DICLOFENAC 50mg Enteric Coated Tablet

COMPOSITION :

Diclofenac Sodium Enteric coated tablet 50 mg, each enteric coated tablet contains : Diclofenac sodium 50 mg.

 

DESCRIPTIONS : 

Diclofenac Sodium contains Diclofenac sodium is available in enteric coated tablet 50 mg.

 

INDICATIONS :  

• Inflamatory and degenerative forms of rheumatism : Rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis and spondyl-arthritis.
• Painful syndromes of the vertebral column.
• Non-articular rheumatism.
• Acute attacks of gout.

 

DOSAGE AND ADMINISTRATIONS : 

• Maximum dose of 100 mg daily (maximum initial dose 150 mg daily on the first day) in divided doses and with as short as possible duration.

• If according physician assessment higher doses is required, there should be consideration the benefit-risk properly.

 

OVERDOSAGE : 

• Symptoms
  There is no typical clinical picture resulting from Diclofenac overdosage. Overdosage can cause symptoms such as vomiting, gastrointestinal haemorrhage, diarrhoea, dizziness, tinnitus or convulsions. In the event of significant poisoning, acute renal failure and liver damage are possible.

• Therapeutic measures
  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 haemoperfusion are probably of on help in eliminating NSAIDs, including Diclofenac, due to the high protein binding and extensive metabolism.
  Activated charcoal may be considered after ingestion of a potentially toxic overdosage and gastric decontamination (e.g., vomiting, gastric lavage) after ingestion of a potentially life threatening overdosage.

 

CONTRAINDICATIONS :  

• Known hypersensitivity to the active substance, sodium metabisulphite (solution for injection only) or to any of the other excipients.

• Active gastric or intestinal ulcer, bleeding or perforation (see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS).

• Last trimester of pregnancy (see WARNINGS AND PRECAUTIONS).

• Severe hepatic, renal and cardiac failure (see WARNINGS AND PRECAUTIONS).

• Like other non-steroidal anti-inflammatory drugs (NSAIDs), Diclofenac Sodium is also contraindicated in patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs (see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS).

• Contraindicated for patients with diseases : Ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, congestive heart failure (New York Heart Association [NYHA] classification II-IV).

 

WARNINGS AND PRECAUTIONS :   

CARDIOVASCULAR EFFECTS 

• Cardiovascular thrombotic events

Clinical trials of severe COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increase risk of serious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal.

All NSAIDs, both COX-2 selective and nonselective, may have similar risk. Patients with known CV disease or risk factor for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the sign and/or symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of Aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of Aspirin and an NSAID does increase the risk of serious GI events (see GI WARNINGS).

• Hypertension

NSAIDs, including Diclofenac Sodium can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking Thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Diclofenac Sodium, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

• Congestive heart failure and oedema

Fluid retention and oedema have been observed in some patients taking NSAIDs. Diclofenac Sodium should be used with caution in patients with fluid retention or hearts failure.

GASTROINTESTINAL (GI) EFFECTS

• Risk of GI ulceration, bleeding and perforation

NSAIDs, including Diclofenac Sodium, can cause serious gastrointestinal adverse events, including inflammation, bleeding, ulceration and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop serious upper GI adverse events of NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 – 6 months and in about 2 – 4% of patients treated for one year. These trends continue with longer duration of use, increasing the like hood of developing a serious GI event at some time, during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in patients with prior history of ulcer disease or gastrointestinal bleeding. Patients with prior history of ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed compared to patients with neither of these risk factor. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral Corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age and poor general health status. Most spontaneous reports of fatal GI events are in the elderly or debilitated patients and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event, in patients treated with NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.

• Gastrointestinal effects

Gastrointestinal bleeding (haematemesis, melaena) ulceration or perforation, which can be fatal have been reported with all NSAIDs including Diclofenac, and may occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. They generally have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving Diclofenac Sodium, the medicinal product should be withdrawn.
As with all NSAIDs, including Diclofenac, close medical surveillance is imperative and particular caution should be excised when prescribing Diclofenac Sodium in patients with symptoms indicative of gastrointestinal (GI) disorders, or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see ADVERSE REACTIONS). The risk of GI bleeding is higher with increasing NSAID doses and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly.
To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly, 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.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding). Caution is recommended in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, anti-platelet agents or selective serotonin-reuptake inhibitors (see DRUG INTERACTIONS).
Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn’s disease, as their conditions may be exacerbated (see ADVERSE REACTIONS).

OTHERS 

• Pre-existing asthma
  In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions on NSAIDs like asthma exacerbations (so called intolerance to analgesics/analgesics asthma), Quincke’s oedema or urticaria are more frequent than in other patients. Therefore, special precaution is recommended in such patients (readiness for emergency). This is applicable as well for patients who are allergic to other substances, e.g., with skin reactions, pruritus or urticaria.
  Special caution is recommended when Diclofenac Sodium is used parenterally in patients with bronchial asthma because symptoms may be exacerbated.

