Anastrozole by Ascend Laboratories, LLC ANASTROZOLE tablet

Anastrozole by

Drug Labeling and Warnings

Anastrozole by is a Prescription medication manufactured, distributed, or labeled by Ascend Laboratories, LLC. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • SPL UNCLASSIFIED SECTION

    _________________________________________________________________________________
    FULL PRESCRIBING INFORMATION: CONTENTS*

    1 INDICATIONS AND USAGE
       1.1 Adjuvant Treatment
       1.2 First-Line Treatment
       1.3 Second-Line Treatment

    2 DOSAGE AND ADMINISTRATION
       2.1 Recommended Dose
       2.2 Patients with Hepatic Impairment

    3 DOSAGE FORMS AND STRENGTHS

    4 CONTRAINDICATIONS
       4.1 Pregnancy and Premenopausal Women
       4.2 Hypersensitivity

    5 WARNINGS AND PRECAUTIONS
       5.1 Ischemic Cardiovascular Events
       5.2 Bone Effects
       5.3 Cholesterol

    6 ADVERSE REACTIONS
       6.1 Clinical Trials Experience
             Adjuvant Therapy
             First-Line Therapy
             Second-Line Therapy
       6.2 Post-Marketing Experience

    7 DRUG INTERACTIONS
       7.1 Tamoxifen
       7.2 Estrogen
       7.3 Warfarin
       7.4 Cytochrome P450

    8 USE IN SPECIFIC POPULATIONS
       8.1 Pregnancy
       8.3 Nursing mothers
       8.4 Pediatric Use
       8.5 Geriatric Use
       8.6 Renal Impairment
       8.7 Hepatic Impairment

    10 OVERDOSAGE

    11 DESCRIPTION

    12 CLINICAL PHARMACOLOGY
       12.1 Mechanism of Action
       12.2 Pharmacodynamics
       12.3 Pharmacokinetics

    13 NONCLINICAL TOXICOLOGY
       13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
       13.2 Animal Pharmacology and/or Toxicology

    14 CLINICAL STUDIES
       14.1 Adjuvant Treatment of Breast Cancer in Postmenopausal Women
       14.2 First-Line Therapy in Postmenopausal Women with Advanced Breast Cancer
       14.3 Second-Line Therapy in Postmenopausal Women with Advanced Breast Cancer who had Disease Progression following Tamoxifen Therapy

    16 HOW SUPPLIED/STORAGE AND HANDLING
       Storage:

    17 PATIENT COUNSELING INFORMATION
       17.1 Pregnancy
       17.2 Allergic (Hypersensitivity) Reactions
       17.3 Ischemic Cardiovascular Events
       17.4 Bone Effects
       17.5 Cholesterol
       17.6 Tamoxifen
       17.7 FDA-Approved Patient Labeling

    * Sections or subsections omitted from the full prescribing information are not listed
    _________________________________________________________________________________
    FULL PRESCRIBING INFORMATION

  • INDICATIONS & USAGE


    1. INDICATIONS AND USAGE

    1.1. Adjuvant Treatment
        Anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.

  • INDICATIONS & USAGE

    1.2. First-Line Treatment
        Anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.

  • INDICATIONS & USAGE

    1.3. Second-Line Treatment
        Anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets.

  • DOSAGE & ADMINISTRATION


    2. DOSAGE AND ADMINISTRATION

    2.1. Recommended Dose
        The dose of anastrozole tablets are one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression. Anastrozole tablets can be taken with or without food.
        For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial anastrozole tablets were administered for five years. [see Clinical Studies (14.1)]
        No dosage adjustment is necessary for patients with renal impairment or for elderly patients. [see Use in Specific Populations (8.6)]

  • DOSAGE & ADMINISTRATION

    2.2. Patients with Hepatic Impairment
        No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. Anastrozole tablets have not been studied in patients with severe hepatic impairment. [see Use in Specific Populations (8.7)]

  • DOSAGE FORMS & STRENGTHS


    3 DOSAGE FORMS AND STRENGTHS
        The tablets are white, biconvex, film-coated containing 1 mg of anastrozole. The tablets are debossed with “AN” and “1” on one side and plain surface on the other side.

  • CONTRAINDICATIONS


    4 CONTRAINDICATIONS

    4.1. Pregnancy and Premenopausal Women
        Anastrozole tablets may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole tablets are contraindicated in women who are or may become pregnant. There are no adequate and well controlled studies in pregnant women using anastrozole tablets. If anastrozole tablets are used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus or potential risk for loss of the pregnancy. [see Use in Specific Populations (8.1)]

  • CONTRAINDICATIONS

    4.2. Hypersensitivity
        Anastrozole tablets are contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria. [see Adverse Reactions (6.2)]

  • WARNINGS AND PRECAUTIONS


    5 WARNINGS AND PRECAUTIONS

    5.1. Ischemic Cardiovascular Events
        In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with anastrozole tablets in the ATAC trial (17% of patients on anastrozole tablets and 10% of patients on tamoxifen). Consider risk and benefits of anastrozole tablets therapy in patients with pre-existing ischemic heart disease. [see Adverse Reactions (6.1)]

  • WARNINGS AND PRECAUTIONS

    5.2. Bone Effects
        Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole tablets had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline [see Adverse Reactions, (6.1)].

  • WARNINGS AND PRECAUTIONS

    5.3. Cholesterol
        During the ATAC trial, more patients receiving anastrozole tablets were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions, (6.1)].

  • ADVERSE REACTIONS


    6 ADVERSE REACTIONS
        Serious adverse reactions with anastrozole tablets occurring in less than 1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling [see Adverse Reactions, (6.2)].
        Common adverse reactions (occurring with an incidence of >10%) in women taking anastrozole tablets included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, pain, headache, bone pain, peripheral edema, increased cough, dyspnea, pharyngitis and lymphedema.
        In the ATAC trial, the most common reported adverse reaction (>0.1%) leading to discontinuation of therapy for both treatment groups was hot flashes, although there were fewer patients who discontinued therapy as a result of hot flashes in the anastrozole tablets group.
        Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

  • ADVERSE REACTIONS

    6.1 Clinical Trials Experience
    Adjuvant Therapy
        Adverse reaction data for adjuvant therapy are based on the ATAC trial [see Clinical Studies (14.1)]. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole tablets 1 mg and tamoxifen 20 mg, respectively.
        Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in Table 1.

    Table 1 – Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment, or within 14 days of the end of treatment in the ATAC trial*
    Body system and adverse reactions
    by COSTART† preferred term
    		Anastrozole tablets 1mg
    (N    § = 3092)
    		Tamoxifen 20mg
    (N    § = 3094)
    Body as a whole
    Asthenia
    Pain
    Back pain
    Headache
    Abdominal pain
    Infection
    Accidental injury
    Flu syndrome
    Chest pain
    Neoplasm
    Cyst
    Cardiovascular
    Vasodilatation
    Hypertension
    Digestive
    Nausea
    Constipation
    Diarrhea
    Dyspepsia
    Gastrointestinal disorder
    Hemic and lymphatic
    Lymphedema
    Anemia
    Metabolic and nutritional
    Peripheral edema
    Weight gain
    Hypercholesterolemia
    Musculoskeletal
    Arthritis
    Arthralgia
    Osteoporosis
    Fracture
    Bone pain
    Arthrosis
    Joint Disorder
    Myalgia
    Nervous system
    Depression
    Insomnia
    Dizziness
    Anxiety
    Paresthesia
    Respiratory
    Pharyngitis
    Cough increased
    Dyspnea
    Sinusitis
    Bronchitis
    Skin and appendages
    Rash
    Sweating
    Special Senses
    Cataract Specified
    Urogenital
    Leukorrhea
    Urinary tract infection
    Breast pain
    Breast Neoplasm
    Vulvovaginitis
    Vaginal Hemorrhage¶
    Vaginitis
    575 (19)
    533 (17)
    321 (10)
    314 (10)
    271 (9)
    285 (9)
    311 (10)
    175 (6)
    200 (7)
    162 (5)
    138 (5)

    1104 (36)
    402 (13)

    343 (11)
    249 (8)
    265 (9)
    206 (7)
    210 (7)

    304 (10)
    113 (4)

    311 (10)
    285 (9)
    278 (9)

    512 (17)
    467 (15)
    325 (11)
    315 (10)
    201 (7)
    207 (7)
    184 (6)
    179 (6)

