Letrozole
Indications:
Each tablet contains Letrozole BP 2.5 mg.
Precautions & Warnings:
In breast cancer patients with moderate hepatic dysfunction, no dosage adjustment is necessary, but caution is recommended since letrozole elimination depends mainly on intrinsic metabolic clearance. Renal impairment (calculated creatinine clearance: 20 to 50 ml/min) did not affect steady-state plasma letrozole concentration at a dose of 2.5 mg or 5 mg. Hence, no dose adjustment is necessary for such renal function impairment. It is anticipated that letrozole could be removed from the blood by dialysis since it is weakly bound to plasma proteins. The potential risks and benefits to such patients should be considered carefully before prescribing letrozole. In some cases, fatigue and dizziness have been observed with the use of letrozole. Patients should, therefore, be advised that their physical and/or mental abilities required for operating machinery or driving a car may be impaired.
Overdose:
There is no clinical experience of overdosage. There is no specific antidote to letrozole. Since letrozole is not highly protein-bound, dialysis may be helpful. Emesis may be induced if the patient is alert. In general, supportive care and frequent monitoring of vital signs are appropriate.
Storage:
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
Therapeutic Class: Gynecological (Hormonal Chemotherapy)
Indications:
- Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
- Extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy.
- First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
- Treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
Each tablet contains Letrozole BP 2.5 mg.
Description:
Letrozole is a nonsteroidal aromatase inhibitor. It exerts its antitumor effect by depriving estrogen-dependent breast cancer cells of their growth stimulus. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues.
Letrozole is a nonsteroidal aromatase inhibitor. It exerts its antitumor effect by depriving estrogen-dependent breast cancer cells of their growth stimulus. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues.
Dosage & Administration:
The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Endofree® tablet should be continued until tumor progression is evident.Treatment should be discontinued at tumor relapse.
The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Endofree® tablet should be continued until tumor progression is evident. Treatment should be discontinued at tumor relapse.
Renal Impairment
No dosage adjustment is required for patients with renal impairment if creatinine clearance is 10 ml/min.
Hepatic Impairment
No dosage adjustment is recommended for patients with mild to moderate hepatic impairment. The dose of Endofree® in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50%. The recommended dose for such patients is 2.5 mg administered every other day.
Interaction:
Clinical interaction studies with cimetidine and warfarin indicated that the co-administration of letrozole with these drugs does not result in clinically significant drug reactions, even though cimetidine is a known inhibitor of one of the cytochrome P450 isoenzymes capable of metabolizing letrozole in vitro.
Contraindications:
Letrozole is contraindicated in known or suspected hypersensitivity to letrozole, other aromatase inhibitors, or to any of their ingredients. It is contraindicated during pregnancy, lactation, and in pre-menopausal women. It is also contraindicated in severe hepatic dysfunction.
Side Effects:
Adverse events associated with letrozole are generally mild to moderate and rarely severe enough to require discontinuation. Many can be attributed to either the underlying disease or the normal pharmacological consequence of estrogen deprivation (hot flushes, hair thinning). The most frequently reported adverse events are musculoskeletal pain, arthralgia, headache, fatigue, nausea, dyspnoea, peripheral edema, coughing, constipation, vomiting, chest pain, viral infection, diarrhea, rash, abdominal pain, dyspepsia, and anorexia. Dizziness, weight increase, and pruritus are less commonly seen.
Use in Pregnancy & Lactation:
During pregnancy: Letrozole is contraindicated during pregnancy.
During lactation: Letrozole is contraindicated during lactation.
The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Endofree® tablet should be continued until tumor progression is evident.Treatment should be discontinued at tumor relapse.
The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Endofree® tablet should be continued until tumor progression is evident. Treatment should be discontinued at tumor relapse.
Renal Impairment
No dosage adjustment is required for patients with renal impairment if creatinine clearance is 10 ml/min.
Hepatic Impairment
No dosage adjustment is recommended for patients with mild to moderate hepatic impairment. The dose of Endofree® in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50%. The recommended dose for such patients is 2.5 mg administered every other day.
Interaction:
Clinical interaction studies with cimetidine and warfarin indicated that the co-administration of letrozole with these drugs does not result in clinically significant drug reactions, even though cimetidine is a known inhibitor of one of the cytochrome P450 isoenzymes capable of metabolizing letrozole in vitro.
Contraindications:
Letrozole is contraindicated in known or suspected hypersensitivity to letrozole, other aromatase inhibitors, or to any of their ingredients. It is contraindicated during pregnancy, lactation, and in pre-menopausal women. It is also contraindicated in severe hepatic dysfunction.
Side Effects:
Adverse events associated with letrozole are generally mild to moderate and rarely severe enough to require discontinuation. Many can be attributed to either the underlying disease or the normal pharmacological consequence of estrogen deprivation (hot flushes, hair thinning). The most frequently reported adverse events are musculoskeletal pain, arthralgia, headache, fatigue, nausea, dyspnoea, peripheral edema, coughing, constipation, vomiting, chest pain, viral infection, diarrhea, rash, abdominal pain, dyspepsia, and anorexia. Dizziness, weight increase, and pruritus are less commonly seen.
Use in Pregnancy & Lactation:
During pregnancy: Letrozole is contraindicated during pregnancy.
During lactation: Letrozole is contraindicated during lactation.
Precautions & Warnings:
In breast cancer patients with moderate hepatic dysfunction, no dosage adjustment is necessary, but caution is recommended since letrozole elimination depends mainly on intrinsic metabolic clearance. Renal impairment (calculated creatinine clearance: 20 to 50 ml/min) did not affect steady-state plasma letrozole concentration at a dose of 2.5 mg or 5 mg. Hence, no dose adjustment is necessary for such renal function impairment. It is anticipated that letrozole could be removed from the blood by dialysis since it is weakly bound to plasma proteins. The potential risks and benefits to such patients should be considered carefully before prescribing letrozole. In some cases, fatigue and dizziness have been observed with the use of letrozole. Patients should, therefore, be advised that their physical and/or mental abilities required for operating machinery or driving a car may be impaired.
Overdose:
There is no clinical experience of overdosage. There is no specific antidote to letrozole. Since letrozole is not highly protein-bound, dialysis may be helpful. Emesis may be induced if the patient is alert. In general, supportive care and frequent monitoring of vital signs are appropriate.
Storage:
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.