GENERIC NAME OF THE MEDICINAL PRODUCT:

QUALITATIVE AND QUANTITATIVE COMPOSITION:

THERAPEUTIC INDICATIONS:

Diclofenac Sodium 100mg DR Tablets (Diclotaj) Taj Pharma

  1. Name of the medicinal product

Diclofenac Sodium 50mg DR Tablets (Diclotaj) Taj Pharma

Diclofenac Sodium 75mg DR Tablets (Diclotaj) Taj Pharma

Diclofenac Sodium 100mg DR Tablets (Diclotaj) Taj Pharma

  1. Qualitative and quantitative composition

Each tablet contains:

Diclofenac Sodium        50mg

Each tablet contains:

Diclofenac Sodium      75mg

Each tablet contains:

Diclofenac Sodium     100mg

  1. Pharmaceutical form

Prolonged-release tablet .

  1. Clinical particulars

4.1 Therapeutic indications

Adults and elderly

Relief of all grades of pain and inflammation in a wide range of conditions, including:

(i) arthritic conditions: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout,

(ii) acute musculo-skeletal disorders such as periarthritis (for example frozen shoulder), tendinitis, tenosynovitis, bursitis,

(iii) other painful conditions resulting from trauma, including fracture, low back pain, sprains, strains, dislocations, orthopaedic, dental and other minor surgery.

Children

Diclofenac Sodium 75 mg prolonged-release tablets are not suitable for children.

4.2 Posology and method of administration

Posology

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Adults: One tablet once or twice daily

The recommended maximum daily dose of diclofenac sodium is 150mg.

Special populations

Elderly: Although the pharmacokinetics of Diclofenac sodium are not impaired to any clinically relevant extent in elderly patients, nonsteroidal anti-inflammatory drugs should be used with particular caution in such patients who generally are more prone to adverse reactions. In particular it is recommended that the lowest effective dosage be used in frail elderly patients or those with a low body weight (see also precautions) and the patient should be monitored for GI bleeding during NSAID therapy.

Renal impairment: Diclofenac is contraindicated in patients with severe renal impairment (see section 4.3). No specific studies have been carried out in patients with renal impairment, therefore, no specific dose adjustment recommendations can be made. Caution is advised when administering diclofenac to patients with mild to moderate renal impairment (see section 4.3 and 4.4).

Hepatic impairment: Diclofenac is contraindicated in patients with severe hepatic impairment (see section 4.3). No specific studies have been carried out in patients with hepatic impairment, therefore, no specific dose adjustment recommendations can be made. Caution is advised when administering diclofenac to patients with mild to moderate hepatic impairment (see section 4.3 and 4.4).

Paediatric population: This medicine is not suitable for children.

Method of administration

For oral administration.

To be taken whole with liquid, preferably with or after food.

4.3 Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
  • Active, or gastric or intestinal ulcer, bleeding or perforation.
  • History of gastrointestinal bleeding or perforation, relating to previous NSAIDs therapy.
  • Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
  • Last trimester of pregnancy (see section 4.6).
  • Hepatic failure
  • Renal failure
  • Established congestive heart failure (NYHA-II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
  • Like other non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac is also contraindicated in patients in whom attacks of asthma, angiodema, urticaria or acute rhinitis are precipitated by ibuprofen, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs.

4.4 Special warnings and precautions for use

General

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

The concomitant use of diclofenac 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 section 4.5).

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 (see section 4.2).

As with other nonsteroidal anti-inflammatory drugsincluding diclofenac allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug (see section 4.8).

Like other NSAIDs, diclofenac may mask the signs and symptoms of infection due to its pharmacodynamic properties.

This medicine contains sucrose and therefore is not recommended for patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.

Gastrointestinal effects

Gastrointestinal bleeding (haematemesis, melaena), ulceration or perforation, which can be fatal has 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 (GI) events. They generally have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the medicinal product should be withdrawn.

