Composition and excipients:

Each Diclon 100 S.R.E.C Tablet contains:

• active ingredients: Diclofenac sodium 100mg.
• inactive ingredients:

Core: Eudragit  RS 100, Magnesium Stearate, Talcum.

Film: Eudragit L100-55, Talcum, Polyethylene Glycol,  and Titanium dioxide.

Each Diclon 50 E.C. Tablet contains:

• activity ingredients: Diclofenac sodium 50mg.
• inactive ingredients:

Core: Microcrystalline Cellulose, Sodium Starch Glycolate, Magnesium Stearate, Cross Carmellose Sodium, Talcum, Colloidal anhydrous silica, Lactose Mono Hydrate, and Povidone.

Film: Eudragit L100-55, Talcum, Polyethylene Glycol,  and Titanium dioxide.

Each Diclon Suppository contains:

• active ingredients: Diclofenac sodium 12.5, 25, 50 or 100mg.
• inactive ingredients: Colloidal Anhydrous Silica, Hard fat, B.H.T.

Mode of action:

Diclofenac sodium, a non-steroidal anti-inflammatory compound exhibits pronounced antirheumatic, anti-inflammatory, analgesic, and antipyretic properties. Its mode of action is not known; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.

Pharmacokinetics:

Enteric coated Tablets: Diclofenac is completely absorbed from the enteric coated tablets after their passage through the stomach; the mean peak plasma concentration is attained on average 2 hours after ingestion of one tablet of 50 mg.

Suppositories: Diclofenac shows a rapid onset of absorption from suppositories, after the administration of 50 mg suppositories, peak plasma concentrations are attained on average within 1 hour

Extended release tablet: After ingestion of the diclofenac slow release tablet, it is slowly released into the gastrointestinal contents, Peak plasma concentrations occur about 6-8 hours after administration of the XR tablets when taken with a meal.

Following oral or rectal administration, the active substance is metabolised during its first passage through the liver, Diclofenac bounds to serum proteins 99.7%, mainly to albumin. About 60% of the administered dose is excreted in urine as metabolites. Less than 1% is excreted as unchanged substance. The rest is eliminated as metabolites through the bile in the faeces.

Indications:

Enteric coated tablets:

• Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis and osteoarthritis.
• Relief of acute or chronic pain states in which there is an inflammatory component.
• Symptomatic treatment of primary dysmenorrhoea.

Suppositories:

• Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis and osteoarthritis.
• Short term (up to three days) treatment of post-operative pain in children

XR Tablets:

• For both (100 mg, 75 mg): in the management of chronic conditions, such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis
• For 75 mg: acute gout, acute musculoskeletal disorders such as periarthritis (for example frozen shoulder), tendinitis, tenosynovitis, bursitis, other painful conditions resulting from trauma, including fracture, low back pain, sprains, strains, dislocations, orthopaedic, dental and other minor surgery.

Contraindications:

• hypersensitivity to the active ingredient or any of the excipients
• Gastric, intestinal (e.g. duodenal) ulcer, gastro-intestinal bleeding or perforation.
• History of gastrointestinal bleeding or perforation, relating to previous NSAID therapy. Active, or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding)
• Last trimester of pregnancy
• Severe hepatic (impairment), renal or cardiac failure.
• Established congestive heart failure (NYHA IIIV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
• Treatment of perioperative pain in setting of coronary artery bypass graft surgery (CABG)
• Patients in whom diclofenac, aspirin or other NSAIDs induce asthma, urticaria or other allergic-type reactions, because severe, rarely fatal, anaphylactic type reactions to diclofenac have been reported in such patients.
• Proctitis (only for suppositories)

Side Effects:

Immune system disorders: Rare: Hypersensitivity, anaphylactic and anaphylactoid reactions.

Nervous system disorders: Common: Headache, dizziness, Rare: Somnolence.

Ear disorders: Common: Vertigo.

Cardiac disorders: Uncommon: Myocardial infarction, cardiac failure, palpitations, chest pain.

Respiratory disorders: Rare: Asthma (including dyspnoea).

Gastrointestinal disorders: Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, decreased appetite.  Rare: Gastritis, gastrointestinal haemorrhage, haematemesis, melaena, haemorrhagic diarrhoea, gastrointestinal ulcer, proctitis (for suppositories)

Hepatobiliary disorders: Common: Transaminases increased, Rare: Hepatitis, jaundice, liver disorder.

Skin disorders: Common: Rash, or skin eruptions, Rare:  Urticaria.

General disorders: Common: Application site irritation, Rare: Oedema.

