Letrozole information from DrugsUpdate
P - Contraindicated in pregnancy
L - Contraindicated in lactation
Letrozole is an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery. Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Estrogens then bind to an estrogen receptor, which causes cells to divide. Letrozole prevents the aromatase from producing estrogens by competitive, reversible binding to the heme of its cytochrome P450 unit. The action is specific, and letrozole does not reduce production of mineralo- or corticosteroids.
In contrast, tamoxifen interferes with the estrogen receptor. Tamoxifen is also used to treat hormonally- responsive breast cancer. However, letrozole is effective only in post-menopausal women, in whom estrogen is produced predominantly by the adrenal glands. In pre-menopausal women, estrogen is produced in the ovaries, and letrozole is ineffective. In the BIG 1-98 Study, of post-menopausal women with hormonally-responsive breast cancer, letrozole improved the recurrence of cancer, but not survival, compared to tamoxifen.
Pharmacodynamics
Pharmacokinetics
Letrozole competitively binds to the heme group of aromatase, a cytochrome P450 enzyme which catalyzes conversion of androgen to oestrogen, leading to inhibition of the enzyme and a significant reduction in plasma oestrogen levels.
Absorption
Rapidly and completely absorbed from the GI tract.
Distribution
Weakly bound to plasma proteins and has a large volume of distribution of about 1.9 l/kg.
Metabolism
Slow hepatic metabolism to inactive metabolites.
Excretion
Via urine (6% as unchanged drug); elimination half life of about 2 days.
Letrozole Indications / Letrozole Uses
Information Not Available
Letrozole Adverse Reactions / Letrozole Side Effects
Hot flushes, arthralgia, nausea, vomiting, fatigue, dizziness, headache, dyspepsia, constipation, diarrhoea, anorexia, alopoecia, increased sweating, rash, peripheral oedema, osteoporosis, musculoskeletal pain, vaginal irritation.
Potentially Fatal: Thromboembolic events.
Precautions
Monitor
Consider monitoring bone mineral density.
Hepatic Function
Dose reduction recommended in patients with cirrhosis and/or severe hepatic function impairment.
Hazardous Tasks
May cause drowsiness, fatigue, and/or dizziness.
Special Precautions
Severe renal impairment; severe hepatic impairment; osteoporosis. Caution when driving or operating machinery.
Other Drug Interactions
Plasma levels reduced by tamoxifen.
Other Interactions
Information Not Available
Dosage
Oral
Adjuvant therapy for postmenopausal women with hormone receptor positive early breast cancer, Advanced or locally advanced breast cancer
Adult: 2.5 mg once daily.
Hepatic impairment: Reduce dose by 50% in patients with cirrhosis and severe hepatic impairment; recommended dose: 2.5 mg on alternate days.
Food(before/after)
May be taken with or without food.
List of Contraindications
Letrozole and Pregnancy
Contraindicated in pregnancy
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Letrozole and Lactation
Contraindicated in lactation
Letrozole and Children
Safety and efficacy in children not established.
Letrozole and Geriatic
Information Not Available
Letrozole and Other Contraindications
Premenopausal women and children; hypersensitivity.
Storage
Information Not Available
Lab interference
Information Not Available
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