LETRAZOLE DENK 2.5 2.5MG TABLET

Indications

• Estrogen receptor-positive breast cancer in postmenopausal women
• Adjuvant treatment of early breast cancer
• Treatment of advanced breast cancer in postmenopausal women

Dosage

Adults: The usual recommended dose for adults is 2.5 mg once daily.

Mechanism of action

Letrozole is a non-steroidal type II aromatase inhibitor that competitively binds to the heme of the cytochrome P450 subunit of the aromatase enzyme (CYP19A1). This inhibition prevents the conversion of androgens to estrogens, leading to decreased estrogen biosynthesis in various tissues. The reduced availability of estrogens causes regression of estrogen-dependent tumors, particularly in postmenopausal women where aromatase activity primarily contributes to estrogen production.

Pharmacodynamics

As a third generation aromatase inhibitor, letrozole effectively lowers serum levels of estrone, estradiol, and estrone sulfate, thereby suppressing the stimulation of breast tissue by estrogens. It is used to treat patients with breast cancer, and its long duration of action (with a half-life exceeding 42 hours in patients) allows for convenient dosing. Letrozole's inhibition of estrogen production is significant in reducing the risk of tumor recurrence in estrogen-dependent breast cancers. Potential adverse effects include interstitial lung disease, pneumonitis, QT prolongation, elevated transaminase levels, neutropenia, and embryo-fetal toxicity.

Pharmacokinetics

Letrozole is well absorbed after oral administration, with peak plasma concentrations typically occurring within 1 to 2 hours. It undergoes hepatic metabolism, primarily via cytochrome P450 2A6 and 2C19, and has a half-life of approximately 2 days. The drug is excreted mainly in the urine, with less than 10% eliminated unchanged. Due to its metabolism, interactions with other drugs that affect hepatic enzymes could influence its effectiveness and safety.

Contra-indications

• Pregnancy
• Severe hepatic impairment
• Known hypersensitivity to letrozole or any of its components

Adverse effects

• Hot flushes
• Arthralgia
• Fatigue
• Nausea
• Dizziness
• Bone pain
• Neutropenia
• Increased sweating
• Vaginal dryness
• Hypercholesterolemia
• Interstitial lung disease
• Pneumonitis
• QT prolongation
• Elevated transaminases

Interactions

• Estrogens may reduce the effectiveness of letrozole
• CYP2A6 substrates may have altered metabolism
• CYP2C19 substrates may have altered metabolism
• CYP2C9 substrates may have altered metabolism

Precautions

• Monitor for signs of interstitial lung disease
• Assess liver function before and during treatment
• Evaluate bone density in patients at risk for osteoporosis
• Caution in patients with a history of cardiovascular disease

Pregnancy

Letrozole is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known whether letrozole is excreted in human milk. Caution should be exercised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets 2.5 mg

Mechanism of action

Letrozole is a non-steroidal type II aromatase inhibitor. It blocks the active site, and therefore the electron transfer chain of CYP19A1. This competitive inhibition prevents the conversion of androgens to estrogen. This action leads to a reduction in uterine weight and elevated leuteinizing hormone. In postmenopausal women, the action of aromatase is responsible for the majority of estrogen production. With reduced availability of estrogen, estrogen-dependant tumors regress. Third generation aromatase inhibitors do not significantly affect cortisol, aldosterone, and thyroxine levels. Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. In adult nontumor- and tumor-bearing female animals, letrozole is as effective as ovariectomy in reducing uterine weight, elevating serum LH, and causing the regression of estrogen-dependent tumors. In contrast to ovariectomy, treatment with letrozole does not lead to an increase in serum FSH. Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis. 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. Treatment of women with letrozole significantly lowers serum estrone, estradiol and estrone sulfate and has not been shown to significantly affect adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroid hormones.

Pharmacodynamics

Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue. Letrozole is a third generation type II aromatase inhibitor used to treat estrogen dependant breast cancers. It has a long duration of action as it has a half life of over 42 hours in breast cancer patients. Patients should be counselled regarding the risk of interstitial lung disease, pneumonitis, QT prolongation, elevated transaminase levels, neutropenia, and embryo-fetal toxicity.