"Dec. 5, 2012 -- Doubling the time that breast cancer patients take tamoxifen cuts the risk that the cancer will come back and further lowers the risk of dying of the disease, a new study shows.
The study is expected to change the way"...
Femara Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Femara (letrozole) is used to treat breast cancer in postmenopausal women. It is often given to women who have been taking tamoxifen (Nolvadex, Soltamox) for 5 years. It is a non-steroidal aromatase inhibitor (lowers estrogen production). This medication is available in generic form. Common side effects include hot flashes, hair loss, joint/bone/muscle pain, tiredness, unusual sweating, nausea, diarrhea, dizziness, and trouble sleeping.
The recommended dose of Femara is one 2.5 mg tablet administered once a day, without regard to meals. Other drugs may interact with Femara. Tell your doctor all prescription and over-the-counter medications and supplements you use. Femara must not be used during pregnancy. It may harm a fetus. Femara is used mainly in women after menopause. If you have recently gone through menopause, discuss birth control with your doctor. Do not use birth control containing estrogen. It is unknown if this drug passes into breast milk and may harm a nursing infant. Breast-feeding while using this drug is not recommended.
Our Femara (letrozole) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Patient Information in Detail?
Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.
Femara in Detail - Patient Information: Side Effects
Stop using letrozole and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Less serious side effects may include:
- hot flashes, warmth or redness in your face or chest;
- headache, muscle or joint pain;
- night sweats;
- weight gain;
- fatigue, feeling weak;
- nausea; or
- swelling in your hands, ankles, or feet.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Femara (Letrozole) »
What is Patient Information Overview?
A concise overview of the drug for the patient or caregiver from First DataBank.
Femara Overview - Patient Information: Side Effects
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor immediately if any of these unlikely but serious side effects occur: bone fractures, mental/mood changes (such as depression, anxiety), swelling of arms/legs, blurred vision.
This medication (and cancer) may rarely cause serious problems from blood clots (such as heart attack or stroke). Seek immediate medical attention if you experience: sudden shortness of breath, chest/jaw/left arm pain, confusion, coughing up blood, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, tingling/weakness/numbness in the arms/legs, slurred speech, weakness on one side of the body, vision changes, sudden/severe headache.
Tell your doctor immediately if any of these rare but very serious side effects occur: persistent nausea/vomiting, unusual tiredness, dark urine, yellowing eyes/skin..
A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat/neck), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Read the entire patient information overview for Femara (Letrozole)»
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Femara FDA Prescribing Information: Side Effects
The most serious adverse reactions from the use of Femara are:
Because clinical trials are conducted under widely varying conditions, adverse reactions 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 practice.
Adjuvant Treatment Of Early Breast Cancer
Certain adverse reactions wer e prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs.
Adverse reactions wer e analyzed irrespective of whether a symptom was present or absent at baseline. Most adverse reactions reported (approximately 75% of patients reporting 1 or more AE) were Grade 1 or Grade 2 applying the Common Toxicity Criteria Version 2.0/ Common Terminology Criteria for Adverse Events, version 3.0. Table 1 describes adverse reactions (Grades 1-4) irrespective of relationship to study treatment in the adjuvant trial for the monotherapy arms analysis (safety population).
