Diclofenac Sodium Tablets 25mg
1
NAME OF THE MEDICINAL PRODUCT
Diclofenac Sodium 25mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 25 mg Diclofenac sodium BP
Excipient(s) with known effect
Anhydrous Lactose EP
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Tablet
4.1 Therapeutic indications
Adults and elderly:
Rheumatoid arthritis, osteoarthrosis, low back pain and other acute musculoskeletal disorders, acute gout, control of pain and inflammation in orthopaedic, dental and other minor surgery.
Paediatric population Juvenile Chronic Arthritis.
Children aged 9 years and above:
The 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.
4.2 Posology and method of administration
Posology
Adults:
A total of 75-150mg daily given in two or three divided doses.
Paediatric population 1-3mg/kg body weight 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 2 mg/kg body weight per day in 3 divided doses, depending on the severity of the disorder.
Older people
The older patients are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
Method of administration:
To be taken preferably with or after food.
4.3 Contraindications
• Known hypersensitivity to the active substance or any of the excipients (listed in section 6.1).
• Active gastric or intestinal ulcer, bleeding or perforation.
• History of gastrointestinal bleeding or perforation, relating to previous NSAID 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).
• Severe hepatic, renal and cardiac failure (see section 4.4).
• 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 who have previously shown hypersensitivity reactions (eg. asthma, angioedema, urticaria, or acute rhinitis) precipitated by acetylsalicylic acid or other NSAIDs
• Diclofenac gastro-resistant tablets contain lactose and therefore are not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
4.4 Special warnings and precautions for use
In all patients;
Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
The concomitant use of Diclofenac Sodium Tablets 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).
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur in rare cases with diclofenac without earlier exposure to the drug.
-Like other NSAIDs, Diclofenac may mask the signs and symptoms of infection due to its pharmacodynamic properties.
Older people:
Caution is indicated in the older people 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.
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation, which may be fatal (See section 4.2).
Cardiovascular and cerebrovascular effects:
Clinical trial and epidemiological data suggest that use of diclofenac, particularly at a high dose (150mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
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 patient's need for symptomatic relief and response to therapy should be reevaluated 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.
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. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking).
Gastro-intestinal effects
Gastrointestinal bleeding, 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 events.
They generally have more serious consequences in the older patient. If gastro-intestinal bleeding or ulceration occurs in patients receiving Diclofenac Sodium Tablets, 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 (GI) 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 and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).
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 maintain at the lowest effective dose.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment
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, anti-platelet agents such as aspirin or selective serotonin-reuptake inhibitors (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving Diclofenac, the treatment should be withdrawn
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).
Patients with a history of haematemesis, or melena, should be carefully observed
Hepatic effects:
Close medical surveillance is required when prescribing Diclofenac to patients with impaired 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, if clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash), Diclofenac should be discontinued. Hepatitis may occur with use of diclofenac without prodromal symptoms.
Caution is called for when using Diclofenac in patients with hepatic porphyria, since it may trigger an attack.
Renal effects
As fluid retention and oedema have been reported in association with NS AID 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 section 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.
The importance of prostaglandins in maintaining renal blood flow should be taken into account in patients with impaired cardiac or renal function, those being treated with diuretics or recovering from major surgery. Effects on renal function are usually reversible on withdrawal of Diclofenac Sodium Tablets.
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 (see section 4.8). Patients appear to be at the highest risk of these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Diclofenac Sodium Tablets should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Haematological effects:
Care should be taken when treating patients with haematological abnormalities, or bleeding diathesis. Use of Diclofenac Sodium Tablets is recommended only for short term treatment. During prolonged treatment with Diclofenac, as with other NSAIDs, monitoring of the blood count is recommended.
Like other NSAIDs, Diclofenac may temporarily inhibit platelet aggregation. Patients with defects of haemostasis 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.
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 ).
Impaired Female fertility:
The use of Diclofenac Sodium Tablets 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 Sodium Tablets 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. which may exacerbate cardiac failure, reduce GFR. Monitoring of the serum digoxin level is recommended.