Warnings and precautions:

• Cardiovascular thrombotic events: Studies have indicated that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular events including myocardial infarction and stroke, which may increase with dose or duration of use. Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk. Treatment with it is generally not recommended in patients with established cardiovascular disease or uncontrolled hypertension. If needed, they should be treated with Diclofenac only after careful consideration and only at doses ≤100 mg daily when treatment continues for more than 4 weeks. The patient’s response to therapy should be reevaluated periodically.
• Hypertension: 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; therefore caution is advised in patients with fluid retention or heart failure.
• Gastrointestinal effects: Close medical surveillance is imperative and particular caution should be exercised when prescribing NSAIDs, including diclofenac, in patients with symptoms indicative of gastrointestinal disorders (GI) or with a history suggestive of gastro-intestinal ulceration, bleeding or perforation. Caution is advised in patients at greater risk of developing serious gastrointestinal events, e.g. the elderly, patients with a history of serious gastrointestinal events, smoking and alcoholism. Gastric or duodenal ulceration, perforation or gastrointestinal bleeding, which can be fatal, has been reported in patients receiving diclofenac. To reduce the risk of GI toxicity in patients with a history of ulcer the treatment should be initiated and maintained at the lowest effective dose. Combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered for these patients.
• Severe skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported very rarely in association with the use of NSAIDs, including diclofenac sodium. Patients should be advised of the signs and symptoms of these reactions and to consult their doctor at the first appearance of skin rash or any other sign of hypersensitivity, and diclofenac should be discontinued.
• Pre-existing asthma: In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa, chronic obstructive pulmonary diseases or chronic infections of the respiratory tract, reactions on NSAIDs are more frequent than in other patients. Therefore, special precaution is recommended in such patients

 

• Hepatic effects: Close medical surveillance is required when prescribing diclofenac to patients with impaired hepatic function, as their condition may be exacerbated. Caution should be exercised when using diclofenac in patients with hepatic porphyria, since it may trigger an attack. As with other NSAIDs, elevations of one or more liver enzymes may occur during diclofenac therapy. In addition rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, have been reported.
• Renal effects: NSAIDs have been associated with renal papillary necrosis and other pathology during long-term administration in animals. As fluid retention and oedema have been reported in association with NSAID therapy, including diclofenac, particular caution is called for in patients with impaired cardiac or renal function, history of hypertension, the elderly, patients receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function, and in patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery. Monitoring of renal function is recommended as a precautionary measure when using diclofenac in such cases.
• Lactose Intolerance: diclofenac ECT contain lactose and therefore are not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
• Combination Use of ACE Inhibitors or Angiotensin Receptor Antagonist, Anti-inflammatory Drugs and Thiazide Diuretics at the same time increases the risk of renal impairment, especially when renal function is compromised. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment. Patients should be adequately hydrated and monitoring of renal function after initiation of concomitant therapy and periodically thereafter
• Haematological effects: It may temporarily inhibit platelet aggregation. Patients with defects of haemostasis should be carefully monitored. During prolonged treatment, monitoring of the blood count is recommended.
• Peri-operative Bleeding: Pre-operative administration of diclofenac may increase the risk of post-operative bleeding. The safety of diclofenac suppositories in children has not been established in major operations or in procedures where minor bleeding could pose a critical safety risk therefore the use of the suppositories in children for such procedures is not recommended. Since diclofenac may temporarily inhibit platelet aggregation, children undergoing minor procedures should be carefully monitored.
• As with NSAIDs, allergic reactions, including anaphylactic/anaphlactoid reactions, have been reported with diclofenac.
• Like other NSAIDs, diclofenac may mask the usual signs and symptoms of infection due to its pharmacodynamic properties
• Geriatrics: Caution is indicated in the elderly, it is recommended that the lowest effective dose be used in frail elderly patients, those with a low body weight or who are more prone to adverse reactions. The patient should be monitored for GI bleeding for 4 weeks following initiation of NSAID therapy.
• In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis

Pregnancy (Category: C), Breast-feeding & Fertility:

It should not be used during the first two trimesters of pregnancy unless the expected benefits to the mother outweigh the risks to the foetus. The use of diclofenac during the third trimester of pregnancy is contraindicated because of the possibility of premature closure of the ductus arteriosus and / or uterine inertia.

Diclofenac passes into the breast milk, therefore, it is not recommended for use in nursing women.

As with other NSAIDs, the use of diclofenac may impair female fertility and is not recommended in women attempting to conceive.

