Advertisement

Topics

These highlights do not include all the information needed to use Letrozole Tablets, USP safely and effectively. See full prescribing information for Letrozole Tablets, USP Letrozole Tablets, USPInitial U.S. Approval: 1997 | LETROZOLE

05:18 EDT 27th August 2014 | BioPortfolio

Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

In the adjuvant setting, the optimal duration of treatment with letrozole is unknown. The planned duration of treatment in the study was 5 years with 73% of the patients having completed adjuvant therapy. Treatment should be discontinued at relapse [see Clinical Studies (14.1) ].

In the extended adjuvant setting, the optimal treatment duration with letrozole tablets, USP 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 was 60 months. Seventy-one percent of patients were treated for at least 3 years and 58% of patients completed least 4.5 years of extended adjuvant treatment. The treatment should be discontinued at tumor relapse [see Clinical Studies (14.2)].

Use of letrozole tablets, USP may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. Results of a substudy to evaluate safety 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) [See Adverse reactions (6.1)]. Updated results from the BMD sub-study in the extended adjuvant setting demonstrated that at 2 years patients receiving letrozole had a median decrease from baseline of 3.8% in hip BMD compared to a median decrease of 2.0% 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 (6.2)].

In the adjuvant trial the incidence of bone fractures at any time after randomization was 13.8% for letrozole and 10.5% for tamoxifen. The incidence of osteoporosis was 5.1% for letrozole and 2.7% for tamoxifen [See Adverse Reactions (6.1)]. In the extended adjuvant trial the incidence of bone 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 [see Adverse Reactions (6.3)].

Consideration should be given to monitoring serum cholesterol. In the adjuvant trial hypercholesterolemia was reported in 52.3% of letrozole patients and 28.6% of tamoxifen patients. CTC grade 3-4 hypercholesterolemia was reported in 0.4% of letrozole patients and 0.1% of tamoxifen patients. Also in the adjuvant setting, an increase of ≥1.5 X ULN in total cholesterol (generally non-fasting) was observed in patients on monotherapy who had baseline total serum cholesterol within the normal range (i.e., <=1.5 X ULN) in 151/1843 (8.2%) on letrozole vs 57/1840 (3.2%). Lipid lowering medications were required for 25% of patients on letrozole and 16% on tamoxifen [see Adverse Reactions (6.1)].

The most serious adverse reactions from the use of letrozole tablets, USP are:

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)


 

Grades 1-4

Grades 3-4

Adverse Reaction

Letrozole tablets, USP
N=2448 n (%)

tamoxifen
N=2447 n (%)

Letrozole tablets, USP
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

-

Arthralgia/Arthritis

618

(25.2)

501

(20.4)

85

(3.5)

50

(2)

Night Sweats

357

(14.6)

426

(17.4)

0

-

0

-

Bone FracturesAny time after randomization, including post treatment follow-up

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 FracturesDuring study treatment, based on Safety Monotherapy population

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)

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

-

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)

54

(2.2)

16

(0.7)

17

(0.7)

Constipation

49

(2)

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/Cancer

11/1909

(0.6)

70/1943

(3.6)

-

-

-

-

Endometrial Proliferation Disorders

10

(0.3)

71

(1.8)

0

-

14

(0.6)

Endometrial Hyperplasia/Cancer Excluding women who had undergone hysterectomy before study entry

6/1909

(0.3)

57/1943

(2.9)

-

-

-

-

Other Endometrial Disorders

2

(<0.1)

3

(0.1)

0

-

0

-

Myocardial Infarction

24

(1)

12

(0.5)

-

-

-

-

Myocardial Infarction

37

(1.5)

25

(1)

-

-

-

-

Myocardial Ischemia

6

(0.2)

9

(0.4)

-

-

-

-

Cerebrovascular Accident

52

(2.1)

46

(1.9)

-

-

-

-

Cerebrovascular Accident

70

(2.9)

63

(2.6)

-

-

-

-

Angina

26

(1.1)

24

(1)

-

-

-

-

Angina

32

(1.3)

31

(1.3)

-

-

-

-

Thromboembolic Event

51

(2.1)

89

(3.6)

-

-

-

-

Thromboembolic Event

71

(2.9)

111

(4.5)

-

-

-

-

Other Cardiovascular

260

(10.6)

256

(10.5)

-

-

-

-

Other Cardiovascular

312

(12.7)

337

(13.8)

-

-

-

-

Second Malignancies

53

(2.2)

78

(3.2)

-

-

-

-

Second Malignancies

102

(4.2)

119

(4.9)

-

-

-

-

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, USP 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

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 letrozole tablets, USP was 5.9% (152) and placebo was 5.5% (142). The incidence of self-reported osteoporosis was higher in patients who received letrozole tablets, USP 6.9% (176) than in patients who received placebo 5.5% (141). Bisphosphonates were administered to 21.1% of the patients who received letrozole tablets, USP 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 letrozole tablets, USP 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 ( 5.1 )].

