Idelara

Idelara Adverse Reactions

letrozole

Manufacturer:

Craveri

Distributor:

Apolloplus Capital

Marketer:

Bioprofarma Bago
Full Prescribing Info
Adverse Reactions
Letrozole was generally well tolerated across all studies in first-line and second-line metastatic breast cancer, adjuvant treatment, as well as extended adjuvant treatment in women who have received prior adjuvant tamoxifen treatment.
Generally, the observed adverse reactions are mild or moderate in nature.
Adjuvant treatment of early breast cancer in postmenopausal women: The median duration of adjuvant treatment was 24 months and the median duration of follow-up for safety was 26 months for patients receiving letrozole and tamoxifen.
Certain adverse events were prospectively specified for analysis, based on the known pharmacological properties and side effect profiles of the two drugs.
Adverse events were analyzed irrespective of whether a symptom was present or absent at baseline. Most adverse events reported (82%) were Grade 1 and Grade 2 applying the Common Toxicity Criteria Version 2.0. (See Table 2.)

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When considering all grades, a higher incidence of events were seen for letrozole regarding fractures (5.7% vs. 4), myocardial infarctions (0.6% vs. 0.4%), and arthralgia (21.2% vs. 13.5%) (letrozole vs. tamoxifen, respectively). A higher incidence was seen for tamoxifen regarding thromboembolic events (1.2% vs. 2.8%), endometrial cancer (0.2% vs. 0.4%), and endometrial proliferative disorders (0.3% vs. 1.8%) (letrozole vs. tamoxifen, respectively).
Extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy: The median duration of extended adjuvant treatment was 24 months and the median duration of follow-up for safety was 28 months for patients receiving letrozole and placebo.
Most adverse events reported were Grade 1 and Grade 2 based on the Common Toxicity Criteria version 2.0. In the extended adjuvant setting, the reported drug-related adverse events that were significantly different from placebo were hot flashes, arthralgia/arthritis, and myalgia. (See Table 3.)

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The duration of follow-up for both the main clinical study and the bone study were insufficient to assess fracture risk associated with long-term use of letrozole. Based on a median follow-up of patients for 28 months, the incidence of clinical fractures from the core randomized study in patients who received letrozole was 5.9% (152) and placebo was 5.5% (142). The incidence of self-reported osteoporosis was higher in patients who received letrozole 6.9% (176) than in patients who received placebo 5.5% (141). Bisphosphonates were administered to 21.1% of the patients who received letrozole and 18.7% of the patients who received placebo.
Preliminary results (median duration of follow-up was 20 months) from the bone sub-study (calcium 500 mg and vitamin D 400 IU per day mandatory; bisphosphonates not allowed) demonstrated that at 2 years the mean decrease compared to baseline in hip BMD in letrozole patients was 3% vs. 0.4% for placebo. The mean decrease from baseline BMD results for the lumbar spine at 2 years was letrozole 4.6% decrease and placebo 2.2%. The incidence of cardiovascular ischemic events from the core randomized study was comparable between patients who received letrozole 6.8% (175) and placebo 6.5% (167).
Preliminary results from the lipid sub-study did not show significant differences between the letrozole and placebo groups. The HDL:LDL ratio decreased after the first 6 months of therapy but the decrease was similar in both groups and no statistically significant differences were detected.
A patient-reported measure that captures treatment impact on important symptoms associated with estrogen deficiency demonstrated a difference in favor of placebo for vasomotor and sexual symptom domains.
First-Line Breast Cancer: A total of 455 patients were treated for a median time of exposure of 11 months. The incidence of adverse experiences was similar for letrozole and tamoxifen. The most frequently reported adverse experiences were bone pain, hot flushes, back pain, nausea, arthralgia and dyspnea. Discontinuations for adverse experiences other than progression of tumor occurred in 10/455 (2%) of patients on letrozole and in 15/455 (3%) of patients on tamoxifen. (See Table 4.)

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Other less frequent (≤2%) adverse experiences considered consequential for treatment groups, included peripheral thromboembolic events, cardiovascular events, and cerebrovascular events. Peripheral thromboembolic events included venous thrombosis, thrombophlebitis, portal vein thrombosis and pulmonary embolism. Cardiovascular events included angina, myocardial infarction, myocardial ischemia, and coronary heart disease. Cerebrovascular events included transient ischemic attacks, thrombotic or hemorrhagic strokes and development of hemiparesis.
Second-Line Breast Cancer: Letrozole was generally well tolerated in two controlled clinical trials.
Study discontinuations in the megestrol acetate comparison study for adverse events other than progression of tumor 5/188 (2.7%) on letrozole 0.5 mg, in 4/174 (2.3%) on letrozole 2.5 mg, and in 15/190 (7.9%) on megestrol acetate. There were fewer thromboembolic events at both letrozole doses than on the megestrol acetate arm (0.6% vs. 4.7%). There was also less vaginal bleeding (0.3% vs. 3.2%) on letrozole than on megestrol acetate. In the aminoglutethimide comparison study, discontinuations for reasons other than progression occurred in 6/193 (3.1%) on 0.5 mg letrozole, 7/185 (3.8%) on 2.5 mg letrozole, and 7/178 (3.9%) of patients on aminoglutethimide.
Comparisons of the incidence of adverse events revealed no significant differences between the high and low dose letrozole groups in either study.
Most of the adverse events observed in all treatment groups were mild to moderate in severity and it was generally not possible to distinguish adverse reactions due to treatment from the consequences of the patient's metastatic breast cancer, the effects of estrogen deprivation, or intercurrent illness. (See Table 5.)

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Other less frequent (<5%) adverse experiences considered consequential and reported in at least 3 patients treated with letrozole, included hypercalcemia, fracture, depression, anxiety, pleural effusion, alopecia, increased sweating and vertigo.
First-line and second-line breast cancer: In the combined analysis of the first- and second-line metastatic trials and post-marketing experiences other adverse events that were reported were cataract, eye irritation, palpitations, cardiac failure, tachycardia, dysesthesia (including hypoesthesia/paresthesia), arterial thrombosis, memory impairment, irritability, nervousness, urticaria, increased urinary frequency, leukopenia, stomatitis cancer pain, pyrexia, vaginal discharge, appetite increase, dryness of skin and mucosa (including dry mouth), and disturbances of taste and thirst.
Phase IV experiences: Cases of blurred vision, increased hepatic enzymes, angioedema and anaphylactic reactions have been reported.
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