Other NSAIDs and corticosteroids:
Concomitant administration of Diclofenac and other systemic NSAIDs (including Aspirin) or corticosteroids may increase the risk of adverse effects in particular the frequency of gastrointestinal undesirable effects (see section 4.4).
Diuretics and antihypertensive agents:
Like other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin converting enzyme (ACE) inhibitors) may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients, especially the elderly, should have their blood pressure periodically monitored. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity. Concomitant treatment with potassium-sparing drugs may be associated with increased serum potassium levels, which should therefore be monitored frequently (see section 4.4).
Anticoagulants and antiplatelet 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 isolated reports of an increased risk of haemorrhage in patients receiving diclofenac and anticoagulants concomitantly. Close monitoring of such patients is therefore recommended.
Selective serotonin reuptake inhibitors (SSRIs):
Concomitant administration of systemic NSAIDs, including Diclofenac,and SSRI may cause increased 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 both hypoglycaemic and hyperglycaemic effects,-necessitating changes in the dosage of the antidiabetic agents during treatment with diclofenac. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy.
Methotrexate:
Diclofenac can inhibit the tubular renal clearance of methotrexate hereby increasing plasma methotrexate levels. Caution is recommended when NSAIDs, including diclofenac, are administered less than 24 hours before or after treatment with methotrexate, since blood concentrations of methotrexate may rise and the toxicity of this substance be increased.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
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.
Quinolone antibacterials
There have been isolated reports pertaining to animal study of convulsions which may have been due to concomitant use of quinolones and NSAIDs.
Phenytoin: When using phenytoin concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in exposure to phenytoin.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus. This might be mediated through renal antiprostaglandin effects of both NSAID and calcineurin inhibitor.
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.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen
Potent CYP2C9 inhibitors: “Caution is recommended when co-prescribing diclofenac with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), which could result in a significant increase in peak plasma 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. During the first and second trimester of pregnancy, Diclofenac Sodium should not be given unless clearly necessary. If Diclofenac Sodium 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 is 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.
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.
Patients experiencing visual disturbances, dizziness, drowsiness, vertigo, somnolence or other central nervous system disturbances while taking Diclofenac, should refrain from driving or using machines.
4.8 Undesirable effects
Adverse reactions associated with Diclofenac obtained from clinical studies and postmarketing surveillance are tabulated below according to the system organ classes in MedDRA and 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.
|
Blood and lymphatic system disorders | |
|
Very rare |
Thrombocytopenia, leukopenia, anaemia (including haemolytic and aplastic anaemia), Agranulocytosis. |
|
Immune system disorders | |
|
Rare |
Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock). |
|
Very rare |
Angioneurotic oedema (including face oedema). |
|
Psychiatric disorders | |
|
Very rare |
Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder, anxiety. |
|
Not known |
Confusional state |
|
Nervous system disorders |
|
Common |
Headache, dizziness. |
|
Rare |
Somnolence. |
|
Very rare |
Paraesthesia, memory impairment, convulsion, tremor, meningitis aseptic *, dysgeusia, cerebrovascular accident. |
|
Not known Eye disorders |
Hallucinations, sensory disturbance, malaise |
|
Very rare |
Visual disturbance, vision blurred, diplopia. |
|
Not known Ear and labyrinth disorders |
Optic neuritis |
|
Common |
Vertigo. |
|
Very rare Cardiac disorders |
Tinnitus, hearing impaired. |
|
Very rare Vascular disorders |
Palpitations, chest pain, cardiac failure, myocardial infarction. |
|
Very rare Respiratory, thoracic and mediastinal disorders |
Hypertension, hypotension, vasculitis. |
|
Rare |
Asthma (including dyspnoea). |
|
Very rare Gastrointestinal disorders |
Pneumonitis. |
|
Common |
Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia. |
