenopausal women with operable breast cancer to adjuvant Anastrozole was studied in two controlled clinical trials (0004, a anastrozole 3125 3004 2874 2757 2645 2350 984 51 The growth of many cancers of the breast is stimulated or maintained daily for 16 days. Anastrozole mean steady-state minimum plasma treatment with anastrozole tablets 1 mg daily, tamoxifen 20 mg daily, or North American study; 0005, a predominately European study) in tamoxifen 3116 2992 2835 2709 2575 2273 933 47 had measurable and no measurable disease, patients who were given postmenopausal women with advanced breast cancer who had disease 17.3 Ischemic Cardiovascular Events
by estrogens. Treatment of breast cancer thought to be hormonally concentrations in Caucasian and Japanese postmenopausal women were a combination of the two treatments for fi ve years or until recurrence of Figure 2- Disease-free Survival for Hormone Receptor-Positive
previous adjuvant therapy, the site of metastatic disease and ethnic origin progression following tamoxifen therapy for either advanced or early Patients with pre-existing ischemic heart disease should be informed that responsive (i.e., estrogen and/or progesterone receptor positive or Subpopulation of Patients Randomized to Anastrozole tablets or
were similar for the two treatment groups for both trials. The following breast cancer. Some of the patients had also received previous cytotoxic an increased incidence of cardiovascular events has been observed with receptor unknown) has included a variety of efforts to decrease estrogen The primary endpoint of the trial was disease-free survival (i.e., time to Tamoxifen Monotherapy in the ATAC Trial
table summarizes the hormone receptor status at entry for all randomized treatment. Most patients were ER-positive; a smaller fraction were ER- anastrozole tablets use compared to tamoxifen use. levels (ovariectomy, adrenalectomy, hypophysectomy) or inhibit estrogen occurrence of a distant or local recurrence, or contralateral breast cancer effects (antiestrogens and progestational agents). These interventions renal impairment. Anastrozole renal clearance decreased proportionally or death from any cause). Secondary endpoints of the trial included unknown or ER-negative; the ER-negative patients were eligible only 17.4 Bone Effects
Table 10- Demographic and Other Baseline Characteristics
lead to decreased tumor mass or delayed progression of tumor growth in with creatinine clearance and was approximately 50% lower in volunteers distant disease-free survival, the incidence of contralateral breast if they had had a positive response to tamoxifen. Eligible patients with with severe renal impairment (creatinine clearance <30 mL/min/1.73m2) cancer and overall survival. At a median follow-up of 33 months, the Number (%) of Subjects
measurable and non-measurable disease were randomized to receive estrogen. This may lead to a loss of the mineral content of bones, which compared to controls. Total clearance was only reduced 10%. No combination of anastrozole tablets and tamoxifen did not demonstrate Trial 0030
Trial 0027
either a single daily dose of 1 mg or 10 mg of anastrozole tablets or might decrease bone strength. A possible consequence of decreased In postmenopausal women, estrogens are mainly derived from the dosage adjustment is needed for renal impairment [see Dosage and any effi cacy benefi t when compared with tamoxifen in all patients as well Anastrozole Tamoxifen Anastrozole Tamoxifen
megestrol acetate 40 mg four times a day. The studies were double-blinded mineral content of bones is an increase in the risk of fractures. action of the aromatase enzyme, which converts adrenal androgens Administration (2.1) and Use in Speci c Populations (8.6)]. as in the hormone receptor positive subpopulation. This treatment arm Receptor
Tablets 1 mg
Tablets 1 mg
with respect to anastrozole tablets. Time to progression and objective (primarily androstenedione and testosterone) to estrone and estradiol. 17.5 Cholesterol
was discontinued from the trial. Based on clinical and pharmacokinetic response (only patients with measurable disease could be considered The suppression of estrogen biosynthesis in peripheral tissues and in the partial responders) rates were the primary effi cacy variables. Objective results from the ATAC trial, tamoxifen should not be administered with cancer tissue itself can therefore be achieved by specifi cally inhibiting the be seen while receiving anastrozole tablets. response rates were calculated based on the Union Internationale Contre hepatic cirrhosis related to alcohol abuse. The apparent oral clearance anastrozole [see Drug Interactions (7.1)].
17.6 Tamoxifen
le Cancer (UICC) criteria. The rate of prolonged (more than 24 weeks) (CL/F) of anastrozole was approximately 30% lower in subjects with Demographic and other baseline characteristics were similar among the Patients should be advised not to take anastrozole tablets with Tamoxifen. stable disease, the rate of progression, and survival were also calculated. stable hepatic cirrhosis than in control subjects with normal liver function. three treatment groups (see Table 7).
12 18 24 30 36 42 48 54 60 66 72 78 84 90 signifi cantly lowers serum estradiol concentrations and has no detectable 17.7 FDA-Approved Patient Labeling
However, these plasma concentrations were still with the range of values effect on formation of adrenal corticosteroids or aldosterone.
observed in normal subjects. The effect of severe hepatic impairment was characteristics were similar for the three treatment groups in each anastrozole 2618 2540 2448 2355 2268 2014 830 42 tamoxifen 2598 2516 2398 2304 2189 1932 774 36

Source: http://karalexpharma.com/docs/anastrozole%20PI.pdf