ANASTROZOLE

Sun Pharmaceutical Industries Limited

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use anastrozole tablets safely and effectively. See full prescribing information for Anastrozole Tablets. Anastrozole tablet for oral useInitial U.S. Approval: 1995 INDICATIONS AND USAGE Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer (1.1) First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer (1.2) Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole (1.3) CONTRAINDICATIONS Women of premenopausal endocrine status, including pregnant women (4.1, 8.1) Patients with demonstrated hypersensitivity to anastrozole tablets or any excipient (4.2) WARNINGS AND PRECAUTIONS In women with preexisting ischemic heart disease, an increased incidence of ischemic cardiovascular events occurred with anastrozole use compared to tamoxifen use. Consider risks and benefits. (5.1, 6.1) Decreases in bone mineral density may occur. Consider bone mineral density monitoring. (5.2, 6.1) Increases in total cholesterol may occur. Consider cholesterol monitoring. (5.3, 6.1) Side EffectsTo report SUSPECTED ADVERSE REACTIONS, contact CARACO Pharmaceutical Laboratories Ltd. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatchDRUG INTERACTIONS Tamoxifen: Do not use in combination with anastrozole. No additional benefit seen over tamoxifen monotherapy (7.1, 14.1). Estrogen-containing products: Combination use may diminish activity of anastrozole (7.2). USE IN SPECIFIC POPULATIONS Pediatric patients: Efficacy has not been demonstrated for pubertal boys of adolescent age with gynecomastia or girls with McCune-Albright Syndrome and progressive precocious puberty. (8.4)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 ANASTROZOLE INDICATIONS AND USAGE
  • 1.1 Adjuvant Treatment
  • 1.2 First-Line Treatment
  • 1.3 Second-Line Treatment
• 2 ANASTROZOLE DOSAGE AND ADMINISTRATION
  • 2.1 Recommended Dose
  • 2.2 Patients with Hepatic Impairment
• 3 DOSAGE FORMS AND STRENGTHS
• 4 ANASTROZOLE 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 ANASTROZOLE ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing 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 ANASTROZOLE 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 Toxicology and/or Pharmacology
• 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
• FDA-Approved Patient Labeling
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 1MG

FULL PRESCRIBING INFORMATION

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

The dose of anastrozole tablet is one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression. Anastrozole tablets can be taken with or without food.

For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial, anastrozole tablet was 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)]

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

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)].

5.3 Cholesterol

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

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 trialThe combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up.

Body system and adverse reactions by COSTARTCOSTART Coding Symbols for Thesaurus of Adverse Reaction Terms. preferred termA patient may have had more than 1 adverse reaction, including more than 1 adverse reaction in the same body system.	Anastrozole 1 mg (NN=Number of patients receiving the treatment. = 3092)	Tamoxifen 20 mg (NN=Number of patients receiving the treatment. = 3094)
Body as a whole
Asthenia	575 (19)	544 (18)
Pain	533 (17)	485 (16)
Back pain	321 (10)	309 (10)
Headache	314 (10)	249 (8)
Abdominal pain	271 (9)	276 (9)
Infection	285 (9)	276 (9)
Accidental injury	311 (10)	303 (10)
Flu syndrome	175 (6)	195 (6)
Chest pain	200 (7)	150 (5)
Neoplasm	162 (5)	144 (5)
Cyst	138 (5)	162 (5)
Cardiovascular
Vasodilatation	1104 (36)	1264 (41)
Hypertension	402 (13)	349 (11)
Digestive
Nausea	343 (11)	335 (11)
Constipation	249 (8)	252 (8)
Diarrhea	265 (9)	216 (7)
Dyspepsia	206 (7)	169 (6)
Gastrointestinal disorder	210 (7)	158 (5)
Hemic and lymphatic
Lymphedema	304 (10)	341 (11)
Anemia	113 (4)	159 (5)
Metabolic and nutritional
Peripheral edema	311 (10)	343 (11)
Weight gain	285 (9)	274 (9)
Hypercholesterolemia	278 (9)	108 (3.5)
Musculoskeletal
Arthritis	512 (17)	445 (14)
Arthralgia	467 (15)	344 (11)
Osteoporosis	325 (11)	226 (7)
Fracture	315 (10)	209 (7)
Bone pain	201 (7)	185 (6)
Arthrosis	207 (7)	156 (5)
Joint Disorder	184 (6)	160 (5)
Myalgia	179 (6)	160 (5)
Nervous system
Depression	413 (13)	382 (12)
Insomnia	309 (10)	281 (9)
Dizziness	236 (8)	234 (8)
Anxiety	195 (6)	180 (6)
Paresthesia	215 (7)	145 (5)
Respiratory
Pharyngitis	443 (14)	422 (14)
Cough increased	261 (8)	287 (9)
Dyspnea	234 (8)	237 (8)
Sinusitis	184 (6)	159 (5)
Bronchitis	167 (5)	153 (5)
Skin and appendages
Rash	333 (11)	387 (13)
Sweating	145 (5)	177 (6)
Special Senses
Cataract Specified	182 (6)	213 (7)
Urogenital
Leukorrhea	86 (3)	286 (9)
Urinary tract infection	244 (8)	313 (10)
Breast pain	251 (8)	169 (6)
Breast Neoplasm	164 (5)	139 (5)
Vulvovaginitis	194 (6)	150 (5)
Vaginal HemorrhageVaginal Hemorrhage without further diagnosis.	122 (4)	180 (6)
Vaginitis	125 (4)	158 (5)

