FEMARA

5 mg tablet once daily. In the adjuvant setting, the intended duration of treatment is 5 years. In the extended adjuvant setting, treatment with FEMARA (letrozole) is intended for 5 years and should be initiated within 3 months of completion of approximately 5 years of prior standard adjuvant tamoxifen therapy.

In the first- and second-line advanced breast cancer settings, FEMARA treatment should continue until further tumour progression is evident.

Special populations PrFEMARA® (letrozole) Tablets Page 6 of 68 Hepatic impairment:

No dose adjustment of FEMARA is required for patients with mild to moderate hepatic impairment (Child-Pugh score A or B). Insufficient data are available to recommend a dose adjustment in breast cancer patients with severe hepatic impairment (Child-Pugh C).

However, since letrozole elimination depends mainly on intrinsic metabolic clearance, caution is recommended. 3 Pharmacokinetics).

Renal impairment:

No dosage adjustment is required for patients with renal impairment with a creatinine clearance (CLcr) ≥10 mL/min. 3 Pharmacokinetics).

Pediatrics (< 18 years of age):

FEMARA is contraindicated in children and adolescents. The safety and efficacy of FEMARA in children and adolescents (under 18 years of age) have not been established.

Geriatrics ( 65 years of age):

No dose adjustment is required for elderly patients. 3 Pharmacokinetics, Absorption). 5 Missed Dose The missed dose should be taken as soon as the patient remembers. However, if it is almost time for the next dose, the missed dose should be skipped, and the patient should go back to the regular dosage schedule.

3 Pharmacokinetics).

). 1% vs. 4%, respectively. A significantly higher incidence of events was seen for FEMARA vs. 8% vs. 2% vs. 0%). 8% vs. 5% vs. 4% vs. 4% vs. 2% vs. 2% respectively). 3 % vs. 3%, respectively (a non- significant difference). 80). 1%) than with tamoxifen.

37). 67). 53) (see 8 ADVERSE REACTIONS). 0%)], but the difference was not statistically significant. Of the 19 deaths attributed to a cardiovascular cause in the placebo arm, 12 occurred in the group of 1026 patients who did not switch to FEMARA after study unblinding, and 7 occurred in the group of 1551 patients who switched to FEMARA.

A total of 7 patients died from a stroke – 6 in the FEMARA arm and 1 after switching from placebo to FEMARA after study unblinding. Driving and operating machinery PrFEMARA® (letrozole) Tablets Page 9 of 68 No studies on the effects of FEMARA on the ability to drive and use machines have been performed.

However, since fatigue, dizziness, and uncommonly somnolence have been observed with the use of FEMARA, caution is advised when driving or operating machinery while such symptoms persist.

Endocrine and Metabolism Hyperlipidemia:

The use of aromatase inhibitors, including FEMARA, may increase lipid levels. 6% of patients treated with tamoxifen. In a smaller study (D2407) comparing 2 years of adjuvant treatment with FEMARA or tamoxifen, significant differences were observed between treatments at all time-points in total cholesterol, LDL cholesterol and the HDL: LDL ratio in favour of tamoxifen.

Clinically relevant changes in total cholesterol at 2 years occurred significantly more often for patients treated with FEMARA (17%) than with tamoxifen (5%). Monitoring of serum cholesterol is advised for patients treated with FEMARA.

(see also 8 ADVERSE REACTIONS, 10 CLINICAL PHARMACOLOGY, 14 CLINICAL TRIALS).

, Musculoskeletal 10/2022 RECENT MAJOR LABEL CHANGES ............................................................................................ 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................................

4 1 INDICATIONS ............................................................................................................... 4 2 CONTRAINDICATIONS .................................................................................................

5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 5 4 DOSAGE AND ADMINISTRATION ................................................................................. 6 5 OVERDOSAGE..............................................................................................................

6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 7 7 WARNINGS AND PRECAUTIONS .................................................................................. 12 8 ADVERSE REACTIONS ................................................................................................

28 9 DRUG INTERACTIONS ................................................................................................ 31 10 CLINICAL PHARMACOLOGY .......................................................................................

37 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 39 12 SPECIAL HANDLING INSTRUCTIONS ........................................................................... 39 PART II: SCIENTIFIC INFORMATION .......................................................................................

40 13 PHARMACEUTICAL INFORMATION ............................................................................ 40 14 CLINICAL TRIALS ........................................................................................................

FEMARA is contraindicated in: • Patients who are hypersensitive to letrozole, other aromatase inhibitors, or to any ingredient in the formulation or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• Premenopausal women (see 7 WARNINGS AND PRECAUTIONS). 1 Pregnant Women). 2 Breast-feeding). • Children or adolescents under 18 years of age.