• Skin reactions
  Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including Diclofenac Sodium (see ADVERSE REACTIONS). Patients appear to be at the highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Diclofenac Sodium should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
  As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur in rare cases with Diclofenac without earlier exposure to the drug.

• Hepatic effects
  Close medical surveillance is required when prescribing Diclofenac Sodium to patients with impairment of hepatic function as their condition may be exacerbated.
  As with other NSAIDs, including Diclofenac, values of one or more liver enzymes may increase. During prolonged treatment with Diclofenac Sodium (in the form of tablets or suppositories), regular monitoring of hepatic function is indicated as a precautionary measure. If abnormal liver function tests persist or worsen, clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (eosinophilia, rash), Diclofenac Sodium should be discontinued. Hepatitis may occur with Diclofenac without prodromal symptoms.
  Caution is called for when using Diclofenac Sodium in patients with hepatic porphyria, since it may trigger an attack. 

• Renal effects
  As fluid retention and oedema have been reported in association with NSAIDs 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 those patients with substantial extracellular volume depletion of any cause, e.g., before or after major surgery (see CONTRAINDICATIONS). Monitoring of renal function is recommended as a precautionary measure when using Diclofenac Sodium in such cases. Discontinuation therapy is normally followed by recovery to the pre-treatment state.
  Long term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. 

• Advanced renal disease
  No information is available from controlled clinical studies regarding the use of Diclofenac Sodium in patients with advanced renal disease. Therefore, treatment with Diclofenac Sodium is not recommended in these patients with advanced renal disease. If Diclofenac Sodium therapy must be initiated, close monitoring of the patient’s renal function is advisable.

• Anaphylactoid reactions
  As with other NSAIDs, anaphylactoid reactions may occur with Diclofenac in patients without known prior exposure to the drug. Diclofenac Sodium should not be given to patients with the Aspirin trial. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking Aspirin or other NSAIDs. (see CONTRAINDICATIONS). Emergency help should be sought in cases where an anaphylactoid reaction occurs. 

• Cardiovascular effects
  Treatment with NSAIDs including Diclofenac, particularly at high dose and in long term, nay be associated with a small increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke). To minimize the potential risk of an adverse cardiovascular event in patients taking a NSAID, especially in those with cardiovascular risk factors, the lowest effective dose should be used for the shortest possible duration.

• Haematological effects
  During prolonged treatment with Diclofenac Sodium, as with other NSAIDs, monitoring of the blood count is recommended.
  Like other NSAIDs, Diclofenac Sodium may temporarily inhibit platelet aggregation. Patients with defects of haemostasis should be carefully monitored.

• Geriatrics
  Caution is indicated in the elderly on basic medical grounds. In particular, it is recommended that the lowest effective dose be used in frail elderly patients or those with a low body weight.

• Pregnancy
  There are insufficient data on the use of Diclofenac in pregnant women. Therefore, Diclofenac Sodium should not be used during the first two trimesters of pregnancy unless the expected benefits to the mother outweigh the risks 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 (see CONTRAINDICATIONS).

• Breast feeding
  Like other NSAIDs, Diclofenac passes into the breast milk in small amounts. Therefore, Diclofenac Sodium should not be administered during breast feeding in order to avoid undesirable effects in the infant.

• Fertility
  As with other NSAIDs, the use of Diclofenac Sodium may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Diclofenac Sodium should be considered.

 

DRUG INTERACTIONS :   

• Interactions with NSAIDs
  The concomitant use of Diclofenac Sodium with systemic NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided due to the absence of any evidence demonstrating synergistic benefits and the potential for additive undesirable effects (see DRUG INTERACTIONS).

• Observed interactions to be considered 

1. Potent CYP2C9 inhibitors : Caution is recommended when co-prescribing Diclofenac with potent CYP2C9  inhibitors (such as Voriconazole), which could result in a significant increase in peak plasma concentrations and exposure to Diclofenac due to inhibition of Diclofenac metabolism. 
2. Lithium : If used concomitantly, Diclofenac may raise plasma concentrations of Lithium. Monitoring of  the serum lithium level is recommended.
3. Digoxin : If used concomitantly, Diclofenac may raise plasma concentrations of Digoxin. Monitoring of the serum Digoxin level is recommended.
4. Diuretics and antihypertensive agents : Like other NSAIDs, concomitant use of Diclofenac with diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin converting enzyme (ACE) inhibitors) 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. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity (see WARNINGS AND PRECAUTIONS).
5. Cyclosporin : Diclofenac, like other NSAIDs, may increase the nephrotoxicity of Cyclosporin due to the effect on renal prostaglandins. Therefore, it should be given at doses lower than those that would be used in patients not receiving Cyclosporin.
6. Drugs known to cause hyperkalemia : Concomitant treatment with potassium-sparing diuretics, Cyclosporin, Tacrolimus or Trimethoprim may be associated with increased serum potassium levels, which should therefore be monitored frequently (see WARNINGS AND PRECAUTIONS).
7. Quinolone antibacterials : There have been isolated reports of convulsions which may have been due to concomitant use of Quinolones and NSAIDs.

