Letrozol2.5 mg

Letrozol is a nonsteroidal aromatase inhibitor with established and guideline-supported uses classified below by strength of evidence.

FDA-approved / established indications (postmenopausal women only)

• Adjuvant treatment of hormone receptor (HR)-positive early breast cancer in postmenopausal women.
• Extended adjuvant treatment of HR-positive early breast cancer following completion of approximately 5 years of standard adjuvant tamoxifen therapy.
• First-line treatment of HR-positive, or hormone receptor unknown, locally advanced or metastatic breast cancer in postmenopausal women.
• Second-line treatment of advanced breast cancer in postmenopausal women with disease progression following prior antiestrogen therapy.

Guideline-supported off-label use

• Ovulation induction in women with anovulatory infertility (for example, polycystic ovary syndrome, PCOS). Major reproductive medicine guidelines (e.g., ASRM/ACOG) support Letrozol as a first-line ovulation-induction agent in appropriate candidates; this use is off-label with respect to the original oncology approval and must be supervised by a fertility specialist. In this context Letrozol is intentionally used in premenopausal, reproductive-age women, unlike the breast cancer indication above.

Letrozol is not indicated and is not effective for breast cancer in premenopausal women, because its mechanism of estrogen suppression depends on the postmenopausal hormonal state.

Each film-coated tablet contains Letrozole 2.5 mg as the active ingredient, along with pharmaceutically inert excipients (fillers, binders, coating agents).

Letrozol is a nonsteroidal, competitive aromatase inhibitor belonging to the class of hormonal antineoplastic agents. It is used mainly in postmenopausal women with hormone receptor-positive breast cancer, and, on a guideline-supported off-label basis, for ovulation induction in infertility. Letrozol is supplied as an oral 2.5 mg tablet.

Letrozol belongs to the aromatase inhibitor class of drugs, a subgroup of hormonal (endocrine) antineoplastic agents.

Letrozole works by competitively and reversibly binding to the heme group of the aromatase enzyme (CYP19), which is responsible for converting androgens (androstenedione and testosterone) into estrogens (estrone and estradiol) in peripheral tissues.

• In postmenopausal women, ovarian estrogen production has ceased, so circulating estrogen depends almost entirely on peripheral aromatization. By inhibiting aromatase, Letrozole substantially lowers whole-body estrogen levels, depriving hormone receptor-positive breast cancer cells of the estrogen stimulation that drives their growth.
• In ovulation induction, the estrogen-lowering effect of Letrozole reduces negative feedback on the hypothalamic-pituitary axis, leading to a rise in follicle-stimulating hormone (FSH) and stimulation of ovarian follicular development.

Letrozole is well absorbed orally, extensively metabolized in the liver (primarily via CYP3A4 and CYP2A6) to an inactive metabolite, and has an elimination half-life of approximately 2 days.

Letrozol tablets are taken orally, with or without food, swallowed whole with water, ideally at approximately the same time each day to maintain consistent blood levels.

Only clinically significant, well-verified interactions are listed here.

• Tamoxifen and other estrogen-containing therapies: Concurrent administration of tamoxifen with Letrozol reduces plasma levels of Letrozol and can antagonize its estrogen-lowering, antitumor effect. Estrogen-containing medications (including hormone replacement therapy and hormonal contraceptives) similarly counteract the pharmacologic action of Letrozol. Concomitant use should be avoided.
• Tamoxifen, sequential use: When switching between Letrozol and tamoxifen (e.g., extended adjuvant therapy), an appropriate washout/sequencing interval as directed by the oncologist should be observed.

No clinically significant interactions with common CYP450 inhibitors/inducers have been firmly established, but patients should inform their physician of all medicines being taken.

