- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
AdultsThe recommended daily dose is 100 150 mg in two or three divided doses. For milder cases, 75 100 mg daily in two or three divided doses is usually sufficient. In migraine an initial dose of 50 mg should be taken at the first signs of an impending attack. In cases where relief 2 hours after the first dose is not sufficient, a further dose of 50 mg may be taken. If needed, further doses of 50 mg may be taken at intervals of 4 6 hours, not exceeding a total dose of 200 mg per day.
ChildrenFor children over 14 years of age, the recommended daily dose is 75 100 mg in two or three divided doses. Diclofenac Potassium/ Adacium Rapid 50 mg tablets are not recommended for children under 14 years of age. The use of Diclofenac Potassium/ Adacium Rapid 50 mg tablets in migraine attacks has not been established in children.
ElderlyThe elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used in frail elderly patients or those with a low body weight (also see precautions) and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
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 use of Diclofenac potassium with concomitant 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).
Elderly:The elderly have increased frequency of adverse reactions to NSAIDs especially gastro intestinal bleeding and perforation which may be fatal (see section 4.2). In particular, it is recommended that the lowest effective dose be used in frail elderly patients or those with a low body weight.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.Gastrointestinal: Close medical surveillance is imperative and particular caution should be exercised when prescribing diclofenac in patients with symptoms indicative of gastrointestinal disorders, with a history suggestive of gastric or intestinal ulceration, bleeding or perforation, with ulcerative colitis, or with Crohn's disease as these conditions may be exacerbated (see section 4.8 Undesirable effects). Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding).
Gastrointestinal bleeding, ulceration and perforation:GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events. They generally have more serious consequences in the elderly.The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence and maintain 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).Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.Caution should be advised in patients receiving concomitant medications which increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).When GI bleeding or ulceration occurs in patients receiving diclofenac potassium, the treatment should be withdrawn.NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).
Hypersensitivity reactions:As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, can occur without earlier exposure to the drug (see section 4.8). Like other NSAIDs, Diclofenac Potassium/ Adacium Rapid 50mg tablets may mask the signs and symptoms of infection due to their pharmacodynamic properties.
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, Renal and Hepatic Impairment:The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).
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 patient's need for symptomatic relief and response to therapy should be re-evaluation 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. Clinical trial and epidemiological data suggest that use of diclofenac, particularly at 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).
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 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.Haematological:During prolonged treatment with diclofenac, as with other NSAIDs, monitoring of the blood count is recommended. Diclofenac Potassium/ Adacium Rapid 50mg tablets may reversibly inhibit platelet aggregation (see section 4.5 Interactions). Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored.
Long term treatment:All patients who are receiving long term treatment with non-steroidal, anti-inflammatory agents should be monitored as a precautionary measure e.g. renal function, hepatic function (elevation of liver enzymes may occur) and blood counts. This is particularly important in the elderly.
Pre-existing asthmaIn 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.Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Dermatological: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 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 potassium should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Impaired female fertility:The use of Diclofenac Potassium/ Adacium Rapid 50mg 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 Potassium/ Adacium Rapid 50mg tablets should be considered (see section 4.6).
PregnancyInhibition 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 should not be given unless clearly necessary. 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 is contraindicated during the third trimester of pregnancy.
LactationLike 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.
FertilityAs 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 section 4.4).
|Blood and lymphatic system disorders|
|Very rare||Thrombocytopenia, leucopenia, 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).|
|Very rare||Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder.|
|Nervous system disorders|
|Very rare||Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident.|
|Unknown||Confusion, hallucinations, disturbances of sensation, malaise.|
|Very rare||Visual disturbance, vision blurred, diplopia.|
|Ear and labyrinth disorders|
|Very rare||Tinnitus, hearing impaired.|
|Very rare||Palpitations, chest pain, cardiac failure, myocardial infarction.|
|Very rare||Hypertension, hypertension vasculitis.|
|Respiratory, thoracic and mediastinal disorders|
|Rare||Asthma (including dyspnoea).|
|Common||Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia.|
|Rare||Gastritis, gastrointestinal haemorrhage, haematemesis, diarrhoea haemorrhagic, melaena, gastrointestinal ulcer (with or without bleeding or perforation sometimes fatal particularly in the elderly).|
|Very rare||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.|
|Not known||Ischaemic colitis|
|Rare||Hepatitis, jaundice, liver disorder.|
|Very rare||Fulminant hepatitis, hepatic necrosis, hepatic failure.|
|Skin and subcutaneous tissue disorders|
|Very Rare||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 rare||Acute renal failure haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.|
|General disorders and administration site conditions|
|Reproductive system and breast disorders|
AbsorptionDiclofenac is rapidly and completely absorbed from sugar-coated tablets. Food intake does not affect absorption. Peak plasma concentration after one 50 mg sugar-coated tablet was 3.9 µmol/l after 20-60 minutes. The plasma concentrations show a linear relationship to the size of the dose. Diclofenac undergoes first-pass metabolism and is extensively metabolised.
DistributionDiclofenac is highly bound to plasma proteins (99.7%), chiefly albumin (99.4%) Diclofenac was detected in a low concentration (100ng/mL) in breast milk in one nursing mother. The estimated amount ingested by an infant consuming breast milk is equivalent to a 0.03 mg/kg/day dose (see section 4.6 Fertility, pregnancy and lactation).
EliminationThe total systemic clearance of diclofenac in plasma is 263 ± 56 ml/min (mean ± SD). The terminal half-life in plasma is 1 2 hours. Repeated oral administration of Diclofenac Potassium/ Adacium Rapid 50mg tablets for 8 days in daily doses of 50 mg t.d.s does not lead to accumulation of diclofenac in the plasma. Approx. 60% of the dose administered is excreted in the urine in the form of metabolites, and less than 1% as unchanged substance. The remainder of the dose is eliminated as metabolites through the bile in the faeces.
BiotransformationThe biotransformation of diclofenac involves partly glucuronidation of the intact molecule but mainly single and multiple hydroxylation followed by glucuronidation.
Characteristics in patientsThe age of the patient has no influence on the absorption, metabolism, or excretion of diclofenac. 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 <10 ml/min the theoretical steady-state plasma levels of metabolites are about four times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile. In the presence of impaired hepatic function (chronic hepatitis, non-decompensated cirrhosis) the kinetics and metabolism are the same as for patients without liver disease.
Tablet Coating:Polyvinyl alcohol partially hydrolysedTitanium dioxide E171TalcLecithin Soya E322Iron Oxide red E172Iron Oxide yellow E172Xanthan gum E415
Concordia International- formerly Focus Pharmaceuticals Ltd
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