a) Symptoms
There is no typical clinical picture resulting from Diclofenac-Akri over dosage. Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, dizziness, disorientation, excitation, coma, drowsiness, tinnitus, fainting, occasionally convulsions. In rare cases of significant poisoning acute renal failure and liver damage are possible.
b) Therapeutic measure
Patients should be treated symptomatically as required.
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.
Good urine output should be ensured. Special measures such as forced diuresis, dialysis or haemo-perfusion are probably of no help in eliminating NSAIDs, including Diclofenac-Akri, due to high protein binding and extensive metabolism.
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. Supportive measures should be given for complications such as hypotension, renal failure, gastrointestinal disorder, and respiratory depression.
Other measures may be indicated by the patient's clinical condition.
- Hypersensitivity to the active substance or any of the excipients.
- Active, gastric or intestinal ulcer, bleeding or perforation.
- Active, or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
- NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.
- Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
- Severe heart failure, hepatic failure and renal failure.
- History of gastro-intestinal bleeding or perforation, relating to previous NSAID therapy.
- During the last trimester of pregnancy
- This product contains soya. If you are allergic to peanut or soya, do not use this medicinal product.
Not applicable
Adverse reactions are ranked under the 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, <1/1000); very rare (<1/10,000); Unknown: cannot be estimated from available data.
| The following undesirable effects include those reported with other short-term or long-term use.Blood and lymphatic system disorders | |
| Very rare | Thrombocytopenia, leucopoenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis. |
| Unknown | Neutropenia |
| 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. |
| Nervous system disorders | |
| Common | Headache, dizziness. |
| Rare | Somnolence, tiredness. |
| Very rare | Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis*, taste disturbances, cerebrovascular accident. |
| Unknown | Confusion, hallucinations, disturbances of sensation malaise |
| Eye disorders | |
| Very rare | Visual disturbance, vision blurred, diplopia. |
| Unknown | Optic neuritis. |
| Ear and labyrinth disorders | |
| Common | Vertigo. |
| Very rare | Tinnitus, hearing impaired. |
| Cardiac disorders | |
| Very rare | Palpitations, chest pain, cardiac failure, myocardial infarction. |
| Vascular disorders | |
| Very rare | Hypertension, hypotension, vasculitis. |
| Respiratory, thoracic and mediastinal disorders | |
| Rare | Asthma (including dyspnoea). |
| Very rare | Pneumonitis. |
| Gastrointestinal disorders | |
| 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. |
| Unknown | Ischaemic colitis |
| 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, 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 | |
| Rare | Oedema |
| Reproductive system and breast disorders | |
| Very rare | Impotence |
* especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus, mixed connective tissue disease, with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation.
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-Akri, particularly at high dose (150mg daily) and in long term treatment..
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
Relevant information on the safety of Diclofenac-Akri Potassium Tablets is included in previous sections of this Summary of Product Characteristics.
Rheumatoid arthritis
Osteoarthrosis
Low back pain
Migraine attacks
Acute musculo-skeletal disorders and trauma such as periarthritis (especially frozen shoulder), tendinitis, tenosynovitis, bursitis, sprains, strains and dislocations; relief of pain in fractures
Ankylosing spondylitis
Acute gout
Control of pain and inflammation in orthopaedic, dental and other minor surgery
Pyrophosphate arthropathy and associated disorders
Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAID).
ATC code: M01A B05
Diclofenac-Akri Potassium tablets contain the potassium salt of Diclofenac-Akri, a non-steroidal compound with pronounced and clinically demonstrable analgesic, anti-inflammatory and anti-pyretic properties.
Diclofenac-Akri is a potent inhibitor of prostaglandin biosynthesis and a modulator of arachidonic acid release and uptake.
Diclofenac-Akri Potassium tablets have a rapid onset of action and are therefore suitable for the treatment of acute episodes of pain and inflammation.
In migraine attacks Diclofenac-Akri Potassium tablets have been shown to be effective in relieving the headache and in improving the accompanying symptom of nausea.
Diclofenac-Akri 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-Akri 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-Akri 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-Akri 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-Akri 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-Akri (daily dose 2-3 mg/kg BW, n=22) was comparable with that of indomethacin (daily dose 2-3 mg/kg BW, n=23).
Absorption
Diclofenac-Akri is rapidly and completely absorbed from sugar-coated tablets. Food intake does not affect absorption.
Peak plasma concentration after one 50mg 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-Akri undergoes first-pass metabolism and is extensively metabolised.