Table 2 — Number of Patients with Pre-specified Adverse Reactions in ATAC TrialPatients with multiple events in the same category are counted only once in that category.

	Anastrozole N=3092 (%)	Tamoxifen N=3094 (%)	Odds-ratio	95% CI
Hot Flashes	1104 (36)	1264 (41)	0.8	0.73 to 0.89
Musculoskeletal EventsRefers to joint symptoms, including joint disorder, arthritis, arthrosis and arthralgia.	1100 (36)	911 (29)	1.32	1.19 to 1.47
Fatigue/Asthenia	575 (19)	544 (18)	1.07	0.94 to 1.22
Mood Disturbances	597 (19)	554 (18)	1.1	0.97 to 1.25
Nausea and Vomiting	393 (13)	384 (12)	1.03	0.88 to 1.19
All Fractures	315 (10)	209 (7)	1.57	1.3 to 1.88
Fractures of Spine, Hip, or Wrist	133 (4)	91 (3)	1.48	1.13 to 1.95
Wrist/Colles’ fractures	67 (2)	50 (2)
Spine fractures	43 (1)	22 (1)
Hip fractures	28 (1)	26 (1)
Cataracts	182 (6)	213 (7)	0.85	0.69 to 1.04
Vaginal Bleeding	167 (5)	317 (10)	0.5	0.41 to 0.61
Ischemic Cardiovascular Disease	127 (4)	104 (3)	1.23	0.95 to 1.6
Vaginal Discharge	109 (4)	408 (13)	0.24	0.19 to 0.3
Venous Thromboembolic events	87 (3)	140 (5)	0.61	0.47 to 0.8
Deep Venous Thromboembolic Events	48 (2)	74 (2)	0.64	0.45 to 0.93
Ischemic Cerebrovascular Event	62 (2)	88 (3)	0.7	0.5 to 0.97
Endometrial CancerPercentages calculated based upon the numbers of patients with an intact uterus at baseline	4 (0.2)	13 (0.6)	0.31	0.1 to 0.94

10-year median follow-up Safety Results from the ATAC Trial

• Results are consistent with the previous analyses.
• Serious adverse reactions were similar between anastrozole (50%) and tamoxifen (51%).
• Cardiovascular events were consistent with the known safety profiles of anastrozole and tamoxifen.
• The cumulative incidences of all first fractures (both serious and non-serious, occurring either during or after treatment) was higher in the anastrozole group (15%) compared to the tamoxifen group (11%). This increased first fracture rate during treatment did not continue in the post-treatment follow-up period.
• The cumulative incidence of new primary cancers was similar in the anastrozole group (13.7%) compared to the tamoxifen group (13.9%). Consistent with the previous analyses, endometrial cancer was higher in the tamoxifen group (0.8%) compared to the anastrozole group (0.2%).
• The overall number of deaths (during or off-trial treatment) was similar between the treatment groups. There were more deaths related to breast cancer in the tamoxifen than in the anastrozole treatment group.

