Section 4.3

Changed text 2^nd paragraph

Casodex 150 mg must not be given to any patient who has shown a hypersensitivity reaction to its use the active substance or to any of the excipients of this product.

Section 4.4

Additional text 4^th paragraph

Severe hepatic changes and hepatic failure have been observed rarely with Casodex 150 mg, and fatal outcomes have been reported (see section 4.8). Casodex 150 mg therapy should be discontinued if changes are severe.

Section 4.8

Changed text to side effects

Deleted text after last footnote under table.

Section 5.1

Changed text and the addition of 2 Tables

Section 10

Date of revision of text: 24^th November 2010

Casodex 150mg SPC changes

Section 4.4

Additional text added to fourth paragraph, now reads as,

“Severe hepatic changes and hepatic failure have been observed rarely with Casodex 150 mg, and fatal outcomes have been reported (see section 4.8). Casodex 150 mg therapy should be discontinued if changes are severe.“

Section 4.8

Extensive changes throughout section, including table, now reads,

“In this section, undesirable effects are defined as follows: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data).

Table 1       Frequency of Adverse Reactions

a.       Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy. Periodic liver function testing should be considered (see also section 4.4).

b.       The majority of patients receiving Casodex 150 mg as monotherapy experience gynaecomastia and/or breast pain. In studies these symptoms were considered to be severe in up to 5% of the patients. Gynaecomastia may not resolve spontaneously following cessation of therapy, particularly after prolonged treatment (≤1/10,000), not known (cannot be estimated from the available data).”

Section 10

Revision of text:  26^th July 2010

Section 4.8
Addition of the following:
The frequencies of adverse events are ranked according to the following: Very common (≥10%); Common (≥1% and <10%); Uncommon (≥0.1% and <1%); Rare (≥0.01% and <0.1%).

Table 1        Frequency of Adverse Reactions

1.       Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy (see section 4.4).

2.       The majority of patients receiving Casodex 150 mg as monotherapy experience gynaecomastia and/or breast pain. In studies these symptoms were considered to be severe in up to 5% of the patients. Gynaecomastia may not resolve spontaneously following cessation of therapy, particularly after prolonged treatment.

Deletion of the following:

The pharmacological action of bicalutamide may give rise to certain undesirable effects. These include the following:

Very common (>10%):

Gynaecomastia, breast tenderness. The majority of patients receiving Casodex 150 mg as monotherapy experience gynaecomastia and/or breast pain. In studies these symptoms were considered to be severe in up to 5% of the patients. Gynaecomastia may not resolve spontaneously following cessation of therapy, particularly after prolonged treatment.

Common or frequent (³1% and <10%):

Hot flushes, pruritus, asthenia, alopecia, hair regrowth, dry skin, decreased libido, nausea, impotence and weight gain.

Hepatic changes (elevated levels of transaminases, cholestasis and jaundice), which are rarely severe. The changes were frequently transient, resolving or improving with continued therapy or following cessation of therapy (see section 4.4).

Uncommon or infrequent (³0.1% to <1%):

Abdominal pain, depression, dyspepsia, haematuria and interstitial lung disease.

Hypersensitivity reactions, including angioneurotic oedema and urticaria.

Rare (>0.01% and <0.1%)

Hepatic failure has occurred rarely in patients treated with bicalutamide but a causal relationship has not been established with certainty.  Periodic liver function testing should be considered (see section 4.4).

Section 10
Change date of revision to 12th June 2008

Section 4.1

Deletion of  text in 1^st paragraph and Additional new text as 1^st paragraph:

Casodex 150 mg is indicated either alone or as adjuvant to radical prostatectomy or radiotherapy in patients with locally advanced prostate cancer at high risk for disease progression (see section 5.1).

Section 4.8

Addition of the word “anaemia” as a common or frequent undesirable effect.

Addition of the word “thrombocytopenia” as an uncommon or infrequent undesirable effect.

Section 5.1

Deletion of some text and additional new text, immediately after the two Tables

For patients with localised disease receiving Casodex alone, there was no significant difference in progression free survival.  In these patients there was also a trend toward decreased survival compared with placebo patients (HR=1.16; 95% CI 0.99 to 1.37).  In view of this, the benefit-risk profile for the use of Casodex is not considered favourable in this group of patients.

Section 10

• Section 4.4- Within the title for section 4.4(Special warnings and precautions for use) the word "Special" has been removed, which is found after warnings.
• Section 4.4-Addition of the words "and hepatic failure" within the sentence severe hepatic changes have been observed.
• Section 4.8-Addition of the sentence-"Hepatic changes (elevated levels of transaminases, cholestasis and jaundice), which are rarely severe. The changes were frequently transient, resolving or improving with continued therapy or following cessation of therapy (See section 4.4). Under the sub-title of common or frequent.
• Section 4.8-Removal of the sentence-"Hepatic changes (elevated levels of transaminases, cholestasis and jaundice), which are rarely severe. The changes were frequently transient, resolving or improving with continued therapy or following cessation of therapy (See section 4.4). From under the sub-title of Rare.
• Section 4.8-Removal of the word "very". From the sentence Hepatic failure has occured very rarely in patients treated with bicalutamide but a casual relationship has not been established with certainty.
• Section 10-Change to date of the revision of the text to reflect recent approval date for variation

• Section 4.4- Within the title for section 4.4(Special warnings and precautions for use) the word "Special" has been removed, which is found after warnings.
• Section 4.4-Addition of the words "and hepatic failure" within the sentence severe hepatic changes have been observed.
• Section 4.8-Addition of the sentence-"Hepatic changes (elevated levels of transaminases, cholestasis and jaundice), which are rarely severe. The changes were frequently transient, resolving or improving with continued therapy or following cessation of therapy (See section 4.4). Under the sub-title of common or frequent.
• Section 4.8-Removal of the sentence-"Hepatic changes (elevated levels of transaminases, cholestasis and jaundice), which are rarely severe. The changes were frequently transient, resolving or improving with continued therapy or following cessation of therapy (See section 4.4). From under the sub-title of Rare.
• Section 4.8-Removal of the word "very". From the sentence Hepatic failure has occured very rarely in patients treated with bicalutamide but a casual relationship has not been established with certainty.
• Section 10-Change to date of the revision of the text to reflect recent approval date for variation.