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Change Detail Difene 75mg Capsules Aug 2011
(Deletions with strikethrough and additions in red)
6 Pharmaceutical Particulars
6.1. List of excipients
Printing ink:
Titanium dioxide (E171) Ph Eur
Shellac
soya Lecithin Dimeticone
Propylene Glycol Ph Eur
10 Date of Revision of the Text
August 2011
Jan 2010
6. Pharmaceutical Particulars
Dibutyl Phthalate removed and replaced by Triethyl citrate
6.3. Shelf Life
Reduced form 5 years to 4 years
10. Date of Revision of the Text
Changed from October 2008 to January 2010
Section 2. Qualitative and Quantitative Composition
For excipients see 6.1 change to read For a full list of excipients see section 6.1
Section 4.4 Special warnings and precautions for use
Inserted: Diclofenac should be used with caution in patients with a history of peptic ulceration or inflammatory bowel disease.
Section 4.5. Interaction with other medicinal products and other forms of interaction.
Format update, underlining
Section 4.8. Undesirable effects
Gastrointestinal tract: insertion of (which can be fatal). Insertion of haematemesis.
Section 5.1 Pharmacodynamic Properties
Insertion of the following: M01A B05 Anti-inflmmatory and anti-rheumatic products, non-steroids, acetic acid derivates and related substances, diclofenac.
Ammonio methacrylate copolymer, removed: Eudragit RS & RL added.
Section 9. Date of First Authorisation/Renewal of the Authorisation
30th May 1997/30th May 2002
Changed to
Date of first authorization: 30 May 1997
Date of last renewal: 30 May 2007
Section 10. Date of Revision of the Text
Changed from July 2007 to October 2008
Difene 100mg Dual Release Capsules SPC
Version December 2005 v July 2007
Section 4.2 Posology and method of administration
Slight rewording regarding using lowest effective dose, but meaning unchanged.
Section 4.3. Contraindications
New text inserted regarding gastrointestinal and heart failure contraindications:
“History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Severe heart failure.”
Section 4.4. Special warnings and precautions for use
New text inserted regarding special warnings and precautions for use, as noted below.
In addition, paragraph two (regarding the elderly) has been reworded, but meaning is essentially unchanged.
“The use of Difene Capsules with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2). Prolonged use of NSAIDs in the elderly is not recommended. Where prolonged therapy is required, patients should be reviewed regularly.
Gastrointestinal: Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of previous GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and 4.5).
Patients with a history of GI toxicity especially when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
When GI bleeding or ulceration occurs in patients receiving Difene Capsules, the treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated (see section 4.8 – undesirable effects).
Cardiovascular and cerebrovascular effects
Caution and appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dose (150mg initiating daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with diclofenac after careful consideration. Similar consideration should be made before longer- term treatment of patient with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Serious skin reaction, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see 4.8). Patients appear to be at the highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Difene capsules should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
The use of Difene Capsules may impair the female fertility and is not recommended in women attempting to conceive. In woman who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Difene Capsules should be considered……..
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).”
Following text has been deleted:
“Diclofenac should be used with caution in patients with a history of peptic ulceration or inflammatory bowel disease.”
Section 4.5. Interaction with other medicinal products and other forms of interaction
New text inserted:
“Anti-coagulants: NSAIDSs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4).
Anti-platelet agents and selective serotonin-reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).”
Gastrointestinal tract: new events of abdominal pain and gastritis inserted.
“Cardiovascular system:
Isolated cases: Oedema, palpitations, chest pain, hypertension, congestive heart failure.
Clinical and epidemiological data suggest that use of diclofenac, particularily at high dose (150mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).”
Date of revision of the text updated to July 2007