Recommended Topic Related To:

Femara

"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

Femara

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

The median treatment duration of adjuvant treatment was 60 months and the median duration of follow-up for safety was 73 months for patients receiving Femara and tamoxifen.

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
Femara
N=2448
n (%)
tamoxifen
N=2447
n (%)
Femara
N=2448
n (%)
tamoxifen
N=2447
n (%)
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 population
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
Femara
N=2563
Placebo
N=2573
Femara
N=2563
Placebo
N=2573
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
(N=455)
%
tamoxifen 20 mg
(N=455)
%
General Disorders
  Fatigue 13 13
  Chest Pain 8 9
  Edema Peripheral 5 6
  Pain NOS 5 7
  Weakness 6 4
Investigations
  Weight Decreased 7 5
Vascular Disorders
  Hot Flushes 19 16
  Hypertension 8 4
Gastrointestinal Disorders
  Nausea 17 17
  Constipation 10 11
  Diarrhea 8 4
  Vomiting 7 8
Infections/Infestations
  Influenza 6 4
  Urinary Tract Infection NOS 6 3
Injury, Poisoning and Procedural Complications
  Post-Mastectomy Lymphedema 7 7
Metabolism and Nutrition Disorders
  Anorexia 4 6
Musculoskeletal and Connective Tissue Disorders
  Bone Pain 22 21
  Back Pain 18 19
  Arthralgia 16 15
  Pain in Limb 10 8
Nervous System Disorders
  Headache NOS 8 7
  Psychiatric Disorders
  Insomnia 7 4
Reproductive System and Breast Disorders
  Breast Pain 7 7
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea 18 17
  Cough 13 13
  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
(N=359)
%
Pooled Femara 0.5 mg
(N=380)
%
megestrol acetate 160 mg
(N=189)
%
aminoglutethimide 500 mg
(N=178)
%
Body as a Whole
  Fatigue 8 6 11 3
  Chest Pain 6 3 7 3
  Peripheral Edema1 5 5 8 3
  Asthenia 4 5 4 5
  Weight Increase 2 2 9 3
Cardiovascular
  Hypertension 5 7 5 6
Digestive System
  Nausea 13 15 9 14
  Vomiting 7 7 5 9
  Constipation 6 7 9 7
  Diarrhea 6 5 3 4
  Pain-Abdominal 6 5 9 8
  Anorexia 5 3 5 5
  Dyspepsia 3 4 6 5
Infections/Infestations
  Viral Infection 6 5 6 3
Lab Abnormality
  Hypercholesterolemia 3 3 0 6
Musculoskeletal System
  Musculoskeletal2 21 22 30 14
  Arthralgia 8 8 8 3
Nervous System
  Headache 9 12 9 7
  Somnolence 3 2 2 9
  Dizziness 3 5 7 3
Respiratory System
  Dyspnea 7 9 16 5
  Coughing 6 5 7 5
Skin and Appendages
  Hot Flushes 6 5 4 3
  Rash3 5 4 3 12
  Pruritus 1 2 5 3
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.

Postmarketing Experience

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 Femara (letrozole) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Tamoxifen

Coadministration of Femara and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels of 38% on average. Clinical experience in the second-line breast cancer trials indicates that the therapeutic effect of Femara therapy is not impaired if Femara is administered immediately after tamoxifen.

Cimetidine

A pharmacokinetic interaction study with cimetidine showed no clinically significant effect on letrozole pharmacokinetics.

Warfarin

An interaction study with warfarin showed no clinically significant effect of letrozole on warfarin pharmacokinetics.

Other anticancer agents

There is no clinical experience to date on the use of Femara in combination with other anticancer agents.

Read the Femara Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 1/27/2014
This monograph has been modified to include the generic and brand name in many instances.

A A A

Femara - User Reviews

Femara User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Femara sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Breast Cancer

Find support and advances in treatment.

Related Supplements
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations