1) ] Early breast cancer: Adverse reactions occurring in ≥10% of patients in any treatment group (exemestane tablets vs. tamoxifen) were hot flushes (21% vs. 20%), fatigue (16% vs. 15%), arthralgia (15% vs. 9%), headache (13% vs. 11%), insomnia (12% vs.
9%), and increased sweating (12% vs. 10%). Discontinuation rates due to AEs were similar between exemestane tablets and tamoxifen (6% vs. 5%). 6%. 1 ).
Advanced breast cancer:
Most common adverse reactions 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. 1 ). To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc.
gov/medwatch. 1 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 exemestane tablets in 2325 postmenopausal women with early breast cancer. 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).
9 months for patients receiving exemestane tablets or placebo within the 027 study. 6 months. Median duration of observation was 30 months for both groups in the 027 study. Certain adverse reactions, 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.
1% of patients receiving exemestane or placebo respectively within study 027. 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.
6% in tamoxifen treated patients in the IES study. 3% of tamoxifen treated patients. In the adjuvant treatment of early breast cancer, the most common adverse reactions occurring in ≥10% of patients in any treatment group (exemestane tablets vs.
tamoxifen) were hot flushes (21% vs. 20%), fatigue (16% vs. 15%), arthralgia (15% vs. 9%), headache (13% vs. 11%), insomnia (12% vs. 9%), and increased sweating (12% vs. 10%). Discontinuation rates due to AEs were similar between exemestane tablets and tamoxifen (6% vs.
5%). 6%. 3%. Treatment-emergent adverse reactions 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 Reactions of all Grades Graded according to Common Toxicity Criteria; and Illnesses Occurring in (≥5%) of Patients in Any Treatment Group in Study IES in Postmenopausal Women with Early Breast Cancer % of patients Body system and Adverse Reaction by MedDRA dictionary Exemestane Tablets 25 mg daily (N=2252) Tamoxifen 20 mg daily 75 patients received tamoxifen 30 mg daily; (N=2280) Eye Visual disturbances Event actively sought.
6% vs. 3% vs. 6% vs. 4% vs. 6% vs. 1%]). 2% vs. 2%). 1%). 7% vs. 1%). The majority of patients on exemestane tablets with gastric ulcer received concomitant treatment with non-steroidal anti-inflammatory agents and/or had a prior history. 1% vs.
0% vs. 7% vs. 4% vs. 4%]. Common adverse reactions occurring in study 027 are described in Table 3. Table 3. 1 Edema 6 7 Treatment of Advanced Breast Cancer A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program.
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. 7% of patients discontinued exemestane within the first 10 weeks of treatment.
In the comparative study, adverse reactions were assessed for 358 patients treated with exemestane tablets and 400 patients treated with megestrol acetate. Fewer patients receiving exemestane tablets discontinued treatment because of adverse reactions than those treated with megestrol acetate (2% vs.
5%). Adverse reactions 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 exemestane tablets 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 exemestane tablets (17% vs. 8%). In the treatment of advanced breast cancer, the most common adverse reactions 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 exemestane tablets and megestrol acetate, respectively. Table 4 shows the adverse reactions of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with exemestane tablets or megestrol acetate.
Table 4. Incidence (%) of Adverse Reactions of all Grades Graded according to Common Toxicity Criteria and Causes Occurring in ≥5% of Advanced Breast Cancer Patients In Each Treatment Arm in the Comparative Study Body system and Adverse Reaction by WHO ART dictionary Exemesane Tablets 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 Adverse reactions of any cause (from 2% to 5%) reported in the comparative study for patients receiving exemestane tablets 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.
Additional adverse reactions 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 reactions 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.
2 Post-Marketing Experience The following adverse reactions have been identified during post approval use of exemestane tablets. Because these 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 Musculoskeletal and connective tissue disorder- tenosynovitis stenosans Skin and subcutaneous tissue disorders- acute generalized exanthematous pustulosis, urticaria, pruritus