What Is Letrozole? FDA Approval, Licensing and Reimbursement in Turkey

• FDA Approved: Yes (Initial Approval Date: 1996)
• Brand Names, Manufacturers and Distribution in Turkey: The original brand name is Femara (Novartis). It is also available under various generic brand names: Femveon (Genveon), Ferbezol (Nobel), Letrasan (Deva), Letroks (Biem), Letrol (Koçak) and Letu (Onko).
• Active Ingredient: Letrozole
• Route of Administration: Oral, tablet
• Class: Aromatase inhibitor
• Category: Hormonal agent
• Approved Cancers:
  • First-line treatment of postmenopausal women with hormone receptor-positive locally advanced or metastatic breast cancer.
  • Second-line treatment of postmenopausal women with breast cancer that has progressed after antiestrogen therapy.
  • Adjuvant treatment of postmenopausal women with hormone-positive early-stage breast cancer.
  • Extended adjuvant treatment of early-stage breast cancer in postmenopausal women who have completed 5 years of adjuvant tamoxifen therapy.

What Is Letrozole?

Letrozole is a hormonal (endocrine) treatment for breast cancer belonging to a group of drugs called aromatase inhibitors.

How Does It Work?

• A nonsteroidal, competitive inhibitor of aromatase. It is approximately 200 times more potent than aminoglutethimide.
• It inhibits estrogen synthesis by blocking the conversion of adrenal androgens (androstenedione and testosterone) to estrogens (estrone, estrone sulfate and estradiol). Serum estradiol levels fall by 90% within 14 days and are almost completely suppressed after 6 weeks of treatment.
• It has no inhibitory effect on adrenal corticosteroid biosynthesis.

Licensing in Turkey

• For the adjuvant treatment of postmenopausal women with hormone receptor-positive (estrogen (ER) and/or progesterone (PR) receptor-positive) early-stage invasive breast cancer.
• For extended adjuvant treatment of postmenopausal patients with hormone receptor-positive (ER and/or PR receptor-positive) early-stage invasive breast cancer who have previously received standard tamoxifen therapy (for 5 years).
• Indicated as first-line treatment of postmenopausal women with hormone receptor-positive (ER and/or PR) metastatic or locally advanced breast cancer.
• Also indicated for the treatment of postmenopausal women with breast cancer that has relapsed or progressed after tamoxifen therapy.

Is Letrozole Reimbursed in Turkey?

For cancer treatment, it may be prescribed by specialist physicians on the basis of a medical board report specifying the treatment protocol.

Indications That Do Not Require Additional TİTCK Approval

• Advanced Endometrial Cancer
  • Its use is appropriate in patients with ER positivity whose disease has progressed after at least two lines of chemotherapy.
• Early-Stage Breast Cancer
  • Its use is appropriate in premenopausal breast cancer.
• Stage IV Breast Cancer
  • Its use is appropriate in premenopausal breast cancer.

Price: As of December 2025, Femera 2.5 mg tablets cost 737.99 TL.

Mechanisms of Resistance

• Reduced ER (estrogen receptor) expression.
• ER mutations that reduce binding affinity for letrozole.
• Overexpression of growth factor receptors such as EGFR, HER2/neu, IGF-1R or TGF-β may reduce the inhibitory effects of letrozole.
• The presence of ESR1 mutations.

Pharmacokinetic Properties

• Absorption
  • Rapidly and completely absorbed after oral administration. Food does not affect oral absorption.

•  Distribution
  • Accumulates substantially in peripheral tissues and breast cancer cells.

•  Metabolism
  • Metabolized in the liver by the cytochrome P450 system. Glucuronidation produces inactive metabolites. The parent drug and metabolites are excreted through the kidneys; 75–90% of the dose is excreted in urine.

Dosage

• Metastatic disease: 2.5 mg orally once daily until disease progression.
• Adjuvant treatment: 2.5 mg orally once daily until disease recurrence.

Drug Interactions

• CYP3A4 inducers: Drugs such as phenytoin, carbamazepine, rifampin, phenobarbital and St. John’s Wort may increase the metabolism of letrozole, reducing effective drug levels.
• CYP3A4 inhibitors: Drugs such as ketoconazole, itraconazole, erythromycin and clarithromycin may decrease the metabolism of letrozole, increasing the risk of toxicity.
• Warfarin: Patients taking coumarin-derived anticoagulants should be monitored closely for changes in coagulation parameters (PT and INR) and/or bleeding. Warfarin doses should be adjusted carefully during letrozole treatment.
• Clopidogrel (Plavix): As a CYP2C19 inhibitor, letrozole may reduce the effectiveness of clopidogrel.

Precautions

1. Letrozole is indicated only for postmenopausal women. Efficacy has not been demonstrated in premenopausal women, and the risk of benign ovarian tumors and cystic ovarian disease may increase in this population.
2. It should be used with caution in patients with abnormal liver function. Liver function should be monitored before and during treatment. In patients with cirrhosis or severe hepatic impairment, the dose should be reduced by 50% and 2.5 mg given every other day.
3. Glucocorticoid and/or mineralocorticoid replacement is not required.
4. Women with osteoporosis or at risk of osteoporosis should be monitored by bone densitometry at the start of treatment and at regular intervals. Osteoporosis treatment or preventive therapy should be started if necessary.
5. Letrozole may be taken with or without food.
6. Pregnancy category D. Breastfeeding should be avoided.

What Are the Side Effects of Letrozole?

Side effects have been reported as follows, from most to least common:

• Mild musculoskeletal pain and arthralgia are the most common side effects.
• Headache and fatigue.
• Mild nausea, rarely vomiting and loss of appetite.
• Hot flashes in fewer than 10% of patients.
• Hepatotoxicity with mild elevations in serum transaminases and bilirubin.
• Rare thromboembolic events.