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 letrozole tablets, USP 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 ( 5.2 )]

Manufacturer

APP Pharmaceuticals, LLC

Active Ingredients

Source

Drugs and Medications [15 Associated Drugs and Medications listed on BioPortfolio]

Letrozole [Breckenridge Pharmaceutical, Inc.]

These highlights do not include all the information needed to use letrozole tablets safely and effectively. See full prescribing information for letrozole tablets.Letrozole tablets USP, 2.5 mgInitial ...

Letrozole [Sun Pharmaceutical Industries Limited ]

These highlights do not include all the information needed to use letrozole safely and effectively. See full prescribing information for letrozole tablets. Letrozole Tablets, USPInitial U.S. Approval:...

Letrozole [Kremers Urban Pharmaceuticals Inc.]

These highlights do not include all the information needed to use letrozole tablets safely and effectively. See full prescribing information for letrozole tablets. LETROZOLE Tablets, USPInitial U.S. A...

Letrozole [Qualitest Pharmaceuticals]

These highlights do not include all the information needed to use Letrozole Tablets, USP safely and effectively. See full prescribing information for Letrozole Tablets, USP. Letrozole Tablets, USPInit...

Letrozole [Physicians Total Care, Inc.]

These highlights do not include all the information needed to use letrozole safely and effectively. See full prescribing information for letrozole tablets. Letrozole Tablets, USP Initial U.S. Approval...

Clinical Trials [249 Associated Clinical Trials listed on BioPortfolio]

Pilot of Letrozole for Uterine Myomas

PLUM evaluates the drug letrozole as a treatment for uterine fibroids. This study is a randomized, blinded, placebo-controlled trial of oral letrozole among premenopausal women with sympto...

Endocrinology Profile in Patients Undergoing Clomiphene, Letrozole, and Combination Clomiphene and Letrozole Cycles

The goal of the study is to measure serial hormonal levels in patients undergoing clomiphene, letrozole, and a combination clomiphene and letrozole cycle. This information may help us to ...

Trial of Letrozole +/- Palbociclib in Metastatic Endometrial Cancer

This randomized phase 2 trial is evaluating superiority of Letrozole-palbociclib combination versus letrozole alone in ER positive endometrioid adenocarcinoma of endometrium

A Study of Neoadjuvant Letrozole + GDC-0032 Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)

This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the effect of combining letrozole and GDC-0032 versus letrozole and placebo in postmenopausal wome...

Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone in Post Menopausal Women With Breast Cancer

This is a phase 2 study of bosutinib administered in combination with letrozole versus letrozole alone in post-menopausal women with breast cancer. This is a 2-part study. Subjects in part...

PubMed Articles [23 Associated PubMed Articles listed on BioPortfolio]

A Retrospective Study of Letrozole Treatment Prior to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization at Risk of Ovarian Hyperstimulation Syndrome.

BACKGROUND Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) are given letrozole before a trigger injection of human chorionic gonadotropin (hCG) to lower estrogen (E...

Effects of letrozole and clomiphene citrate on Wnt signaling pathway in endometrium of polycystic ovarian syndrome and healthy women.

Polycystic ovary syndrome (PCOS) is an endocrine disorder in women of reproductive age. In addition to anovulation, endometrial dysfunction can reduce fertility in PCOS. The cyclical changes of endome...

Misclassification in Assessment of First Trimester In-Utero Exposure to Drugs used Proximally to Conception - The Example of Letrozole Utilization for Infertility Treatment.

Letrozole is an aromatase inhibitor with an unapproved use for ovulation induction with infertility. Because of the proximity of this use to conception, we selected letrozole to explore the effect of ...

Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice.

Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proc...

Comparison of the pregnancy outcomes and the incidence of fetal congenital abnormalities in infertile women treated with letrozole and clomiphene citrate.

The aim of the study was to evaluate the incidence of congenital fetal anomalies reported among infertile Iranian women treated with letrozole compared to those treated with Clomiphene Citrate (CC).

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Osteoporosis
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...


Drugs and Medication Quicklinks


Searches Linking to this Drug Record

  Number (%) of Patients with Grade 1-4 Adverse Reaction Number (%) of Patients with Grade 3-4 Adverse Reaction
Letrozole Tablets, USP
N=2563
Placebo
N=2573
Letrozole Tablets, USP
N=2563
Placebo
N=2573