Pharmacology: Pharmacodynamics: Diclofenac sodium inhibits the activity of the enzyme cyclo-oxygenase, resulting in decreased formation of precursors of prostaglandin and thromboxanes from arachidonic acid.
Antirheumatic action: It acts via analgesic and anti-inflammatory mechanisms.
Analgesic action: Diclofenac block pain impulse generation via a peripheral action that involve reduction of the activity of prostaglandin, and possibly by inhibiting other substances responsible for sensitization of pain receptors to various stimulants.
Anti-inflammatory action: The exact mechanism of action of diclofenac have not been determined. Diclofenac acts by reducing prostaglandin activity in the inflamed tissues.
Diclofenac probably acts also by inhibiting leukocyte migration, inhibition of lysosomal enzyme.
Pharmacokinetics: The onset of action for diclofenac tablet is 30 minutes and duration of action is up to 8 hrs.
Synovial fluid concentrations.
Diclofenac enters the synovial fluid and that, several hrs. after administration of single dose, synovial fluid concentrations equal or exceed the simultaneously measured plasma concentrations. Diclofenac achieves maximum synovial concentrations of 0.28 microgram/mL after three hours (steady state - 50mg three times a day). The synovial fluid half-life is up to 6 hrs.
Dicloran is indicated for acute and chronic treatment of the signs and symptoms of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.
As a general recommendation, the dose should be individually adjusted and the lowest effective dose given for the shortest possible duration. The tablets should be swallowed whole with liquid, preferably before meals, and must not be divided or chewed.
Adults: The recommended initial daily dose is 100 to 150 mg. In milder cases, as well as for long term therapy, 100 mg daily is usually sufficient.
The total daily dose should generally be divided into 2 to 3 doses. To suppress nocturnal pain and morning stiffness, treatment with tablets during the day can be supplemented by the administration of a suppository at bedtime (up to a total maximum daily dose of 150 mg).
In primary dysmenorrhoea, the daily dose should be individually adjusted and is generally 50 to 150 mg. A dose of 50 to 100 mg should be given initially and, if necessary, increased over the course of several menstrual cycles up to a maximum of 200 mg/day. Treatment should be started on appearance of the first symptoms and, depending on the symptomatology, continued for a few days.
Children and adolescents: Children aged 1 year or over and adolescents should be given 0.5 to 2 mg/kg body weight daily in 2 to 3 divided doses, depending on the severity of the disorder. For treatment of juvenile rheumatoid arthritis, the daily dose can be raised up to a maximum of 3 mg/kg daily, given in divided doses. The maximum daily dose of 150 mg should not be exceeded.
Because of their dosage strength, Diclofenac Sodium Enteric Coated Tablet 50 mg are not recommended for use in children and adolescents below 14 years of age.
DOSAGE: As a general recommendation, the dose should be individually adjusted. Adverse Effects may be minimized using the lowest effective dose for the shortest duration necessary to control symptoms (see PRECAUTIONS).
Established cardiovascular disease or significant cardiovascular risk factors: Treatment with diclofenac is generally not recommended in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension. If needed, patients with established cardiovascular disease, uncontrolled hypertension, or significant risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus and smoking) should be treated with diclofenac only after careful consideration and only at doses ≤ 100mg daily if treated for more than 4 weeks (see PRECAUTIONS).
MODE OF ADMINISTRATION: Oral.
Symptoms: Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions. In cases of significant poisoning, acute renal failure and liver damage are possible.
Therapeutic measures: Patients 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.
Other measures may be indicated by the patient's clinical condition.
Patients with hypersensitivity to it, in whom, Dicloran, aspirin or other non steroidal antiinflammatory drugs induce asthma, urticaria or other allergic type reaction. Rhinitis.
Severe cardiac failure (see PRECAUTIONS).
RISK OF GI ULCERATION, BLEEDING AND PERFORATION WITH NSAID: Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms. In patients treated with NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common, usually developing early. In therapy, prescribers should remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Patients with prior history of serious GI events and other risk factors associated with peptic ulcer disease (e.g. alcoholism, smoking, and corticosteroid therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.
Warnings: Gastro-intestinal: Close medical surveillance is imperative in patients with symptoms indicative of gastro-intestinal disorders, with a history suggestive of gastric or intestinal ulceration, with ulcerative colitis, or with Crohn's disease.
