Each enteric-coated tablet contains: Diclofenac (as sodium), USP 50 mg.
Pharmacology: Pharmacodynamics: In rheumatic diseases, the anti-inflammatory and analgesic properties of diclofenac elicit a clinical response characterized by marked relief from signs and symptoms such as pain at rest, pain on movement, morning stiffness, and swelling of the joints, as well as by an improvement in function. In post-traumatic and post-operative inflammatory conditions, diclofenac rapidly relieves both spontaneous pain and pain on movement and reduces inflammatory, swelling and wound edema. In clinical trials diclofenac has also been found to exert a pronounced analgesic effect in moderate and severe pain of non-rheumatic origin.
Clinical studies have also revealed that, in primary dysmenorrhea, diclofenac is capable of relieving the pain and reducing the extent of bleeding.
Pharmacokinetics: Diclofenac is rapidly absorbed when given as an oral solution, rectal suppository, or by intramuscular injection. It is absorbed more slowly when given as enteric-coated tablet, especially when this dosage form is given with food. Although orally-administered diclofenac is almost completely absorbed, it is subjected to first-pass metabolism so that about 50% of the drug reaches the systemic circulation in the unchanged form. Diclofenac is also absorbed percutaneously, at therapeutic concentrations it is more than 99% bound to plasma proteins. Diclofenac penetrates synovial fluid where concentrations may persist even when plasma concentrations fall; diclofenac has been detected in breast milk. The terminal plasma half-life is about 1 to 2 hours. Diclofenac is metabolized to 4-hydroxydiclofenac, 5-hydroxydiclofenac, 3-hydroxydiclofenac and 4,5-dihydroxydiclofenac. It is then excreted in the form of glucuronide and sulphate conjugates mainly in the urine (about 60%) but also in the bile (about 35%) less than 1% is excreted as unchanged diclofenac.
Diclofenac is used mainly as the sodium salt for the relief of pain and inflammation in various conditions: musculoskeletal and joint disorders such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis; peri-articular disorders such as bursitis and tendinitis; soft-tissue disorders such as sprains and strains; and other painful conditions such as renal colic, acute gout, dysmenorrhea and post-operative pain.
One tablet two to three times a day or as prescribed by the physician.
There is no typical clinical picture resulting from diclofenac overdosage. Overdosage can cause symptoms such as vomiting, gastrointestinal hemorrhage, diarrhea, dizziness, tinnitus or convulsions. In the event of significant poisoning, acute renal failure and liver damage are possible.
Management of acute poisoning with NSAIDs, including diclofenac essentially consists of supportive measures and symptomatic treatment. Supportive measures and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal disorder and respiratory depression. Special measures such as forced diuresis, dialysis or hemoperfusion are probably of no help in eliminating NSAIDs, including diclofenac, due to high protein binding and extensive metabolism. Activated charcoal may be considered after ingestion of a potentially toxic overdose, and gastric decontamination (e.g. vomiting gastric lavage) after ingestion of a potentially life-threatening overdose.
Known hypersensitivity to the active substance or to any of the excipients.
Active gastric or intestinal ulcer, bleeding or perforation.
Last trimester of pregnancy.
Severe hepatic, renal or cardiac failure.
Like other non-steroidal anti-inflammatory drug (NSAIDs), diclofenac is also contraindicated in patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs.
Not to be given to those patients who have a history of: Stroke: cerebrovascular accident, CVA.
Heart attack: Myocardial infarction, MI.
Coronary artery bypass graft: CABG.
Congestive heart failure (CHF NYHA II-IV).
Should not be given to patients with history of peptic ulcers, asthma or bronchospasm, bleeding disorders and to those receiving coumarin anticoagulants. Patients with cardiac decompensation, hypertension and renal disease; suffering from severe hepatic or renal damage; pregnancy.
Pregnancy: There are insufficient data on the use of diclofenac in pregnant women. Therefore, it should not be used during the first two trimester of pregnancy unless the expected benefits to the mother outweigh the risk to the fetus. As with other NSAIDs, use of diclofenac during the third trimester of pregnancy is contraindicated owing to the possibility of uterine inertia and/or premature closure of the ductus arteriosus.
Lactation: Like other NSAIDs, diclofenac passes into the breast milk in small amounts. Therefore, it should not be administered during breast-feeding in order to avoid undesirable effects in the infant.
The most common side-effects occurring during therapy with NSAIDs are generally gastrointestinal discomfort, nausea, and diarrhea; these are usually mild and reversible but in some patients peptic ulceration and severe gastrointestinal bleeding may occur.
Interactions involving NSAIDs include enhancement of the effects of oral anticoagulants (especially by azapropazone and phenylbutazone) and increased plasma concentrations of lithium, methotrexate, and cardiac glycosides.
The risk of nephrotoxicity may be increased if given with ACE inhibitors, ciclosporin, tacrolimus, or diuretics. Effects on renal function may lead to reduced excretion of some drugs. There may also be an increased risk of hyperkalaemia with ACE inhibitors and some diuretics, including potassium sparing diuretics. The antihypertensive effects of some antihypertensives including ACE inhibitors, beta blockers, and diuretics may be reduced. Convulsions may occur due to an interaction with quinolones. NSAIDs may increase the effects of phenytoin and sulfonylurea antidiabetics. Use of more than one NSAID together (including aspirin) should be avoided because of the increased risk of adverse effects. The risk of gastrointestinal bleeding and ulceration associated with NSAIDs is increased when used with corticosteroids, the SSRIs, the SNRI venlafaxine, the antiplatelets, or pentoxifylline. There may be an increased risk of hemotoxicity if zidovudine is used with NSAIDs. Ritonavir may increase the plasma concentrations of NSAIDs. Licensed product information for mifepristone advises of a theoretical risk that prostaglandin synthetase inhibition by NSAIDs or aspirin may alter the efficacy of mifepristone. There have been occasional reports of increased adverse effects when NSAIDs or aspirin may alter the efficacy of mifepristone. There have been occasional reports of increased adverse effects when NSAIDs were given with misoprostol although such combinations have sometimes been used to decrease the gastrointestinal toxicity of NSAIDs.
Store at temperatures not exceeding 30°C. Protect from light.
M01AB05 - diclofenac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.
Difenax tab 50 mg