|
Rare |
Gastritis, gastrointestinal haemorrhage, haematemesis, diarrhoea haemorrhagic, melaena, gastrointestinal ulcer** (sometimes fatal particularly in elderly). |
|
Very rare |
Colitis***, constipation, stomatitis (including ulcerative stomatitis), mouth ulceration, glossitis, oesophageal disorder, crohn's disease , large intestinal stricture, pancreatitis. |
|
Hepatobiliary disorders | |
|
Common |
Transaminases increased. |
|
Rare |
Hepatitis, jaundice, liver disorder. |
|
Very rare |
Fulminant hepatitis, hepatic necrosis, hepatic failure. |
|
Skin and subcutaneous tissue disorders | |
|
Common |
Rash. |
|
Rare |
Urticaria. |
|
Very rare |
Bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), dermatitis exfoliative, alopecia, photosensitivity reaction, purpura , henoch-Schonlein purpura, , pruritus. |
|
Renal and urinary disorders | |
|
Very rare |
Acute renal failure, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis. |
|
Reproductive system disorders | |
|
Not known |
Erectile dysfunction |
|
General disorders and administration site condition | |
|
Rare |
Generalized Oedema |
*Meningitis aseptic (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation
** Gastrointestinal ulcer could be with or without bleeding or perforation
*** Colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis),
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 section 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
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
(a) 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 event of significant poisoning acute renal failure and liver damage are possible.Other complications that might be encountered include hypotension, respiratory depression and gastro-intestinal irritation.
(b) Therapeutic measure
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.
Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.
Renal and liver function should be closely monitored.
Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam.
Other measures may be indicated by the patient’s clinical condition.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal, anti-inflammatory drug (NSAID) with
analgesic/anti-inflammatory and antipyretic properties
ATC code: M01AB05
Mechanism of action
Diclofenac is an inhibitor of prostaglandin synthetase. (cyclooxygenase).
Clinical efficacy and safety
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 2-3 mg/kg BW diclofenac was compared with acetylsalicylic acid (ASS, 50-100 mg/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 2-3 mg/kg BW, n=22) was comparable with that of indomethacin (daily dose 2-3 mg/kg BW, n=23).
5.2 Pharmacokinetic properties
Absorption
Diclofenac sodium is almost totally absorbed after oral administration and it is subject to significant first-pass metabolism.
Distribution
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.
Biotransformation
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 1-2 hours.
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 they remain higher for up to 12 hours.
Elimination
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.
Characteristics in patient
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.
5.3 Preclinical safety data
Diclofenac Sodium was considered to be unsafe in patients with acute
porphyria because it has been shown to be porphyrinogenic in animals or invitro systems.
Multiple dose studies were performed in rats, dogs and monkeys. At toxic doses there were gastrointestinal ulcers and disorders in the blood picture in all species. Genetic toxicology studies with diclofenac sodium show that diclofenac is not a mutagen.
Carcinogenicity studies have been conducted in mice and rats. No carcinogenic effect has been seen.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Anhdrous Lactose EP
Microcrystalline Cellulose BP Maize Starch EP Magnesium Stearate EP (E572)
Colloidal Silicon Dioxide USP (E551)
Coating:
Cellulose Acetate Phthalate EP Carbowax 6000 HSE Castor Oil EP
Opaspray, K-l-2433 HSE or Orange Dispersion F00223 HSE Acetone BP (ND)
Methylene Chloride EP (ND)
6.2 Incompatibilities
None stated.
6.3
Shelf life
3 years: polypropylene containers.
6.4 Special precautions for storage
Store in a dry place below 250C
6.5 Nature and contents of container
Polypropylene tamper evident containers: 100 84, 70, 56, 42, 28, 21, 15 and
14 tablets.
Blister pack (composed of PVdC coated PVC and aluminium foil): 84, 70, 56,
42, 28,
21, 15 and 14 tablets.
6.6 Special precautions for disposal
None
7 MARKETING AUTHORISATION HOLDER
Mercury Pharmaceuticals Ltd,
Capital House,
85 King William Street,
London EC4N 7BL, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 12762/0420
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
4th July 1995
10 DATE OF REVISION OF THE TEXT
17/08/2016