Sorry Splodge... no help at all other than keep up with the choccy while
you're waiting for someone to come along with something sensible.

Best of luck with the Arimidex and fingers crossed that 'bad' side effects
don't happen.

Every anti-cancer drug has an adverse effect on the Musculoskeletal (and
other) systems of the body.

Arimidex

SIDE EFFECTS
Adjuvant Therapy

Adverse reaction data for adjuvant therapy are based on the adjuvant trial
(see CLINICAL PHARMACOLOGY - Clinical Studies - Adjuvant Treatment of Breast
Cancer in Postmenopausal Women). At a median follow-up of 33 months, the
combination of ARIMIDEX 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. The median duration of adjuvant treatment for safety
evaluation was 59.8 months and 59.6 months for patients receiving ARIMIDEX 1
mg and tamoxifen 20 mg, respectively.

Adverse events 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 8.

Table 8 - Adverse events occurring with an incidence of at least 5% in
either treatment group during treatment, or within 14 days of the end of
treatment

Body system and adverse event by
COSTART-preferred term* ARIMIDEX 1 mg
(N = 3092) Tamoxifen 20 mg
(N = 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
Lymphoedema 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)
Paraesthesia 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 Hemorrhage? 122 (4) 180 (6)
Vaginitis 125 (4) 158 (5)

COSTART Coding Symbols for Thesaurus of Adverse Reaction Terms.

N = Number of patients receiving the treatment.
*A patient may have had more than 1 adverse event, including more han 1
adverse event in the same body system.
?Vaginal Hemorrhage without further diagnosis.
**The combination arm was discontinued due to lack of efficacy at 33 months
of follow up.

Certain adverse events and combinations of adverse events were prospectively
specified for analysis, based on the known pharmacologic properties and side
effect profiles of the two drugs (See table 9).

Table 9 - Number (%) of patients with Pre-Specified Adverse Event in ATAC
Trial1

  ARIMIDEX
N=3092
(%) Tamoxifen
N=3094
(%) Odds-ratio 95% CI
Hot Flashes 1104 (36) 1264 (41) 0.8 0.73 - 0.89
Musculoskeletal Events2 1100 (36) 911 (29) 1.32 1.19-1.47
Fatigue/Asthenia 575 (19) 544 (18) 1.07 0.94 - 1.22
Mood Disturbances 597 (19) 554 (18) 1.1 0.97 - 1.25
Nausea and Vomiting 393 (13) 384 (12) 1.03 0.88 - 1.19
All Fractures 315 (10) 209 (7) 1.57 1.30 - 1.88
Fractures of Spine, Hip, or Wrist 133 (4) 91 (3) 1.48 1.13 - 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 - 1.04
Vaginal Bleeding 167 (5) 317 (10) 0.5 0.41 - 0.61
Ischemic Cardiovascular Disease 127 (4) 104 (3) 1.23 0.95 - 1.60
Vaginal Discharge 109 (4) 408 (13) 0.24 0.19 - 0.30
Venous Thromboembolic events 87 (3) 140 (5) 0.61 0.47 - 0.80
Deep Venous Thromboembolic
Events 48 (2) 74 (2) 0.64 0.45 - 0.93
Ischemic Cerebrovascular Event 62 (2) 88 (3) 0.7 0.50 - 0.97
Endometrial Cancer3 4 (0.2) 13 0.6) 0.31 0.10 - 0.94

1Patients with multiple events in the same category are counted only once in
that category.
2Refers to joint symptoms, including joint disorder, arthritis, arthrosis
and arthralgia.
3Percentages calculated based upon the numbers of patients with an intact
uterus at baseline.
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Patients receiving ARIMIDEX had an increase in joint disorders (including
arthritis, arthrosis and arthralgia) compared with patients receiving
tamoxifen. Patients receiving ARIMIDEX had 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
ARIMIDEX had a decrease in hot flashes, vaginal bleeding, vaginal discharge,
endometrial cancer, venous thromboembolic events and ischemic
cerebrovascular events compared with patients receiving tamoxifen.

