Diclofenac Sodium Delayed-Release Tablets USP 25mg Taj Pharma

1. Name of the medicinal product

Diclofenac Sodium Delayed-Release Tablets USP 25mg Taj Pharma
Diclofenac Sodium Delayed-Release Tablets USP 50mg Taj Pharma
Diclofenac Sodium Delayed-Release Tablets USP 75mg Taj Pharma

2. Qualitative and quantitative composition

a) Diclofenac Sodium Delayed-Release Tablets USP 25mg Taj Pharma
Each delayed –release tablets contain:
Diclofenac Sodium USP 25mg
Excipients: Q.S.

b) Diclofenac Sodium Delayed-Release Tablets USP 50mg Taj Pharma
Each delayed –release tablets contain:
Diclofenac Sodium USP 50mg
Excipients: Q.S.

c) Diclofenac Sodium Delayed-Release Tablets USP 75mg Taj Pharma
Each delayed –release tablets contain:
Diclofenac Sodium USP 75mg
Excipients: Q.S.

Excipients(s) with known effect

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Delayed-Release tablet.

4. Clinical particulars
   • 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

Children aged 1-12 years: for treatment of juvenile chronic arthritis

Children aged 9 years and above: for short term treatment of fever related to infections of the ear, nose or throat (ENT), e.g. pharyngotonsillitis, otitis media. As monotherapy or as adjunct therapy with morphine or other opiates (due to its opiate-sparing effect) for the relief of acute post-operative pain

• 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). 75mg to 150mg daily in two or three divided doses.

The recommended maximum daily dose of Diclofenac Sodium Taj Pharma is 150mg.

Special populations

Elderly:

Although the pharmacokinetics of Diclofenac Sodium Taj Pharma 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:

For treatment of Juvenile chronic arthritis the following dosage should be given: Children (aged 1-12 years): 1-3mg/kg per day in divided doses. For the short term treatment of fever related to infections of the ear, nose or throat (ENT) and post-operative pain the following dosage should be given:

Children aged 9 years (min. 35 kg BW) or over and adolescents should be given up to 2mg/kg body weight per day in 3 divided doses, depending on the severity of the disorder.

Method of administration

For oral administration.

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

• 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.

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 drugs including diclofenac, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug (see section 4.8). Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction. Presenting symptoms of such reactions can include chest pain occurring in association with an allergic reaction to diclofenac.

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

This medicine contains lactose and therefore is not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

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 gastrointestinal disorders, or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see section 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).

NSAIDs, including diclofenac, may be associated with increased risk of gastro-intestinal anastomotic leak. Close medical surveillance and caution are recommended when using diclofenac after gastro-intestinal surgery.

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 Taj Pharma 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 Taj Pharma 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).

• Interaction with other medicinal products and other forms of interaction

The following interactions include those observed with diclofenac Delayed-Release 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.

Tacrolimus: Possible 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 to 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 glycosides: Concomitant 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 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 concentration and exposure to diclofenac due to inhibition of diclofenac metabolism.

• 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 Taj Pharma 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).

• Effects on ability to drive and use machines

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

• 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

*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 (150mg daily) and in long term treatment (see sections 4.3 and 4.4 ).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

• 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 caseof 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.

5. Pharmacological properties

• Pharmacodynamic properties

Pharmacotherapeutic group

Non-steroidal anti-inflammatory drugs (NSAlDs).

Mechanism of action

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

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

There is limited clinical trial experience of the use of diclofenac in JRA/JIA paediatric patients. In a randomised, double-blind, 2-week, parallel group study in children aged 3-15 years with JRA/JIA, the efficacy and safety of daily 2-3mg/kg BW diclofenac was compared with acetylsalicylic acid (ASS, 50-100mg/kg BW/d) and placebo – 15 patients in each group. In the global evaluation, 11 of 15 diclofenac patients, 6 of 12 aspirin and 4 of 15 placebo patients showed improvement with the difference being statistically significant (p < 0.05). The number of tender joints decreased with diclofenac and ASS but increased with placebo. In a second randomised, double-blind, 6-week, parallel group study in children aged 4-15 years with JRA/JIA, the efficacy of diclofenac (daily dose 2-3mg/kg BW, n=22) was comparable with that of indomethacin (daily dose 2-3mg/kg BW, n=23).

