- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Dosage RecommendationsUndesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4 Special warnings and precautions for use).
AdultsOne tablet to be taken once or twice a day swallowed whole, preferably with or after food.
ChildrenDiclofenac sodium is not suitable for use in children.
The ElderlyThe elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
ElderlyThe elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).
Respiratory disordersCaution is required if administered to patients suffering from, or with a previous history of bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Cardiovascular, Renal and Hepatic ImpairmentThe administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3). On stopping diclofenac, effects on renal function are usually reversible.Diclofenac should be stopped if liver function tests show abnormalities that persist or worsen, or if liver disease develops or if other symptoms such as eosinophilia or rash occur.Diclofenac sodium may trigger an attack in patients with hepatic porphyria.Monitoring of renal function, hepatic function (elevation of liver enzymes may occur) and blood counts should be performed on long-term NSAID patients, as a precautionary measure.
Cardiovascular and cerebrovascular effectsAppropriate 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 (150 mg 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 significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with diclofenac after careful consideration. As the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically.
Gastrointestinal bleeding, ulceration and perforationGI 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 serious 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 patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.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).When GI bleeding or ulceration occurs in patients receiving diclofenac, the treatment should be withdrawn.NSAIDs should be given with care in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease, haematemesis, melaena, haematological abnormalities, or bleeding diathesis) as these conditions may be exacerbated (see section 4.8). SLE and mixed connective tissue diseaseIn patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).
DermatologicalSerious skin reactions, 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 section 4.8). Patients appear to be at highest risk for these early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first appearance of skin rash, mucosal lesions, or any signs of hypersensitivity.
Impaired female fertilityThe use of Volsaid may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Volsaid should be considered.
Other analgesics including cyclooxygenase-2 selective inhibitorsAvoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).
Anti-hypertensivesReduced anti-hypertensive effect.
DiureticsReduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs. Increased serum potassium levels may result when diclofenac is given concomitantly with potassium-sparing diuretics. Serum potassium levels should therefore be monitored.
Cardiac GlycosidesNSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
LithiumDecreased elimination of lithium.
MethotrexateDecreased elimination of methotrexate. Methotrexate and NSAIDs should only be administered within 24 hours of each other if given with extreme caution.
CiclosporinIncreased risk of nephrotoxicity. Ciclosporin may increase the bioavailability of diclofenac.
Quinolone AntibioticsAnimal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.Anticoagulants and anti-platelet agents: Caution is recommended since concomitant administration could increase the risk of bleeding. Although clinical investigations do not appear to indicate that diclofenac affects the action of anticoagulants, there are reports of an increased risk of haemorrhage in patients receiving diclofenac and anticoagulants concomitantly. Close monitoring of such patients is therefore recommended.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs)Increased risk of gastrointestinal bleeding (see section 4.4).
Oral Hypoglycaemic AgentsIt has been reported that hypo- and hyperglycaemic effects have occurred rarely when diclofenac and oral antidiabetic agents have been given together and adjustment of the hypoglycaemic may be required. Inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia have also been reported.
AminoglycosidesReduction in renal function in susceptible individuals, decreased elimination of aminoglycosides and increased plasma concentrations have been reported.
ProbenecidReduction in metabolism and elimination of NSAID and metabolites occurs with probenecid.
MifepristoneNSAIDs should not be used for 8 to 12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
CorticosteroidsIncreased risk of gastrointestinal ulceration or bleeding. (See section 4.4).
TacrolimusPossible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.ZidovudineIncreased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
GastrointestinalThe most commonly observed adverse events are gastrointestinal in nature.Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, constipation, anorexia, dyspepsia, flatulence and abdominal pain, melaena, haematemesis, ulcerative stomatitis, glossitis, oesophageal lesions, aphthous stomatitis, exacerbation of colitis and Crohn's disease (See section 4.4) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.Ischaemic colitis has been reported with a frequency not known.
CardiovascularOedema, hypertension and cardiac failure have been reported in association with NSAID treatment.Clinical trial and epidemiological data consistently point towards an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) associated with the use of diclofenac, particularly at high dose (150 mg daily) and in long term treatment (see section 4.3 and 4.4 for Contraindications and Special warnings and precautions for use).
Hypersensitivity ReactionsHypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of: - non-specific allergic reactions and anaphylaxis - respiratory tract reactivity comprising of asthma, aggravated asthma, bronchospasm or dyspnoea - assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and more rarely Stevens-Johnson syndrome, Lyell's syndrome, eczema, erythroderma, hair loss, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme)Other adverse reactions reported less commonly include:
Neurological and Special SensesVisual disturbances, optic neuritis, headache, paraesthesia, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation, (see section 4.4), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue, drowsiness, tiredness, impaired hearing, anorexia, insomnia, convulsions, irritability, anxiety, psychotic reactions, tremors, memory disturbance, disturbance of vision, nightmares and taste alterations.
Dermatological ReactionBullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity
RenalNephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure. Occasional effects on the kidney include acute renal insufficiency, urinary abnormalities (e.g., haematuria, proteinuria) and papillary necrosis.
HepaticEffects on the liver include occasional reports of elevation of serum aminotransferase enzymes (ALT, ST) and rarely abnormal liver function, hepatitis and jaundice.
Haematological ReactionsThrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia, haemolytic anaemia and leucopenia.Other rarely reported reactions include hypotension, hypertension, palpitation, impotence and chest pain.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
SymptomsSymptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions, hypotension and respiratory depression. In cases of significant poisoning acute renal failure and liver damage are possible.
ManagementPatients should be treated symptomatically as required.Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively in adults gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.Good urine output should be ensured.Renal and liver function should be closely monitored.Patients should be observed for at least four hours after ingestion of potentially toxic amounts.Frequent or prolonged convulsions should be treated with intravenous diazepam.The correction of severe electrolyte abnormalities may need to be considered. Other measures may be indicated by the patient's clinical condition.
Chiesi Limited, 333 Styal Road, Manchester, M22 5LG
0800 009 2329
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