As with all NSAIDs, including diclofenac, close medical surveillance is imperative and particular caution should be exercised when prescribing diclofenac in patients with symptoms indicative of gastrointstinal disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see 4.8). The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses including diclofenac and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation.

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).

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. misoprostol or proton pump inhibitors ) should be considered for these patients, and also for patients requiring concomitant use of medicinal products containing low dose acetylsalicylic acid (ASA/aspirin), or other medicinal products likely to increase gastrointestinal risk (see below and section 4.5).

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 such as warfarin, selective serotonin-reuptake inhibitors (SSRIs) or anti-platelet agents such as acetylsalicylic acid (see section 4.5).

Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn’s disease, as their condition may be exacerbated (see section 4.8).

Hepatic impairment

Close medical surveillance is required when prescribing diclofenac 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, 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 should be discontinued.

Hepatitis may occur with diclofenac without prodromal symptoms.

Caution is called for when using diclofenac in patients with hepatic porphyria, since it may trigger an attack.

Renal impairment

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 those patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery (see 4.3). Monitoring of renal function is recommended as a precautionary measure when using diclofenac in such cases. Discontinuation of therapy is usually followed by recovery to the pre-treatment state.

Skin effects

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 (see section 4.8). Patients appear to be at highest risk for 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 tablets should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

SLE and mixed connective tissue disease

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).

Cardiovascular and cerebrovascular effects

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with diclofenac after careful consideration. As the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The pateint’s need for symptomatic relief and response to therapy should be re-evaluated periodically.

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy including diclofenac.

Clinical trial and epidemiological data consistently point towards increased risk of arterial thrombotic events (for example myocardial infarction or stroke) associated with the use of diclofenac, particularly at high dose (150mg daily) and in long term treatment.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with diclofenac after careful consideration.

Haematological effects

During prolonged treatment with diclofenac, as with other NSAIDs, monitoring of the blood count is recommended.

Diclofenac may reversibly inhibit platelet aggregation (see anticoagulants in section 4.5). Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored.

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.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can precipitate bronchospasm if administered to patients suffering from, or with a previous history of bronchial asthma.

Female fertility:

The use of Diclofenac may impair female fertility and is not recommended in women attempting to conceive. In women who may have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Diclofenac should be considered (see section 4.6).

4.5 Interaction with other medicinal products and other forms of interaction

The following interactions include those observed with diclofenac gastro-resistant tablets and/or other pharmaceutical forms of diclofenac.

Lithium: If used concomitantly, diclofenac may raise plasma concentrations of lithium. Monitoring of the serum lithium level is recommended.

Digoxin: If used concomitantly, diclofenac may raise plasma concentrations of digoxin. Monitoring of the serum digoxin level is recommended.

Diuretics and Anti-hypertensive 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 via inhibition of vasodilatory prostaglandin synthesis. 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.

Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium levels, which should therefore be monitored frequently (see section 4.4).

Anticoagulants and anti-platelet agents: Caution is recommended since concomitant administration could increase the risk of bleeding (see section 4.4). 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 (see section 4.4). Therefore, to be certain that no change in anticoagulant dosage is required, close monitoring of such patients is required. As with other nonsteroidal anti-inflammatory agents, diclofenac in high dose can reversibly inhibit platelet aggregation.

Other NSAIDS including cyclo-oxygenase-2selective inhibitors and corticosteroids: Co-administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. Avoid concomitant use of two or more NSAIDs (see section 4.4).

Selective serotonin reuptake inhibitors (SSRIs):Concomitant administration of SSRIs may increase the risk of gastrointestinal bleeding (see section 4.4).

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 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.

Methotrexate: Diclofenac can inhibit the tubular renal clearance of methotrexate hereby increasing methotrexate levels. Caution is recommended when NSAIDs, including diclofenac, are administered less than 24 hours before treatment with methotrexate, since blood concentrations of methotrexate may rise and the toxicity of this substance be increased.

Cases of serious toxicity have been reported when methotrexate and NSAIDs including diclofenac are given within 24 hours of each other. This interaction is mediated through accumulation of methotrexate resulting from impairment of renal excretion in the presence of the NSAID.

Ciclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of ciclosporin 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 ciclosporin.

TacrolimusPossible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus. This might be mediated through renal antiprostagladin effects of both NSAID and calcineurin inhibitor.

Quinolone antimicrobials: Convulsions may occur due an interaction between quinolones and NSAIDs. This may occur in patients with or without a previous history of epilepsy or convulsions. Therefore, caution should be exercised when considering the use of a quinolone in patients who are already receiving an NSAID.

Phenytoin: When using phenytoin concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in exposure to phenytoin.

Colestipol and cholestyramine: These agents can induce a delay or decrease in absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least one hour before or 4 to 6 hours after administration of colestipol/ cholestyramine.

Cardiac glycosidesConcomitant use of cardiac glycosides and NSAIDs in patients may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

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

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

4.6 Fertility, pregnancy and lactation

Pregnancy:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %.

The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality.

In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. If diclofenac is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

– cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

– renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

the mother and the neonate, at the end of pregnancy, to:

– possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

– inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, diclofenac sodium tablets are contraindicated during the third trimester of pregnancy.

Breast-feeding:

Like other NSAIDs, diclofenac passes into the breast milk in small amounts. Therefore, diclofenac should not be administered during breast feeding in order to avoid undesirable effects in the infant (see section 5.2).

Female Fertility

As with other NSAIDs, the use of diclofenac 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 should be considered (see also section 4.4 regarding female fertility).

4.7 Effects on ability to drive and use machines

Patients who experience visual disturbances, dizziness, vertigo, somnolence central nervous system disturbances, drowsiness or fatigue while taking NSAIDs should refrain from driving or operate machinery.

4.8 Undesirable effects

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common: (>1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); Not known: cannot be estimated from the available data.

The following undesirable effects include those reported with either short-term or long-term use.

Table 1

Blood and lymphatic system disorders
Very rareThrombocytopenia, leucopoenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis.
Immune system disorders
Rare
Very rare
Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock).

Angioneurotic oedema (including face oedema).

Psychiatric disorders
Very rareDisorientation, depression, insomnia, nightmare, irritability, psychotic disorder.
Nervous system disorders
Common

Rare

Very rare
Unknown

Headache, dizziness.

Somnolence, tiredness.

Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident.

Confusion, hallucinations, disturbances of sensation, malaise.

Eye disorders
Very rare

Unknown

Visual disturbance, vision blurred, diplopia.

Optic neuritis.

Ear and labyrinth disorders
Common

Very rare

Vertigo.

Tinnitus, hearing impaired.

Cardiac disorders
Uncommon*Myocardial infarction, cardiac failure, palpitations, chest pain.
Vascular disorders
Very rareHypertension, hypotension, vasculitis.
Respiratory, thoracic and mediastinal disorders
Rare

Very rare

Asthma (including dyspnoea).

Pneumonitis.

Gastrointestinal disorders
Common

Rare

Very rare

Unknown

Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia.

Gastritis, gastrointestinal haemorrhage, haematemesis, diarrhoea haemorrhagic, melaena, gastrointestinal ulcer with or without bleeding or perforation (sometimes fatal particularly in the elderly).

Colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis.

Ischaemic colitis

Hepatobiliary disorders
Common

Rare

Very rare

Transaminases increased.

Hepatitis, jaundice, liver disorder.

Fulminant hepatitis, hepatic necrosis, hepatic failure.

Skin and subcutaneous tissue disorders
Common

Rare

Very rare

Rash.

Urticaria.

Bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), dermatitis exfoliative, loss of hair, photosensitivity reaction, purpura , allergic purpura, pruritus.

Renal and urinary disorders
Very rareAcute renal failure, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.
Reproductive system and breast disorders
Very rareImpotence
General disorders and administration site conditions
RareOedema

*The frequency reflects data from long-term treatment with a high dose (150mg/day).

