COMPOSITION

Each film coated tabletcontains:

Letrozole USP                      2.5 mg

Excipients                              q.s.


DESCRIPTION

Letrozole is a third generation, non-steroidal aromatase inhibitor. It is chemically described as 4,4'-(1H-1,2,4-Triazol-1-ylmethylene) dibenzonitrile.

 

CLINICAL PHARMACOLOGY Mechanism of Action

Aromatase is the enzyme responsible for converting androgens to estrogens. Letrozole by inhibiting aromatase reduces the production of estrogens. This results in enhanced stimulation of gonadotropin releasing hormone (GnRH) which inturn leads to increased secretion of  follicle  stimulating hormone (FSH)  &  luteinizing hormone (LH).  The outcome is normal ovarian follicular development & ovulation.

 

Pharmacokinetics

Letrozole is rapidly absorbed after oral administration.Absorption is not affected by the food. The maximum plasmalevels reached about 1 hour after ingestion. Letrozole has a bioavailability of 99.9 %. Plasma protein binding  of Letrozole  is approximately 60% mainly to albumin (55%). It is metabolized by CPY2A6 and CYP3A4 to inactive carbinol metabolite  (4, 4' methanolbisbenzonitrile) which is excreted  in urine. The elimination half-life is about40-42 hours

The usual dose is 2.5 mg to be taken for 5 days from day 3 to day 7 of menstrual cycle. Higher doses up to 5 mgmay be used in women  who do not get desired results with lower dose.

 

CONTRAINDICATIONS

Letrozole is contraindicated in patients who are hypersensitive to Letrozole, pregnancy, liver dysfunction, abnormaluterine bleeding, uncontrolled thyroid  or adrenal dysfunction or in the presence of an organic intracranial lesionsuch as pituitary tumor.

 

DRUG INTERACTIONS

No clinically significant interaction of  Letrozole  has  been  reported  with  cimetidine, warfarin & diazepam.

 

ADVERSE EFFECTS

Clinical trials evaluating ovulation induction with Letrozole  have proven  that it is well tolerated. The only side effect reported in these trials was flushing. Use of Letrozole is not  associated with  increased risk  of  congenital malformations in  humans   since Letrozole is eliminated from the body before conception owing to its short half life.Also, cardiac  anomalies have  occurred  less  frequently in  Letrozole group  (0.2%)  than general population(0.4-1.2%).