• Pharmacokinetic properties

Absorption

Absorption is complete but onset is delayed until passage through the stomach, which may be affected by food which delays stomach emptying. The mean peak plasma diclofenac concentration reached at about 2 hours (50mg dose produces 1511± 466 ng/ml).

Bioavailability:

About half of the administered diclofenac is metabolised during its first passage through the liver (“first-pass” effect), the area under the concentrations curve (AUC) following oral administration is about half that following an equivalent parenteral dose.

Pharmacokinetic behaviour does not change on repeated administration. Accumulation does not occur, provided the recommended dosage intervals are observed. The plasma concentrations attained in children given equivalent doses (mg/kg, b.w.) are similar to those obtained in adults.

Distribution

The active substance is 99.7% protein bound, mainly to albumin (99.4%).

Diclofenac enters the synovial fluid, where maximum concentrations are measured 2-4 hours after the peak plasma values have been attained. The apparent half-life for elimination from the synovial fluid is 3-6 hours. Two hours after reaching the peak plasma values, concentrations of the active substance are already higher in the synovial fluid than they are in the plasma and remain higher for up to 12 hours.

Diclofenac was detected in a low concentration (100 ng/mL) in breast milk in one nursing mother. The estimated amount ingested by an infant consuming breast milk is equivalent to a 0.03mg/kg/day dose (see section 4.6).

Metabolism

Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.

Elimination

The total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value ± SD). The terminal half-life in plasma is 1-2 hours. Four of the metabolites, including the two active ones, also have short plasma half-lives of 1-3 hours.

About 60% of the administered dose is excreted in the urine in the form of the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% is excreted as unchanged substance. The rest of the dose is eliminated as metabolites through the bile in the faeces.

Characteristics in patients

Elderly: No relevant age-dependent differences in the drug’s absorption, metabolism, or excretion have been observed, other than the finding that in five elderly patients, a 15 minute iv infusion resulted in 50% higher plasma concentrations than expected with young healthy subjects.

Patients with renal impairment: In patients suffering from renal impairment, no accumulation of the unchanged active substance can be inferred from the single-dose kinetics when applying the usual dosage schedule. At a creatinine clearance of less than 10 mL/min, the calculated steady-state plasma levels of the hydroxy metabolites are about 4 times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile.

Patients with hepatic impairment: In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.

• Preclinical safety data

None stated.

6. Pharmaceutical particulars
   • List of excipients

Granulating fluid:

Copolyvidone

Core:

Lactose

Microcrystalline cellulose, Maize starch, Crospovidone, Colloidal silicon dioxide, Magnesium stearate

Enteric coat:

Triethyl citrate, Methacrylic acid-ethylacrylate copolymer

Talc

Pigmented film coat:

Hydroxypropyl methylcellulose, Iron oxide yellow, Polyethylene glycol, Titanium dioxide
Sunset yellow

Polish:

Carnauba Wax

• Incompatibilities

Not applicable.

• Shelf life

3 years.

• Special precautions for storage

Do not store above 25°C.

• 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. Pack sizes of 25, 50, 84, 100 and 500 tablets per carton are available.

Not all pack sizes may be marketed.

• Special precautions for disposal and other handling

No special requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com

Diclofenac Sodium Delayed-Release Tablets USP 25mg Taj Pharma

Package leaflet Information for patient

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 have 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 DICLOFENAC TAJ PHARMA Sodium  is and what  it is used for
2. What you need to know before you take DICLOFENAC TAJ PHARMA Sodium
3. How to take DICLOFENAC TAJ PHARMA Sodium
4. Possible side effects
5. How to store DICLOFENAC TAJ PHARMA Sodium
6. Contents of the pack and other information

1.WHAT DICLOFENAC TAJ PHARMA Sodium IS AND WHAT IT IS USED FOR

Diclofenac Taj Pharma Sodium, the active ingredient in DICLOFENAC TAJ PHARMA Sodium , is one of a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs reduce pain and inflammation.

