Each ml contains: Diclofenac Sodium 25 mg, Benzyl Alcohol 4% w/v (as preservative).
Pharmacology: Pharmacodynamics: Dicloran contains a non steroidal compound with pronounced anti-inflammatory and analgesic properties. Inhibition of prostaglandin biosynthesis, which has demonstrated experimentally is regarded as having an important bearing on its mechanism of action. Prostaglandin plays an important role in the causation of inflammation, pain and fever.
In rheumatic diseases, the anti-inflammatory and analgesic properties of Dicloran elicit a clinical response characterized by marked relief from signs and symptoms such as pain at rest, pain on movement, morning stiffness, post traumatic inflammatory conditions.
Dicloran rapidly relieves both spontaneous pain and pain on movement and diminishes inflammatory swelling and wound oedema.
Pharmacokinetics: Approximately 20 minutes after intramuscular injection of 75 mg diclofenac, a mean peak plasma concentration of 2.5μg/ml (8μmol/litre) is attained.
The plasma concentration is in linear reaction to the dose. The area under the concentration curve (AUC) is about twice as large as it is following oral dose of equal size, because about half the active substance is metabolized during its first passage through the liver (first pass effect) when administered via the oral route.
Diclofenac becomes bound to serum proteins are at a rate of 99.7% chiefly to albumin (99.4%). The total systemic clearance of diclofenac in plasma is 263±56 ml/min (mean value ±SD). The terminal half life in plasma is 1-2 hours. Pharmacokinetic behavior remains unchanged following repeated administration. No accumulation occurs provided the recommended dosage intervals are observed. Diclofenac enters the synovial fluid where maximum concentrations are measured 2-4 hours after the peak plasma values have been attained.
The apparent half life for elimination from the synovial fluid is 3-6 hours. Only 4-6 hours after administration, therefore, concentration of active substance are already higher in the synovial fluid than they are in the plasma and remain higher for up to 12 hours.
The biotransformation of diclofenac involves partly glucordination of the intact molecule but mainly single and multiple hydroxylation followed by glucordination. About 60% of the administered dose is excreted in the urine in the form of metabolites from one of the two processes: less than 1% is excreted as unchanged substance in the faeces.
The age of the patient has no influence on the absorption, metabolism or excretion of diclofenac. In patients suffering from renal impairment, no accumulation of the unchanged active substance can be inferred from the single dose kinetics when applying the usual dosage schedule. At a creatinine clearance of 10 ml/min, the theoretical steadystate plasma levels of metabolites are about 4 times higher than in normal subjects. However the metabolites are ultimately cleared through the bile.
In the presence of impaired hepatic function (chronic hepatitis, non decompensated cirrhosis), the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
Acute, severe pain due to inflammatory and degenerative form of rheumatism; rheumatoid arthritis; ankylosing spondylitis; osteoarthrosis. Painful post traumatic inflammation and swelling. Pain following dental surgery. Acute attack of gout.
Adults: For adults the dosage is generally one ampoule daily injected deep intragluteally into the upper outer quadrant, by way of exception, in severe cases two injections, separated by an interval of a few hours, can be given per day (one into each buttock). Alternatively it is possible to combine one ampoule with Dicloran tablets upto a maximum daily dosage of 150 mg. Dicloran ampoules should not be given for more than 2 days: if necessary, the treatment can be continued with Dicloran tablets.
Children: Dicloran ampoules are not suitable for children.
After assessing the risk/benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used.
Mode of Administration: Intramuscular.
Management of acute poisoning with non steroidal anti-inflammatory agents consists essentially supportive and symptomatic measures. There is no typical picture resulting from an overdosage of diclofenac.
The therapeutic measures to be taken in case of overdosage are as follows: supportive and symptomatic treatment should be given for complications, such as hypotension, renal failure, convulsions, gastrointestinal irritation and respiratory depression.
Special therapies, such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating non steroidal anti-inflammatory agents, because of their high protein binding rate and extensive metabolism.