Table 3 – Adverse Reactions Occurring with an Incidence of at Least 5% in Trials 0030 and 0027

	Number (%) of subjects
Body system Adverse ReactionA patient may have had more than 1 adverse event.	Anastrozole (N=506)	Tamoxifen (N=511)
Whole body
Asthenia	83 (16)	81 (16)
Pain	70 (14)	73 (14)
Back pain	60 (12)	68 (13)
Headache	47 (9)	40 (8)
Abdominal pain	40 (8)	38 (7)
Chest pain	37 (7)	37 (7)
Flu syndrome	35 (7)	30 (6)
Pelvic pain	23 (5)	30 (6)
Cardiovascular
Vasodilation	128 (25)	106 (21)
Hypertension	25 (5)	36 (7)
Digestive
Nausea	94 (19)	106 (21)
Constipation	47 (9)	66 (13)
Diarrhea	40 (8)	33 (6)
Vomiting	38 (8)	36 (7)
Anorexia	26 (5)	46 (9)
Metabolic and Nutritional
Peripheral edema	51 (10)	41 (8)
Musculoskeletal
Bone pain	54 (11)	52 (10)
Nervous
Dizziness	30 (6)	22 (4)
Insomnia	30 (6)	38 (7)
Depression	23 (5)	32 (6)
Hypertonia	16 (3)	26 (5)
Respiratory
Cough increased	55 (11)	52 (10)
Dyspnea	51 (10)	47 (9)
Pharyngitis	49 (10)	68 (13)
Skin and appendages
Rash	38 (8)	34 (8)
Urogenital
Leukorrhea	9 (2)	31 (6)

Table 4 – Number of Patients with Pre-specified Adverse Reactions in Trials 0030 and 0027

	Number (n) and Percentage of Patients
Adverse ReactionA patient may have had more than 1 adverse reaction.	Anastrozole 1 mg (N = 506) n (%)	Tamoxifen Citrate 20 mg (N = 511) n (%)
Depression	23 (5)	32 (6)
Tumor Flare	15 (3)	18 (4)
Thromboembolic DiseaseIncludes pulmonary embolus, thrombophlebitis, retinal vein thrombosis.	18 (4)	33 (6)
VenousIncludes pulmonary embolus, thrombophlebitis, retinal vein thrombosis.	5	15
Coronary and CerebralIncludes myocardial infarction, myocardial ischemia, angina pectoris, cerebrovascular accident, cerebral ischemia and cerebral infarct.	13	19
Gastrointestinal Disturbance	170 (34)	196 (38)
Hot Flushes	134 (26)	118 (23)
Vaginal Dryness	9 (2)	3 (1)
Lethargy	6 (1)	15 (3)
Vaginal Bleeding	5 (1)	11 (2)
Weight Gain	11 (2)	8 (2)

Table 5 - Number (N) and Percentage of Patients with Adverse Reactions in Trials 0004 and 0005

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

6.2 Postmarketing 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 Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Adjuvant Treatment of Breast Cancer in Postmenopausal Women

Table 7 - Demographic and Baseline Characteristics for ATAC Trial

Demographic Characteristic	Anastrozole 1 mg (NN=Number of patients randomized to the treatment=3125)	Tamoxifen 20 mg (NN=Number of patients randomized to the treatment=3116)	Anastrozole 1 mg plus TamoxifenThe combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up 20 mg (NN=Number of patients randomized to the treatment=3125)
Mean age (yrs.)	64.1	64.1	64.3
Age Range (yrs.)	38.1 to 92.8	32.8 to 94.9	37 to 92.2
Age Distribution (%)
<45 yrs.	0.7	0.4	0.5
45 to 60 yrs.	34.6	35	34.5
>60 <70 yrs.	38	37.1	37.7
>70 yrs.	26.7	27.4	27.3
Mean Weight (kg)	70.8	71.1	71.3
Receptor Status (%)
PositiveIncludes patients who were estrogen receptor (ER) positive or progesterone receptor (PgR) positive, or both positive	83.5	83.1	84
NegativeIncludes patients with both ER negative and PgR negative receptor status	7.4	8	7
OtherIncludes all other combinations of ER and PgR receptor status unknown	8.8	8.6	9
Other Treatment (%) prior to Randomization
Mastectomy	47.8	47.3	48.1
Breast conservationAmong the patients who had breast conservation, radiotherapy was administered to 95% of patients in the anastrozole arm, 94.1% in the tamoxifen arm and 94.5% in the anastrozole plus tamoxifen arm.	52.3	52.8	51.9
Axillary surgery	95.5	95.7	95.2
Radiotherapy	63.3	62.5	61.9
Chemotherapy	22.3	20.8	20.8
Neoadjuvant Tamoxifen	1.6	1.6	1.7
Primary Tumor Size (%)
T1 (≤2 cm)	63.9	62.9	64.1
T2 (>2 cm and ≤5 cm)	32.6	34.2	32.9
T3 (>5 cm)	2.7	2.2	2.3
Nodal Status (%)
Node positive	34.9	33.6	33.5
1 to 3 (# of nodes)	24.4	24.4	24.3
4 to 9	7.5	6.4	6.8
>9	2.9	2.7	2.3
Tumor Grade (%)
Well-differentiated	20.8	20.5	21.2
Moderately differentiated	46.8	47.8	46.5
Poorly/undifferentiated	23.7	23.3	23.7
Not assessed/recorded	8.7	8.4	8.5