Clinical trial and epidemiological data consistently point towards an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) associated with the use of diclofenac, particularly at high dose (150 mg daily) and in long term treatment (see sections 4.3 and 4.4 ).

4.9 Overdose

Symptoms:

There is no typical clinical picture resulting from diclofenac over dosage. Over dosage can cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal haemorrhage, diarrhoea, dizziness, disorientation, excitation, coma, drowsiness, tinnitus, fainting or convulsions. In the case 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 haemo-perfusion are probably of no 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 overdose, and gastric decontamination (e.g. vomiting, gastric lavage) after ingestion of a potentially life threatening overdose

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group

Non-steroidal anti-inflammatory drugs (NSAlDs).

Mechanism of action:

Diclofenac sodium is a non-steroidal agent with marked analgesic/anti inflammatory properties. It is an inhibitor of prostaglandin synthetase, (cyclo-oxygenase).

Diclofenac sodium in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to the concentrations reached in human beings.

5.2 Pharmacokinetic properties

After ingestion of the diclofenac slow release tablet, the active principle is slowly released into the gastrointestinal contents. Once released from the tablet, diclofenac is rapidly absorbed from the gastrointestinal tract but is subject to first-pass metabolism. Peak plasma concentrations occur about 4.5 hours after administration of the prolonged release tablets when taken with a meal. Food and antacids decrease the rate but not the extent of absorption of diclofenac. The systemic availability of diclofenac from the SR formulations is on average 82% of that achieved with the same dose of enteric-coated tablets (possibly due to release rate dependent first-pass metabolism). The active substance is 99.7% bound to plasma proteins, mainly albumin.

Diclofenac enters the synovial fluid and peak synovial fluid concentrations at steady state exceed plasma concentrations. Furthermore, elimination from the synovial fluid is slower than from plasma. Diclofenac and its metabolites cross the placenta and traces of diclofenac have been found in the milk of lactating women. The half-life for the terminal elimination phase is 3 hours. Approximately 60% of the administered dose is excreted via the kidneys in the form of metabolites and less than 1% in unchanged form. About 30% of the dose is excreted via the bile in metabolised form. In patients with impaired renal function, accumulation of diclofenac sodium has not been reported. However, half-life of diclofenac may be prolonged in patients with severe renal impairment.

Five Diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4′-hydroxy-, 5-hydroxy-, 3′-hydroxy-, 4′,5-dihydroxy- and 3′-hydroxy-4′-methoxy-Diclofenac. The major Diclofenac metabolite, 4′-hydroxy-Diclofenac, has very weak pharmacologic activity. The formation of 4′-hydroxy Diclofenac is primarily mediated by CYP2C9. Both Diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CYP2C8 may also play a role in Diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy- and 3′-hydroxy-Diclofenac. In patients with renal dysfunction, peak concentrations of metabolites 4′-hydroxy- and 5-hydroxy-Diclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects.

5.3 Preclinical safety data

None stated

  1. Pharmaceutical particulars

6.1 List of excipients

Cetostearyl Alcohol, Colloidal Anhydrous Silica, Compressible Sugar, Talc, Povidone, Magnesium Stearate, Copovidone, Sucrose, Opadry, Carnauba Wax.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

The tablets are presented in aluminium/PVC or PVDC-coated-PVC blisters, strips of which are contained within a printed cardboard carton. Cartons of 28 and 56 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

  1. Manufactured in india by:
    TAJ PHARMACEUTICALS LTD;
    Plot No. 220, Mahagujarat Industrial Estate, Moraiyya,
    Tal-Sanand, Dist-Ahmedabad, Gujarat.

