LETROZOLE (letrozole)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Lactation
Pregnancy

There are 2 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Disease of liver
Osteoporosis

There are 4 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Cerebrovascular disorder
Hypercholesterolemia
Osteopenia
Thromboembolic disorder

There are 22 severe adverse reactions.

More Frequent	Less Frequent
None.	Acute myocardial infarction Dyspnea Fracture Hypertension Influenza Osteopenia Osteoporosis

Rare/Very Rare
Abnormal hepatic function tests Anaphylaxis Angioedema Cerebrovascular accident Endometrial hyperplasia Erythema multiforme Hepatitis Hypersensitivity drug reaction Leukopenia Ovarian cyst Stevens-johnson syndrome Tendon rupture Tenosynovitis Thromboembolic disorder Toxic epidermal necrolysis

There are 53 less severe adverse reactions.

More Frequent	Less Frequent
Arthralgia Dizziness Drug-induced hot flash Edema Flushing General weakness Headache disorder Hypercholesterolemia Hyperhidrosis Nausea Weight gain	Abdominal pain with cramps Abnormal vaginal bleeding Alopecia Arthritis Back pain Bone pain Chest pain Constipation Cough Depression Diarrhea Drowsy Fatigue Insomnia Mastalgia Musculoskeletal pain Myalgia Pain in extremities Peripheral edema Pruritus of skin Skin rash Symptoms of anxiety Vomiting Vulvovaginal dryness Weight loss

Rare/Very Rare
Anorexia Blurred vision Carpal tunnel syndrome Cataracts Dry skin Dysesthesia Dysgeusia Increased appetite Memory impairment Nervousness Palpitations Tendonitis Trigger finger Urinary tract infection Urticaria Vaginal discharge Xerostomia

Letrozole is contraindicated in women who are pregnant since the drug can cause fetal toxicity when administered to pregnant women. The manufacturer states that a pregnancy test should be performed prior to initiation of letrozole therapy in females of reproductive potential and that such women should be advised to use effective contraceptive methods while receiving the drug and for at least 3 weeks after discontinuance of the drug. If letrozole is administered during pregnancy or if the patient becomes pregnant while receiving the drug, inform the patient of the potential hazard to the fetus.

Spontaneous abortion and congenital birth defects have been reported during postmarketing experience when the drug was used in pregnant women; however, postmarketing reports on letrozole use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes. In animal reproduction studies, letrozole administered to pregnant rats and rabbits during organogenesis was associated with increased pregnancy loss (increased postimplantation loss, increased resorption, and decreased number of live fetuses) and teratogenicity (skeletal and renal malformations) at dosages approximately 0.1 times the maximum recommended human dosage on a mg/m2 basis.

It is not known whether letrozole is distributed into human milk or if the drug has any effects on nursing infants or on milk production. Because many drugs are distributed into milk and because impaired reproductive performance has been observed in male offspring of lactating rats and letrozole has the potential to cause serious adverse reactions in nursing infants, women should be advised to discontinue breast-feeding during letrozole therapy and for at least 3 weeks after discontinuance of the drug.

In the clinical trial evaluating letrozole as initial adjuvant therapy for early-stage breast cancer, 36% of patients were 65 years of age or older at enrollment, while 12% were 75 years of age or older. Adverse effects generally occurred more frequently in geriatric patients regardless of their assigned study treatment; however, no overall differences in safety and efficacy of letrozole versus tamoxifen were observed between geriatric patients and younger adults. In the clinical trial evaluating letrozole as extended adjuvant therapy for early-stage breast cancer, 41% of patients were 65 years of age or older at enrollment, while 12% were 75 years of age or older.

Although no overall differences in safety or efficacy were observed between geriatric patients and younger adults, and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out. In clinical trials evaluating letrozole as first-line or second-line therapy for advanced or metastatic breast cancer, about one-third of patients were 70 years of age or older (median age: 64-65 years). Among patients receiving letrozole as first-line therapy in a clinical trial, higher response rate and longer time to tumor progression were observed in geriatric patients (70 years or older) compared with younger patients.