Distribution
Diclofenac-Akri is highly bound to plasma proteins (99.7%), chiefly albumin (99.4%)
Diclofenac-Akri 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.
Elimination
The total systemic clearance of Diclofenac-Akri in plasma is 263 ± 56 ml/min (mean ± SD).
The terminal half-life in plasma is 1-2 hours.
Repeated oral administration of Diclofenac-Akri Potassium tablets for 8 days in daily doses of 50mg t.d.s does not lead to accumulation of Diclofenac-Akri in the plasma.
Approximately 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.
Biotransformation
The biotransformation of Diclofenac-Akri involves partly glucuronidation of the intact molecule but mainly single and multiple hydroxylation followed by glucuronidation.
Characteristics in patients
The age of the patient has no influence on the absorption, metabolism, or excretion of Diclofenac-Akri.
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 <10ml/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.
The use of Diclofenac-Akri 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.
Elderly
Caution is indicated in the elderly on basic medical grounds. The elderly have increased frequency of adverse reactions to NSAIDs especially gastro intestinal bleeding and perforation which may be fatal. In particular, it is recommended that the lowest effective dose be used in frail elderly patients or those with a low body weight.
Gastrointestinal
Close medical surveillance is imperative 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.
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.
GI bleeding (haematemesis, melaena), 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.).
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.
When GI bleeding or ulceration occurs in patients receiving Diclofenac-Akri potassium, the treatment should be withdrawn.
Hypersensitivity reactions
As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, can occur without earlier exposure to the drug.
Infection
Like other NSAIDs, Diclofenac-Akri Potassium 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.
Cardiovascular, Renal and Hepatic Impairment
The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. As fluid retention and oedema have been reported in association with NSAIDs therapy, including Diclofenac-Akri, 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 those patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery. Monitoring of renal function is recommended as a precautionary measure when using Diclofenac-Akri in such cases. Discontinuation therapy is usually followed by recovery to the pre-treatment state.
Hepatic
Close medical surveillance is required when prescribing Diclofenac-Akri to patients with impairment of hepatic function as their condition may be exacerbated.
As with other NSAIDs, including Diclofenac-Akri, values of one or more liver enzymes may increase. During prolonged treatment with Diclofenac-Akri, 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-Akri Potassium tablets should be discontinued.
Hepatitis may occur without prodromal symptoms.
Use of Diclofenac-Akri Potassium tablets in patients with hepatic porphyria may trigger an attack.
Haematological
Diclofenac-Akri Potassium tablets may reversibly inhibit platelet aggregation. 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 eg renal function, hepatic function (elevation of liver enzymes may occur) and blood counts. This is particularly important in the elderly.
Respiratory disorders
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-Akri sodium and other NSAIDs can precipitate bronchospasm if administered to patients suffering from, or with a previous history of bronchial asthma.
Cardiovascular and cerebrovascular effects
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-Akri.
Clinical trial and epidemiological data suggest that use of Diclofenac-Akri, 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).
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease and with significant risk factors for cardiovascular events (e.g. hyperlipidaemia, diabetes mellitus, smoking) should only be treated with Diclofenac-Akri after careful consideration.
As the cardiovascular risks of Diclofenac-Akri 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-evaluated periodically.
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, including Diclofenac-Akri Potassium. 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-Akri Potassium tablets should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Impaired female fertility
The use of Diclofenac-Akri Potassium 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-Akri Potassium tablets should be considered.
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
For oral administration.
To be taken preferably with or after food.
The tablets should be swallowed whole with liquid
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Adults
The recommended daily dose is 100-150mg in two or three divided doses. For milder cases, 75-100mg daily in two or three divided doses is usually sufficient.
In migraine an initial dose of 50mg 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 50mg may be taken. If needed, further doses of 50mg may be taken at intervals of 4-6 hours, not exceeding a total dose of 200mg per day.
Paediatric population
For children over 14 years of age, the recommended daily dose is 75-100mg in two or three divided doses. Diclofenac-Akri Potassium 25mg Tablets are not recommended for children under 14 years of age.
The use of Diclofenac-Akri Potassium 25mg tablets in migraine attacks has not been established in children.
Elderly
The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, it is recommended that the lowest effective dosage be used in frail elderly patient or those with low body weight, and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
Renal impairment
No adjustment of the starting dose is required for renally impaired patients.
Hepatic impairment
No adjustment of the starting dose is required for hepatically impaired patients.
Not applicable.
Administrative data