PATIENT INFORMATION LEAFLET
Diclotaj 75mg DR and 50mg DR, (Diclotaj) Taj Pharma
Diclofenac sodium

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

In this leaflet

  1. What DICLOTAJ 75MG DR and DICLOTAJ DR 50mg are and what they are used for
    2. What you need to know before you take DICLOTAJ 75MG DR or DICLOTAJ DR 50mg
    3. How to take DICLOTAJ 75MG DR or DICLOTAJ DR 50mg
    4. Possible side effects
    5. How to store DICLOTAJ 75MG DR and DICLOTAJ DR 50mg
    6. Contents of the pack and other information1. WHAT DICLOTAJ 75MG DR and DICLOTAJ DR 50mg ARE AND WHAT THEY ARE USED FOR

Diclofenac sodium, the active ingredient in DICLOTAJ 75MG DR and DICLOTAJ DR 50mg  tablets, is one of a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs reduce pain and inflammation. DICLOTAJ 75MG DR and DICLOTAJ DR 50mg  tablets are especially formulated to release the diclofenac sodium slowly.

DICLOTAJ 75MG DR and DICLOTAJ DR 50mg tablets relieve pain, reduce swelling and ease inflammation in conditions affecting the joints, muscles and tendons including:

  • Rheumatoid arthritis, osteoarthritis, acute gout (painful inflammation of the joints especially in the feet and hands), ankylosing spondylitis (form of spinal arthritis).
  • Backache, sprains and strains, soft tissue sports injuries, frozen shoulder, dislocations and fractures
  • Conditions affecting the tendons for example, tendonitis, tenosynovitis, bursitis.

They are also used to treat pain and inflammation associated with dental and minor surgery.

DICLOTAJ 75MG DR and DICLOTAJ DR 50mg tablets are not suitable for children.

  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE DICLOTAJ 75MG DR OR DICLOTAJ DR 50mg

Do not take DICLOTAJ 75MG DR or DICLOTAJ DR 50mg  if

  • you are allergic to diclofenac sodium, aspirin, ibuprofen or any other NSAID, or to any of the other ingredients of DICLOTAJ 75MG DR and DICLOTAJ DR 50mg tablets (these are listed under section 6 “CONTENTS OF THE PACK AND OTHER INFORMATION” of the leaflet). Signs of a hypersensitivity reaction include swelling of the face and mouth (angioedema), breathing problems, chest pain, runny nose, skin rash or any other allergic type reaction.
  • you have now, or have ever had, a stomach (gastric) or duodenal (peptic) ulcer, or bleeding in the digestive tract (this can include blood in vomit, bleeding when emptying bowels, fresh blood in faeces or black, tarry faeces)
  • you have had stomach or bowel problems after you have taken other NSAIDs
  • you have severe heart, kidney or liver failure
  • you have established heart disease and/or cerebrovascular disease, e.g. if you have had a heart attack, stroke, mini-stroke (TIA) or blockages to blood vessels to the heart or brain or an operation to clear or bypass blockages.
  • you have or have had problems with your blood circulation (peripheral arterial disease).
  • you are more than six months pregnant

Warnings and precautions

Talk to your doctor or pharmacist before taking Diclofenac if:

  • you suffer from any stomach or bowel disorders including ulcerative colitis or Crohn’s disease
  • you have kidney or liver problems, or you are elderly
  • you have a condition called porphyria
  • you suffer from any blood or bleeding disorder. If you do, your doctor may ask you to go for regular check-ups while you are taking these tablets.
  • you ever had asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (nasal polyps), chronic pulmonary diseases or infections of the respiratory tract.
  • you are breast feeding
  • you have angina, blood clots, high blood pressure, raised cholesterol or raised triglycerides
  • you have heart problems or if you had a stroke or you think you might be at risk of these conditions (for example, if you have high blood pressure, diabetes or high cholesterol or are a smoker)
  • you have diabetes
  • you smoke
  • you have Systemic Lupus Erythematosus SLE (inflammatory, auto-immune disorder which causes symptoms such as joint pain, joint inflammation, skin rashes, fever) or any similar condition
  • you have an intolerance to some sugars such as sucrose (these tablets contain sucrose)

Tell your doctor if you recently had or you are going to have a surgery of the stomach or intestinal tract before taking DICLOTAJ 75MG DR or DICLOTAJ DR 50mg  as DICLOTAJ can sometimes worsen wound healing in your gut after surgery.

