Axcel Diclofenac-50

Orange, round, biconvex enteric coated tablet, 8 mm in diameter.
Each tablet contains Diclofenac Sodium 50 mg.

Pharmacology: Mechanism of Action: Diclofenac, a phenylacetic acid derivative, is a non-steroidal anti-inflammatory drugs (NSAIDs). As with other NSAIDs drug, its mode of action is not known but may be related to its ability to inhibit prostaglandin synthesis. It has been proposed that NSAIDs may act through inhibition of cyclo-oxygenase-1 and cyclo-oxygenase-2 and that inhibition of Cox-1 is associated with adverse gastrointestinal effects while inhibition of Cox-2 is associated with anti-inflammatory activity. Both Cyclo-oxygenase-1 and -2 are involved in biosynthesis of prostaglandin that plays a major role in the pathogenesis of inflammation, pain and fever.
Pharmacokinetics: Axcel Diclofenac-50 Tablet is in a pharmaceutical formulation that resists dissolution in the low pH of gastric fluid but allows a rapid release of drug in the higher pH-environment of the duodenum. Diclofenac is rapidly absorbed from the gastrointestinal tract. Although orally administered diclofenac is almost completely absorbed, due to the first-pass metabolism, only about 50% of the absorbed dose is systemically available. At therapeutic concentration, it is more than 99% bound to plasma protein. Diclofenac penetrates synovial fluid where concentrations may persist even when plasma concentrations fall; diclofenac has been detected in breast milk. The minimal plasma half-life is about 1 to 2 hours. It is metabolised in the liver and excreted in the form of glucuronide and sulphate conjugates mainly in the urine (about 35%) but also in the bile (about 35%).

Inflammatory, degenerative and non-articular forms of rheumatism and juvenile arthritis. Acute gout. Post-traumatic and post-operative inflammatory and swelling. Primary dysmenorrhea.

To be taken after meal. Treatment should begin at the onset of symptoms and continue for 1-2 weeks for non-chronic conditions. Adult: 75-150 mg (3-6 tablets) daily in 2-3 divided doses. In primary dysmenorrhoea: The daily dosage which should be individually adapted, is generally 50-150 mg (2-6 tablets). The initial dose should be 50-100 mg (2-4 tablets) and, if necessary, this dose can be raised over a number of menstrual cycles up to a maximum dose of 200 mg (4-8 tablets) daily. Treatment should be started as soon as symptoms begin and continued for several days, depending on the symptomatology. Mild and prolonged use for Rheumatoid Arthritis: 75 mg once daily. Max: 100-150 mg daily.
As a general recommendation, the dose should be individually adjusted. Adverse effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
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 ≤100 mg daily if treated for more than 4 weeks.

Overdosage of diclofenac includes GI complaints, confusion, drowsiness or general hypotonia. There was reported of vomiting and drowsiness after an overdose of 2.37 g of diclofenac. In case of acute overdosage, it is recommended that stomach be emptied by vomiting or gastric lavage.

Contraindicated in patient with a history of hypersensitivity to aspirin or any other NSAIDs. Also contraindicated in patients with severe cardiac failure, peptic ulcerations, attacks of asthma, urticaria or acute rhinitis.

Risk of GI Ulceration, Bleeding and Perforation with NSAIDs: Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated with NSAIDs 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 adverse 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.

Diclofenac should be used with caution in the elderly and in patients with a history of peptic ulceration. Also used with cautions in patients with haemorrhagic disorders, asthma, a history of hypersensitivity reactions to aspirin and other NSAIDs, hypertension and impaired renal, hepatic or cardiac function. Peptic ulceration and gastrointestinal bleeding have been reported in patients receiving diclofenac.
Cardiovascular Effects: 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 ≤100 mg 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 continues 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 patients taking antihypertensive with NSAIDs may have an impaired anti-hypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAIDs 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 Effects: The concurrent use of aspirin and NSAIDs including diclofenac, may be associated with increased risk of gastrointestinal anastomotic leak. Close medical surveillance and caution are recommended when using diclofenac after gastrointestinal surgery.
Severe Skin Reactions: Severe cutaneous reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), have been reported with diclofenac sodium. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients treated with diclofenac sodium should be closely monitored for signs of hypersensitivity reactions. Discontinue diclofenac sodium immediately if rash occurs.
Use in Pregnancy & Lactation: See USE IN PREGNANCY & LACTATION section for further information.
Use in Children: Diclofenac should not be used for children below 1 year old.