    413 (13)
    309 (10)
    236 (8)
    195 (6)
    215 (7)

    443 (14)
    261 (8)
    234 (8)
    184 (6)
    167 (5)

    333 (11)
    145 (5)

    182 (6)

    86 (3)
    244 (8)
    251 (8)
    164 (5)
    194 (6)
    122 (4)
    125 (4)
    544 (18)
    485 (16)
    309 (10)
    249 (8)
    276 (9)
    276 (9)
    303 (10)
    195 (6)
    150 (5)
    144 (5)
    162 (5)

    1264 (41)
    349 (11)

    335 (11)
    252 (8)
    216 (7)
    169 (6)
    158 (5)

    341 (11)
    159 (5)

    343 (11)
    274 (9)
    108 (3.5)

    445 (14)
    344 (11)
    226 (7)
    209 (7)
    185 (6)
    156 (5)
    160 (5)
    160 (5)

    382 (12)
    281 (9)
    234 (8)
    180 (6)
    145 (5)

    422 (14)
    287 (9)
    237 (8)
    159 (5)
    153 (5)

    387 (13)
    177 (6)

    213 (7)

    286 (9)
    313 (10)
    169 (6)
    139 (5)
    150 (5)
    180 (6)
    158 (5)
    * The combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up.
    † COSTART Coding Symbols for Thesaurus of Adverse Reaction Terms.
    ‡ A patient may have had more than 1 adverse reaction, including more than 1 adverse reaction in the same body system.
    § N=Number of patients receiving the treatment.
    ¶ Vaginal Hemorrhage without further diagnosis.


        Certain adverse reactions and combinations of adverse reactions were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs (see Table 2).

    Table 2 – Number of Patients with Pre-specified Adverse Reactions in ATAC Trial*

    		Anastrozole tablets
    N=3092 (%)
    		Tamoxifen
    N=3094(%)
    		Odds-ratio
    		95% CI
    Hot Flashes
    Musculoskeletal Events†
    Fatigue/Asthenia
    Mood Disturbances
    Nausea and Vomiting
    All Fractures
    Fractures of Spine, Hip, or Wrist
      Wrist/Colles’ fractures
      Spine fractures
      Hip fractures
    Cataracts
    Vaginal Bleeding
    Ischemic Cardiovascular Disease
    Vaginal Discharge
    Venous Thromboembolic events
    Deep Venous Thromboembolic Events
    Ischemic Cerebrovascular Event
    Endometrial Cancer‡
    		1104 (36)
    1100 (36)
    575 (19)
    597 (19)
    393 (13)
    315 (10)
    133 (4)
    67 (2)
    43 (1)
    28 (1)
    182 (6)
    167 (5)
    127 (4)
    109 (4)
    87 (3)
    48 (2)
    62 (2)
    4 (0.2)
    		1264(41)
    911 (29)
    544 (18)
    554 (18)
    384 (12)
    209 (7)
    91 (3)
    50 (2)
    22 (1)
    26 (1)
    213 (7)
    317 (10)
    104 (3)
    408 (13)
    140 (5)
    74 (2)
    88 (3)
    13 (0.6)
    		0.80
    1.32
    1.07
    1.10
    1.03
    1.57
    1.48



    0.85
    0.50
    1.23
    0.24
    0.61
    0.64
    0.70
    0.31
    		0.73 - 0.89
    1.19 - 1.47
    0.94 - 1.22
    0.97 - 1.25
    0.88 - 1.19
    1.30 - 1.88
    1.13 - 1.95



    0.69 - 1.04
    0.41 - 0.61
    0.95 - 1.60
    0.19 - 0.30
    0.47 - 0.80
    0.45 - 0.93
    0.50 - 0.97
    0.10 - 0.94
    * Patients with multiple events in the same category are counted only once in that category.
    † Refers to joint symptoms, including joint disorder, arthritis, arthrosis and arthralgia.
    ‡ Percentages calculated based upon the numbers of patients with an intact uterus at Baseline

    Ischemic Cardiovascular Events
        Between treatment arms in the overall population of 6186 patients, there was no statistical difference in ischemic cardiovascular events (4% anastrozole tablets vs. 3% tamoxifen).
        In the overall population, angina pectoris was reported in 71/3092 (2.3%) patients in the anastrozole tablets arm and 51/3094 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37/3092 (1.2%) patients in the anastrozole tablets arm and 34/3094 (1.1%) patients in the tamoxifen arm.
        In women with pre-existing ischemic heart disease 465/6186 (7.5%), the incidenc e of ischemic cardiovascular events was 17% in patients on anastrozole tablets and 10% in patients on tamoxifen. In this patient population, angina pectoris was reported in 25/216 (11.6%) patients receiving anastrozole tablets and 13/249 (5.2%) patients receiving tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients receiving anastrozole tablets and 8/249 (3.2%) patients receiving tamoxifen.

    Bone Mineral Density Findings
        Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole tablets had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline.
        Because anastrozole tablets lowers circulating estrogen levels it may cause a reduction in bone mineral density.
        A post-marketing trial assessed the combined effects of anastrozole tablets and the bisphosphonate risedronate on changes from baseline in BMD and markers of bone resorption and formation in postmenopausal women with hormone receptor-positive early breast cancer. All patients received calcium and vitamin D supplementation. At 12 months, small reductions in lumbar spine bone mineral density were noted in patients not receiving bisphosphonates. Bisphosphonate treatment preserved bone density in most patients at risk of fracture.
        Postmenopausal women with early breast cancer scheduled to be treated with anastrozole tablets should have their bone status managed according to treatment guidelines already available for postmenopausal women at similar risk of fragility fracture.

    Cholesterol
        During the ATAC trial, more patients receiving anastrozole tablets were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively).
        A post-marketing trial also evaluated any potential effects of anastrozole tablets on lipid profile. In the primary analysis population for lipids (anastrozole tablets alone), there was no clinically significant change in LDL-C from baseline to 12 months and HDL-C from baseline to 12 months
        In secondary population for lipids (anastrozole tablets+risedronate), there also was no clinically significant change in LDL-C and HDL-C from baseline to 12 months.
        In both populations for lipids, there was no clinically significant difference in total cholesterol (TC) or serum triglycerides (TG) at 12 months compared with baseline.
        In this trial, treatment for 12 months with anastrozole tablets alone had a neutral effect on lipid profile. Combination treatment with anastrozole tablets and risedronate also had a neutral effect on lipid profile.
        The trial provides evidence that postmenopausal women with early breast cancer scheduled to be treated with anastrozole tablets should be managed using the current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations.

    Other Adverse Reactions
        Patients receiving anastrozole tablets have an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving tamoxifen. Patients receiving anastrozole tablets have an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving tamoxifen [209 (7%)].
        Patients receiving anastrozole tablets have a higher incidence of carpal tunnel syndrome [78 (2.5%)] compared with patients receiving tamoxifen [22 (0.7%)].
        Vaginal bleeding occurred more frequently in the tamoxifen-treated patients versus the anastrozole tablets-treated patients 317 (10%) versus 167 (5%), respectively.
        Patients receiving anastrozole tablets have a lower incidence of hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving tamoxifen.

    First-Line Therapy
        Adverse reactions occurring with an incidence of at least 5% in either treatment group of trials 0030 and 0027 during or within 2 weeks of the end of treatment are shown in Table 3.
    Table 3 – Adverse Reactions Occurring with an Incidence of at Least 5% in Trials 0030 and 0027
    Body system
    Adverse Reaction*
    		Number (%) of subjects
    Anastrozole tablets(n=506)
    		Number (%) of subjects
    Tamoxifen(n=511)
    Whole body
    Asthenia
    Pain
    Back pain
    Headache
    Abdominal pain
    Chest pain
    Flu syndrome
    Pelvic pain
    Cardiovascular
    Vasodilation
    Hypertension
    Digestive
    Nausea
    Constipation
    Diarrhea
    Vomiting
    Anorexia
    Metabolic and Nutritional
    Peripheral edema
    Muscoloskeletal
    Bone pain
    Nervous
    Dizziness
    Insomnia
    Depression
    Hypertonia
    Respiratory
    Cough increased
    Dyspnea
    Pharyngitis
    Skin and appendages
    Rash
    Urogenital
    Leukorrhea
    83 (16)
    70 (14)
    60 (12)
    47 (9)
    40 (8)
    37 (7)
    35 (7)
    23 (5)

    128 (25)
    25 (5)

    94 (19)
    47 (9)
    40 (8)
    38 (8)
    26 (5)

    51 (10)

    54 (11)

    30 (6)
    30 (6)
    23 (5)
    16 (3)

    55 (11)
    51 (10)
    49 (10)

    38 (8)

    9 (2)
    81 (16)
    73 (14)
    68 (13)
    40 (8)
    38 (7)
    37 (7)
    30 (6)
    30 (6)

    106 (21)
    36 (7)

    106 (21)
    66 (13)
    33 (6)
    36 (7)
    46 (9)

    41 (8)

    52 (10)

    22 (4)
    38 (7)
    32 (6)
    26 (5)

    52 (10)
    47 (9)
    68 (13)

    34 (8)

    31 (6)
    * A patient may have had more than 1 adverse event.

