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Arimidex (Anastrozole) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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
1
2
3
4
5

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)

1 COSTART Coding Symbols for Thesaurus of Adverse Reaction Terms.
2 N = Number of patients receiving the treatment.
3 *A patient may have had more than 1 adverse event, including more than 1 adverse event in the same body system.
4 Vaginal Hemorrhage without further diagnosis.
5 ** The combination arm was discontinued due to lack of efficacy benefit 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

1
2

Hot Flashes

1104 (36)

1264 (41)

0.80

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)

1.10

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)

0.50

0.41 − 0.61

Ischemic Cardiovascular Disease3 3

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)

0.70

0.50 − 0.97

Endometrial Cancer4 4

4 (0.2)

13 (0.6)

0.31

0.10 − 0.94

1 1Patients with multiple events in the same category are counted only once in that category.
2 2Refers to joint symptoms, including joint disorder, arthritis, arthrosis and arthralgia.
3 3 The observed difference was associated with a sub-group of patients with pre-existing ischemic heart disease
4 4 Percentages calculated based upon the numbers of patients with an intact uterus as baseline

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
1

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)

1 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
1
2
3

Number (n) and Percentage of Patients

ARIMIDEX

1 mg

(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)

1 a A patient may have had more than 1 adverse event
2 bIncludes pulmonary embolus, thrombophlebitis, retinal vein thrombosis
3 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:

1

Adverse Event

ARIMIDEX

1 mg

(n = 262)

n %

ARIMIDEX

10 mg

(n = 246)

n%

Megesterol

Acetate

160 mg

(n = 253)

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)

1 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

Adverse Event Group

ARIMIDEX

1 mg

(n = 262)

n (%)

ARIMIDEX

10 mg

(n = 246)

n (%)

Megestrol Acetate

160 mg

(n = 253)

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.

Post-Marketing Experience

Hepatobiliary events including increases in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase have been reported commonly (> 1% and <10%) and gamma-GT, bilirubin and hepatitis have been reported uncommonly (> 0.1% and <1%) in patients receiving ARIMIDEX.

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.

Carpal tunnel syndrome was reported more frequently in patients receiving ARIMIDEX than in those receiving tamoxifen in clinical trials; carpal tunnel has also been reported during post-marketing experience with ARIMIDEX. The majority of these reports occurred in patients with identifiable risk factors for the condition.

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.



REPORTS OF SUSPECTED ARIMIDEX SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Arimidex. The information is not vetted and should not be considered as verified clinical evidence.

Possible Arimidex side effects / adverse reactions in 52 year old female

Reported by a consumer/non-health professional from Australia on 2011-10-03

Patient: 52 year old female

Reactions: Breast Cancer, Hepatic Failure

Adverse event resulted in: death

Suspect drug(s):
Arimidex



Possible Arimidex side effects / adverse reactions in 88 year old female

Reported by a consumer/non-health professional from Australia on 2011-10-03

Patient: 88 year old female

Reactions: Pneumonia, Neoplasm Malignant

Adverse event resulted in: death

Suspect drug(s):
Arimidex



Possible Arimidex side effects / adverse reactions in 59 year old female

Reported by a consumer/non-health professional from Australia on 2011-10-03

Patient: 59 year old female

Reactions: Neoplasm Malignant

Adverse event resulted in: death

Suspect drug(s):
Arimidex



See index of all Arimidex side effect reports >>

Drug label data at the top of this Page last updated: 2007-07-17

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