Section 4.8

Addition of “Arthritis”; amend “Joint pain/stiffness, mainly mild or moderate in nature” to “Arthralgia/Joint Stiffness”; Addition of “Cutaneous vasculitis (including some reports of Henoch-Schonlein purpura).”

Section 10

Revision date of text: 21^st April 2011

Section 4.8

update section in line with the approved core safety profile following PSUR worksharing procedure and in line with current SPC guidelines (medDRA classification).

Section 10

Changes to SmPC, Arimidex Film-coated tablet 1mg

Section 9

Now reads,

“Date of first authorisation: 18 June 2000

Date of latest renewal: 15 February 2010”

Section 10

Now reads,

“15 February 2010”

Section 4.2

Change of text for heading ‘Children’:

Arimidex is not recommended for use in children due to insufficient data on safety and efficacy (see sections 4.4 and 5.1)

Section 4.4

New text second paragraph

Arimidex should not be used in boys with growth hormone deficiency in addition to growth hormone treatment. In the pivotal clinical trial, efficacy was not demonstrated and safety was not established (see section 5.1). Since anastrozole reduces estradiol levels, Arimidex must not be used in girls with growth hormone deficiency in addition to growth hormone treatment. Long-term safety data in children and adolescents are not available.

Section 5.1

New additional text

Arimidex is not indicated for use in children. Efficacy has not been established in the paediatric populations studied (see below). The number of children treated was too limited to draw any reliable conclusions on safety. No data on the potential long-term effects of anastrozole treatment in children are available (see also section 5.3).

The European Medicines Agency has waived the obligation to submit the results of studies with Arimidex in one or several subsets of the paediatric population in short stature due to growth hormone deficiency (GHD), testotoxicosis, gynaecomastia, and McCune-Albright syndrome.

Short stature due to Growth Hormone Deficiency

A randomised, double-blind, multi-centre study evaluated 52 pubertal boys (aged 11-16 years inclusive) with GHD treated for 12 to 36 months with Arimidex 1 mg/day or placebo in combination with growth hormone. Only 14 subjects on anastrozole completed 36 months.

After 3 years anastrozole was found to statistically significantly slow bone maturation in pubertal boys on growth hormone therapy. No statistically significant difference with placebo was observed for the growth related parameters of predicted adult height, height, height SDS, and height velocity. Final height data were not available. While the number of children treated was too limited to draw any reliable conclusions on safety, there was an increased fracture rate and a trend towards reduced bone mineral density in the anastrozole arm compared to placebo.

Testotoxicosis

An open-label, non-comparative, multi-centre study evaluated 14 male patients (aged 2-9) with familial male-limited precocious puberty, also known as testotoxicosis, treated with combination of Arimidex and bicalutamide. The primary objective was to assess the efficacy and safety of this combination regimen over 12 months. Thirteen out of the 14 patients enrolled completed 12 months of combination treatment (one patient was lost to follow-up). There was no significant difference in growth rate after 12 months of treatment, relative to the growth rate during the 6 months prior to entering the study.

Section 5.3

New additional text:

Reproductive toxicology

In a fertility study weanling male rats were dosed orally with 50 or 400 mg/l anastrozole via their drinking water for 10 weeks. Measured mean plasma concentrations were 44.4 (± 14.7) ng/ml and 165 (±90) ng/ml respectively. Mating indices were adversely affected in both dose groups, whilst a reduction in fertility was evident only at the 400 mg/l dose level. The reduction was transient as all mating and fertility parameters were similar to control group values following a 9‑week treatment-free recovery period.

Section 10

4.8

Addition of text

Common

(³ 1% and < 10%)

Uncommon

(³ 0.1% and <1%)

Deletion of 3^rd paragraph

Elevated gamma-GT and alkaline phosphatase have been reported uncommonly (³0.1% and <1%).  A causal relationship for these changes has not been established.

5.3

Addition of text after the 4^th paragraph

Reproductively toxicology

Oral administration of anastrozole to female rats produced a high incidence of infertility at 1 mg/kg/day and increased pre-implantation loss at 0.02 mg/kg/day.  These effects occurred at clinically relevant doses.  An effect in man cannot be excluded.  These effects were related to the pharmacology of the compound and were completely reversed after a 5-week compound withdrawal period.

10

Date of revision of text 20^th July 2007

Section 4.1

• Sentence added:

Adjuvant treatment of early breast cancer in hormone receptor positive postmenopausal women who have received 2 to 3 years of adjuvant tamoxifen.

Section 5.1

• Addition of underlined heading:

Primary adjuvant treatment of early breast cancer

• Addition of underlined heading with 2 paragraphs of text

Adjuvant treatment of early breast cancer for patients being treated with adjuvant tamoxifen

• Addition of Table ABCSG 8 trial endpoint and results summary

and 2 paragraphs of text