| Generic Name: |
Letrozole
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| Therapeutic Category: |
Anti-neoplastic agent
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| Pharmacological Class: |
Non-steroidal aromatase inhibitor (inhibitor of estrogen biosynthesis)
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| Composition: |
Each tablet contains: Letrozole 2.5 mg
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| Pregnancy Category: |
D
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| Presentation: |
Available in the pack size as 5 tablets X 10 blisters
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| Mechanism of Action: |
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.
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| Indications: |
- Adjuvant treatment of postmenopausal women with hormone receptor positive invasive early breast cancer.
- Extended adjuvant treatment of early breast cancer; Postmenopausal women, who have received 5 yr of adjuvant tamoxifen therapy.
- First-line treatment in postmenopausal women with hormone-dependent advanced breast cancer.
- Advanced breast cancer after relapse or disease progression, in women with natural or artificially induced postmenopausal endocrine status, who have previously been treated with anti-estrogens.
- Neoadjuvant treatment of postmenopausal women with hormone receptor positive, HER-2 negative breast cancer where chemotherapy is not suitable and immediate surgery not indicated.
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| Dosage: |
Route of administration: Oral
- The usual dose in 2.5 mg tablet once a day.
- In patients with advanced or metastatic breast cancer, treatment with letrozole tablets should continue until tumor progression is evident.
- In the neoadjuvant setting, treatment with letrozole tablets could be continued for 4 to 8 months in order to establish optimal tumor reduction. If the response is not adequate, treatment with letrozole tablets should be discontinued and surgery scheduled and/or further treatment options discussed with the patient.
- Only women with post menopausal endocrine status must receive Letrozole.
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| Pharmacokinetics: |
Letrozole is 99.9% orally bioavailable.
The volume of distribution of letrozole is 1.87 L/kg.
Letrozole is 60% bound to proteins.
Letrozole is 90% eliminated in the urine.
The terminal elimination half-life of letrozole is approximately 42h in healthy volunteers, but longer in breast cancer patients.
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| Adverse Effects: |
Letrozole is generally well tolerated.
The most frequently reported side effects in clinical studies were hot flushes, hypercholesterolemia, arthralgia, fatigue, increased sweating and nausea. Many adverse reactions can be attributed to the normal pharmacological consequences of estrogen deprivation (e.g. hot flushes, alopecia and vaginal bleeding).
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| Contraindications: |
This medication should not be used if you have the following conditions:
- In patients with known hypersensitivity to letrozole or to any of the excipients listed in section 9.1.
- Patients with premenopausal endocrine status.
- Patients with premenopausal, pregnant or lactating women.
- Children.
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| Special warnings and precautions : |
Before using Letrozole, inform your doctor about your current list of medications, over the counter products, allergies, pre-existing diseases, and current health conditions. The following conditions are to be considered while using this medication:
- In patients whose menopausal status is unclear, luteinizing 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.
- Letrozole has not been investigated in a sufficient number of patients with a creatinine clearance lower than 10 ml/min. The potential risk/benefit to such patients should be carefully considered before administration of letrozole.
- In patients with severe hepatic impairment (Child-Pugh C), systemic exposure and terminal half-life were approximately doubled compared to healthy volunteers. Such patients should therefore be kept under close supervision.
- Women with a history of osteoporosis and/or fractures, or who are at increased risk of osteoporosis, should have their bone mineral density formally assessed prior to the commencement of adjuvant and extended adjuvant treatment and monitored during and following treatment with letrozole.
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