Tell your doctor or pharmacist if you have any of these conditions because DICLOTAJ 75MG DRor DICLOTAJ DR 50mg  might not be the right medicine for you.

Children

DICLOTAJ 75MG DR and DICLOTAJ DR 50mg  tablets are not suitable for children.

Other medicines and Diclotaj 75mg DR and DICLOTAJ DR 50mg

Some medicines can interfere with your treatment. Please tell your doctor or pharmacist if you are takingany of the following:

  • Medicines to treat diabetes
  • Anticoagulants (blood thinning tablets like warfarin)
  • Diuretics (water tablets)
  • Lithium (used to treat some mental problems)
  • Methotrexate (for treatment of some inflammatory diseases and some cancers)
  • Ciclosporin and tacrolimus (used to treat some inflammatory diseases and after transplants)
  • Trimethoprim (a medicine used to prevent or treat urinary tract infections)
  • Quinolone antibiotics (for infections)
  • Any other NSAID or COX-2 (cyclo-oxygenase-2) inhibitor, for example aspirin or ibuprofen
  • Mifepristone (a medicine used to terminate pregnancy)
  • Cardiac glycosides (for example digoxin), used to treat heart problems
  • Medicines known as SDRIs (used to treat depression)
  • Oral steroids (an anti-inflammatory drug)
  • Medicines used to treat heart conditions or high blood pressure, for example beta blockers or ACE inhibitors
  • Voriconazole (a medicine used to treat fungal infections).
  • Phenytoin (a medicine used to treat seizures)
  • Colestipol/cholestyramine (used to lower cholesterol)

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

DICLOTAJ 75MG DR or DICLOTAJ DR 50mg  with food and drink

Take this medicine with or after food

Pregnancy and breast-feeding

  • Although not common, abnormalities have been reported in babies whose mothers have taken NSAIDs during pregnancy. You should not take DICLOTAJ 75MG DR or DICLOTAJ DR 50mg tablets during the last 3 months of pregnancy as it may affect the baby’s circulation.
  • You should advise your doctor or pharmacist if you think you might be pregnant or are up to 6 months pregnant.
  • Taking DICLOTAJ 75MG DR or DICLOTAJ DR 50mg tablets may make it more difficult to become pregnant. You should talk to your doctor if you are planning to become pregnant, or if you have problems getting pregnant.
  • You should avoid taking DICLOTAJ 75MG DR or DICLOTAJ DR 50mg whilst breast feeding.

Driving and using machines

Very occasionally people have reported that diclofenac sodium tablets have made them feel dizzy, tired or sleepy. Problems with eyesight have also been reported. If you are affected in this way, you should not drive or operate machinery.

Other special warnings

  • You should take the lowest effective dose of Diclofenac Sodium for the shortest possible time particularly if you are underweight or elderly.
  • There is a small increased risk of heart attack or stroke when you are taking any medicine like Diclofenac Sodium. The risk is higher if you are taking high doses for a long time. Always follow the doctor’s instructions on how much to take and how long to take it for.
  • Whilst you are taking these medicines your doctor may want to give you a check-up from time to time.
  • If you have a history of stomach problems when you are taking NSAIDs, particularly if you are elderly, you must tell your doctor straight away if you notice any unusual symptoms.
  • Because it is an anti-inflammatory medicine, Diclofenac Sodium tablets may reduce the symptoms of infection, for example, headache, and high temperature. If you feel unwell and need to see a doctor, remember to tell him or her that you are taking Diclofenac Sodium tablets.

DICLOTAJ 75MG DR and DICLOTAJ DR 50mg contains

DICLOTAJ 75MG DR and DICLOTAJ DR 50mg contain sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

  1. HOW TO TAKE DICLOTAJ 75MG DR or DICLOTAJ DR 50mg

The doctor will tell you how many DICLOTAJ 75MG DR or DICLOTAJ DR 50mg to take and when to take them. Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has told you. You should check with your doctor or pharmacist if you are not sure.