        Less frequent adverse experiences reported in patients receiving anastrozole tablets l mg in either Trial 0030 or Trial 0027 were similar to those reported for second-line therapy.
        Based on results from second-line therapy and the established safety profile of tamoxifen, the incidences of 9 pre-specified adverse event categories potentially causally related to one or both of the therapies because of their pharmacology were statistically analyzed. No significant differences were seen between treatment groups.

    Table 4 – Number of Patients with Pre-specified Adverse Reactions in Trials 0030 and 0027
    Adverse Reaction*
    		Number (n) and Percentage of Patients
    Anastrozole tablets 1 mg
    (n=506)
    n (%)
    		Number (n) and Percentage of Patients
    NOLVADEX 20 mg
    (n=511)
    n (%)
    Depression
    Tumor Flare
    Thromboembolic Disease†
    Venous†
    Coronary and Cerebral‡
    Gastrointestinal Disturbance
    Hot Flushes
    Vaginal Dryness
    Lethargy
    Vaginal Bleeding
      Weight Gain
    		23 (5)
    15 (3)
    18 (4)
    5
    13
    170 (34)
    134 (26)
    9 (2)
    6 (1)
    5 (1)
    11 (2)
    		32 (6)
    18 (4)
    33 (6)
    15
    19
    196 (38)
    118 (23)
    3 (1)
    15 (3)
    11 (2)
    8 (2)
    * A patient may have had more than 1 adverse event.
    † Includes pulmonary embolus, thrombophlebitis, retinal vein thrombosis.
    ‡ Includes myocardial infarction, myocardial ischemia, angina pectoris, cerebrovascular accident, cerebral ischemia and cerebral infarct.


    Second-Line Therapy
        Anastrozole tablets were tolerated in two controlled clinical trials (i.e., Trials 0004 and 0005), with less than 3.3% of the anastrozole tablets-treated patients and 4.0% of the megestrol acetate-treated patients withdrawing due to an adverse reaction.
        The principal adverse reaction more common with anastrozole tablets than megestrol acetate was diarrhea. Adverse reactions reported in greater than 5% of the patients in any of the treatment groups in these two controlled clinical trials, regardless of causality, are presented below:

    Table 5 – Number (N) and Percentage of Patients with Adverse Reactions in Trials 0004 and 0005
    Adverse Reaction*
    		Anastrozole
    tablets 1 mg
    (n=262)
    n
    		Anastrozole
    tablets 1 mg
    (n=262)
    %
    		Anastrozole
    tablets 10 mg
    (n=246)
    n
    		Anastrozole
    tablets 10 mg
    (n=246)
    %
    		Megestrol
    Acetate 160 mg
    (n=253)
    n
    		Megestrol
    Acetate 160 mg
    (n=253)
    %
    Asthenia
    Nausea
    Headache
    Hot Flashes
    Pain
    Back Pain
    Dyspnea
    Vomiting
    Cough Increased
    Diarrhea
    Constipation
    Abdominal Pain
    Anorexia
    Bone Pain
    Pharyngitis
    Dizziness
    Rash
    Dry Mouth
    Peripheral Edema
    Pelvic Pain
    Depression
    Chest Pain
    Paresthesia
    Vaginal Hemorrhage
    Weight Gain
    Sweating
      Increased Appetite
    		42
    41
    34
    32
    28
    28
    24
    24
    22
    22
    18
    18
    18
    17
    16
    16
    15
    15
    14
    14
    14
    13
    12
    6
    4
    4
    0
    		(16)
    (16)
    (13)
    (12)
    (11)
    (11)
    (9)
    (9)
    (8)
    (8)
    (7)
    (7)
    (7)
    (6)
    (6)
    (6)
    (6)
    (6)
    (5)
    (5)
    (5)
    (5)
    (5)
    (2)
    (2)
    (2)
    (0)
    		33
    48
    44
    29
    38
    26
    27
    26
    18
    18
    18
    14
    19
    26
    23
    12
    15
    11
    21
    17
    6
    18
    15
    4
    9
    3
    1
    		(13)
    (20)
    (18)
    (11)
    (15)
    (11)
    (11)
    (11)
    (7)
    (7)
    (7)
    (6)
    (8)
    (12)
    (9)
    (5)
    (6)
    (4)
    (9)
    (7)
    (2)
    (7)
    (6)
    (2)
    (4)
    (1)
    (0)
    		47
    28
    24
    21
    29
    19
    53
    16
    19
    7
    21
    18
    11
    19
    15
    15
    19
    13
    28
    13
    5
    13
    9
    13
    30
    16
    13
    		(19)
    (11)
    (9)
    (8)
    (11)
    (8)
    (21)
    (6)
    (8)
    (3)
    (8)
    (7)
    (4)
    (8)
    (6)
    (6)
    (8)
    (5)
    (11)
    (5)
    (2)
    (5)
    (4)
    (5)
    (12)
    (6)
    (5)
    * A patient may have had more then one adverse reaction.

        Other less frequent (2% to 5%) adverse reactions reported in patients receiving anastrozole tablets l mg in either Trial 0004 or Trial 0005 are listed below. These adverse experiences are listed by body system and are in order of decreasing frequency within each body system regardless of assessed causality
    Body as a Whole: Flu syndrome; fever; neck pain; malaise; accidental injury; infection
    Cardiovascular: Hypertension; thrombophlebitis
    Hepatic: Gamma GT increased; SGOT increased; SGPT increased
    Hematologic: Anemia; leukopenia
    Metabolic and Nutritional: Alkaline phosphatase increased; weight loss Mean serum total cholesterol levels increased by 0.5 mmol/L among patients receiving anastrozole tablets. Increases in LDL cholesterol have been shown to contribute to these changes.
    Musculoskeletal: Myalgia; arthralgia; pathological fracture
    Nervous: Somnolence; confusion; insomnia; anxiety; nervousness
    Respiratory: Sinusitis; bronchitis; rhinitis
    Skin and Appendages: Hair thinning (alopecia); pruritus
    Urogenital: Urinary tract infection; breast pain
        The incidences of the following adverse event groups potentially causally related to one or both of the therapies because of their pharmacology, were statistically analyzed: weight gain, edema, thromboembolic disease, gastrointestinal disturbance, hot flushes, and vaginal dryness. These six groups, and the adverse reactions captured in the groups, were prospectively defined. The results are shown in the table below.

    Table 6 – Number (n) and Percentage of Patients with Pre-specified Adverse Reactions in Trials 0004 and 0005
    Adverse Event Group
    		Anastrozole
    tablets 1 mg
    (N=262)
    N
    		Anastrozole
    tablets 1 mg
    (N=262)
    (%)
    		Anastrozole
    tablets 10 mg
    (N=246)
    N
    		Anastrozole
    tablets 10 mg
    (N=246)
    (%)
    		Megestrol
    Acetate 160 mg
    (N=253)
    N
    		Megestrol
    Acetate 160 mg
    (N=253)
    (%)
    Gastrointestinal Disturbance
    Hot Flushes
    Edema
    Thromboembolic Disease
    Vaginal Dryness
    Weight Gain
    		77
    33
    19
    9
    5
    4
    		(29)
    (13)
    (7)
    (3)
    (2)
    (2)
    		81
    29
    28
    4
    3
    10
    		(33)
    (12)
    (11)
    (2)
    (1)
    (4)
    		54
    35
    35
    12
    2
    30
    		(21)
    (14)
    (14)
    (5)
    (1)
    (12)

  • ADVERSE REACTIONS

    6.2 Post-Marketing Experience
        Hepatobiliary events including increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase have been reported (≥1% and <10%) and gamma-GT, bilirubin and hepatitis have been reported (≥0.1% and <1%) in patients receiving anastrozole tablets.
        Anastrozole tablets may also be associated with rash including cases of mucocutaneous disorders such as erythema multiforme and Stevens-Johnson syndrome.
        Cases of allergic reactions including angioedema, urticaria and anaphylaxis have been reported in patients receiving anastrozole tablets. [see Contraindications (4.2)]
        Trigger finger has been reported (>0.1% and <1%) in patients receiving anastrozole tablets

  • DRUG INTERACTIONS


    7 DRUG INTERACTIONS

    7.1 Tamoxifen
        Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. However, the coadministration of anastrozole and tamoxifen did not affect the pharmacokinetics of tamoxifen or Ndesmethyltamoxifen. At a median follow-up of 33 months, the combination of anastrozole tablets and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. [see Clinical Studies (14.1)]. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole.

