(a) Symptoms
There is no typical clinical picture resulting from diclofenac over dosage. Symptoms can include headache, nausea, vomiting, epigastric pain, GI bleeding, diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, or convulsions. In cases of significant poisoning, acute renal failure and liver damage are possible.
(b) 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, GI 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.
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.
- Known hypersensitivity to diclofenac sodium or to any of the excipients.
- Active gastric or intestinal ulcer, bleeding or perforation.
- History of gastrointestinal (GI) bleeding or perforation, related to previous non-steroidal anti-inflammatory drug (NSAID) therapy.
- Active or history of recurrent peptic ulcer or haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
- Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other NSAIDs.
- Acute porphyria.
- Severe hepatic, renal or cardiac failure.
- During the last trimester of pregnancy.
- Established congestive heart failure (NYHA II-IV), ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
None known.
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); 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, leucopenia, 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. |
| Unknown | Confusion, hallucinations. |
| Nervous system disorders | |
| Common | Headache, dizziness. |
| Rare | Somnolence. |
| Very rare | Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation; taste disturbances, cerebrovascular accident. |
| Unknown | Optic neuritis. |
| Eye disorders | |
| Very rare | Visual disturbance, vision blurred, diplopia. |
| 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, vasculitis. |
| Respiratory, thoracic and mediastinal disorders | |
| Rare | Asthma (including dyspnoea). |
| Very rare | Pneumonitis. |
| Unknown | Aggravated asthma, bronchospasm. |
| 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. |
| Unknown | Fatigue, malaise. |
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.
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 at: www.mhra.gov.uk/yellowcard
The results of the preclinical tests do not add anything of further significance to the prescriber.
For rheumatoid arthritis; osteoarthritis; low back pain; 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.
Pharmacotherapeutic Group: Acetic acid derivatives and related substances, ATC Code: M01A B05
Diclofenac Sodium is a non-steroidal agent with marked analgesic/anti-inflammatory and anti-pyretic properties. It is an inhibitor of prostaglandin synthetase (cyclo-oxygenase).
Diclofenac Sodium is rapidly absorbed from the gut and is subject to first-pass metabolism. Capsules give peak plasma concentrations after approximately 2.5 hours. The active substance is 99.7% protein bound and plasma half-life for the terminal elimination phase is 1-2 hours. Approximately 60% of the administered dose is excreted via the kidneys in the form of metabolites and less than 1% in unchanged form. About 30% of the dose is excreted via the bile in metabolised form.
The Диклоберл slow release preparation:
- Increases the duration of action of the drug
- Maintains relatively constant rate of absorption in the gastro-intestinal tract over a longer period of time
- Increases the fraction of the ingested dose absorbed in the GI tract
- Regulates the rate at which the drug is made available for absorption, thereby reducing the possibility of malabsorption and occurrence of side-effects.
General:
Caution is indicated in the elderly on basic medical grounds. As with all NSAIDs, Диклоберл should only be given to the elderly after other forms of treatment have been carefully considered, as the elderly have an increased frequency of adverse reactions to NSAIDs especially GI 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.
The use of Диклоберл with concomitant 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.
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.
As Диклоберл contains lactose and sucrose, patients with rare hereditary problems of fructose/galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Gastrointestinal effects:
GI bleeding, ulceration or perforation, which can be fatal, has been reported with NSAID therapy, including diclofenac, and can occur 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. If GI bleeding or ulceration occurs in patients receiving Диклоберл, the treatment 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 GI disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation. 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 , and in the elderly.
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.
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 advised in patients receiving concomitant medications that 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.
Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's disease, as their condition may be exacerbated.
Hepatic effects:
Close medical surveillance is required when prescribing Диклоберл 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 Диклоберл, 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), Диклоберл should be discontinued. Hepatitis may occur with use of diclofenac without prodromal symptoms.
Caution is called for when using Диклоберл in patients with hepatic porphyria, since it may trigger an attack.
Renal effects:
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.
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. Monitoring of renal function is recommended as a precautionary measure when using Диклоберл in such cases. Discontinuation of therapy is usually followed by recovery to the pre-treatment state.
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-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.
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.
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.
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma, since NSAIDs have been reported to cause bronchospasm in such patients.
Haematological:
During prolonged treatment with diclofenac, as with other NSAIDs, monitoring of the blood count is recommended.
Диклоберл, in common with other NSAIDs, can reversibly inhibit platelet aggregation. Patients with defects of haemostasis should be carefully monitored.
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.
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. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of reaction occurring in the majority of cases within the first month of treatment. Диклоберл should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Impaired Female fertility:
The use of Диклоберл 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 Диклоберл should be considered.
Patients who experience visual disturbances, dizziness, vertigo, somnolence, central nervous system disturbances, drowsiness or fatigue while taking Диклоберл, should refrain from driving or operating machinery.
For oral use.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Adults
One 100mg capsule taken whole daily, preferably with food or after food.
Children
Not recommended.
Elderly
The elderly are at an increased risk of serious consequences of adverse reactions. Studies indicate the pharmacokinetics of diclofenac sodium are not impaired to any clinical extent in the elderly, however, as with all non-steroidal anti-inflammatory drugs, Диклоберл should be used with caution in elderly patients and the lowest effective dose used for the shortest possible duration. These patients should be monitored regularly for GI bleeding during NSAID therapy.
No special instructions needed.