DICLOFENAC TAJ PHARMA Sodium 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. In children aged 1-12 years DICLOFENAC TAJ PHARMA Sodium 25mg tablets are used to treat juvenile chronic arthritis. In children aged 9 years and above DICLOFENAC TAJ PHARMA  Sodium 25mg tablets are used for short term treatment of fever related to infections of the ear, nose or throat, and for relief of acute post-operative pain.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE DICLOFENAC TAJ PHARMA Sodium
   Do not take DICLOFENAC TAJ PHARMA  Sodium  if:

• you are allergic to Diclofenac Taj Pharma Sodium, aspirin, ibuprofen or any other NSAID, or to any of the other ingredients of DICLOFENAC TAJ PHARMA Sodium  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 Taj Pharma 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 lactose (these tablets contain lactose)

Tell your doctor if you recently had or you are going to have a surgery of the stomach or intestinal tract before taking DICLOFENAC TAJ PHARMA Sodium , as DICLOFENAC TAJ PHARMA  can sometimes worsen wound healing in your gut after surgery

Tell your doctor or pharmacist if you have any of these conditions because Diclofenac Taj Pharma Sodium might not be the right medicine for you.

Children In children aged 1-12 years DICLOFENAC TAJ PHARMA Sodium 25mg tablets are used to treat juvenile chronic arthritis.

Other medicines and Diclofenac Taj Pharma Sodium
Some medicines can interfere with your treatment. Please tell your doctor or pharmacist if you are taking any 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 SSRIs (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.
• Diclofenac Taj Pharma Sodium 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 DICLOFENAC TAJ PHARMA Sodium 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 Diclofenac Taj Pharma Sodium 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 Diclofenac Taj Pharma Sodium whilst breast feeding.

Driving and using machines

Very occasionally people have reported that Diclofenac Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma Sodium tablets.

Diclofenac Taj Pharma Sodium tablets contains

Diclofenac Taj Pharma Sodium 25mg/50mg/75mg contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product. Diclofenac Taj Pharma Sodium 25mg/50mg/75mg contains a colouring agent, sunset yellow , which may cause allergic reactions.

3. HOW TO TAKE DICLOFENAC TAJ PHARMA Sodium

The doctor will tell you how many Diclofenac Taj Pharma Sodium 25mg/50mg/75mg tablets 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. 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.

The recommended dose is:

Adults and children over 12 years old 75 to 150mg daily in two or three divided doses. The number of tablets which you take will depend on the strength the doctor has given you.

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. Your doctor may also want to check closely that the Diclofenac Taj Pharma Sodium tablets are not affecting your stomach.

Children aged 1 to 12 years Doses vary with the age and weight of the child. These tablets may be given to children but not to infants, where applicable, within the daily dose range of 1-3mg per kilogram of body weight in two or three separate doses.

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 Diclofenac Taj Pharma Sodium than you should

If you, or anyone else, accidentally take too much Diclofenac Taj Pharma Sodium, 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 Diclofenac Taj Pharma Sodium
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 150mg 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.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Diclofenac Taj Pharma Sodium can cause side effects, although not everybody gets them. Some side effects can be serious STOP TAKING Diclofenac Taj Pharma Sodium tablets 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 Diclofenac Taj Pharma Sodium and followed by rectal bleeding or bloody diarrhea usually within 24 hours of the onset of abdominal pain.
• Stevens Johnson syndrome (serious illness 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 Taj Pharma 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. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE DICLOFENAC TAJ PHARMA Sodium

Keep out of the sight and reach of children. Do not use Diclofenac Taj Pharma Sodium 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.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Diclofenac Taj Pharma Sodium25mg/50mg/75mg tablets contain the name of your medicine is Diclofenac Taj Pharma Sodium25mg/50mg/75mg.

Diclofenac Taj Pharma Sodium25mg/50mg/75mg: Each Delayed-Release tablet contains 25mg/50mg/75mg of the active ingredient Diclofenac Taj Pharma Sodium, and also contains the following inactive ingredients:

Tablet core: copolyvidone, microcrystalline cellulose, colloidal anhydrous silica, lactose, maize starch, magnesium stearate, crospovidone. Tablet enteric coat: triethyl citrate, methacrylic acid-ethylacrylate copolymer (1:1) dispersion 30%, talc.

Tablet film coat: hydroxypropylmethylcellulose, polyethylene glycol, iron oxide yellow, sunset yellow, titanium dioxide. Polish: carnauba wax.

What Diclofenac Taj Pharma Sodium25mg/50mg/75mg tablets look like and contents of the pack

Diclofenac Taj Pharma Sodium 25mg/50mg/75mg tablets are Delayed-Release tablets

Diclofenac Taj Pharma  Sodium 25mg/50mg/75mg Delayed-Release tablets are Packed in sizes of 25, 50, 84, 100 and 500 tablets as per carton are available and tablets are also in foil blister strips.

Not all pack sizes may be marketed.

Manufactured in India by:
CEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com