Table 1: Patients with
Adverse Reactions (CTC Grades 1-4, Irrespective of Relationship to Study Drug)
in the Adjuvant Study - Monotherapy Arms Analysis (Median Follow-up 73 Months;
Median Treatment 60 Months)
|Adverse Reaction||Grades 1-4||Grades 3-4|
|Pts with any adverse event||2310 (94.4)||2214 (90.5)||635 (25.9)||604 (24.7)|
|Hypercholesterolemia||1280 (52.3)||700 (28.6)||11 ( 0.4)||6 ( 0.2)|
|Hot Flashes/Flushes||821 (33.5)||929 (38.0)||0 -||0 -|
|Arthralgia/Arthritis||618 (25.2)||501 (20.4)||85 ( 3.5)||50 ( 2.0)|
|Night Sweats||357 (14.6)||426 (17.4)||0 -||0 -|
|Bone Fractures2||338 (13.8)||257 (10.5)||- -||- -|
|Weight Increase||317 (12.9)||378 (15.4)||27 ( 1.1)||39 ( 1.6)|
|Nausea||283 (11.6)||277 (11.3)||6 ( 0.2)||9 ( 0.4)|
|Bone Fractures1||247 (10.1)||174 ( 7.1)||- -||- -|
|Fatigue (Lethargy, Malaise, Asthenia)||235 ( 9.6)||250 (10.2)||6 ( 0.2)||7 ( 0.3)|
|Myalgia||217 ( 8.9)||212 ( 8.7)||18 ( 0.7)||14 ( 0.6)|
|Edema||164 ( 6.7)||160 ( 6.5)||3 ( 0.1)||1 ( < 0.1)|
|Weight Decrease||140 ( 5.7)||129 ( 5.3)||8 ( 0.3)||5 ( 0.2)|
|Vaginal Bleeding||128 ( 5.2)||320 (13.1)||1 ( < 0.1)||8 ( 0.3)|
|Back Pain||125 ( 5.1)||136 ( 5.6)||7 ( 0.3)||11 ( 0.4)|
|Osteoporosis NOS||124 ( 5.1)||66 ( 2.7)||10 ( 0.4)||5 ( 0.2)|
|Bone pain||123 ( 5.0)||109 ( 4.5)||6 ( 0.2)||4 ( 0.2)|
|Depression||119 ( 4.9)||114 ( 4.7)||16 ( 0.7)||14 ( 0.6)|
|Vaginal Irritation||111 ( 4.5)||77 ( 3.1)||2 ( < 0.1)||2 ( < 0.1)|
|Headache||105 ( 4.3)||94 ( 3.8)||9 ( 0.4)||5 ( 0.2)|
|Pain in extremity||103 ( 4.2)||79 ( 3.2)||6 ( 0.2)||4 ( 0.2)|
|Osteopenia||87 ( 3.6)||74 ( 3.0)||0 -||2 ( < 0.1)|
|Dizziness/Light-Headedness||84 ( 3.4)||84 ( 3.4)||1 ( < 0.1)||6 (0.2)|
|Alopecia||83 ( 3.4)||84 ( 3.4)||0 -||0 -|
|Vomiting||80 ( 3.3)||80 ( 3.3)||3 ( 0.1)||5 (0.2)|
|Cataract||49 ( 2.0)||54 ( 2.2)||16 ( 0.7)||17 ( 0.7)|
|Constipation||49 ( 2.0)||71 ( 2.9)||3 ( 0.1)||1 ( < 0.1)|
|Breast pain||37 ( 1.5)||43 ( 1.8)||1 ( < 0.1)||0 -|
|Anorexia||20 ( 0.8)||20 ( 0.8)||1 ( < 0.1)||1 ( < 0.1)|
|Endometrial Hyperplasia/ Cancer2, 3||11/1909 ( 0.6)||70/1943 ( 3.6)||-||-|
|Endometrial Proliferation Disorders||10 (0.3)||71 (1.8)||0 -||14 (0.6)|
|Endometrial Hyperplasia/ Cancer1, 3||6/1909 ( 0.3)||57/1943 (2.9)||-||-|
|Other Endometrial Disorders||2 ( < 0.1)||3 ( 0.1)||0||0|
|Myocardial Infarction1||24 ( 1.0)||12 ( 0.5)||-||-|
|Myocardial Infarction2||37 ( 1.5)||25 (1.0)||-||-|
|Myocardial Ischemia||6 ( 0.2)||9 ( 0.4)||-||-|
|Cerebrovascular Accident1||52 ( 2.1)||46 ( 1.9)||-||-|
|Cerebrovascular Accident2||70 ( 2.9)||63 ( 2.6)||-||-|
|Angina1||26 ( 1.1)||24 ( 1.0)||-||-|
|Angina2||32 ( 1.3)||31 ( 1.3)||-||-|
|Thromboembolic Event1||51 ( 2.1)||89 ( 3.6)||-||-|
|Thromboembolic Event2||71 ( 2.9)||111 ( 4.5)||-||-|
|Other Cardiovascular1||260 (10.6)||256 (10.5)||-||-|
|Other Cardiovascular2||312 (12.7)||337 (13.8)||-||-|
|Second Malignancies1||53 ( 2.2)||78 ( 3.2)||-||-|
|Second Malignancies2||102 ( 4.2)||119 ( 4.9)||-||-|
|1During study treatment, based on Safety Monotherapy
2Any time after randomization, including post treatment follow-up
3Excluding women who had undergone hysterectomy before study entry
Note: Cardiovascular (including cerebrovascular and thromboembolic), skeletal and urogenital/endometrial events and second malignancies were collected life-long. All of these events were assumed to be of CTC Grade 3 to 5 and were not individually graded.
When considering all grades during study treatment, a higher incidence of events was seen for Femara regarding fractures (10.1% vs 7.1%), myocardial infarctions (1.0% vs 0.5%), and arthralgia (25.2% vs 20.4%) (Femara vs tamoxifen respectively). A higher incidence was seen for tamoxifen regarding thromboembolic events (2.1% vs 3.6%), endometrial hyperplasia/cancer (0.3% vs 2.9%), and endometrial proliferation disorders (0.3% vs 1.8%) (Femara vs tamoxifen respectively).
