Femara Side Effects

Generic Name: Letrozole

Please note - some side effects for Femara may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Femara - for the consumer

Femara

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Femara:

Arthritis; back, bone, leg, or arm pain; breast pain; constipation; cough; diarrhea; dizziness; headache; hot flushes; flu-like symptoms; flushing; increased sweating; indigestion; infection; joint or muscle pain; loss of appetite; nausea; night sweats; pain; sleeplessness; stomach pain; tiredness; urinary tract infection; vaginal dryness; vomiting; weakness; weight gain or loss.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); calf pain or tenderness; chest pain; confusion; numbness of an arm or leg; one-sided weakness; severe stomach pain; shortness of breath; sudden severe headache, vomiting, dizziness, or fainting; swelling of the ankles or feet; unexplained sore throat or fever; unexplained vaginal bleeding or discharge; vision or speech changes.

For the professional

Femara

Femara® (letrozole tablets) 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 Femara and tamoxifen.

      Certain adverse events were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs.

      Adverse events have been 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. Table 13 describes adverse events (Grades 1-4) irrespective of relationship to study treatment in the adjuvant BIG 1-98 trial (safety population, during treatment or within 30 days of stopping treatment).

1 Based on safety population excluding patients who had undergone hysterectomy; time frame is any time after randomization; no CTC grades collected (yes/no response)

 2 Based on the intent-to-treat population; time frame is any time after randomization; no CTC grades collected (yes/no response)

When considering all grades, a higher incidence of events were seen for Femara regarding fractures (5.7% vs 4%), myocardial infarctions (0.6% vs 0.4%), and arthralgia (21.2% vs 13.5%)( Femara 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%), endometrial proliferative disorders (0.3% vs 1.8%) Femara 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 Femara  and placebo.

      Table 14 describes the adverse events occurring at a frequency of at least 5% in any treatment group during treatment. 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.

      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 Femara. 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 Femara was 5.9% (152) and placebo was 5.5% (142). The incidence of self-reported osteoporosis was higher in patients who received Femara 6.9% (176) than in patients who received placebo 5.5% (141). Bisphosphonates were administered to 21.1% of the patients who received Femara 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 Femara patients was 3% vs 0.4% for placebo. The mean decrease from baseline BMD results for the lumbar spine at 2 years were Femara 4.6% decrease and placebo 2.2%.

      The incidence of cardiovascular ischemic events from the core randomized study was comparable between patients who received Femara 6.8% (175) and placebo 6.5% (167). 

      Preliminary results (median duration of follow-up was 30 months) from the lipid sub-study did not show significant differences between the Femara 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 was treated for a median time of exposure of 11 months. The incidence of adverse experiences was similar for Femara 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 Femara and in 15/455 (3%) of patients on tamoxifen.

      Adverse events, regardless of relationship to study drug, that were reported in at least 5% of the patients treated with Femara 2.5 mg or tamoxifen 20 mg in the first-line treatment study are shown in Table 15.

      Other less frequent (≤2%) adverse experiences considered consequential for both 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

Femara 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 Femara 0.5 mg, in 4/174 (2.3%) on Femara 2.5 mg, and in 15/190 (7.9%) on megestrol acetate. There were fewer thromboembolic events at both Femara doses than on the megestrol acetate arm (0.6% vs 4.7%). There was also less vaginal bleeding (0.3% vs 3.2%) on Femara 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 Femara, 7/185 (3.8%) on 2.5 mg Femara, 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 Femara 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.

      Adverse events, regardless of relationship to study drug, that were reported in at least 5% of the patients treated with Femara 0.5 mg, Femara 2.5 mg, megestrol acetate, or aminoglutethimide in the two controlled trials are shown in Table 16.

1      Includes peripheral edema, leg edema, dependent edema, edema

2      Includes musculoskeletal pain, skeletal pain, back pain, arm pain, leg pain

3      Includes rash, erythematous rash, maculopapular rash, psoriasiform rash, vesicular rash

      Other less frequent (<5%) adverse experiences considered consequential and reported in at least 3 patients treated with Femara, 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, dysaesthesia (including hypoaesthesia/paraesthesia), 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.

Post-Marketing Experiences

Cases of blurred vision and increased hepatic enzyme have been uncommonly (<1%) reported since market introduction.

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