Should be avoided in late pregnancy because it will cause premature closure of the ductus arteriosus. Not recommended for nursing mother since diclofenac has been detected in the breast milk.

The side effect of Diclofenac vary in severity and frequency.
Gastrointestinal Tract: The most frequent side effects reported in patients given Diclofenac are gastrointestinal in nature. Typical reactions include epigastric pain, nausea, vomiting and diarrhoea. Rarely peptic ulcer and gastrointestinal bleeding have occurred. Diclofenac has also been implicated as the causative agent in colonic ulceration, small bowel perforated and pseudomembranous colitis.
Hematological Reactions: Blood disorders have also occurred such as haemolytic anaemia, thrombocytopenia, neutropenia and agranulocytosis in patient given Diclofenac.
Hepatic: Elevations of serum aminotransferase activity and clinical hepatitis, including fatal fulminant hepatitis have occurred in patients taking Diclofenac. Rarely, liver failure.
Dermatological Reactions: 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.
Renal: Renal papillary necrosis and nephrotic syndrome have been reported in patients taking Diclofenac. Other side effects include hypersensitivity reactions, headache, dizziness, vertigo, hearing disturbances such as tinnitus and photosensitivity.
Cardiac Disorders: Uncommon*: Myocardial infarction, cardiac failure, palpitations, and chest pain.
*The frequency reflects data from long-term treatment with a high dose (150 mg/day).
Kounis syndrome: Frequency "not known".
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 the use of Diclofenac, particularly at a high dose (150 mg daily) and during long-term treatment.

Care should be taken in patients treated with any of the drugs mentioned as follows because, as with other NSAIDs, diclofenac has the potential to induce the following reactions.
Lithium: Diclofenac may raise plasma concentrations of lithium (by the impairment of its excretion from the kidneys).
Methotrexate: Methotrexate should not be administered within 24 hours of each other if given with extreme caution. NSAIDs are reported to increase the plasma levels of methotrexate resulting in increase toxicity.
Other Analgesics: If other systemic NSAIDs or aspirin are given concomitantly with diclofenac sodium the frequency side effects may be increased.
Cyclosporin: NSAIDs may increase cyclosporin nephrotoxicity as a result of their effect on renal prostaglandins. Cyclosporin may increase the bioavailability of diclofenac.
Quinolone Antibiotics: There is an increased risk of convulsions if quinolone antibiotics are given while NSAIDs are being taken. Caution is advised when considering their use because patients taking NSAIDs and quinolones may have an increased risk of developing convulsion.
Diuretics: The activity of diuretics may be inhibited by some NSAIDs. Increased serum potassium levels may result when diclofenac is given concomitantly with potassium-sparing diuretics. Serum potassium levels should therefore be monitored.
Anticoagulants: Care is required when giving anticoagulants with NSAIDs as diclofenac may reversibly inhibit platelet aggregation. Monitoring is recommended to ensure the desired response to the anticoagulants is maintained, as there are rare reports of increase risk of haemorrhage with combined diclofenac and anticoagulant therapy.
Oral Hypoglycaemic Agents: It has been reported hypo and hyperglycaemic effects have occurred rarely when diclofenac and oral antidiabetic agents have been given together and adjustment of hypoglycaemic may be required. Inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia have also been reported.
Aminoglycosides: Reduction in renal function in susceptible individuals, decreased elimination of aminoglycosides and increased plasma concentrations have been reported.
Probenecid: Reduction in metabolism and elimination of NSAIDs and metabolites occurs with probenecid.
Anti-hypertensives: There may be a reduction in the effect of anti-hypertensives.
Cardiac Glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycosides (e.g. digoxin) levels.
Mifepristone: In common with other NSAIDs, diclofenac should be avoided for at least 8 to 12 days following mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Corticosteroids: There is increased risk of gastrointestinal bleeding with corticosteroids.

Keep container well closed. Store below 30°C. Protect from light.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AB05 - diclofenac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.

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