[Inserted text; Deleted text]

4.4       Special warnings and precautions for use

[..]

Patients with rare hereditary problems of galactose intolerance, the Lapptotal lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

[..]

4.8       Undesirable effects

[..]

Reporting of suspected adverse reactions

[..]

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

[..]

10. DATE OF REVISION OF THE TEXT

14^th January 2019 28th July 2020

[Inserted text; Deleted text]

Package leaflet: Information for the patient

[..]

2. What you need to know before you take Casodex

[..]

Casodex contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

[..]

6. Contents of the pack and other information

What Casodex 50mg Film-coated Tablets contain

[..]

The other ingredients are lactose monohydrate (see section 2, ‘Casodex contains lactose’), magnesium stearate, hypromellose, macrogol 300, povidone, sodium starch glycolate (see section 2, ‘Casodex contains sodium’) and titanium dioxide (E171).

[..]

This leaflet was last revised in April May 2020.

[..]

ONC 20 00015a

Section 7 – Marketing Authorisation Holder details updated

Section 8 – Marketing Authorisation numbers updated

Section 10 – date of revision updated

Section 4.4 - Update with information on the potentiation of coumarin anticoagulant effects which have been reported in patients receiving concomitant Casodex therapy

Section 4.5- Interaction information amended with warfarin and other coumarin anticoagulants when co-administered with Casodex

Section 4.6 - Editorial updates to align with QRD template 

Section 4.6 - Update to the fertility section relating to adequate contraception

Section 4.8 - Update with information on the interaction of coumarin anticoagulants with Casodex

Section 5.3 - Update to preclinical safety data in animal studies

Section 10- Change to the date of revision

Section 4.1 LHRH has been unabridged.

Section 4.2 Editorial changes to reflect the QRD template (older to elderly and others)

Section 4.4 Statement on sperm morphology changes & contraception has been added

Section 10 Updated revision date

Section 2 updated in line with QRD

Section 4.2 updated in line with QRD

Section 4.3 updated in line with QRD

Section 4.4 addition of inforamtion on androgen deprivation therapy may prolong the QT interval

Section 4.5 addition of information on concomitant use of Casdoex with medicinal products knoen to prolong the QT internal or able to induce Torsade de pointes

Section 4.6 updated in line with QRD

Section 4.8 addition of QT prolongation as a ‘not known’ frequency adverse event

Section 4.8 amendment of adverse event reporting details (IMB to HPRA details change)

Section 5.1 updated in line with QRD

Section 5.2 updated in line with QRD

Section 6.6 updated in line with QRD

Section 8 updated in line with QRD

Section 9 updated in line with QRD

Section 10 updated date of revision

- Section 4.8 Add photosensitivity reaction as a rare adverse reaction in the table

- Section 4.8 Add the Reporting of suspected adverse reactions paragraph, email address etc...

- Section 10 New date of revision

Update to the SPC in line with the PSUR WS procedure
 
Section 4.8 

Changes to table footnotes.

Section 4.8

Include myocardial infarction, correct the frequency descriptor for cardiac failure from uncommon to common.

 

Section 10

Date of revision of text: 11^th April 2011

SPC changes – Casodex 50mg IR

 

Section 4.3

Text updated in first and second paragraphs, now reads,

 

“Casodex is contraindicated in females and children (see section 4.6).

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

 

Section 4.8

Text updated in table, now reads,

 

“Table 1      Frequency of Adverse Reactions

System Organ Class	Frequency	Event
Blood and lymphatic system disorders	Very common	Anaemia
Immune system disorders	Uncommon	Hypersensitivity, angioedema and urticaria
Metabolism and nutrition disorders	Common	Decreased appetite
Psychiatric disorders	Common	Decreased libido Depression
Nervous system disorders	Very common	Dizziness
	Common	Somnolence
Cardiac disorders	Uncommon	Cardiac failure4
Vascular disorders	Very common	Hot flush
Respiratory, thoracic and mediastinal disorders	Uncommon	Interstitial lung disease. Fatal outcomes have been reported.
Gastrointestinal disorders	Very common	Abdominal pain Constipation Nausea
	Common	Dyspepsia Flatulence
Hepato-biliary disorders	Common	Hepatotoxicity, jaundice, hypertransaminasaemia1
	Rare	Hepatic failure2. Fatal outcomes have been reported.
Skin and subcutaneous tissue disorders	Common	Alopecia Hirsuitism/hair re-growth Dry skin Pruritis Rash
Renal and urinary disorders	Very common	Haematuria
Reproductive system and breast disorders	Very common	Gynaecomastia and breast tenderness3
	Common	Erectile dysfunction
General disorders and administration site conditions	Very common	Asthenia Oedema
	Common	Chest pain
Investigations	Common	Weight increased

 

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

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

3.     May be reduced by concomitant castration.

4.     Observed in a pharmaco-epidemiology study of LHRH agonists and anti-androgens used in the treatment of prostate cancer. The risk appears to be increased when Casodex 50 mg was used in combination with LHRH agonists but no increase in risk was evident when Casodex 150 mg was used as a monotherapy to treat prostate cancer.”