Take the tables with or after food.

Swallow the tablets whole with a glass of water. DO NOT crush or chew the tablets as this will affect the special “slow release” system.

The recommended dose is:

Adults: 100-150mg daily divided into two or three doses. The number of tablets which you take will depend on the strength the doctor has given you.

Your doctor may wish to increase your daily dose if required to 150mg.

Elderly: The lowest effective dose should be used. Your doctor may advise you to take a dose that is lower than the usual adult dose if you are elderly. Close surveillance is advisable.

Children: These tablets are not suitable for children.

The doctor may also prescribe another drug to protect the stomach to be taken at the same time, particularly if you have had stomach problems before, or if you are elderly, or taking certain other drugs as well.

If you take more DICLOTAJ 75MG DR or DICLOTAJ DR 50mg than you should

If you, or anyone else, accidentally takes too much DICLOTAJ 75MG DR or DICLOTAJ DR 50mg , tell your doctor or go to your nearest hospital casualty department immediately. Take your medicine pack with you so that people can see what you have taken.

Symptoms of an overdose can include: headache, nausea (feeling sick), vomiting, abdominal pain, stomach or intestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, ringing in the ears, fainting, or occasionally convulsions (seizures, uncontrolled fits).

If you forget to take DICLOTAJ 75MG DR or DICLOTAJ DR 50mg

It is important that you do not miss a dose. If you forget to take a dose, take one as soon as you remember. If it is nearly time for your next dose, just take the next dose and forget about the one you missed. Do NOT take a double dose to make up for a forgotten tablet. Do not take more than 150 mg in 24 hours. If you have trouble remembering to take the tablets, tell your doctor or pharmacist.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, DICLOTAJ 75MG DR or DICLOTAJ DR 50mg can cause side effects, although not everybody gets them.

Some side effects can be serious

STOP TAKING DICLOTAJ 75MG DR or DICLOTAJ DR 50mg  and tell your doctor straight away if you notice:

  • Stomach pain, indigestion, heartburn, wind, nausea (feeling sick) or vomiting (being sick)
  • Any sign of bleeding in the stomach or intestine, for example, when emptying your bowels, blood in vomit or black, tarry faeces
  • Allergic reactions which can include skin rash, itching, bruising, painful red areas, peeling or blistering
  • Wheezing or shortness of breath (bronchospasm)
  • Swollen face, lips, hands or fingers
  • Yellowing of your skin or the whites of your eyes
  • Persistent sore throat or high temperature
  • An unexpected change in the amount of urine produced and/or its appearance.
  • Mild cramping and tenderness of the abdomen, starting shortly after the start of the treatment with DICLOTAJ 75MG DR or DICLOTAJ DR 50mg and followed by rectal bleeding or bloody diarrhea usually within 24 hours of the onset of abdominal pain
  • Stevens-Johnson syndrome (serious illnesses with blistering of the skin, mouth, eyes and genitals)

If you notice that you are bruising more easily than usual or have frequent sore throats or infections, tell your doctor.

Tell your doctor immediately if you notice the following:

  • Chest pain, which can be a sign of a potentially serious allergic reaction called Kounis syndrome

The side effects listed below have also been reported.

Common (may affect up to 1 in 10 people):

  • Stomach pain, heartburn, nausea, vomiting, diarrhea, indigestion, wind, loss of appetite
  • Headache, dizziness, vertigo
  • Skin rash or spots
  • Raised levels of liver enzymes in the blood

Rare (may affect up to 1 in 1,000 people):

  • Stomach ulcers or bleeding (there have been very rare reported cases resulting in death, particularly in the elderly)
  • Gastritis (inflammation, irritation or swelling of the stomach lining)
  • Vomiting blood
  • Diarrhoea with blood in it or bleeding from the back passage
  • Black, tarry faeces or stools
  • Drowsiness, tiredness
  • Hypotension (low blood pressure, symptoms of which may include faintness, giddiness or light headedness)
  • Skin rash and itching
  • Fluid retention, symptoms of which include swollen ankles
  • Liver function disorders, including hepatitis and jaundice