Patients with a history of or active or suspected gastro-intestinal ulcers or bleeding.
Patients who have previously shown hypersensitivity reactions (e.g. asthma, urticaria or acute rhinitis) to diclofenac sodium, aspirin of other non-steroidal anti-inflammatory drugs.
Hypersensitivity to the excipients sodium metabisulphite, benzyl alcohol, propylene glycol, mannitol.
Specifically for iv use: Concomitant NSAID or anticoagulant use (including low dose heparin).
History of haemorrhagic diathesis, a history of confirmed or suspected cerebrovascular bleeding.
Operations associated with a high risk of haemorrhage.
A history of asthma.
Moderate or severe renal impairment (serum creatinine >160mol/l). Hypovolaemia or dehydration from any cause.
Use in Pregnancy & Lactation: Insufficient data are available as yet on the use of Dicloran ampoules during pregnancy and lactation. For this reason, their use is not recommended during pregnancy.
Warnings: Hypersensitivity reactions: As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug. Like other NSAIDs, Dicloran may mask the signs and symptoms of infection due to its pharmacodynamic properties.
Gastro-intestinal: Close medical surveillance is imperative in patients with symptoms indicative of gastrointestinal disorders, with a history suggestive of gastro-intestinal ulceration, with ulcerative colitis or with Crohn's disease.
Gastro-intestinal bleeding or ulcerative/perforation, haematemesis and melaena have in general more serious consequences in the elderly. They can occur at any time during treatment, with or without warning symptoms or a previous history. In the rare instances where gastro-intestinal bleeding or ulceration occurs in patients receiving Dicloran, the drug should be withdrawn.
Hepatic: Close medical surveillance is also imperative in patients suffering from severe impairment or hepatic function.
Precautions: Cardiovascular Thrombotic Events: Observational studies have indicated that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular events, principally myocardial infarction, which may increase with dose or duration of use. Patients with cardiovascular disease or cardiovascular risk of an adverse cardiovascular event in patient taking NSAID, especially in those with cardiovascular risk factors, the lowest effective dose should be used for the shortest possible duration.
There is no consistent evidence that the concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.
Hypertension: NSAIDs may lead to the onset of new hypertension or worsening the pre-existing hypertension and patients taking antihypertensive with NSAIDs may have an impaired antihypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.
Heart Failure: Fluid retention and oedema have been observed in some patients taking NSAIDs, there caution is advised in patients with fluid retention or heart failure.
Gastrointestinal Events: All NSAIDs can cause gastrointestinal discomfort and rarely serious. Potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation which may increase with dose or duration of use, but can occur at any time without warning. Caution is advised in patients with risk factors for gastrointestinal events e.g. the elderly, those with a history of serious gastrointestinal events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately. Doctors should warn patient about signs and symptoms of serious gastrointestinal toxicity. The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.
Severe Skin Reactions: NSAIDs may very rarely cause serious cutaneous adverse events such as exfoliative dermatitis, toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of a skin rash or any other sign of hypersensitivity.
Insufficient data are available as yet on the use of Dicloran ampoules during pregnancy and lactation. For this reason, their use is not recommended during pregnancy.
If serious side effects occur, Dicloran should be withdrawn.
Central Nervous System: Occasional: Headache, dizziness, or vertigo. Rare: Drowsiness, tiredness. In isolated cases: Disturbances of sensation, paraesthesia, memory disturbance, disorientation, insomnia, irritability, convulsions, depression, anxiety, nightmares, tremor, psychotic reactions, aseptic meningitis.
Gastro-intestinal tract: Occasional: Epigastric pain, other gastro-intestinal disorders (e.g. nausea, vomiting, diarrhoea, abdominal cramps, dyspepsia, flatulence, anorexia). Rare: Gastro-intestinal bleeding (haematemesis, melaena, bloody diarrhoea), gastrointestinal ulcers with or without bleeding or perforation. In isolated cases: Aphthous stomatitis, glossitis, oesophageal lesions, lower gut disorders (e.g. non-specific haemorrhagic colitis and exacerbations of ulcerative colitis or Crohn's proctocolitis, colonic damage and stricture formation), pancreatitis, constipation.