Patients receiving ARIMIDEX had an increase in hypercholesterolemia (278
[9%]) compared to patients receiving tamoxifen (108 [3.5%]). Angina pectoris
was reported in 71 [2.3%] patients in the ARIMIDEX arm and 51 [1.6%]
patients in the tamoxifen arm; myocardial infarction was reported in 37
[1.2%] patients in the ARIMIDEX arm and in 34 [1.1%] patients in the
tamoxifen arm.

Results from the ATAC trial bone substudy, at 12 and 24 months demonstrated
that patients receiving ARIMIDEX 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.
----------------------------------------------------------------------------
-------------------------
First Line Therapy

ARIMIDEX was generally well tolerated in two well-controlled clinical trials
(ie, Trials 0030 and 0027). Adverse events 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 10.

Table 10

Body system
Adverse eventa Number (%) of subjects
ARIMIDEX
(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)

Muscoloskeletal
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)

aA patient may have had more than 1 adverse event.

Less frequent adverse experiences reported in patients receiving ARIMIDEX 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 prespecified 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 11

  Number (n) and Percentage of Patients
ARIMIDEX
1mg
(n =506) NOLVADEX
20 mg
(n = 511)
Adverse Event Groupa n(%) n (%)
Depression 23(5) 32 (6)
Tumor Flare 15(3) 18 (4)
Thromboembolic Diseasea 18(4) 33 (6)
Venousb 5 15
Coronary and Cerebralc 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)

aA patient may have had more than 1 adverse event
bIncludes pulmonary embolus, thrombophlebitis, retinal vein thrombosis
cIncludes myocardial infarction, myocardial ischemia, angina pectoris,
cerebrovascular accident, cerebral ischemia and cerebral infarct

Despite the lack of estrogenic activity for ARIMIDEX, there was no increase
in myocardial infarction or fracture when compared with tamoxifen.

Second Line Therapy

ARIMIDEX was generally well tolerated in two well-controlled clinical trials
(ie, Trials 0004 and 0005), with less than 3.3% of the ARIMIDEX-treated
patients and 4.0% of the megestrol acetate-treated patients withdrawing due
to an adverse event.

The principal adverse event more common with ARIMIDEX than megestrol acetate
was diarrhea. Adverse events reported in greater than 5% of the patients in
any of the treatment groups in these two well-controlled clinical trials,
regardless of causality, are presented below:

Table 12- Number (n) and Percentage of Patients with Adverse Event?

  ARIMIDEX ARIMIDEX Megesterol
  1 mg
(n = 262) 10 mg
(n = 246) Acetate
160 mg
(n = 253)
Adverse Event n % n % n %
Asthenia 42 (16) 33 (13) 47 (19)
Nausea 41 (16) 48 (2)0) 28 (11)
Headache 34 (13) 44 (1)8) 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)

?A patient may have more than one adverse event.

Other less frequent (2% to 5%) adverse experiences reported in patients
receiving ARIMIDEX 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 ARIMIDEX. 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; 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 events captured in the groups, were prospectively
defined. The results are shown in the table below.

Table 13 - Number (n) and Percentage of Patients

  ARIMIDEX ARIMIDEX Megestrol Acetate
  1 mg
(n = 262) 10 mg
(n = 246) 160 mg
(n = 253)
Adverse Event Group n (%) n (%) n (%)
Gastrointestinal Disturbance 77 (29) 81 (33) 54 (21)
Hot Flushes 33 (13) 29 (12) 35 (14)
Edema 19 (7) 28 (11) 35 (14)
Thromboembolic Disease 9 (3) 4 (2) 12 (5)
Vaginal Dryness 5 (2) 3 (1) 2 (1)
Weight Gain 4 (2) 10 (4) 30 (12)

More patients treated with megestrol acetate reported weight gain as an
adverse event compared to patients treated with ARIMIDEX 1 mg (p<0.0001).
Other differences were not statistically significant.