Final paragraph in previous version has been deleted.

Section 9
Now reads as,
“Date of first authorisation:        21 April 2000

Date of last renewal:     21 April 2010”

 

Section 10

Date of revision of text,

”13 July 2010”

 

 

 

SPC Changes – Casodex 50mg

 

Section 2

Text changes, now reads,

 

“Each film-coated tablet contains 50 mg of bicalutamide.

Excipients: 61 mg lactose monohydrate per tablet.

For a full list of excipients, see section 6.1.”

 

Section 4.2

Fourth paragraph, the word ‘special’ has been deleted before the word precautions in the final sentence.

 

Section 9

Date of last renewal is now 21 April 2010.

 

Section 10

Date of revision of text is now, 25 June 2010.

 

Changes to SPC, Casodex 50mg

 

Section 4.4

New Text to 4^th paragraph:

 

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

 

Section 4.8

Changes to table:  Changed made in bold text.

 

System Organ Class	Frequency	Event
Blood and lymphatic system disorders	Very common	Anaemia
Immune system disorders	Uncommon	Hypersensitivity reactions (including angioneurotic oedema and urticaria)
Metabolism and nutrition disorders	Common	Anorexia
Psychiatric disorders	Common	Decreased libido Depression
Nervous system disorders	Very common	Dizziness
	Common	Somnolence
Vascular disorders	Very common	Hot flush
Respiratory, thoracic and mediastinal disorders	Uncommon	Interstitial lung disease. Fatal outcomes have been reported.
Gastrointestinal disorders	Very common	Abdominal pain Constipation Nausea
	Common	Dyspepsia Flatulence
Hepato-biliary disorders	Common	Hepatic changes (including elevated levels of transaminases, jaundice)/hepato-biliary disorders1
	Rare	Hepatic failure2. Fatal outcomes have been reported.
Skin and subcutaneous tissue disorders	Common	Alopecia Hirsuitism/hair re-growth Dry skin Pruritis Rash
Renal and urinary disorders	Very common	Haematuria
Reproductive system and breast disorders	Very common	Gynaecomastia and breast tenderness3
	Common	Impotence
General disorders and administration site conditions	Very common	Asthenia Chest pain Oedema
	Common	Chest pain
Investigations	Common	Weight gain

 

 

Section 10

25^th January 2010

Section 4.3 Contraindications

Additional last paragraph

“Co-administration of terfenadine, astemizole or cisapride with Casodex is contraindicated (see section 4.5).”

Section 4.4 Special warnings and precautions for use
Major amendments to text, inclusions and deletions.

Section 4.5 Interaction with other medicinal products and other forms of interaction
Major amendments to text, inclusions and deletions.

Section 4.7
Additional wording at end of first paragraph,
”However, it should be noted that occasionally somnolence may occur.  Any affected patients should exercise caution.”

Section 4.8 including Table 1
Major amendments to section.

Section 10
10^th March 2009

• Section 4.3 Removal of text-Each tablet of casodex contains 61mg of lactose.....
• Section 4.4-Addition of the word hepatic failure in the 4th paragraph of section 4.4
• Section 4.4-Addition of the text-each tablet of casodex contains...
• Section 4.8-Addition of text under the subtitle rare-Hepato-billiary disorders-Heaptic failure
• Section 5.2-Removal of the letter S, in the word micrograms.
• Section 5.2-Addition of the text-In a clinical study, the mean concentration of...
• Section 10-change in the date of the revision of the text-to reflect the updated approval date

 

Section 1: Addition of: 50 mg Film-coated Tablets to name of medicinal product

 

Section 2: Addition of: “For excipients, see 6.1.”

 

Section 4.3: Addition of paragraph on galactose intolerance

 

Section 4.8: Deletion of the following sentence: "Casodex in general, has been well tolerated with few withdrawals due to adverse events".

 

Addition of: "Casodex 50 mg is only used in combination with surgical or medical castration.  The reported adverse drug profile of Casodex 50 mg therefore includes effects that may also be seen with castration therapy alone.  The most common reactions reported reflect the pharmacological activity; with the majority (53%) of patients reporting hot flushes and lower proportions (approximately 10%) reporting gynaecomastia or breast tenderness".

 

Deletion of footnote: "May be reduced by concomitant castration". From Frequency of Adverse Reactions table

 

Section 6.1: Addition of 'Monohydrate' after 'Lactose'.

 

Addition of (E171) after Titanium Dioxide

 

Section 6.2: Deletion of “None known” and changed to “Not applicable.”

 

Section 6.6: Change from “no precautions required” to “no requirements”

 

Section 9: Change to date of renewal