Gastro-intestinal bleeding or ulceration/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 when gastro-intestinal bleeding or ulceration occur in patients receiving Dicloran, the drug should be withdrawn.
Hepatic: Close medical surveillance is also imperative in patients suffering from severe impairment of hepatic function.
Hypersensitivity reactions: As with other nonsteroidal 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.
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.
Treatment with NSAIDs including diclofenac, particularly at high dose and in long term, maybe associated with an increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke). Treatment with diclofenac is generally not recommended in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension. If needed, patients with established cardiovascular disease, uncontrolled hypertension, or significant risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus and smoking) should be treated with diclofenac only after careful consideration and only at doses ≤100mg daily when treatment continues for more than 4 weeks.
As the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the lowest effective daily dose should be used for the shortest duration possible. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially when treatment continuous for more than 4 weeks.
Patients should remain alert for the signs and symptoms of serious arteriothrombotic events (e.g. Chest pain, shortness of breath, weakness, slurring of speech), which can occur without warnings. Patients should be instructed to see a physician immediately in case of such an event.
Hypertension: NSAIDs may lead to the onset of new hypertension or worsening the pre-existing hypertension and patient taking anti hypertensive 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 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 occurs in patients receiving NSAIDs, the drug shoule 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: Severe cutaneous reactions, including Stevens - Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), have been reported with diclofenac sodium. Patients treated with diclofenac sodium should be closely monitored for signs of hypersensitvity reactions. Discontinue diclofenac sodium immediately if rash occurs.
The following adverse events have been reported with NSAIDs: Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohns disease have been reported following administration. Less frequently, gastritis, has been observed.
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of: non specific allergic reactions and anaphylaxis;
respiratory tract reactivity comprising asthma, bronchospasms or dyspnoea, or;
assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Cardiovascular: Oedema has been reported in association with NSAID treatment.
Other adverse events reported less commonly include: Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
Hepatic: Abnormal liver function, hepatitis and jaundice.
Neurological & special senses: Visual disturbances, optic neuritis, headaches, 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, depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.
Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Dermatological: Occasional: rashes or skin eruptions cases of hair loss, bullous eruptions, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), and photosensitivity reactions have been reported.
Cardiac Disorders: Uncommon*: Myocardial infarction, cardiac failure, palpitations, chest pain.
*The frequency reflects data from long-term treatment with a high dose (150mg/day).
Description of selected adverse drug reactions: Arteriothrombotic events: Meta-analysis and pharmacoepidemiological data point towards an increased risk of arteriothrombotic events (for example myocardial infarction) associated with use of diclofenac, particularly at a high dose (150mg daily) and during long-term treatment (see PRECAUTIONS).
Lithium: Dicloran may increase plasma concentrations and decrease elimination of lithium.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin.
Antidiabetic agents: Clinical studies have shown that Dicloran can be given together with oral hypoglycaemic agents without influencing their clinical effect. However there have been isolated reports of hyperglycaemic and hypoglycaemic effects, which have required adjustments to the dosage of hypoglycaemic agents.
Ciclosporin: Ciclosporin nephrotoxicity may be increased by the effect of NSAIDs on renal prostaglandins.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Methotrexate: Caution should not be exercised if NSAIDs and methotrexate are administered within 24 hours of each other, since NSAIDs may increase methotrexate plasma levels with decreased elimination, resulting in increased toxicity.
Quinolone antibiotics: Animal 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.
Other analgesics: Concomitant therapy with other systemic NSAIDs (including aspirin) may increase the frequency of side effects.
Corticosteroids: Corticosteroids can increase the risk of gastrointestinal bleeding.
Diuretics: Various NSAIDs are liable to inhibit the activity of diuretics. Diuretics can increase the risk of nephrotoxicity of NSAIDs. Concomitant treatment with potassium sparing diuretics may be associated with increased serum potassium levels, hence serum potassium should be monitored.
Anti-hypertensives: Reduced anti-hypertensive effect.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Store in a dry place below 30°C. Protect from light.
Shelf-Life: 3 years 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.
Dicloran DR tab 50 mg
10 × 10 × 10's;10 × 10's
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