  • DRUG INTERACTIONS

    7.2 Estrogen
        Estrogen-containing therapies should not be used with anastrozole tablets as they may diminish its pharmacological action.

  • DRUG INTERACTIONS

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

  • DRUG INTERACTIONS

    7.4 Cytochrome P450
        Based on in vitro and in vivo results, it is unlikely that co-administration of anastrozole tablets 1 mg will affect other drugs as a result inhibition of cytochrome P450 [see Clinical Pharmacology (12.3)].

  • USE IN SPECIFIC POPULATIONS


    8 USE IN SPECIFIC POPULATIONS

  • PREGNANCY

    8.1 Pregnancy
        PREGNANCY CATEGORY X [see Contraindications (4.1)]
        Anastrozole tablets may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole tablets are contraindicated in women who are or may become pregnant. In animal studies, anastrozole caused pregnancy failure, increased pregnancy loss, and signs of delayed fetal development. There are no studies of anastrozole tablets use in pregnant women. If anastrozole tablets are used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus and potential risk for pregnancy loss.
        In animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 1 (rats) and 1/3 (rabbits) the recommended human dose on a mg/m2 basis. In both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses). In rats, these effects were dose related, and placental weights were significantly increased. Fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (AUC0-24hr 9 times higher). In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m2 basis. [see Animal Toxicology and/or Pharmacology (13.2)]

  • NURSING MOTHERS

    8.3 Nursing Mothers
        It is not known if anastrozole is excreted in human milk. Because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

  • PEDIATRIC USE

    8.4 Pediatric Use
        Clinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with McCune-Albright Syndrome and progressive precocious puberty. The efficacy of anastrozole tablets in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with McCune-Albright Syndrome has not been demonstrated.
    Gynecomastia Study
        A randomized, double-blind, placebo-controlled, multi-center study enrolled 80 boys with pubertal gynecomastia aged 11 to 18 years. Patients were randomized to a daily regimen of either anastrozole tablets 1 mg or placebo. After 6 months of treatment there was no statistically significant difference in the percentage of patients who experienced a ≥50% reduction in gynecomastia (primary efficacy analysis). Secondary efficacy analyses (absolute change in breast volume, the percentage of patients who had any reduction in the calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. Serum estradiol concentrations at Month 6 of treatment were reduced by 15.4 % in the anastrozole tablets group and 4.5% in the placebo group.
        Adverse reactions that were assessed as treatment-related by the investigators occurred in 16.3% of the anastrozole tabletstreated patients and 8.1% of the placebo-treated patients with the most frequent being acne (7% anastrozole tablets and 2.7% placebo) and headache (7% anastrozole tablets and 0% placebo); all other adverse reactions showed small differences between treatment groups. One patient treated with anastrozole tablets discontinued the trial because of testicular enlargement. The mean baseline-subtracted change in testicular volume after 6 months of treatment was + 6.6 ± 7.9 cm3 in the anastrozole tablets-treated patients and + 5.2 ± 8.0 cm3 in the placebo group).
    McCune- Albright Syndrome Study
        A multi-center, single-arm, open-label, study was conducted in 28 girls with McCune-Albright Syndrome and progressive precocious puberty aged 2 to <10 years. All patients received a 1 mg daily dose of anastrozole tablets. The trial duration was 12 months. Patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) McCune-Albright syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. Patients’ baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean Tanner stage for breast of 2.7 ± 0.81. Compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). There were no clinically significant changes in Tanner staging, mean ovarian volume, mean uterine volume and mean predicted adult height. A small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in McCune-Albright Syndrome patients.
        Five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole tablets. These were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transa minase, and allergic dermatitis.
    Pharmacokinetics in Pediatric Patients
        Following 1 mg once daily multiple administration in pediatric patients, the mean time to reach the maximum anastrozole concentration was 1 hr. The mean (range) disposition Parameters of anastrozole in pediatric patients were described by a CL/F of 1.54 L/h (0.77 - 4.53 L/h) and V/F of 98.4 L (50.7-330.0 L). The terminal elimination half life was 46.8 h, 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 was similar in boys with pubertal gynecomastia and girls with McCune- Albright Syndrome.

  • GERIATRIC USE

    8.5 Geriatric Use
        In studies 0030 and 0027 about 50% of patients were 65 or older. Patients ≥ 65 years of age had moderately better tumor response and time to tumor progression than patients < 65 years of age regardless of randomized treatment. In studies 0004 and 0005 50% of patients were 65 or older. Response rates and time to progression were similar for the over 65 and younger patients.
        In the ATAC study 45% of patients were 65 years of age or older. The efficacy of anastrozole tablets compared to tamoxifen in patients who were 65 years or older (N=1413 for anastrozole tablets and N=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 (95% CI: 0.80, 1.08)) was less than efficacy observed in patients who were less than 65 years of age (N=1712 for anastrozole tablets and N=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 (95% CI: 0.67, 0.94)).
        The pharmacokinetics of anastrozole are not affected by age.

  • SPL UNCLASSIFIED SECTION

    8.6 Renal Impairment
        Since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not influence the total body clearance. Dosage adjustment in patients with renal impairment is not necessary [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

  • SPL UNCLASSIFIED SECTION

    8.7 Hepatic Impairment
        The plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. Therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. Anastrozole tablets have not been studied in patients with severe hepatic impairment [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

  • OVERDOSAGE


    10 OVERDOSAGE
        Clinical trials have been conducted with anastrozole tablets, up to 60 mg in a single dose given to healthy male volunteers and up to 10 mg daily given to postmenopausal women with advanced breast cancer; these dosages were tolerated. A single dose of anastrozole tablets that results in life-threatening symptoms has not been established. There is no specific antidote to overdosage and treatment must be symptomatic. In the management of an overdose, consider that multiple agents may have been taken. Vomiting may be induced if the patient is alert. Dialysis may be helpful because anastrozole tablets are not highly protein bound. General supportive care, including frequent monitoring of vital. signs and close observation of the patient, is indicated.

  • DESCRIPTION

        Anastrozole tablets for oral administration contain 1 mg of anastrozole, a non-steroidal aromatase inhibitor. It is chemically described as 1,3-Benzenediacetonitrile, a, a, a’, a’-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl). Its molecular formula is C17H19N5 and its structural formula is:

    Anastrozole Chemical Structure

        Anastrozole is an off-white powder with a molecular weight of 293.4. Anastrozole has moderate aqueous solubility (0.5 mg/mL at 25°C); solubility is independent of pH in the physiological range. Anastrozole is freely soluble in methanol, acetone, ethanol, and tetrahydrofuran, and very soluble in acetonitrile.
        Each tablet contains as inactive ingredients: lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycol, povidone, sodium starch glycolate and titanium dioxide.


  • CLINICAL PHARMACOLOGY


    12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action
        The growth of many cancers of the breast is stimulated or maintained by estrogens. Treatment of breast cancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive or receptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy, adrenalectomy, hypophysectomy) or inhibit estrogen effects (antiestrogens and progestational agents). These interventions lead to decreased tumor mass or delayed progression of tumor growth in some women.
        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. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme.
        Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.

