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Letrozole is a brand name for Letrozole. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Letrozole tablet is an aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer ( 1.1 ) Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen…
Verbatim from this product's FDA label. Tap a section to expand.
5 mg tablet administered once a day, without regard to meals. 2 Use in Adjuvant Treatment of Early Breast Cancer In the adjuvant setting, the optimal duration of treatment with letrozole is unknown. In both the adjuvant study and the post approval adjuvant study, median treatment duration was 5 years.
1 )]. 3 Use in Extended Adjuvant Treatment of Early Breast Cancer In the extended adjuvant setting, the optimal treatment duration with letrozole tablet is not known. The planned duration of treatment in the study was 5 years. In the final updated analysis, conducted at a median follow-up of 62 months, the median treatment duration for letrozole tablets was 60 months.
5 years of extended adjuvant treatment. 2 )]. 5 )] . 5 Use in Hepatic Impairment No dosage adjustment is recommended for patients with mild to moderate hepatic impairment, although letrozole tablets blood concentrations were modestly increased in subjects with moderate hepatic impairment due to cirrhosis.
3 )]. 5 mg administered every other day. The effect of hepatic impairment on letrozole tablets exposure in noncirrhotic cancer patients with elevated bilirubin levels has not been determined. 3 )] .
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. 4 )] The most common adverse reactions (greater than 20%) were hot flashes, arthralgia; flushing, asthenia, edema, arthralgia, headache, dizziness, hypercholesterolemia, sweating increased, bone pain and musculoskeletal ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. gov/medwatch . 1 Clinical Trials Experience 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 In study, BIG 1-98, the median treatment duration of adjuvant treatment was 60 months and the median duration of follow-up for safety was 96 months for patients receiving letrozole and tamoxifen.
Certain adverse reactions were prospectively specified for analysis (see Table 1), based on the known pharmacologic properties and side effect profiles of the two drugs. Adverse reactions were analyzed irrespective of whether a symptom was present or absent at baseline.
0. Table 1 describes adverse reactions (Grades 1-4 and Grades 3-4) irrespective of relationship to study treatment in the adjuvant trial for the monotherapy arms analysis (safety population). e. e. during treatment + 30 days after discontinuation of treatment) for letrozole tablets and tamoxifen (range up to 68 months) 3 Excluding women who had undergone hysterectomy before study entry TIA = Transient ischemic attack Note: Cardiovascular events (including cerebrovascular and thromboembolic events), skeletal and urogenital/endometrial events and second primary malignancies were collected life -long.
1% vs. 0% vs. 2% vs. 4%) (letrozole vs. tamoxifen respectively). 1% vs. 3% vs. 3% vs. 8%) (letrozole vs. tamoxifen respectively). 4%) regarding fractures. 6% vs. 9% vs. 4%) (tamoxifen vs. letrozole, respectively). 0001). 9) developed osteoporosis during the treatment period (assessment by central review).
5 WARNINGS AND PRECAUTIONS Decreases in bone mineral density may occur. 1 ) Increases in total cholesterol may occur. Consider cholesterol monitoring. 2 ) Fatigue, dizziness and somnolence may occur. 4 ) Embryo-Fetal toxicity: Can cause fetal harm when administered to pregnant women.
Obtain a pregnancy test in females of reproductive potential. 1 Bone Effects Use of letrozole may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. 0001) [see Adverse Reactions ( 6 )] . 0% in the placebo group.
The changes from baseline in lumbar spine BMD in letrozole and placebo treated groups were not significantly different [see Adverse Reactions ( 6 )]. 4% for tamoxifen at a median follow-up of 96 months. 7% for tamoxifen [see Adverse Reactions ( 6 )] .
8% for placebo at a median follow-up of 62 months. 8% for placebo [see Adverse Reactions ( 6 )]. 2 Cholesterol Consideration should be given to monitoring serum cholesterol. 6% of tamoxifen patients. 1% of tamoxifen patients. 9%) patients on tamoxifen.
Lipid lowering medications were required for 29% of patients on letrozole and 20% on tamoxifen [see Adverse Reactions ( 6 )]. 3 )] . Therefore, a dose reduction is recommended for this patient population. 5 )]. 4 Fatigue and Dizziness Because fatigue, dizziness, and somnolence have been reported with the use of letrozole, caution is advised when driving or using machinery until it is known how the patient reacts to letrozole use.