An examination of the magnitude of change in weight in all patients was also
conducted. Thirty-four percent (87/253) of the patients treated with
megestrol acetate experienced weight gain of 5% or more and 11% (27/253) of
the patients treated with megestrol acetate experienced weight gain of 10%
or more. Among patients treated with ARIMIDEX 1 mg, 13% [33/262] experienced
weight gain of 5% or more and 3% [6/262] experienced weight gain of 10% or
more. On average, this 5 to 10% weight gain represented between 6 and 12
pounds.

No patients receiving ARIMIDEX or megestrol acetate discontinued treatment
due to drug-related weight gain.

Vaginal bleeding has been reported infrequently, mainly in patients during
the first few weeks after changing from existing hormonal therapy to
treatment with ARIMIDEX. If bleeding persists, further evaluation should be
considered.

During clinical trials and postmarketing experience joint pain/stiffness has

been reported in association with the use of ARIMIDEX.

ARIMIDEX may also be associated with rash including very rare cases of
mucocutaneous disorders such as erythema multiforme and Stevens-Johnson
syndrome. Very rare cases of allergic reactions including angioedema,
urticaria and anaphylaxis have been reported in patients receiving ARIMIDEX.

DRUG INTERACTIONS
(See CLINICAL PHARMACOLOGY) Anastrozole inhibited in vitro metabolic
reactions catalyzed by cytochromes P450 1A2, 2C8/9, and 3A4 but only at
relatively high concentrations. Anastrozole did not inhibit P450 2A6 or the
polymorphic P450 2D6 in human liver microsomes. Anastrozole did not alter
the pharmacokinetics of antipyrine. Although there have been no formal
interaction studies other than with antipyrine, based on these in vivo and
in vitro studies, it is unlikely that co-administration of a 1 mg dose of
ARIMIDEX with other drugs will result in clinically significant drug
inhibition of cytochrome P450-mediated metabolism of the other drugs.

An interaction study with warfarin showed no clinically significant effect
of anastrozole on warfarin pharmacokinetics or anticoagulant activity.

At a median follow-up of 33 months, the combination of ARIMIDEX 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 CLINICAL PHARMACOLOGY - Drug
Interactions and CLINICAL PHARMACOLOGY - Clinical Studies - Adjuvant
Treatment of Breast Cancer in Postmenopausal Women subsections).
Co-administration of anastrozole and tamoxifen resulted in a reduction of
anastrozole plasma levels by 27% compared with those achieved with
anastrozole alone.

Estrogen-containing therapies should not be used with ARIMIDEX as they may
diminish its pharmacologic action.

Drug/Laboratory Test Interactions

No clinically significant changes in the results of clinical laboratory
tests have been observed.

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PRECAUTIONS
General

ARIMIDEX is not recommended for use in premenopausal women as safety and
efficacy has not been established (see CLINICAL PHARMACOLOGY,
Pharmacodynamics, Effect on Estradiol section).

Before starting treatment with ARIMIDEX, pregnancy must be excluded (see
WARNINGS). ARIMIDEX should be administered under the supervision of a
qualified physician experienced in the use of anticancer agents.

Laboratory Tests

Results from the ATAC trial bone substudy, at 12 and 24 months demonstrated
that patients receiving ARIMIDEX 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 ARIMIDEX lowers circulating estrogen levels it may cause a reduction
in bone mineral density.

During the ATAC trial, more patients receiving ARIMIDEX were reported to
have an elevated serum cholesterol compared to patients receiving tamoxifen
(9% versus 3.5%, respectively).

Carcinogenesis

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 50
mg/kg/day, plasma AUC levels in mice were 35 to 40 times higher than the
level exhibited in postmenopausal volunteers at the recommended dose.