  • PHARMACODYNAMICS

    12.2 Pharmacodynamics

    Effect on Estradiol
        Mean serum concentrations of estradiol were evaluated in multiple daily dosing trials with 0.5, 1, 3, 5, and 10 mg of anastrozole tablets in postmenopausal women with advanced breast cancer. Clinically significant suppression of serum estradiol was seen with all doses. Doses of 1 mg and higher resulted in suppression of mean serum concentrations of estradiol to the lower limit of detection (3.7 pmol/L). The recommended daily dose, anastrozole tablets 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 with anastrozole tablets 1 mg.
        The effect of anastrozole tablets in premenopausal women with early or advanced breast cancer has not been studied. Because aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women, anastrozole tablets would not be expected to lower estradiol levels in premenopausal women.

    Effect on Corticosteroids
        In multiple daily dosing trials with 3, 5, and 10 mg, the selectivity of anastrozole was assessed by examining effects on corticosteroid synthesis. For all doses, anastrozole did not affect cortisol or aldosterone secretion at baseline or in response to ACTH. No glucocorticoid or mineralocorticoid replacement therapy is necessary with anastrozole.

    Other Endocrine Effects
        In multiple daily dosing trials with 5 and 10 mg, thyroid stimulating hormone (TSH) was measured; there was no increase in TSH during the administration of anastrozole tablets. Anastrozole tablets does not possess direct progestogenic, androgenic, or estrogenic activity in animals, but does perturb the circulating levels of progesterone, androgens, and estrogens.

  • PHARMACOKINETICS

    12.3 Pharmacokinetics

    Absorption
        Inhibition of aromatase activity is primarily due to anastrozole, the parent drug. Absorption of anastrozole is rapid and maximum plasma concentrations typically occur within 2 hours of dosing under fasted conditions. Studies with radiolabeled drug have demonstrated that orally administered anastrozole is well absorbed into the systemic circulation. 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. The pharmacokinetics of anastrozole are linear over the dose range of 1 to 20 mg, and do not change with repeated dosing. The pharmacokinetics of anastrozole were similar in patients and healthy volunteers.

    Distribution
        Steady-state plasma levels are approximately 3- to 4-fold higher than levels observed after a single dose of anastrozole tablets. Plasma concentrations approach steady-state levels at about 7 days of once daily dosing. Anastrozole is 40% bound to plasma proteins in the therapeutic range.

    Metabolism
        Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. Three metabolites of anastrozole (triazole, a glucuronide conjugate of hydroxy-anastrozole, and a glucuronide conjugate of anastrozole itself) have been identified in human plasma and urine. The major circulating metabolite of anastrozole, triazole, lacks pharmacologic activity.
        Anastrozole inhibited reactions catalyzed by cytochrome P450 1A2, 2C8/9, and 3A4 in vitro with Ki values which were approximately 30 times higher than the mean steady-state Cmax values observed following a 1 mg daily dose. Anastrozole had no inhibitory effect on reactions catalyzed by cytochrome P450 2A6 or 2D6 in vitro. Administration of a single 30 mg/kg or multiple 10 mg/kg doses of anastrozole to healthy subjects had no effect on the clearance of antipyrine or urinary recovery of antipyrine metabolites.

    Excretion
        Eighty-five percent of radiolabeled anastrozole was recovered in feces and urine. Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance. The mean elimination halflife of anastrozole is 50 hours.

    Effect of Gender and Age
        Anastrozole pharmacokinetics have been investigated in postmenopausal female volunteers and patients with breast cancer. No age related effects were seen over the range <50 to >80 years.

    Effect of Race
        Estradiol and estrone sulfate serum levels were similar between Japanese and Caucasian postmenopausal women who received 1 mg of anastrozole daily for 16 days. Anastrozole mean steady-state minimum plasma concentrations in Caucasian and Japanese postmenopausal women were 25.7 and 30.4 ng/mL, respectively.

    Effect of Renal Impairment
        Anastrozole pharmacokinetics have been investigated in subjects with renal impairment. Anastrozole renal clearance decreased proportionally with creatinine clearance and was approximately 50% lower in volunteers with severe renal impairment (creatinine clearance < 30 mL/min/1.73m2) compared to controls. Total clearance was only reduced 10%. No dosage adjustment is needed for renal impairment. [see Dosage and Administration (2.1) and Use in Specific Populations (8.6)]
    Effect of Hepatic Impairment
        Anastrozole pharmacokinetics have been investigated in subjects with hepatic cirrhosis related to alcohol abuse. The apparent oral clearance (CL/F) of anastrozole was approximately 30% lower in subjects with stable hepatic cirrhosis than in control subjects with normal liver function. However, these plasma concentrations were still with the range of values observed in normal subjects. The effect of severe hepatic impairment was not studied. No dose adjustment is necessary for stable hepatic cirrhosis. [see Dosage and Administration (2.2) and Use in Specific Populations (8.7)]

  • NONCLINICAL TOXICOLOGY


    13 NONCLINICAL TOXICOLOGY

  • CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
        A conventional carcinogenesis study in rats at doses of 1.0 to 25 mg/kg/day (about 10 to 243 times the daily maximum recommended human dose on a mg/m2 basis) administered by oral gavage for up to 2 years revealed an increase in the incidence of hepatocellular adenoma and carcinoma and uterine stromal polyps in females and thyroid adenoma in males at the high dose. A dose related increase was observed in the incidence of ovarian and uterine hyperplasia in females. At 25 mg/kg/day, plasma AUC0-24 hr levels in rats were 110 to 125 times higher than the level exhibited in postmenopausal volunteers at the recommended dose. A separate carcinogenicity study in mice at oral doses of 5 to 50 mg/kg/day (about 24 to 243 times the daily maximum recommended human dose on a mg/m2 basis) for up to 2 years produced an increase in the incidence of benign ovarian stromal, epithelial and granulosa cell tumors at all dose levels. A dose related increase in the incidence of ovarian hyperplasia was also observed in female mice. These ovarian changes are considered to be rodent-specific effects of aromatase inhibition and are of questionable significance to humans. The incidence of lymphosarcoma was increased in males and females at the high dose. At 50mg/kg/day, plasma AUC levels in mice were 35 to 40 times higher than the level exhibited in postmenopausal volunteers at the recommended dose.
        Anastrozole tablets have not been shown to be mutagenic in in vitro tests (Ames and E. coli bacterial tests, CHO-K1 gene mutation assay) or clastogenic either in vitro (chromosome aberrations in human lymphocytes) or in vivo (micronucleus test in rats).
        Oral administration of anastrozole to female rats (from 2 weeks before mating to pregnancy day 7) produced significant incidence of infertility and reduced numbers of viable pregnancies at 1 mg/kg/day (about 10 times the recommended human dose on a mg/m2 basis and 9 times higher than the AUC0-24 hr found in postmenopausal volunteers at the recommended dose). Preimplantation loss of ova or fetus was increased at doses equal to or greater than 0.02 mg/kg/day (about one-fifth the recommended human dose on a mg/m2 basis). Recovery of fertility was observed following a 5-week non-dosing period which followed 3 weeks of dosing. It is not known whether these effects observed in female rats are indicative of impaired fertility in humans.
        Multiple-dose studies in rats administered anastrozole for 6 months at doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 19 and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose) resulted in hypertrophy of the ovaries and the presence of follicular cysts. In addition, hyperplastic uteri were observed in 6-month studies in female dogs administered doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 22 times and 16 times higher than the respective values found in postmenopausal women at the recommended dose). It is not known whether these effects on the reproductive organs of animals are associated with impaired fertility in premenopausal women.

  • ANIMAL PHARMACOLOGY & OR TOXICOLOGY

    13.2 Animal Toxicology and/or Pharmacology
    Reproductive Toxicology
        Anastrozole has been found to cross the placenta following oral administration of 0.1 mg/kg in rats and rabbits (about 1 and 1.9 times the recommended human dose, respectively, on a mg/m2 basis). Studies in both rats and rabbits at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively (about 1 and 1/3, respectively, the recommended human dose on a mg/m2 basis), administered during the period of organogenesis showed that anastrozole increased pregnancy loss (increased pre- and/or postimplantation loss, increased resorption, and decreased numbers of live fetuses); effects were dose related in rats. Placental weights were significantly increased in rats at doses of 0.1 mg/kg/day or more.
        Evidence of fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), was observed in rats administered doses of 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 19 times and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose). There was no evidence of teratogenicity in rats administered doses up to 1.0 mg/kg/day. In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m2 basis); there was no evidence of teratogenicity in rabbits administered 0.2 mg/kg/day (about 3 times the recommended human dose on a mg/m2 basis).

