Generic

Letrozole

Indications

Letrozole is indicated for the first-line treatment of advanced / metastatic breast cancer (hormone receptor positive or receptor unknown status) in postmenopausal women.

Pharmacology

Letrozole is a potent and highly specific non-steroidal aromatase inhibitor. It inhibits aromatase by competitively binding with the heme of the cytochrome P450 subunit of the enzyme, resulting in a decrease in estrogen biosynthesis in all tissues. Letrozole exerts its anti-tumor effect by depriving the growth stimulation of estrogen-dependent breast cancer cells. In postmenopausal women, estrogen is mainly derived from the action of aromatase, which mainly converts adrenal androgens into androstenedione and testosterone into estrone (E1) and estradiol (E2). The inhibition of estrogen biosynthesis in peripheral tissues and malignant tissues can be achieved by specifically inhibiting aromatase.

Dosage & Administration

The recommended dose of letrozole is 2.5 mg once a day. As long as a tumor response is observed, letrozole treatment should continue. If the tumor stops responding based on tumor progression, the drug should be discontinued. For elderly patients, there is no need to modify the normal adult dosing regimen. Patients with mild to moderate hepatic or renal insufficiency do not need to adjust the dose.

Interaction

The clinical interaction studies of cimetidine and warfarin show that co-administration of letrozole and these drugs will not cause clinically significant drug reactions, even if cimetidine is a kind of letrozole that can metabolize letrozole in vitro Known inhibitor of cytochrome P450 isoenzymes.

Contraindications

Letrozole is contraindicated in patients known or suspected to be allergic to letrozole, other aromatase inhibitors, or any of their ingredients. It is contraindicated for pregnant, lactating and premenopausal women. It is also contraindicated for severe liver dysfunction.

Side Effects

Adverse events related to letrozole are usually mild to moderate and rarely serious enough to require discontinuation. Many normal pharmacological consequences (hot flashes, thinning hair) that can be attributed to underlying disease or estrogen deprivation. The most frequently reported adverse events were musculoskeletal pain, arthralgia, headache, fatigue, nausea, dyspnea, peripheral edema, cough, constipation, vomiting, chest pain, viral infection, diarrhea, skin rash, abdominal pain, indigestion, and anorexia. Dizziness, weight gain, and itching are less common.

Pregnancy & Lactation

Oral administration of letrozole to pregnant rats at 0.03 mg / kg can cause teratogenicity and maternal toxicity. Embryonic toxicity and fetal toxicity were observed at doses> 0.003 mg / kg, and the incidence of fetal malformations increased in treated animals. However, there are no adequate and well-controlled studies of letrozole in pregnant women and its use is not recommended in these patients. It is unknown whether letrozole is excreted in human milk. Because many drugs are excreted in human milk, letrozole should not be given to breast-feeding women.

Precautions & Warnings

For breast cancer patients with moderate hepatic impairment, no dose adjustment is necessary, but it is recommended to use it with caution, because the elimination of letrozole is mainly dependent on internal metabolic clearance. Renal impairment (calculated creatinine clearance: 20 to 50 ml / min) does not affect the steady-state plasma concentration of letrozole at doses of 2.5 mg or 5 mg. Therefore, no dose adjustment is necessary for this type of kidney failure. It is expected that letrozole can be removed from the blood by dialysis due to its weak binding to plasma proteins. Before prescribing letrozole, the potential risks and benefits for these patients should be carefully considered. In some cases, letrozole is used to cause fatigue and dizziness. Therefore, patients should be informed that the physical and/or mental abilities required to operate machines or drive cars may be affected.

Therapeutic Class

Hormonal Chemotherapy

Storage Conditions

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Phamaceutical Name

Incepta Pharmaceuticals Ltd.