• Anticipated interactions to be considered

1. Other NSAIDs and corticosteroids : Concomitant administration of Diclofenac and other systemic. NSAIDs or corticosteroids may increase the frequency of gastrointestinal undesirable effects (see WARNINGS AND PRECAUTIONS).
2. Anticoagulants and anti-platelet agents : Caution is recommended since concomitant administration could increase the risk of bleeding (see WARNINGS AND PRECAUTIONS). Although clinical investigations do not appear to indicate that Diclofenac affects the action of anticoagulants, there are reports of an increased risk of haemorrhage in patients receiving Diclofenac and anticoagulants concomitantly. Close monitoring of such patients is therefore recommended.
3. Selective serotonin reuptake inhibitors (SSRIs) : Concomitant administration of systemic NSAIDs, including Diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding (see WARNINGS AND PRECAUTIONS).
4. Antidiabetics : Clinical studies have shown that Diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect. However, there have been isolated reports of both hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage of the antidiabetic agents during treatment with Diclofenac. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy.
5. 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 of this substance be increased.
6. Phenytoin : When using Phenytoin concomitantly with Diclofenac, monitoring of Phenytoin plasma concentrations is recommended due to an expected increase in exposure to Phenytoin.
7. Aspirin : When Diclofenac Sodium is administered Aspirin, its protein binding is reduced. The clinical significance of this interaction is not known, however, as with other NSAIDs, concomitant administration of Diclofenac and Aspirin is not generally recommended because of the potential of increased adverse effect.
8. ACE inhibitors : Report suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.

 

ADVERSE REACTIONS :  

• Blood  and lymphatic system disorders : Very rare : Thrombocytopenia, leucopenia, anaemia (hemolytic anaemia, aplastic anemia), agranulocytosis.

• Immune system disorders : Rare : Hypersensitivity anaphylactic and anaphylactoid reactions (including hypertension and shock). Very rare : Angioedema (including face edema).

• Psychiatric disorders : Very rare : Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder.

• Nervous system disorders : Common : Headache, dizziness. Rare : Somnolence. Very rare : Paresthesia, memory impairment, convulsion, anexiety, tremor, meningitis aseptic, dysgeusia, cerebrovascular accident, drowsiness.

• Eye disorders : Very rare : Visual impairment, vision blurred, diplopia. 

• Ear and labyrinth disorders : Common : Vertigo. Very rare : Tinnitus, hearing impaired.

• Cardiac disorders : Very rare : Palpitations, chest pain, cardiac failure, myocardial infraction.

• Vascular disorders : Very rare : Hypertension, vasculitis, syncope.

• Respiratory, thoracic and mediastinal disorders : Rare : Asthma (including dyspnoea). Very rare : Pneumonitis.

• Gastrointestinal disorders : Common : Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, decreased appetite. Rare : Gastritis, gastrointestinal hemorrhage, hematemesis, melaena, diarrhea, hemorrhagic, gastrointestinal ulcer (with or without bleeding or perforation). Very rare : Colitis (including haemorrhagic and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis, glossitis, oesophageal disorder, intestinal diaphragm disease, pancreatitis.

• Hepatobiliary disorders : Common : Transaminases increased. Rare : Hepatitis, jaundice, liver disorder. Very rare : Hepatitis fulminant, hepatic necrosis, hepatic failure.

• Skin and subcutaneous tissue disorders : Common : Rash. Rare : Uticaria. Very rare : Dermatitis bullous, eczema, erythema, erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), dermatitis exfoliative, alopecia, photosensitivity reaction, purpura, Henoch-Schonlein purpura, pruritus.

• Renal and urinary disorders : Very rare :  Renal failure acute, hematuria, proteinuria, nephrolic syndrome, tubulointerstitial nephritis, renal papillary necrolisis.

• General disorders and administration site conditions : Rare : Edema.

 

PRESENTATIONS :

Diclofenac Sodium Enteric coated tablet 50 mg                  Box, 10 blisters @ 10 enteric coated tablets

Reg. No. : GKL0302332815A1

 

STORAGE : STORE BELOW 30ºC, PROTECT FROM LIGHT

 

ON MEDICAL PRESCRIPTION ONLY

 

Manufactured by :

PT. BERNOFARM

Sidoarjo – Indonesia