Letrostad Adverse Reactions

Approximately one third of the patients treated with Letrozole in the metastatic setting, approximately 70-75% of the patients in the adjuvant setting (both Letrozole and Tamoxifen arms), and approximately 40% of the patients in the extended adjuvant treatment group (both Letrozole and placebo arms) experienced adverse reactions. In general, the observed adverse reactions were mainly mild or moderate in nature, and mostly associated with oestrogen deprivation (e.g. hot flushes).
In patients of the metastatic setting, the most frequently reported adverse reactions in the clinical trials were hot flushes (10.8%), arthralgia, nausea (6.9%) and fatigue (5.0%). Many adverse reactions can be attributed to the normal pharmacological consequences of oestrogen deprivation (e.g. hot flushes, alopecia and vaginal bleeding).
During extended adjuvant treatment the following adverse events irrespective of causality were reported significantly more often with Letrozole than with placebo: hot flushes (50.7% vs. 44.3%), arthralgia/arthritis (28.5% vs. 23.2%) and myalgia (10.2% vs. 7.0%). The majority of these adverse events were observed during the first year of treatment. There was a higher but non significant incidence of osteoporosis and bone fractures in patients treated with Letrozole than in those who received placebo (7.5% vs. 6.3% and 6.7% vs. 5.9%, respectively).
In the adjuvant setting, irrespective of causality, the following adverse events occurred at any time following randomisation in the Letrozole and Tamoxifen groups, respectively: thromboembolic events (1.5% vs. 3.2%, P<0.001), angina pectoris (0.8% vs. 0.8%), myocardial infarction (0.7% vs. 0.4%) and cardiac failure (0.9% vs. 0.4%, P=0.006).