Drug Interactions:

Lithium and Digoxin: the concomitant use may raise their plasma concentrations, Monitoring of their concentrations level is recommended.

Diuretics and antihypertensive agents: The concomitant use with diclofenac may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients; especially the elderly should have their blood pressure periodically monitored.

Other NSAIDs and corticosteroids: the concomitant administration with diclofenac may increase the frequency of gastrointestinal undesirable effects therefore it should be avoided.

Anticoagulants and anti-platelet agents: Caution is recommended since concomitant administration could increase the risk of bleeding.

Selective serotonin reuptake inhibitors (SSRIs): The Concomitant administration with diclofenac may increase the risk of gastrointestinal bleeding.

Antidiabetics: monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy with NSAIDs.

Methotrexate: Caution is recommended when NSAIDs, including diclofenac, are administered less than 24 hours before or after treatment with methotrexate, since blood concentrations of methotrexate may rise and the toxicity be increased.

Cyclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine due to the effect on renal prostaglandins. Therefore, diclofenac should be given at lower doses.

Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium levels; therefore it should be monitored frequently.

Quinolone antibacterials: There have been isolated reports of convulsions which may have been due to the concomitant use with diclofenac.

Phenytoin: with the concomitant adminstration, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in exposure to phenytoin.

Potent CYP2C9 inhibitors: Caution is recommended when co-prescribing diclofenac with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), which could result in a significant increase in peak plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.

Colestipol and cholestyramine: it is recommended to administer diclofenac at least one hour before or 4 to 6 hours after administration of these drugs because they can induce a delay or decrease in absorption of diclofenac.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as it can reduce the effect of mifepristone.

Tacrolimus: Possible increased risk of nephrotoxicity with the concomitant use of NSAIDs.

Zidovudine: Increased risk of haematological toxicity with the concomitant use of NSAIDs.

Dosage and administration:

• The tablets should be swallowed whole with liquid, preferably before meals, and must not be divided or chewed.
• The suppositories should be inserted well into the rectum. It is recommended to insert the suppositories after passing stools.
• Patients on long-term treatment should be reviewed regularly with regards to efficacy, the risk factors and the on-going need for therapy.
• After assessing the risk/benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used.

Suppository and EC Tablets: 

Adults:

• Initial dosage is 75 to 150 mg daily.
• For long-term therapy 75 to 100 mg daily is usually sufficient.
• The daily dosage should generally be in 2 or 3 fractional 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 maximum daily dose of 150 mg).
• In primary dysmenorrhoea the daily dosage, which should be individually adapted, is generally 50 to 150 mg. Initially a dose of 50 to 100 mg should be given and, if necessary, raised in the course of several menstrual cycles up to a maximum of 200 mg/day. Treatment should be started upon appearance of the first symptoms and, depending on the symptomatology, continued for a few days.

Post-operative analgesia in children:

• A first dose of 1-2 mg/kg followed by 1 mg/kg three times daily for a maximum of three days total therapy. The maximum daily dose is 3 mg/kg.
• The safety and efficacy of diclofenac suppositories in children under 12 months has not been established.
• A maximum daily dose of 150 mg should not be exceeded.
• Diclofenac 12.5 mg or 25 mg suppositories are recommended for use in children and adolescents below 14 years of age.
• Diclofenac 50 mg suppositories are not recommended for children and adolescents below 14 years of age.
• Diclofenac 100 mg suppositories are not suitable for children and adolescents.
• The use of diclofenac suppositories for peri-operative pain is not recommended in these patients.

XR Tablets:

Adults: One tablet daily (100mg) or twice daily (for 75mg), the recommended maximum daily dose is 150 mg.

Elderly: the standard adult dose may be used. If necessary a lower strength formulation is to be prescribed.

Children: The XR Tablets are not recommended for use in children.

Overdosage:

Overdosage can cause symptoms such as vomiting, gastrointestinal haemorrhage, diarrhoea, dizziness, tinnitus or convulsions. Supportive and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression.

How supplied :

Diclon 100 S.R.E.C Tablet: 10 or 20 tablets are packed in a printed mono-carton.

Diclon 50 E.C Tablet: 10, 20 tablets are packed in a printed mono-carton.

Diclon suppositories: 10 suppositories are packed in a printed mono-carton.

Storage Conditions:

Diclon 100 S.R.E.C Tablet: Store at temperature below 30° C, Protected from moisture.

Diclon 50 E.C Tablet: Store at temperature below 30° C, Protected from moisture.

Diclon suppositories: Store at room temperature between (15-25)° C.