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Aromasin

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Aromasin

Side Effects
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SIDE EFFECTS

AROMASIN was generally well tolerated and adverse events were usually mild to moderate.

In the adjuvant treatment of early breast cancer, adverse events occurring in ≥ 10% of patients in any treatment group (AROMASIN vs. tamoxifen) were hot flushes (21.2% vs. 19.9%), fatigue (16.1% vs. 14.7%), arthralgia (14.6% vs. 8.6%), headache (13.1% vs. 10.8%), insomnia (12.4% vs. 8.9%), and increased sweating (11.8% vs. 10.4%). Discontinuation rates due to AEs were similar between AROMASIN and tamoxifen (6.3% vs. 5.1%). Incidences of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) were AROMASIN 1.6%, tamoxifen 0.6%. Incidence of cardiac failure: AROMASIN 0.4%, tamoxifen 0.3%.

In the treatment of advanced breast cancer, the most common adverse events were mild to moderate and included hot flushes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%) for AROMASIN and megestrol acetate, respectively.

Clinical Trial Experience

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 clinical practice.

Adjuvant Therapy

The data described below reflect exposure to AROMASIN in 2325 postmenopausal women with early breast cancer. AROMASIN tolerability in postmenopausal women with early breast cancer was evaluated in two well-controlled trials: the IES study (14.1) and the 027 study (a randomized, placebo-controlled, double-blind, parallel group study specifically designed to assess the effects of exemestane on bone metabolism, hormones, lipids, and coagulation factors over 2 years of treatment).

The median duration of adjuvant treatment was 27.4 months and 27.3 months for patients receiving AROMASIN or tamoxifen, respectively, within the IES study and 23.9 months for patients receiving AROMASIN or placebo within the 027 study. Median duration of observation after randomization for AROMASIN was 34.5 months and for tamoxifen was 34.6 months. Median duration of observation was 30 months for both groups in the 027 study.

Certain adverse events, which were expected based on the known pharmacological properties and side effect profiles of test drugs, were actively sought through a positive checklist. Signs and symptoms were graded for severity using CTC in both studies. Within the IES study, the presence of some illnesses/conditions was monitored through a positive checklist without assessment of severity. These included myocardial infarction, other cardiovascular disorders, gynecological disorders, osteoporosis, osteoporotic fractures, other primary cancer, and hospitalizations.

AROMASIN was generally well tolerated and adverse events were usually mild to moderate. Within the IES study, discontinuations due to adverse events occurred in 6.3% and 5.1% of patients receiving AROMASIN and tamoxifen, respectively, and in 12.3% and 4.1% of patients receiving exemestane or placebo respectively within study 027.

Deaths due to any cause were reported for 1.3% of the exemestane treated patients and 1.4% of the tamoxifen treated patients within the IES study. There were 6 deaths due to stroke on the exemestane arm compared to 2 on tamoxifen. There were 5 deaths due to cardiac failure on the exemestane arm compared to 2 on tamoxifen.

The incidence of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) was 1.6% in exemestane treated patients and 0.6% in tamoxifen treated patients in the IES study. Cardiac failure was observed in 0.4% of exemestane treated patients and 0.3% of tamoxifen treated patients.

Treatment-emergent adverse events and illnesses including all causalities and occurring with an incidence of ≥ 5% in either treatment group of the IES study during or within one month of the end of treatment are shown in Table 2.

Table 2: Incidence (%) of Adverse Events of all Grades1 and Illnesses Occurring in ( ≥ 5%) of Patients in Any Treatment Group in Study IES in Postmenopausal Women with Early Breast Cancer

Body system and Adverse Event by MedDRA dictionary % of patients
AROMASIN 25 mg daily
(N=2252)
Tamoxifen 20 mg daily2
(N=2280)
Eye
  Visual disturbances3 5 3.8
Gastrointestinal
  Nausea3 8.5 8.7
General Disorders
  Fatigue3 16.1 14.7
Musculoskeletal
  Arthralgia 14.6 8.6
  Pain in limb 9.0 6.4
  Back pain 8.6 7.2
  Osteoarthritis 5.9 4.5
Nervous System
  Headache3 13.1 10.8
  Dizziness3 9.7 8.4
Psychiatric
  Insomnia3 12.4 8.9
  Depression 6.2 5.6
Skin & Subcutaneous Tissue
  Increased sweating 11.8 10.4
  Vascular
  Hot flushes3 21.2 19.9
  Hypertension 9.8 8.4
1Graded according to Common Toxicity Criteria;
275 patients received tamoxifen 30 mg daily;
3Event actively sought.