At a median follow up of 73 months, a higher incidence of events was seen for Femara (13.8%) than for tamoxifen (10.5%) regarding fractures. A higher incidence was seen for tamoxifen compared to Femara regarding thromboembolic events (4.5% vs 2.9%), and endometrial hyperplasia or cancer (2.9% vs 0.4%) (tamoxifen vs Femara, respectively).
Bone Study: Results of a phase 3 safety trial in 262 postmenopausal women with resected receptor positive early breast cancer in the adjuvant setting comparing the effect on lumbar spine (L2-L4) bone mineral density (BMD) of adjuvant treatment with letrozole to that with tamoxifen showed at 24 months a median decrease in lumbar spine BMD of 4.1% in the letrozole arm compared to a median increase of 0.3% in the tamoxifen arm (difference = 4.4%) (P < 0.0001). No patients with a nor mal BMD at baseline became osteoporotic over the 2 years and only 1 patient with osteopenia at baseline (T score of -1.9) developed osteoporosis during the treatment period (assessment by central review). The results for total hip BMD were similar, although the differences between the two treatments were less pronounced. During the 2 year period, fractures were reported by 4 of 103 patients (4%) in the letrozole arm, and 6 of 97 patients (6%) in the tamoxifen arm.
Lipid Study: In a phase 3 safety trial in 262 postmenopausal women with resected receptor positive early breast cancer at 24 months comparing the effects on lipid profiles of adjuvant letrozole to tamoxifen, 12% of patients on letrozole had at least one total cholesterol value of a higher CTCAE grade than at baseline compared with 4% of patients on tamoxifen.
Extended Adjuvant Treatment Of Early Breast Cancer, Median Treatment Duration Of 24 Months
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 2 describes the adverse reactions occurring at a frequency of at least 5% in any treatment group during treatment. Most adverse reactions 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 reactions that were significantly different from placebo were hot flashes, arthralgia/arthritis, and myalgia.
Table 2: Percentage of
Patients with Adverse Reactions
|Number (%) of Patients with Grade 1-4 Adverse Reaction||Number (%) of Patients with Grade 3-4 Adverse Reaction|
|Any Adverse Reaction||2232 (87.1)||2174 (84.5)||419 (16.3)||389 (15.1)|
|Vascular Disorders||1375 (53.6)||1230 (47.8)||59 (2.3)||74 (2.9)|
|Flushing||1273 (49.7)||1114 (43.3)||3 (0.1)||0|
|General Disorders||1154 (45)||1090 (42.4)||30 (1.2)||28 (1.1)|
|Asthenia||862 (33.6)||826 (32.1)||16 (0.6)||7 (0.3)|
|Edema NOS||471 (18.4)||416 (16.2)||4 (0.2)||3 (0.1)|
|Musculoskeletal Disorders||978 (38.2)||836 (32.5)||71 (2.8)||50 (1.9)|
|Arthralgia||565 (22)||465 (18.1)||25 (1)||20 (0.8)|
|Arthritis NOS||173 (6.7)||124 (4.8)||10 (0.4)||5 (0.2)|
|Myalgia||171 (6.7)||122 (4.7)||8 (0.3)||6 (0.2)|
|Back Pain||129 (5)||112 (4.4)||8 (0.3)||7 (0.3)|
|Nervous System Disorders||863 (33.7)||819 (31.8)||65 (2.5)||58 (2.3)|
|Headache||516 (20.1)||508 (19.7)||18 (0.7)||17 (0.7)|
|Dizziness||363 (14.2)||342 (13.3)||9 (0.4)||6 (0.2)|
|Skin Disorders||830 (32.4)||787 (30.6)||17 (0.7)||16 (0.6)|
|Sweating Increased||619 (24.2)||577 (22.4)||1 (<0.1)||0|
|Gastrointestinal Disorders||725 (28.3)||731 (28.4)||43 (1.7)||42 (1.6)|
|Constipation||290 (11.3)||304 (11.8)||6 (0.2)||2 ( < 0.1)|
|Nausea||221 (8.6)||212 (8.2)||3 (0.1)||10 (0.4)|
|Diarrhea NOS||128 (5)||143 (5.6)||12 (0.5)||8 (0.3)|
|Metabolic Disorders||551 (21.5)||537 (20.9)||24 (0.9)||32 (1.2)|
|Hypercholesterolemia||401 (15.6)||398 (15.5)||2 ( < 0.1)||5 (0.2)|
|Reproductive Disorders||303 (11.8)||357 (13.9)||9 (0.4)||8 (0.3)|
|Vaginal Hemorrhage||123 (4.8)||171 (6.6)||2 ( < 0.1)||5 (0.2)|
|Vulvovaginal Dryness||137 (5.3)||127 (4.9)||0||0|
|Psychiatric Disorders||320 (12.5)||276 (10.7)||21 (0.8)||16 (0.6)|
|Insomnia||149 (5.8)||120 (4.7)||2 ( < 0.1)||2 ( < 0.1)|
|Respiratory Disorders||279 (10.9)||260 (10.1)||30 (1.2)||28 (1.1)|
|Dyspnea||140 (5.5)||137 (5.3)||21 (0.8)||18 (0.7)|
|Investigations||184 (7.2)||147 (5.7)||13 (0.5)||13 (0.5)|
|Infections and Infestations||166 (6.5)||163 (6.3)||40 (1.6)||33 (1.3)|
|Renal Disorders||130 (5.1)||100 (3.9)||12 (0.5)||6 (0.2)|
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.
