A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Arimidex Side Effects, and Drug Interactions - Anastrozole
Arimidex Side Effects, and Drug Interactions - Anastrozole
ADVERSE REACTIONS
Adjuvant Therapy: The median duration of adjuvant treatment for safety evaluation was 37.3 months, 36.9 months, and 36.5 months for
patients receiving ARIMIDEX 1 mg, tamoxifen 20 mg, and the combination of ARIMIDEX 1 mg plus tamoxifen 20 mg, respectively.
Adverse events occurring with an incidence of at least 5% in any treatment group during treatment or within 14 days of the end of treatment
are presented in Table 7.
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 than 1 adverse event in the same body system.
Non-pathologic fractures were reported more frequently in the ARIMIDEX-treated patients (219 [7%]) than in the tamoxifen-treated patients
(137 [4%]).
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 8). Patients receiving ARIMIDEX had an increase in musculoskeletal events
and fractures (including fractures of spine, hip and wrist) compared with patients receiving tamoxifen. Patients receiving ARIMIDEX had
a decrease in hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events (including deep venous
thrombosis) and ischemic cerebrovascular events compared with patients receiving tamoxifen.
Angina pectoris was reported more frequently in the ARIMIDEX-treated patients (52 [1.7%]) than in the tamoxifen-treated patients
(30 [1.0%]); the incidence of myocardial infarction was comparable (ARIMIDEX 24 patients [0.8%]; tamoxifen 25 patients [0.8%]).
Preliminary results from the ATAC trial bone substudy 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 9.
Less frequent adverse experiences reported in patients receiving ARIMIDEX 1 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.
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 (i.e., 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:
Other less frequent (2% to 5%) adverse experiences reported in patients receiving ARIMIDEX 1 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.
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.
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.
Drug/Laboratory Test Interactions: No
clinically significant changes in the results of clinical
laboratory tests have been
observed.
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