  • CLINICAL STUDIES

    14 CLINICAL STUDIES

    14.1 Adjuvant Treatment of Breast Cancer in Postmenopausal Women
        A multicenter, double-blind trial (ATAC) randomized 9,366 postmenopausal women with operable breast cancer to adjuvant treatment with anastrozole tablets 1 mg daily, tamoxifen 20 mg daily, or a combination of the two treatments for five years or until recurrence of the disease.
        The primary endpoint of the trial was disease-free survival (i.e., time to occurrence of a distant or local recurrence, or contralateral breast cancer or death from any cause). Secondary endpoints of the trial included distant disease-free survival, the incidence of contralateral breast cancer and overall survival. At a median follow-up of 33 months, the combination of anastrozole tablets and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor positive subpopulation. This treatment arm was discontinued from the trial. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole. [see Drug Interactions (7.1)]
        Demographic and other baseline characteristics were similar among the three treatment groups (see Table 7).
    Table 7 – Demographic and Baseline Characteristics for ATAC Trial
    Demographic
    Characteristic
    		Anastrozole tablets
    1 mg
    (N=3125)
    		Tamoxifen
    20 mg
    (N=3116)
    		Anastrozole tablets 1 mg
    plus Tamoxifen 20 mg
    (N=3125)
    Mean age (yrs.)
    Age Range (yrs.)
    Age Distribution (%)
    <45 yrs.
    45-60 yrs.
    >60 <70 yrs.
    >70 yrs.
    Mean Weight (kg)
    Receptor Status(%)
    Positive‡
    Negative§
    Other
    Other Treatment (%) prior to Randomization
    Mastectomy
    Breast conservation#
    Axillary surgery
    Radiotherapy
    Chemotherapy
    Neoadjuvant Tamoxifen
    Primary Tumor Size (%)
    T1 (≤2 cm)
    T2 (>2 cm and ≤5 cm)
    T3 (>5 cm)
    Nodal Status (%)
    Node positive
    1-3 (#of nodes)
    4-9
    >9
    Tumor Grade (%)
    Well-differentiated
    Moderately differentiated
    Poorly/undifferentiated
    Not assessed/recorded
    		64.1
    38.1 - 92.8

    0.7
    34.6
    38.0
    26.7
    70.8

    83.5
    7.4
    8.8

    47.8
    52.3
    95.5
    63.3
    22.3
    1.6

    63.9
    32.6
    2.7

    34.9
    24.4
    7.5
    2.9

    20.8
    46.8
    23.7
    8.7
    		64.1
    32.8 - 94.9

    0.4
    35.0
    37.1
    27.4
    71.1

    83.1
    8.0
    8.6

    47.3
    52.8
    95.7
    62.5
    20.8
    1.6

    62.9
    34.2
    2.2

    33.6
    24.4
    6.4
    2.7

    20.5
    47.8
    23.3
    8.4
    		64.3
    37.0 – 92.2

    0.5
    34.5
    37.7
    27.3
    71.3

    84.0
    7.0
    9.0

    48.1
    51.9
    95.2
    61.9
    20.8
    1.7

    64.1
    32.9
    2.3

    33.5
    24.3
    6.8
    2.3

    21.2
    46.5
    23.7
    8.5

    * N=Number of patients randomized to the treatment
    † The combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up
    ‡ Includes patients who were estrogen receptor (ER) positive or progesterone receptor (PgR) positive, or both positive
    § Includes patients with both ER negative and PgR negative receptor status
    ¶ Includes all other combinations of ER and PgR receptor status unknown
    # Among the patients who had breast conservation, radiotherapy was administered to 95.0% of patients in the anastrozole tablets arm, 94.1% in the tamoxifen arm and 94.5% in the anastrozole tablets plus tamoxifen arm.

        Patients in the two monotherapy arms of the ATAC trial were treated for a median of 60 months (5 years) and followed for a median of 68 months. Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.87, 95% CI: 0.78, 0.97, p=0.0127 in the anastrozole tablets arm compared to the tamoxifen arm. In the hormone receptorpositive subpopulation representing about 84% of the trial patients, disease-free survival was also statistically significantly improved (HR =0.83, 95% CI: 0.73, 0.94, p=0.0049) in the anastrozole tablets arm compared to the tamoxifen arm.
    Figure 1

    Figure 2

        The survival data with 68 months follow-up is presented in Table 9.

        In the group of patients who had previous adjuvant chemotherapy (N=698 for anastrozole tablets and N=647 for tamoxifen), the hazard ratio for disease-free survival was 0.91(95% CI: 0.73 to 1.13) in the anastrozole tablets arm compared to the tamoxifen arm.
        The frequency of individual events in the intent-to-treat population and the hormone receptor-positive subpopulation are described in Table 8.

    Table 8 – All Recurrence and Death Events*
                                                                               
    		Intent-To-Treat Population‡
    		Hormone Receptor-Positive
    Subpopulation‡

    		Anastrozole
    tablets 1 mg
    (N†=3125)
    		Tamoxifen
    20 mg
    (N†=3116)
    		Anastrozole
    tablets 1 mg
    (N†=2618)
    		Tamoxifen
    20 mg
    (N†=2598)
    Median Duration of Therapy (mo)
    Median Efficacy Follow-up (mo)
    Loco-regional recurrence
    Contralateral breast cancer
    Invasive
    Ductal carcinoma in situ
    Unknown
    Distant recurrence
    Death from Any Cause
    Death breast cancer
    Death other reason (including unknown)
    		60
    68
    119 (3.8)
    35 (1.1)
    27 (0.9)
    8 (0.3)
    0
    324 (10.4)
    411 (13.2)
    218 (7.0)
    193 (6.2)
    		60
    68
    149 (4.8)
    59 (1.9)
    52 (1.7)
    6 (0.2)
    1 (<0.1)
    375 (12.0)
    420 (13.5)
    248 (8.0)
    172 (5.5)
    		60
    68
    76 (2.9)
    26 (1.0)
    21 (0.8)
    5 (0.2)
    0
    226 (8.6)
    296 (11.3)
    138 (5.3)
    158 (6.0)
    		60
    68
    101 (3.9)
    54 (2.1)
    48 (1.8)
    5 (0.2)
    1 (<0.1)
    265 (10.2)
    301 (11.6)
    160 (6.2)
    141 (5.4)
    * The combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up
    † N=Number of patients randomized
    ‡ Patients may fall into more than one category.

    A summary of the study efficacy results is provided in Table 9.

    Table 9 – ATAC Efficacy Summary*
                                                                          Intent-To-Treat Population
    		Hormone Receptor-Positive
    Subpopulation
                                                          
    		Anastrozole
    tablets 1 mg
    (N=3125)
    		Tamoxifen
    20 mg
    (N=3116)
    		Anastrozole
    tablets 1 mg
    (N=2618)
    		Tamoxifen
    20 mg
    (N=2598)
                                                            
    		   Number of Events  
    		   Number of Events  
    Disease free Survival
    Hazard ratio
    2-sided 95% CI
    p-value
    Distant Disease-free Survival
    Hazard ratio
    2-sided 95% CI
    Overall Survival
    Hazard ratio
    2-sided 95% CI
    		575



    500


    411
    0.87
    0.78 to 0.97
    0.0127

    0.94
    0.83 to 1.06

    0.97
    0.85 to 1.12
    		651



    530


    420


    		  
    		424



    370


    296
    0.83
    0.73 to 0.94
    0.0049

    0.93
    0.80 to 1.07

    0.97
    0.83 to 1.14
    		497



    394


    301
    * The combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up.
  • CLINICAL STUDIES

    14.2 First-Line Therapy in Postmenopausal Women with Advanced Breast Cancer
        Two double-blind, controlled clinical studies of similar design (0030, a North American study and 0027, a predominately European study) were conducted to assess the efficacy of anastrozole tablets compared with tamoxifen as first-line therapy for hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer in postmenopausal women. A total of 1021 patients between the ages of 30 and 92 years old were randomized to receive trial treatment. Patients were randomized to receive 1 mg of anastrozole tablets once daily or 20 mg of tamoxifen once daily. The primary end points for both trials were time to tumor progression, objective tumor response rate, and safety.
        Demographics and other baseline characteristics, including patients who had measurable and no measurable disease, patients who were given previous adjuvant therapy, the site of metastatic disease and ethnic origin were similar for the two treatment groups for both trials. The following table summarizes the hormone receptor status at entry for all randomized patients in trials 0030 and 0027.