Adverse effects of Letrozol vary somewhat by indication but commonly include:

Very common (often treatment-limiting)

• Hot flashes / flushing
• Arthralgia (joint pain and stiffness) — one of the most common and sometimes treatment-limiting effects; patients should report persistent or worsening joint symptoms
• Fatigue, asthenia
• Night sweats, headache, nausea

Common, requiring monitoring

• Bone loss / decreased bone mineral density with long-term use, increasing fracture and osteoporosis risk (see Precautions and Warnings)
• Hypercholesterolemia (elevated blood cholesterol)
• Peripheral edema, weight changes, mood changes including depression
• Hair thinning (alopecia)

Less common / rare

• Cardiovascular ischemic events (in patients with pre-existing risk factors)
• Carpal tunnel syndrome, blurred vision
• Rash, urinary tract infection
• When used for ovulation induction: multiple pregnancy (lower rate than with clomiphene) and, rarely, ovarian hyperstimulation

Pregnancy: Letrozol is contraindicated during pregnancy. It can cause fetal harm, and animal studies have shown congenital malformations and pregnancy loss at doses well below the human therapeutic dose. Letrozol must not be used by pregnant women, and women of reproductive potential should be confirmed not to be pregnant before starting therapy and should use effective non-hormonal contraception during treatment and for a period after stopping, as advised by their physician.

Ovulation induction context: when Letrozol is used off-label for ovulation induction, it is given deliberately to women trying to conceive, but strictly before ovulation/conception is confirmed and under fertility-specialist supervision; it must be discontinued once pregnancy is confirmed, and is not to be continued into or resumed during an established pregnancy.

Lactation: it is not known whether Letrozol passes into human breast milk; because of the potential for serious adverse effects in a nursing infant, breastfeeding is not recommended during treatment with Letrozol. A physician should be consulted regarding breastfeeding.

Bone health

Letrozol lowers estrogen levels and is associated with decreased bone mineral density and increased fracture risk with long-term use. Bone mineral density should be assessed at baseline and monitored periodically during treatment; calcium/vitamin D supplementation or bone-protective therapy may be considered per physician judgment.

Cholesterol and cardiovascular risk

Hypercholesterolemia has been observed more frequently with Letrozol than with comparator therapy. Periodic monitoring of serum cholesterol is advised, particularly in patients with pre-existing cardiovascular risk factors, who should be monitored for cardiovascular events during treatment.

Hepatic impairment

In patients with severe hepatic impairment (cirrhosis), exposure to Letrozol is increased; a reduced dosing frequency is recommended (see Dosage and Administration). Use with caution in mild-to-moderate hepatic impairment.

Fatigue and dizziness

Letrozol has been associated with fatigue and dizziness; patients should exercise caution when driving or operating machinery until they know how they respond to the medicine.

Specialist supervision

Because of the medical complexity of the conditions treated, Letrozol should be prescribed and monitored by an oncologist (for breast cancer) or a fertility specialist (for ovulation induction), with dosing individualized and adjusted based on response and tolerability.

Limited clinical experience with overdose exists. In the event of a suspected overdose of Letrozol, seek immediate medical attention or contact a poison control center / emergency services promptly. Management is supportive, including monitoring of vital signs and general symptomatic care; there is no specific antidote. Do not attempt unsupervised home treatment of an overdose.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Elderly: No dose adjustment of Letrozol is required based on age alone.
• Hepatic impairment: Dose reduction (every-other-day dosing) is recommended in severe hepatic impairment (cirrhosis); use with caution in mild-to-moderate impairment.
• Renal impairment: No dose adjustment is required when creatinine clearance is above 10 mL/min; data in more severe renal impairment are limited.
• Pediatric patients: Safety and efficacy of Letrozol have not been established in children; not recommended for pediatric use outside specialist research settings.
• Premenopausal women: Not indicated for breast cancer in premenopausal women (see Contraindications). May be used, under fertility-specialist supervision, for ovulation induction in premenopausal women trying to conceive.

Treatment duration with Letrozol depends on the indication and is determined by the treating physician: adjuvant breast cancer therapy is typically continued for about 5 years; extended adjuvant and advanced/metastatic disease therapy continues as long as clinical benefit is seen and toxicity is acceptable, per oncologist assessment; ovulation induction courses are short (typically 5 days per cycle), repeated over a limited number of cycles as directed by the fertility specialist.

Letrozole is classified as a nonsteroidal aromatase inhibitor, within the broader category of hormonal (endocrine) antineoplastic agents.

Letrozole reversibly inhibits the aromatase enzyme, blocking the conversion of androgens into estrogens, which substantially lowers circulating and tissue estrogen levels — reducing estrogen-driven stimulation of hormone receptor-positive breast cancer cells, and, in the reproductive context, reducing negative feedback on the pituitary to stimulate FSH release and follicular development.

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The safety and efficacy of Letrozol have not been established in pediatric patients. Letrozol is not recommended for use in children outside of specialist research protocols.