Oral Adjuvant therapy for postmenopausal women with hormone receptor positive early breast cancer
Adult: 2.5 mg once daily; continue for 5 years or until tumour relapse occurs (whichever comes first). Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Hormone receptor positive, HER2-negative breast cancer in postmenopausal women
Adult: As neoadjuvant treatment in patients where chemotherapy is not suitable and immediate surgery is not indicated: 2.5 mg once daily; continue for 4-8 months to establish optimal tumour reduction. If response is inadequate, discontinue treatment and schedule for surgery and/or further treatment options discussed with the patient. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Early breast cancer in postmenopausal women
Adult: Extended adjuvant treatment in patients who have received 5 years of adjuvant tamoxifen therapy: 2.5 mg once daily; continue for 5 years or until tumour relapse occurs (whichever comes first). Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Advanced breast cancer in postmenopausal women, Metastatic breast carcinoma in postmenopausal women
Adult: As 1st-line treatment in patients with hormone receptor positive or unknown, locally advanced or metastatic breast cancer: 2.5 mg once daily; continue until tumour progression is evident. As treatment of advanced breast cancer in patients with natural or artificially induced postmenopausal status, who have previously been treated with anti-estrogens: 2.5 mg once daily; continue until tumour progression is evident. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Hepatic Impairment
Adjuvant therapy for postmenopausal women with hormone receptor positive early breast cancer; Early breast cancer in postmenopausal women; Advanced breast cancer in postmenopausal women; Metastatic breast carcinoma in postmenopausal women:
Severe (Child-Pugh class C): 2.5 mg every other day. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Administration
May be taken with or without food.
Contraindications
Premenopausal endocrine status. Pregnancy and lactation.
Special Precautions
Patient with history of osteoporosis and/or fracture or who are at increased risk of osteoporosis; preexisting CV disease (including ischaemic heart disease) or risk factors associated with CV disease. Severe hepatic impairment (Child-Pugh class C).
Adverse Reactions
Significant: Increased total serum cholesterol, decreased BMD, osteoporosis, bone fracture; angina pectoris, acute MI; new-onset or exacerbation of existing arthralgia, joint stiffness, and/or ostealgia; tenosynovitis (trigger finger), carpal tunnel syndrome. Rarely, tendonitis and tendon ruptures. Cardiac disorders: Palpitations, chest pain. Gastrointestinal disorders: Nausea, vomiting, constipation, diarrhoea, dyspepsia, abdominal pain. General disorders and administration site conditions: Fatigue, asthenia, malaise, peripheral oedema. Investigations: Weight gain. Metabolism and nutrition disorders: Anorexia, increased appetite. Musculoskeletal and connective tissue disorders: Myalgia, arthritis. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Depression. Reproductive system and breast disorders: Vaginal bleeding. Skin and subcutaneous tissue disorders: Increased sweating, alopecia, dry skin, rash (including erythematous, maculopapular, psoriasiform and vesicular rash). Vascular disorders: Hot flush, hypertension.
This drug may cause somnolence, dizziness or fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
Evaluate pregnancy status and confirm postmenopausal status before treatment initiation. Monitor CV and hepatic function; cholesterol panel and BMD. Assess for signs of hypertension, dyspnoea and gastrointestinal upset.
Drug Interactions
Tamoxifen, other anti-estrogens or estrogen-containing drugs may reduce the pharmacological effect of letrozole. Concurrent use with strong CYP3A4 inhibitors (e.g. clarithromycin, telithromycin, ketoconazole, itraconazole, voriconazole, ritonavir) and CYP2A6 inhibitors (e.g. methoxsalen) may increase the exposure to letrozole. Decreased plasma concentrations with CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital).
Food Interaction
Decreased plasma concentrations with St. John's wort.
Action
Description: Mechanism of Action: Letrozole is a competitive and selective non-steroidal aromatase inhibitor. It binds to the haeme group of the aromatase cytochrome P450 enzyme, leading to the inhibition of the enzyme and a significant reduction in plasma estrogen (e.g. estrone, estradiol, estrone sulfate). Pharmacokinetics: Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Distribution: Rapidly and extensively distributed to tissues. Volume of distribution: Approx 1.9 L/kg. Plasma protein binding: Approx 60%, mainly to albumin. Metabolism: Metabolised in the liver by CYP3A4 and CYP2A6 isoenzymes into inactive carbinol metabolite. Excretion: Via urine (approx 90%; 6% as unchanged drug, 75% as glucuronide carbinol metabolite, 9% as unidentified metabolites). Terminal elimination half-life: Approx 2 days.
Chemical Structure
Letrozole Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3902, Letrozole. https://pubchem.ncbi.nlm.nih.gov/compound/Letrozole. Accessed Jan. 26, 2024.
Storage
Store between 15-30°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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