    Table 10 – Demographic and Other Baseline Characteristics
                                        
    		Number (%) of subjects
                                    
    		Trial 0030
    		Trial 0027
    Receptor status
    		Anastrozole
    tablets 1 mg
    (n=171)
    		Tamoxifen
    20 mg
    (n=182)
    		Anastrozole
    tablets 1 mg
    (n=340)
    		Tamoxifen
    20 mg
    (n=328)
    ER* and/or PgR†
    ER* unknown, PgR† Unknown
    		151 (88.3)
    19 (11.1)
    		162 (89.0)
    20 (11.0)
    		154 (45.3)
    185 (54.4)
    		144 (43.9)
    183 (55.8)

    * ER=Estrogen receptor
    † PgR=Progesterone receptor

        For the primary endpoints, trial 0030 showed that anastrozole tablets had a statistically significant advantage over tamoxifen (p=0.006) for time to tumor progression; objective tumor response rates were similar for anastrozole tablets and tamoxifen. Trial 0027 showed that anastrozole tablets and tamoxifen had similar objective tumor response rates and time to tumor progression (see Table 11 and Figure 3 and 4)

        Table 11 below summarizes the results of trial 0030 and trial 0027 for the primary efficacy endpoints.

    Table 11 – Efficacy Results of First –line Treatment
    Endpoint           
    		Trial 0030
    		Trial 0027
                                              
    		Anastrozole  
    tablets 1 mg
    (N=171)
    		Tamoxifen
    20 mg
    (N=182)
    		Anastrozole  
    tablets 1 mg
    (N=340)
    		Tamoxifen
    20 mg
    (N=328)
    Time to progression (TTP)
       Median TTP (months)
    Number (%) of subjects
    Who progressed Hazard ratio (LCL*)†
    2-sided 95% CI‡
    p-value§
    Best objective response rate
       Number (%) of subjects
    With CR + PR# Odds Ratio (LCL*)♠
    		11.1

    114 (67%)



    36 (21.1%)


    1.42 (1.15)
    (1.11, 1.82)
    0.006


    1.30 (0.83)
    		5.6

    138 (76%)



    31 (17.0%)


    		 
    		8.2

    249 (73%)



    112 (32.9%)


    1.01 (0.87)
    0.85, 1.20)
    0.920


    1.01 (0.77)
    		8.3

    247 (75%)



    107 (32.6%)
    * LCL=Lower Confidence Limit
    † Tamoxifen:Anastrozole tablets
    ‡ CI=Confidence Interval
    § Two-sided Log Rank
    ¶ CR=Complete Response
    # PR=Partial Response
    ♠ Anastrozole tablets:Tamoxifen

    Figure 3

    Figure 4

        Results from the secondary endpoints were supportive of the results of the primary efficacy endpoints. There were too few deaths occurring across treatment groups of both trials to draw conclusions on overall survival differences.


  • CLINICAL STUDIES

    14.3 Second-Line Therapy in Postmenopausal Women with Advanced Breast Cancer who had Disease Progression following Tamoxifen Therapy
        Anastrozole was studied in two controlled clinical trials (0004, a North American study; 0005, a predominately European study) in postmenopausal women with advanced breast cancer who had disease progression following tamoxifen therapy for either advanced or early breast cancer. Some of the patients had also received previous cytotoxic treatment. Most patients were ERpositive; a smaller fraction were ER-unknown or ER-negative; the ER-negative patients were eligible only if they had had a positive response to tamoxifen. Eligible patients with measurable and non-measurable disease were randomized to receive either a single daily dose of 1 mg or 10 mg of anastrozole tablets or megestrol acetate 40 mg four times a day. The studies were double-blinded with respect to anastrozole tablets. Time to progression and objective response (only patients with measurable disease could be considered partial responders) rates were the primary efficacy variables. Objective response rates were calculated based on the Union Internationale Contre le Cancer (UICC) criteria. The rate of prolonged (more than 24 weeks) stable disease, the rate of progression, and survival were also calculated.
        Both trials included over 375 patients; demographics and other baseline characteristics were similar for the three treatment groups in each trial. Patients in the 0005 trial had responded better to prior tamoxifen treatment. Of the patients entered who had prior tamoxifen therapy for advanced disease (58% in Trial 0004; 57% in Trial 0005), 18% of these patients in Trial 0004 and 42% in Trial 0005 were reported by the primary investigator to have responded. In Trial 0004, 81% of patients were ER-positive, 13% were ER-unknown, and 6% were ER-negative. In Trial 0005, 58% of patients were ER-positive, 37% were ER-unknown, and 5% were ER-negative. In Trial 0004, 62% of patients had measurable disease compared to 79% in Trial 0005. The sites of metastatic disease were similar among treatment groups for each trial. On average, 40% of the patients had soft tissue metastases; 60% had bone metastases; and 40% had visceral (15% liver) metastases.
        Efficacy results from the two studies were similar as presented in Table 12. In both studies there were no significant differences between treatment arms with respect to any of the efficacy parameters listed in the table below.

    Table 12 – Efficacy Results of Second-line Treatment

    		Anastrozole tablets
    1 mg
    		Anastrozole tablets
    10 mg
    		Megestrol Acetate
    160 mg
    Trial 0004 (N. America)
    Median Fol1ow-up (months)*
    Median Time to Death (months)
    2 Year Survival Probability (%)
    Median Time to Progression (months)
    Objective Response (all patients ) (%)
    Stable Disease for >24 weeks (%)
    Progression (%)
    Trial 0005 (Europe, Australia, S. Africa)
    Median Follow-up (months)*
    Median Time to Death (months)
    2 Year Survival Probability (%)
    Median Time to Progression (months)
    Objective Response (all patients) (%)
    Stable Disease for >24 weeks (%)
    Progression (%)
    		(N=128)
    31.3
    29.6
    62.0
    5.7
    12.5
    35.2
    86.7
    (N=135)
    31.0
    24.3
    50.5
    4.4
    12.6
    24.4
    91.9
    		(N=130)
    30.9
    25.7
    58.0
    5.3
    10.0
    29.2
    85.4
    (N=118)
    30.9
    24.8
    50.9
    5.3
    15.3
    25.4
    89.8
    		(N=128)
    32.9
    26.7
    53.1
    5.1
    10.2
    32.8
    90.6
    (N=125)
    31.5
    19.8
    39.1
    3.9
    14.4
    23.2
    92.0
    * Surviving Patients

        When data from the two controlled trials are pooled, the objective response rates and median times to progression and death were similar for patients randomized to anastrozole tablets 1 mg and megestrol acetate. There is, in this data, no indication that anastrozole tablets 10 mg are superior to anastrozole tablets 1 mg.

    Table 13 – Pooled Efficacy Results of Second-line Treatment
    Trials 0004 & 0005
    (Pooled Data)
    		Anastrozole tablets
    1 mg
    N=263
    		Anastrozole tablets
    10 mg
    N=248
    		Megestrol Acetate
    160 mg
    N=253
    Median Time to Death (months)
    2 Year Survival Probability (%)
    Median Time to Progression
    Objective Response (all patients) (%)
    		26.7
    56.1
    4.8
    12.5
    		25.5
    54.6
    5.3
    12.5
    		22.5
    46.3
    4.6
    12.3

  • HOW SUPPLIED


    16 HOW SUPPLIED/STORAGE AND HANDLING
        These tablets are supplied in bottles of 30 tablets (NDC: 67877-171-30)

    Storage
        Store at controlled room temperature, 20-25°C (68-77°F) [see USP].

  • SPL UNCLASSIFIED SECTION


    17 PATIENT COUNSELING INFORMATION

    17.1 Pregnancy
        Patients should be advised that anastrozole tablets may cause fetal harm. They should also be advised that anastrozole tablets are not for use in premenopausal women; therefore, if they become pregnant they should stop taking anastrozole tablets and immediately contact their doctor.

  • SPL UNCLASSIFIED SECTION

    17.2 Allergic (Hypersensitivity) Reactions
        Patients should be informed of the possibility of serious allergic reactions with swelling of the face, lips, tongue and/or throat (angioedema) which may cause difficulty in swallowing and/or breathing and to immediately report this to their doctor.