Special senses: Isolated cases: Disturbances of vision (blurred vision, diplopia), impaired hearing, tinnitus, taste disturbances.
Skin: Occasional: Rashes or skin eruptions. Rare: Urticaria. In isolated cases: Bullous eruptions, eczema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome, (acute toxic epidermolysis), erythroderma (exfoliative dermatitis), loss of hair, photosensitivity reactions, purpura including allergic purpura.
Blood: In isolated cases: Thrombocytopenia, leucopenia, agranulocytosis, haemolytic anaemia, aplastic anaemia.
Liver: Occasional: Elevation of serum aminotransferase enzymes (ALT, AST). Rare: Liver function disorders including hepatitis (in isolated cases fulminant) with or without jaundice.
Kidney: Rare: Oedema. In isolated cases: Acute renal insufficiency, urinary abnormalities (e.g. haematuria, proteinuria), interstitial nephritis, nephrotic syndrome, papillary necrosis.
Cardiovascular system: Isolated cases: Palpitations, chest pain, hypertension, congestive heart failure.
Hypersensitivity: Rare: Hypersensitivity reactions (e.g. bronchospasm, anaphylactic/anaphylactoid systemic reactions including hypotension). Isolated cases: Vasculitis, pneumonitis.
Other organ systems: Isolated cases: Impotence.
Reactions to the intramuscular injection: Occasional: Reactions such as local pain and induration. Isolated cases: Abscesses and local necrosis at the intramuscular injection site.
Antidiabetic agents: Clinical studies have shown that Dicloran can be given together with oral antidiabetic agents without influencing their clinical effect. However, there have been isolated reports of hypoglycaemic effects which have required adjustments to the dosage of hypoglycaemic agents.
Anticoagulant: Although clinical investigations do not appear to indicate that Dicloran has an influence on the effect of anticoagulants, there are isolated reports of an increased risk of haemorrhage with the combined use of diclofenac and anticoagulant therapy. Therefore, to be certain that no change in anticoagulant dosage is required, close monitoring of such patients is required. As with other non-steroidal anti-inflammatory agents, diclofenac in a high dose can reversibly inhibit platelet aggregation.
Lithium and Digoxin: Dicloran may increase plasma concentrations of lithium and digoxin.
Methotrexate: Cases of serious toxicity have been reported when methotrexate and NSAIDS are given within 24 hours of each other. This interaction is mediated through accumulation of methotrexate resulting from impairment of renal excretion in the presence of the NSAID.
Cyclosporin: Cases of nephrotoxicity have been reported in patients receiving concomitant cyclosporin and NSAIDS, including Dicloran. This might be mediated through combined renal antiprostaglandin effects of both the NSAID and cyclosporin.
Other NSAIDS and corticosteroids: Co-administration of Dicloran with aspirin or corticosteroids may increase the risk of gastro-intestinal bleeding. Avoid concomitant use of two or more NSAIDs.
Quinolone antimicrobials: Convulsions may occur due to an interaction between quinolones and NSAIDS. This may occur in patients without a previous history of epilepsy or convulsions. Therefore, caution should be exercised when considering the use of a quinolone in patients who are already receiving an NSAID.
Diuretics: Like other NSAIDS, Dicloran may inhibit the activity of diuretics. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels, which should therefore be monitored frequently.
Cardiac glycosides: Concomitant use of cardiac glycosides and NSAIDs in patients may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Anti-hypertensives: Concomitant use of NSAIDs with antihypertensive drugs (i.e. beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics) may cause a decrease in their antihypertensive effect via inhibition of vasodilatory prostaglandin synthesis.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Store below 30°C. Do not freeze. Protect from light.
Shelf-Life: 30 months from the date of manufacture.
M01AB05 - diclofenac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.
Soln for inj 25 mg/mL (a clear, colourless to slightly yellow solution in amp) x 3 mL x 5's.