Very rare (may affect up to 1 in 10,000 people):

Effects on the nervous system:

Tingling or numbness in the fingers, tremor, blurred or double vision, hearing loss or impairment, tinnitus (ringing in the ears), sleeplessness, nightmares, mood changes, depression, anxiety, mental disorders, disorientation and loss of memory, fits, headaches together with a dislike of bright lights, fever and a stiff neck, disturbances in sensation

Effects on the stomach and digestive system:

Constipation, inflammation of the tongue, mouth ulcers, inflammation of the inside of the mouth or lips, taste changes, lower gut disorders (including of the colon or worsening of ulcerative colitis or Crohn’s disease).

Effects on the heart, chest or blood:

Palpitations (fast or irregular heart beat), chest pain, hypertension (high blood pressure), inflammation of blood vessels (vasculitis), inflammation of the lung (pneumonitis), heart disorders, including congestive heart failure or heart attack, blood disorders (including anaemia).

Effects on the liver or kidneys:

Kidney or severe liver disorders including liver failure, presence of blood or protein in the urine

Effects on skin or hair:

Serious skin rashes including Stevens-Johnson syndrome, Lyell’s syndrome and other skin rashes which may be made worse by exposure to sunlight.

Hair loss

Other side effects that have also been reported include:

Inflammation of the pancreas, impotence. Facial swelling, inflammation of the lining of the brain (meningitis), stroke, throat disorders, confusion, hallucinations, malaise (general feeling of discomfort), inflammation of the nerves in the eye.

Do not be alarmed by this list – most people take Diclofenac Sodium Tablets without any problems.

If any of the side effects becomes serious, or if you notice side effects not listed in this leaflet, please tell your doctor. He/she may want to give you a different medicine.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE DICLOTAJ 75MG DR and DICLOTAJ DR 50mg

Keep out of the sight and reach of children.

Do not use DICLOTAJ 75MG DR or DICLOTAJ DR 50mg  tablets after the expiry date which is printed after ‘Exp’on the carton.

Do not store above 25°C. Keep the tablets in their original pack.

Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What DICLOTAJ 75MG DR and DICLOTAJ DR 50mg  contain

The name of your medicine is DICLOTAJ 75MG DR or DICLOTAJ DR 50mg .

DICLOTAJ 75MG DR: Each prolonged-release tablet contains 75mg of the active ingredient diclofenac sodium, and also contains the following inactive ingredients: tablet core: cetostearyl alcohol, colloidal anhydrous silica, compressible sugar, talc, povidone and magnesium stearate. Subcoat: copovidone and sucrose. Tablet film coat: hydroxypropylmethylcellulose, polyethylene glycol, iron oxide red, titanium dioxide and gum acasia. Polish: carnauba wax.

DICLOTAJ DR 50mg: Each prolonged-release tablet contains 50mg of the active ingredient diclofenac sodium, and also contains the following inactive ingredients: tablet core: cetostearyl alcohol, colloidal anhydrous silica, compressible sugar, talc, povidone, magnesium stearate. Subcoat: copovidone and sucrose. Tablet film coat: hydroxypropylmethylcellulose, polyethylene glycol, iron oxide red, titanium dioxide and gum acasia. Polish: carnauba wax.

What DICLOTAJ 75MG DR and DICLOTAJ DR 50mg look like and contents of the pack

DICLOTAJ 75MG DR prolonged-release tablets are packed in cartons containing 28 tablets or 56 tablets in foil blister strips.

DICLOTAJ DR 50mg prolonged-release tablets are packed in cartons containing 28 tablets in foil blister strips.

Not all pack sizes may be marketed.

  1. Manufactured in india by:
    TAJ PHARMACEUTICALS LTD;
    Plot No. 220, Mahagujarat Industrial Estate, Moraiyya,
    Tal-Sanand, Dist-Ahmedabad, Gujarat.