MAMAZOL Letrozole 2.5mg Film-Coated Tablet 1's
Indications/Uses
Dosage/Direction for Use
No dosage adjustment is required for patients with mild to moderate hepatic impairment or renal impairment.
Method of administration: Oral Route of Administration
Overdosage
Since letrozole is not highly protein bound, dialysis may be helpful. Emesis may be induced if the patient is alert. In general, supportive care and frequent monitoring of vital signs is appropriate.
Administration
Contraindications
Special Precautions
Renal impairment: Renal impairment (calculated creatinine clearance: 20 to 50 ml/min) did not affect steady state plasma letrozole concentration at a dose of 2.5 mg or 5 mg. Hence, no dose adjustment is necessary for such renal function impairment. It is anticipated that letrozole could be removed from blood by dialysis since it is weakly bound to plasma proteins. The potential risks and benefits to such patients should be considered carefully before prescribing letrozole.
In some cases, fatigue and dizziness have been observed with the use of Letrozole. Patients should therefore, be advised that their physical and/or mental abilities required for operating machinery or driving a car may be impaired.
Use In Pregnancy & Lactation
Oral administration of Letrozole in pregnant rats resulted in teratogenicity and maternal toxicity at 0.03 mg/kg. Embryotoxicity and fetotoxicity were seen at doses 0.003 mg/kg and there was an increase in the incidence of foetal malformation among the animals treated. However, there are no adequate and well-controlled studies of letrozole in pregnant women and its use in these patients is not recommended.
It is not known whether letrozole is excreted in human milk. Because many drugs are excreted in human milk, letrozole should not be administered to a nursing woman.
Adverse Reactions
Other reported effects include hair thinning, vaginal dryness or bleeding, myalgia, arthralgia, and bone fractures. Abnormalities in liver enzyme values, thromboembolism, and increases in total cholesterol. Very rare cases of erythema multiforme, Stevens-Johnson syndrome, and allergic reactions (including angioedema, urticaria, and anaphylaxis) have occurred.
Reduction in bone mineral density can occur during use of Letrozole. Patients with or at risk of osteoporosis should therefore have their bone density assessed at the start of therapy and at regular intervals thereafter.
Storage
Shelf-life: 24 months.
Action
Letrozole exerts its antitumor effect by depriving estrogen-dependent breast cancer cells of their growth stimulus. In postmenopausal women, estrogens are derived mainly from the action of the aromatase enzyme, which converts adrenal androgens primarily androstenedione and testosterone to oestrone (E1) and oestradiol (E2). The suppression of estrogen biosynthesis in the peripheral tissues and the malignant tissues can be achieved by specifically inhibiting the aromatase enzyme.
In healthy postmenopausal women, single doses of 0.1, 0.5 and 2.5 mg letrozole suppress serum oestrone and oestradiol by 75-78% and 78% from baseline respectively. Maximum suppression is achieved in 48-78 hours.
In postmenopausal patients, with advanced breast cancer, daily doses of 0.1 to 5 mg suppress plasma concentration of oestradiol, oestrone and oestrone sulphate by 78-95% from baseline in all patients treated.
Letrozole had no effect on plasma androgen concentrations (androstenedione and testosterone) among healthy postmenopausal women after single doses of 0.1 to 0.5 mg and 2.5 mg indicating that the blockade of estrogen biosynthesis does not lead to accumulation of androgenic precursors. Impairment of adrenal steroidogenesis has not been observed.
Pharmacokinetics: Letrozole is rapidly and completely absorbed from the gastrointestinal tract (absolute bioavailability 99.9%). Food slightly decreases the rate of absorption, but the extent of absorption remains unchanged. The minor effect of the absorption rate is not considered to be of clinical relevance and therefore Letrozole may be taken after, with or before food. Plasma protein binding of Letrozole is approximately 60%, mainly to albumin (55%). The concentration of Letrozole in erythrocytes is about 80% of that in plasma.
Metabolic clearance to a pharmacologically inactive carbinol metabolite is the major elimination pathway of Letrozole but is relatively slow when compared to hepatic blood flow. The cytochrome P450 isoenzymes 3A4 and 2A6 were found to be capable of converting Letrozole to this metabolite in vitro but their individual contributions to Letrozole metabolism in vivo have not been established.
MedsGo Class
Features
- Letrozole