5 Laboratory Test Abnormalities No dose-related effect of letrozole on any hematologic or clinical chemistry parameter was evident. 5 mg. This depression was transient in about half of those affected. Two patients on letrozole developed thrombocytopenia; relationship to the study drug was unclear.
Patient withdrawal due to laboratory abnormalities, whether related to study treatment or not was infrequent. 6 Embryo-Fetal Toxicity Based on post-marketing reports, findings from animal studies and the mechanism of action, letrozole can cause fetal harm and is contraindicated for use in pregnant women.
1 )] . 1 )] . Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions ( 6 )] . Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions ( 6 )] . Pregnancy ( 4 ) Known hypersensitivity to the active substance, or to any of the excipients ( 4 )
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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 safety trial in 263 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.
In another postapproval randomized, multicenter, open label, study of letrozole vs anastrozole in the adjuvant treatment of postmenopausal women with hormone receptor and node positive breast cancer (FACE, NCT00248170), the median duration of treatment was 60 months for both treatment arms.
Table 2 describes adverse reactions (Grades 1-4 and Grades 3-4) irrespective of relationship to study treatment in the adjuvant study (safety population). 3) The following adverse reactions were also identified in less than 5% of the 2049 patients treated with letrozole and not included in the table: fall, vertigo, hyperbilirubinemia, jaundice, and chest pain.
Extended Adjuvant Treatment of Early Breast Cancer, Median Treatment Duration of 24 Months In study MA-17, 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 tablets and placebo.
Table 3 describes the adverse reactions occurring at a frequency of at least 5% in any treatment group during treatment. 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.
5% (142). 5% (141). 7% of the patients who received placebo. 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.
1 )].
Lipid Substudy :
In the extended adjuvant setting, based on a median duration of follow-up of 62 months, there was no significant difference between letrozole 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.
2 )]. Updated Analysis, Extended Adjuvant Treatment of Early Breast Cancer, Median Treatment Duration of 60 Months The extended adjuvant treatment trial (MA-17) was unblinded early [see Adverse Reactions ( 6 )] . At the updated (final analysis), overall the side effects seen were consistent to those seen at a median treatment duration of 24 months.
4%). 8% for placebo. 8% for placebo. 0% for placebo. 8% for placebo.
Lipid Substudy :
In the extended adjuvant setting (MA-17), based on a median duration of follow-up of 62 months, there was no significant difference between letrozole 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.
2 )] First-Line Treatment of Advanced Breast Cancer In study P025 a total of 455 patients were treated for a median time of exposure of 11 months in the letrozole arm (median 6 months in the tamoxifen arm). The incidence of adverse reactions was similar for letrozole 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 letrozole and in 15/455 (3%) of patients on tamoxifen.
5 mg or tamoxifen 20 mg in the first-line treatment study are shown in Table 4. 5 mg 20 mg (N=455) (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 (less than or equal to 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. 9%) on megestrol acetate. 7%). 2%) on letrozole than on megestrol acetate. 9%) of patients on aminoglutethimide.
Comparisons of the incidence of adverse reactions revealed no significant differences between the high and low dose letrozole 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.
5 mg, megestrol acetate, or aminoglutethimide in the two controlled trials AR/BC2 and AR/BC3 are shown in Table 5. 5 mg 160 mg 500 mg (N=359) (N=380) (N=189) (N=178) % % % % Body as a Whole Chest Pain 6 3 7 3 Peripheral Edema 1 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 Musculoskeletal 2 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 Rash 3 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 (less than 5%) adverse reactions 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 and Second-Line Treatment of Advanced Breast Cancer In the combined analysis of the first- and second-line metastatic trials and postmarketing 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.
2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of letrozole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Eye Disorders: blurred vision Hepatobiliary Disorders: increased hepatic enzymes, hepatitis Immune System Disorders: anaphylactic reactions, hypersensitivity reactions Nervous System Disorders: carpal tunnel syndrome, trigger finger Pregnancy: spontaneous abortions, congenital birth defects Skin and subcutaneous disorders: angioedema, toxic epidermal necrolysis, erythema multiforme
In post-marketing reports, use of letrozole during pregnancy resulted in cases of spontaneous abortions and congenital birth defects. Letrozole caused embryo-fetal toxicities in rats and rabbits at maternal exposures that were below the maximum recommended human dose (MHRD) on a mg/m 2 basis.
Advise pregnant women of the potential risk to a fetus. 1 )].