Letrozole

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 therapy ( 1.2 ) First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer ( 1.3 ) 1.1 Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. …

• Letrozole tablets are taken orally without regard to meals : Recommended dose: 2.5.mg once daily Patients with cirrhosis or severe hepatic impairment: 2.5 mg every other day Recommended Dose The recommended dose of letrozole tablet is one 2.5 mg tablet administered once a day, without regard to meals
• 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
• Treatment should be discontinued at relapse [see Clinical Studies ]
• 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
• Seventy-one percent (71%) of patients were treated for at least 3 years and 58% of patients completed at least 4.5 years of extended adjuvant treatment
• The treatment should be discontinued at tumor relapse [see Clinical Studies ]
• Use in First and Second-Line Treatment of Advanced Breast Cancer In patients with advanced disease, treatment with letrozole tablets should continue until tumor progression is evident [see Clinical Studies ] . …

2.5 mg tablets: yellow round, biconvex, film coated tablets imprinted with 'LT' on one side and plain on other side. 2.5 mg tablets ( 3 )

• The safety and effectiveness
• In pediatric patients have not been established
• Letrozole administration to young (postnatal day 7) rats for 12 weeks duration at 0.003, 0.03, 0.3 mg/kg/day by oral gavage resulted in adverse skeletal/growth effects (bone maturation, bone mineral density) and neuroendocrine and reproductive developmental perturbations of the hypothalamic-pituitary axis
• Administration of 0.3 mg/kg/day resulted in AUC values that were similar to the AUC in adult patients receiving the recommended dose of 2.5 mg/day. …

The median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64 to 65 years. About 1/3 of the patients were greater than or equal to 70 years old. In the first-line study, patients greater than or equal to 70 years of age experienced longer time to tumor progression and higher response rates than patients less than 70. …

• Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during letrozole therapy and for at least 3 weeks after the last dose
• Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with letrozole tablets [see Warnings and Precautions , and Use in Specific Populations , ] Lactation Advise women not to breastfeed during letrozole tablets treatment and for at least 3 weeks after the last dose [see Use in Specific Populations . …

• Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations ]
• Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations ]
• Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions ]
• Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions ]
• Pregnancy Known hypersensitivity to the active substance, or to any of the excipients

Tamoxifen Coadministration of letrozole and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels of 38% on average (Study P015). Clinical experience in the second-line breast cancer trials (AR/BC2 and AR/BC3) indicates that the therapeutic effect of letrozole therapy is not impaired if letrozole is administered immediately after tamoxifen. Cimetidine A pharmacokinetic interaction study with cimetidine (Study P004) showed no clinically significant effect on letrozole pharmacokinetics. Warfarin An interaction study (P017) with warfarin showed no clinically significant effect of letrozole on warfarin pharmacokinetics. …

Decreases in bone mineral density may occur. Consider bone mineral density monitoring ( 5.1 ) Increases in total cholesterol may occur. Consider cholesterol monitoring. ( 5.2 ) Fatigue, dizziness and somnolence may occur. Exercise caution when operating machinery ( 5.4 ) Embryo-Fetal Toxicity: Can cause fetal harm when administered to pregnant women. Obtain a pregnancy test in females of reproductive potential. Advise females of reproductive potential to use effective contraception ( 5.6 , 8.1 , 8.3 ) 5.1 Bone Effects Use of letrozole may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. …

The following adverse reactions are discussed in greater detail in other sections of the labeling. Bone effects [see Warnings and Precautions ( 5.1 )] Increases in cholesterol [see Warnings and Precautions ( 5.2 )] Fatigue and Dizziness [see Warnings and Precautions ( 5.4 )] 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. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

8.1 Pregnancy Risk Summary Based on postmarketing reports, findings from animal studies and the mechanism of action, letrozole can cause fetal harm and is contraindicated for use in pregnant women. In post-marketing reports, use of letrozole during pregnancy resulted in cases of spontaneous abortions and congenital birth defects; however, the data are insufficient to inform a drug-associated risk [see Contraindications ( 4 ), Warnings and Precaut …

Isolated cases of letrozole overdose have been reported. In these instances, the highest single dose ingested was 62.5 mg or 25 tablets. While no serious adverse reactions were reported in these cases, because of the limited data available, no firm recommendations for treatment can be made. However, emesis could be induced if the patient is alert. In general, supportive care and frequent monitoring of vital signs are also appropriate. In single-dose studies, the highest dose used was 30 mg, which was well tolerated; in multiple-dose trials, the largest dose of 10 mg was well tolerated. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.