In the IES study, as compared to tamoxifen, AROMASIN was associated with a higher incidence of events in musculoskeletal disorders and in nervous system disorders, including the following events occurring with frequency lower than 5% (osteoporosis [4.6% vs. 2.8%], osteochondrosis and trigger finger [0.3% vs. 0 for both events], paresthesia [2.6% vs. 0.9%], carpal tunnel syndrome [2.4% vs. 0.2%], and neuropathy [0.6% vs. 0.1%]). Diarrhea was also more frequent in the exemestane group (4.2% vs. 2.2%). Clinical fractures were reported in 94 patients receiving exemestane (4.2%) and 71 patients receiving tamoxifen (3.1%). After a median duration of therapy of about 30 months and a median follow-up of about 52 months, gastric ulcer was observed at a slightly higher frequency in the AROMASIN group compared to tamoxifen (0.7% vs. < 0.1%). The majority of patients on AROMASIN with gastric ulcer received concomitant treatment with non-steroidal anti-inflammatory agents and/or had a prior history.

Tamoxifen was associated with a higher incidence of muscle cramps [3.1% vs. 1.5%], thromboembolism [2.0% vs. 0.9%], endometrial hyperplasia [1.7% vs. 0.6%], and uterine polyps [2.4% vs. 0.4%].

Common adverse events occurring in study 027 are described in Table 3.

Table 3: Incidence of Selected Treatment-Emergent Adverse Events of all CTC Grades* Occurring in ≥ 5% of Patients in Either Arm in Study 027

Adverse Event Exemestane
N=73
(% incidence)
Placebo
N=73
(% incidence)
Hot flushes 32.9 24.7
Arthralgia 28.8 28.8
Increased sweating 17.8 20.6
Alopecia 15.1 4.1
Hypertension 15.1 6.9
Insomnia 13.7 15.1
Nausea 12.3 16.4
Fatigue 11 19.2
Abdominal pain 11 13.7
Depression 9.6 6.9
Diarrhea 9.6 1.4
Dizziness 9.6 9.6
Dermatitis 8.2 1.4
Headache 6.9 4.1
Myalgia 5.5 4.1
Edema 5.5 6.9
Anxiety 4.1 5.5
* Most events were CTC grade 1–2

Treatment of Advanced Breast Cancer

A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program. Only one death was considered possibly related to treatment with exemestane; an 80-year-old woman with known coronary artery disease had a myocardial infarction with multiple organ failure after 9 weeks on study treatment. In the clinical trials program, only 3% of the patients discontinued treatment with exemestane because of adverse events, mainly within the first 10 weeks of treatment; late discontinuations because of adverse events were uncommon (0.3%).

In the comparative study, adverse reactions were assessed for 358 patients treated with AROMASIN and 400 patients treated with megestrol acetate. Fewer patients receiving AROMASIN discontinued treatment because of adverse events than those treated with megestrol acetate (2% vs. 5%). Adverse events that were considered drug related or of indeterminate cause included hot flashes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%) for AROMASIN and megestrol acetate, respectively. The proportion of patients experiencing an excessive weight gain ( > 10% of their baseline weight) was significantly higher with megestrol acetate than with AROMASIN (17% vs. 8%). Table 4 shows the adverse events of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with AROMASIN or megestrol acetate.

Table 4: Incidence (%) of Adverse Events of all Grades* and Causes Occurring in ≥ 5% of Advanced Breast Cancer Patients In Each Treatment Arm in the Comparative Study

Body system and Adverse Event by WHO ART dictionary AROMASIN 25 mg once daily
(N=358)
Megestrol Acetate 40 mg QID
(N=400)
Autonomic Nervous
  Increased sweating 6 9
Body as a Whole
  Fatigue 22 29
  Hot flashes   13 6
  Pain 13 13
  Influenza-like symptoms 6 5
  Edema (includes edema, peripheral edema, leg edema) 7 6
Cardiovascular
  Hypertension 5 6
Nervous
  Depression 13 9
  Insomnia 11 9
  Anxiety 10 11
  Dizziness 8 6
  Headache 8 7
Gastrointestinal
  Nausea 18 12
  Vomiting 7 4
  Abdominal pain 6 11
  Anorexia 6 5
  Constipation 5 8
  Diarrhea 4 5
  Increased appetite 3 6
Respiratory
  Dyspnea 10 15
  Coughing 6 7
* Graded according to Common Toxicity Criteria

Less frequent adverse events of any cause (from 2% to 5%) reported in the comparative study for patients receiving AROMASIN 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.

Additional adverse events of any cause observed in the overall clinical trials program (N = 1058) in 5% or greater of patients treated with exemestane 25 mg once daily but not in the comparative study included pain at tumor sites (8%), asthenia (6%), and fever (5%). Adverse events of any cause reported in 2% to 5% of all patients treated with exemestane 25 mg in the overall clinical trials program but not in the comparative study included chest pain, hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain, infection, upper respiratory tract infection, pharyngitis, rhinitis, and alopecia.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of AROMASIN. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders-hypersensitivity

Hepatobiliary disorders-hepatitis including cholestatic hepatitis

Nervous system disorders-paresthesia

Skin and subcutaneous tissue disorders-acute generalized exanthematous pustulosis, urticaria, pruritus

Read the Aromasin (exemestane) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Co-medications that induce CYP 3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's wort) may significantly decrease exposure to exemestane. Dose modification is recommended for patients who are also receiving a strong CYP 3A4 inducer [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Read the Aromasin Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 5/23/2014
This monograph has been modified to include the generic and brand name in many instances.

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