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).
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.
Bone Sub-study: [see WARNINGS AND PRECAUTIONS].
Lipid Sub-study: In the extended adjuvant setting, based on a median duration of follow-up of 62 months, there was no significant difference between Femara and placebo in total cholesterol or in any lipid fraction at any time over 5 years. Use of lipid lowering drugs or dietary management of elevated lipids was allowed. [see WARNINGS AND PRECAUTIONS].
Updated Analysis, Extended Adjuvant Treatment Of Early Breast Cancer, Median Treatment Duration Of 60 Months
The extended adjuvant treatment trial was unblinded early. At the updated (final analysis), overall the side effects seen were consistent to those seen at a median treatment duration of 24 months.
During treatment or within 30 days of stopping treatment (median duration of treatment 60 months) a higher rate of fractures was observed for Femara (10.4%) compared to placebo (5.8%), as also a higher rate of osteoporosis (Femara 12.2% vs placebo 6.4%).
Based on 62 months median duration of follow-up in the randomized letrozole arm in the Safety population the incidence of new fractures at any time after randomization was 13.3% for letrozole and 7.8% for placebo. The incidence of new osteoporosis was 14.5% for letrozole and 7.8% for placebo.
During treatment or within 30 days of stopping treatment (median duration of treatment 60 months) the incidence of cardiovascular events was 9.8% for Femara and 7.0% for placebo.
Based on 62 months median duration of follow-up in the randomized letrozole arm in the Safety population the incidence of cardiovascular disease at any time after randomization was 14.4% for letrozole and 9.8% for placebo.
Lipid sub-study: In the extended adjuvant setting, based on a median duration of follow-up of 62 months, there was no significant difference between Femara and placebo in total cholesterol or in any lipid fraction over 5 years. Use of lipid lowering drugs or dietary management of elevated lipids was allowed. [see WARNINGS AND PRECAUTIONS]
First-Line Treatment Of Advanced Breast Cancer
A total of 455 patients were treated for a median time of exposure of 11 months. The incidence of adverse reactions was similar for Femara and tamoxifen. The most frequently reported adverse reactions were bone pain, hot flushes, back pain, nausea, arthralgia and dyspnea. Discontinuations for adverse reactions other than progression of tumor occurred in 10/455 (2%) of patients on Femara and in 15/455 (3%) of patients on tamoxifen.
Adverse reactions, 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 3.
Table 3: Percentage (% ) of
Patients with Adverse Reactions
|AdverseReaction||Femara 2.5 mg
|tamoxifen 20 mg
|Urinary Tract Infection NOS||6||3|
|Injury, Poisoning and Procedural Complications|
|Metabolism and Nutrition Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|Pain in Limb||10||8|
|Nervous System Disorders|
|Reproductive System and Breast Disorders|
|Respiratory, Thoracic and Mediastinal Disorders|
|Chest Wall Pain||6||6|
Other less frequent ( ≤ 2%) adverse reactions 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 Treatment Of Advanced Breast Cancer
Study discontinuations in the megestrol acetate comparison study for adverse reactions other than progression of tumor were 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 reactions revealed no significant differences between the high and low dose Femara groups in either study. Most of the adverse reactions 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 reactions, 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 4.
Table 4: Percentage (% ) of
Patients with Adverse Reactions
|Adverse Reaction||Pooled Femara 2.5 mg
|Pooled Femara 0.5 mg
|megestrol acetate 160 mg
|aminoglutethimide 500 mg
|Body as a Whole|
|Skin and Appendages|
|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 reactions 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 And Second-Line Treatment Of Advanced Breast Cancer
In the combined analysis of the first-and second-line metastatic trials and post-marketing experiences other adverse reactions that were reported were cataract, eye irritation, palpitations, cardiac failure, tachycardia, dysesthesia (including hypesthesia/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.
Cases of blurred vision, increased hepatic enzymes, angioedema, anaphylactic reactions, toxic epidermal necrolysis, erythema multiforme, and hepatitis have been reported. Cases of carpal tunnel syndrome and trigger finger have been identified during post approval use of Femara.
Read the entire FDA prescribing information for Femara (Letrozole) »
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