Table 8- All Recurrence and Death EventsThe combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up

	Intent-To-Treat PopulationPatients may fall into more than one category.		Hormone Receptor-Positive SubpopulationPatients may fall into more than one category.
	Anastrozole 1 mg (NN=Number of patients randomized=3125)	Tamoxifen 20 mg (NN=Number of patients randomized=3116)	Anastrozole 1 mg (NN=Number of patients randomized=2618)	Tamoxifen 20 mg (NN=Number of patients randomized=2598)
Median Duration of Therapy (mo)	60	60	60	60
Median Efficacy Follow-up (mo)	68	68	68	68
Loco-regional recurrence	119 (3.8)	149 (4.8)	76 (2.9)	101 (3.9)
Contralateral breast cancer	35 (1.1)	59 (1.9)	26 (1)	54 (2.1)
Invasive	27 (0.9)	52 (1.7)	21 (0.8)	48 (1.8)
Ductal carcinoma in situ	8 (0.3)	6 (0.2)	5 (0.2)	5 (0.2)
Unknown	0	1 (<0.1)	0	1 (<0.1)
Distant recurrence	324 (10.4)	375 (12)	226 (8.6)	265 (10.2)
Death from Any Cause	411 (13.2)	420 (13.5)	296 (11.3)	301 (11.6)
Death breast cancer	218 (7)	248 (8)	138 (5.3)	160 (6.2)
Death other reason (including unknown)	193 (6.2)	172 (5.5)	158 (6)	141 (5.4)

Table 9 - ATAC Efficacy SummaryThe combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up.

	Intent-To-Treat Population		Hormone Receptor-Positive Subpopulation
	Anastrozole 1 mg (N=3125)	Tamoxifen 20 mg (N=3116)	Anastrozole 1 mg (N=2618)	Tamoxifen 20 mg (N=2598)
	Number of Events		Number of Events
Disease-free Survival	575	651	424	497
Hazard ratio	0.87		0.83
2-sided 95% CI	0.78 to 0.97		0.73 to 0.94
p-value	0.0127		0.0049
Distant Disease-free Survival	500	530	370	394
Hazard ratio	0.94		0.93
2-sided 95% CI	0.83 to 1.06		0.8 to 1.07
Overall Survival	411	420	296	301
Hazard ratio	0.97		0.97
2-sided 95% CI	0.85 to 1.12		0.83 to 1.14

Figure 4 - Disease-Free Survival for Hormone Receptor-Positive Subpopulation of Patients Randomized to Anastrozole or Tamoxifen Monotherapy in the ATAC Trial^(b)

14.2 First-Line Therapy in Postmenopausal Women with Advanced Breast Cancer

Table 11 – Demographic and Other Baseline Characteristics

	Number (%) of subjects
	Trial 0030		Trial 0027
Receptor status	Anastrozole 1 mg (N=171)	Tamoxifen 20 mg (N=182)	Anastrozole 1 mg (N=340)	Tamoxifen 20 mg (N=328)
ERER=Estrogen receptor and/or PgRPgR=Progesterone receptor	151 (88.3)	162 (89)	154 (45.3)	144 (43.9)
ER* unknown, PgR† Unknown	19 (11.1)	20 (11)	185 (54.4)	183 (55.8)

Table 12 – Efficacy Results of First-line Treatment Endpoint

Endpoint	Trial 0030		Trial 0027
	Anastrozole 1 mg (N=171)	Tamoxifen 20 mg (N=182)	Anastrozole 1 mg (N=340)	Tamoxifen 20 mg (N=328)
Time to progression (TTP)
Median TTP (months)	11.1	5.6	8.2	8.3
Number (%) of subjects Who progressed	114 (67%)	138 (76%)	249 (73%)	247 (75%)
Hazard ratio (LCLLCL=Lower Confidence Limit)Tamoxifen:Anastrozole	1.42 (1.15)		1.01 (0.87)
2-sided 95% CICI=Confidence Interval	(1.11, 1.82)		(0.85, 1.2)
p-valueTwo-sided Log Rank	0.006		0.92
Best objective response rate
Number (%) of subjects With CRCR=Complete Response + PRPR=Partial Response	36 (21.1%)	31 (17%)	112 (32.9%)	107 (32.6%)
Odds Ratio (LCL*)Anastrozole:Tamoxifen	1.3 (0.83)		1.01 (0.77)