  • SPL UNCLASSIFIED SECTION

    17.3 Ischemic Cardiovascular Events
        Patients with pre-existing ischemic heart disease should be informed that an increased incidence of cardiovascular events has been observed with anastrozole tablets use compared to tamoxifen use.

  • SPL UNCLASSIFIED SECTION

    17.4 Bone Effects
        Patients should be informed that anastrozole tablets lowers the level of estrogen. This may lead to a loss of the mineral content of bones, which might decrease bone strength. A possible consequence of decreased mineral content of bones is an increase in the risk of fractures.

  • SPL UNCLASSIFIED SECTION

    17.5 Cholesterol
        Patients should be informed that an increased level of cholesterol might be seen while receiving anastrozole tablets.

  • SPL UNCLASSIFIED SECTION

    17.6 Tamoxifen
        Patients should be advised not to take anastrozole tablets with Tamoxifen.

  • INFORMATION FOR PATIENTS


    17.7 FDA-Approved Patient Labeling

    PATIENT INFORMATION

    ANASTROZOLE TABLETS

    Read the information that comes with anastrozole tablets before you start taking it and each time you get a refill. The information may have changed. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. Talk with your doctor about anastrozole tablets when you start taking it and at regular checkups.

    What are anastrozole tablets?
    Anastrozole tablet is a prescription medicine used in women who have finished menopause (“the change of life”) for:
    treatment of early breast cancer
       o   after surgery, with or without radiation
       o   in women whose breast cancer is hormone receptor-positive
    first treatment of locally advanced or metastatic breast cancer, in women whose breast cancer is hormone receptor-positive or the hormone receptors are not known.
    treatment of advanced breast cancer, if the cancer has grown, or the disease has spread after tamoxifen therapy.
    Anastrozole tablets does not work in women with breast cancer who have not finished menopause (premenopausal women).

    Who should not take anastrozole tablets?
    Do not take anastrozole tablets if you:
    are pregnant, think you may be pregnant, or plan to get pregnant. Anastrozole tablets may harm your unborn child. If you become pregnant while taking anastrozole tablets, tell your doctor right away.
    have not finished menopause (are premenopausal)
    are allergic to any of the ingredients in anastrozole tablets. See the end of this leaflet for a list of the ingredients in anastrozole tablets.
    are a man or child

    What is the most important information I should know about anastrozole tablets?
    Anastrozole tablets may cause serious side effects including:
    Heart disease. Women with early breast cancer, who have a history of blockages in heart arteries (ischemic heart disease) and who take anastrozole tablets may have a slight increase in this type of heart disease compared to similar patients who take tamoxifen.
       o   Stop taking anastrozole tablets and call your doctor right away if you have chest pain or shortness of breath. These can be symptoms of heart disease.
    Osteoporosis (bone softening and weakening). Anastrozole tablets lowers estrogen in your body, which may cause your bones to become softer and weaker. This can increase your chance of fractures, specifically of the spine, hip and wrist. Your doctor may order a test for you called a bone mineral density study before you start taking anastrozole tablets and during treatment with anastrozole tablets as needed.

    What should I tell my doctor before taking anastrozole tablets?
    Anastrozole tablets may not be right for you. Before taking anastrozole tablets, tell your doctor about all your medical conditions, including if you:
    have not finished menopause. Talk to your doctor if you are not sure. See “Who should not take anastrozole tablets?”
    have had a previous heart problem
    have a condition called osteoporosis
    have high cholesterol
    are pregnant, planning to become pregnant, or breast feeding. See “Who should not take anastrozole tablets?”
    are nursing a baby. It is not known if anastrozole tablets passes into breast milk. You and your doctor should decide if you will take anastrozole tablets or breast feed. You should not do both.

    Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:
    Tamoxifen. You should not take anastrozole tablets with tamoxifen. Taking tamoxifen with anastrozole tablets may lower the amount of anastrozole tablets in your blood and may cause anastrozole tablets not to work as well.
    Medicines containing estrogen. Anastrozole tablets may not work if taken with one of these medicines:
       o   hormone replacement therapy
       o   birth control pills
       o   estrogen creams
       o   vaginal rings
       o   vaginal suppositories
    Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist each time you get a new medicine.

    How should I take anastrozole tablets?
    Take anastrozole tablets exactly as prescribed by your doctor. Keep taking anastrozole tablets for as along as your doctor prescribes it for you.
    Take one anastrozole tablets tablet each day.
    Anastrozole tablets can be taken with or without food.
    If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take your next regularly scheduled dose. Do not take two doses at the same time.
    If you have taken more anastrozole tablets than your doctor has prescribed, contact your doctor right away. Do not take any additional anastrozole tablets until instructed to do so by your doctor.
    Talk with your doctor about any health changes you have while taking anastrozole tablets.

    What are possible side effects of anastrozole tablets?
    Anastrozole tablets can cause serious side effects including:
    See “What is the most important information I should know about anastrozole tablets?”
    increased blood cholesterol (fat in the blood). Your doctor may check your cholesterol while you take anastrozole tablets therapy.
    skin reactions. Stop taking anastrozole tablets and call your doctor right away if you get any skin lesions, ulcers, or blisters.
    severe allergic reactions. Get medical help right away if you have:
    swelling of the face, lips, tongue, or throat.
    trouble swallowing
    trouble breathing
    liver problems. Anastrozole tablets can cause inflammation of the liver and changes in blood tests of the liver function. Your doctor may monitor you for this. Stop taking anastrozole tablets and call your doctor right away if you have any of these signs or symptoms of a liver problem:
    a general feeling of not being well
    yellowing of the skin or whites of the eyes
    pain on the right side of your abdomen

    Common side effects in women taking anastrozole tablets include:
    hot flashes
    weakness
    joint pain
    carpal tunnel syndrome (tingling, pain, coldness, weakness in parts of the hand)
    pain
    sore throat
    mood changes
    high blood pressure
    depression
    nausea and vomiting
    thinning of the hair (hair loss)
    rash
    back pain
    sleep problems
    bone pain
    headache
    swelling
    increased cough
    shortness of breath
    lymphedema (build up of lymph fluid in the tissues of your affected arm)
    trigger finger (a condition in which one of your fingers or your thumb catches in a bent position)

    HOW SHOULD I STORE ANASTROZOLE TABLETS?
    Store anastrozole tablets at 68°F to 77°F (20°C to 25°C).
    Keep anastrozole tablets and all medicines out of the reach of children.

    General information about anastrozole tablets.
    Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take anastrozole tablets for a condition for which it was not prescribed. Do not give anastrozole tablets to other people, even if they have the same symptoms you have. It may harm them.
    This patient information leaflet summarizes the most important information about anastrozole tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about anastrozole tablets that is written for health professionals.

    What are the ingredients in anastrozole tablets?
    Active ingredient: anastrozole
    Inactive ingredients: lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycol, povidone, sodium starch glycolate and titanium dioxide.

    Manufactured by:
    Natco Pharma Limited
    Kothur – 509 228. A.P. India.

    Mfd for:
    Ascend Laboratories, LLC
    Montvale, NJ 07645

    346033

    Rev : 01/Jan/2010

  • PRINCIPAL DISPLAY PANEL

    ASCEND
    Laboratories, LLC

    NDC: 67877-171-30

    ANASTROZOLE TABLETS

    1 mg
    30 tablets
    Rx only

    Dispense in original container

    Mfd by: Natco Pharma Limited
    Kothur - 509 228. A.P. India.

    Ascend Anastrozole Tablets - 1 mg product label

  • INGREDIENTS AND APPEARANCE
    ANASTROZOLE 
    anastrozole tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 67877-171
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ANASTROZOLE (UNII: 2Z07MYW1AZ) (ANASTROZOLE - UNII:2Z07MYW1AZ) ANASTROZOLE1 mg
    Inactive Ingredients
    Ingredient NameStrength
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    HYPROMELLOSES (UNII: 3NXW29V3WO)  
    POLYETHYLENE GLYCOL (UNII: 3WJQ0SDW1A)  
    POVIDONE K30 (UNII: U725QWY32X)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    Product Characteristics
    ColorwhiteScoreno score
    ShapeROUNDSize6mm
    FlavorImprint Code AN;1
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 67877-171-3030 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07922006/28/2010
    Labeler - Ascend Laboratories, LLC (141250469)
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