Letero Special Precautions

Bone effects: Osteoporosis and/or bone fractures have been reported with the use of Letrozole. Therefore monitoring of overall bone health is recommended during treatment (see Pharmacology: Pharmacodynamics under Actions and Adverse Reactions).
Renal impairment: Letrozole has not been investigated in patients with creatinine clearance <10 mL/min. The potential risk/benefit to such patients should be carefully considered before administration of Letrozole.In a study involving volunteers with varying degrees of renal function (24-hour creatinine clearance 9 to 116 mL/min), no effect on the pharmacokinetics systemic exposure of letrozole was found after a single dose of 2.5 mg. Therefore, no dose adjustment is required for patients with renal impairment (CLcr = 10 mL/min). Little information is available in patients with severe impairment of renal function (CLcr <10 mL/min).
Hepatic impairment: In patients with severe hepatic impairment (Child-Pugh score C), systemic exposure and terminal half-life were approximately doubled compared to healthy volunteers. Such patients should therefore be kept under close supervision (see Pharmacology: Pharmacokinetics under Actions).In a similar study involving subjects with varying degrees of hepatic function, the mean AUC values of the volunteers with moderate hepatic impairment (Child-Pugh score B) was 37% higher than in normal subjects, but still within the range seen in subjects without impaired function. In a study comparing the pharmacokinetics of letrozole after a single oral dose in eight subjects with liver cirrhosis and severe hepatic impairment (Child-Pugh score C) to those in healthy volunteers (n=8), AUC and t1/2 increased by 95 and 187%, respectively. Breast-cancer patients with severe hepatic impairment are thus expected to be exposed to higher levels of letrozole than patients without severe hepatic dysfunction. However, since in patients dosed at 5 or 10 mg/day no increase in toxicity was observed, a dose reduction in patients with severe hepatic impairment appears not to be warranted, although such patients should be kept under close supervision. In addition, in two well-controlled studies involving 359 patients with advanced breast cancer, no effect of renal impairment (calculated creatinine clearance: 20 to 50 mL/min) or hepatic dysfunction was found on the letrozole concentration.
Menopausal status: In patients whose menopausal status is unclear, luteinising hormone (LH), follicle-stimulating hormone (FSH) and/or estradiol levels should be measured before initiating treatment with Letrozole. Only women of postmenopausal endocrine status should receive Letrozole.
Fertility: The pharmacological action of letrozole is to reduce estrogen production by aromatase inhibition. In premenopausal women, the inhibition of estrogen synthesis leads to feedback increases in gonadotropin (LH, FSH) levels. Increased FSH levels in turn stimulate follicular growth, and can induce ovulation.
Interactions: Co-administration of Letrozole with tamoxifen, other anti-estrogens or estrogen-containing therapies should be avoided as these substances may diminish the pharmacological action of letrozole. The mechanism of this interaction is unknown (see Interactions).
Driving and using machines: Since fatigue and dizziness have been observed with the use of Letrozole and somnolence has been reported uncommonly, caution is advised when driving or using machines.
Use in Elderly: Age had no effect on the pharmacokinetics of letrozole.