14.3 Second-Line Therapy in Postmenopausal Women with Advanced Breast Cancer who had Disease Progression following Tamoxifen Therapy

Table 13– Efficacy Results of Second-line Treatment

	Anastrozole 1 mg	Anastrozole 10 mg	Megestrol Acetate 160 mg
Trial 0004 (N. America)	(N=128)	(N=130)	(N=128)
Median Follow-up (months)Surviving Patients	31.3	30.9	32.9
Median Time to Death (months)	29.6	25.7	26.7
2 Year Survival Probability (%)	62	58	53.1
Median Time to Progression (months)	5.7	5.3	5.1
Objective Response (all patients) (%)	12.5	10	10.2
Stable Disease for >24 weeks (%)	35.2	29.2	32.8
Progression (%)	86.7	85.4	90.6
Trial 0005 (Europe, Australia, S. Africa)	(N=135)	(N=118)	(N=125)
Median Follow-up (months)*	31	30.9	31.5
Median Time to Death (months)	24.3	24.8	19.8
2 Year Survival Probability (%)	50.5	50.9	39.1
Median Time to Progression (months)	4.4	5.3	3.9
Objective Response (all patients) (%)	12.6	15.3	14.4
Stable Disease for >24 weeks (%)	24.4	25.4	23.2
Progression (%)	91.9	89.8	92

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

FDA-Approved Patient Labeling

• treatment of early breast cancer
  • after surgery, with or without radiation
  • 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.

• are pregnant, think you may be pregnant, or plan to get pregnant. Anastrozole may harm your unborn child. If you become pregnant while taking anastrozole, 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?

• Heart disease. Women with early breast cancer, who have a history of blockages in heart arteries (ischemic heart disease) and who take anastrozole may have a slight increase in this type of heart disease compared to similar patients who take tamoxifen.
  • Stop taking anastrozole 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 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 and during treatment with anastrozole as needed.

What should I tell my doctor before taking anastrozole tablets?

Anastrozole may not be right for you. Before taking anastrozole, 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 passes into breast milk. You and your doctor should decide if you will take anastrozole tablets or breast feed. You should not do both.

• Tamoxifen. You should not take anastrozole with tamoxifen. Taking tamoxifen with anastrozole may lower the amount of anastrozole in your blood and may cause anastrozole not to work as well.
• Medicines containing estrogen. Anastrozole may not work if taken with one of these medicines:
  • hormone replacement therapy
  • birth control pills
  • estrogen creams
  • vaginal rings
  • vaginal suppositories

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 tablet each day.
• Anastrozole 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.

What are possible side effects of anastrozole?

• See “What is the most important information I should know about anastrozole?”
• increased blood cholesterol (fat in the blood). Your doctor may check your cholesterol while you take anastrozole therapy.
• skin reactions. Stop taking anastrozole 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 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 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

• 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)

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

HOW SHOULD I STORE ANASTROZOLE TABLETS?

• Store anastrozole tablets at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F).
• Keep anastrozole and all medicines out of the reach of children.

General information about anastrozole tablets.





What are the ingredients in anastrozole tablets?





Caraco Pharmaceutical Laboratories, Ltd.



Sun Pharmaceutical Industries Ltd.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 1MG

NDC 62756-250-88
Anastrozole Tablets
1 mg
Rx only
100 TABLETS
SUN PHARMACEUTICAL INDUSTRIES LTD.
Pharmacist: Dispense patient leaflet to each patient.

ANASTROZOLE ANASTROZOLE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:62756-250 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Anastrozole ANASTROZOLE 1 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate MAGNESIUM STEARATE POVIDONE K30 SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES polyethylene glycol 400 titanium dioxide Product Characteristics Color Size Imprint Code Shape WHITE (white to off-white) 6 mm A1 ROUND Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:62756-250-83 30 in 1 BOTTLE 2 NDC:62756-250-88 100 in 1 BOTTLE 3 NDC:62756-250-13 500 in 1 BOTTLE 4 NDC:62756-250-18 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091177 2010-07-16