a) General description
The most frequently reported side effects associated with mefenamic acid involve the gastrointestinal tract. Diarrhoea appears to be the most common side effect and is usually dose-related. It generally subsides on dosage reduction, and rapidly disappears on termination of therapy. Some patients may not be able to continue therapy.
b) Table of adverse reactions
Frequency of reactions: Very common ( ≥1/10 ); common ( ≥1/100 to <1/10 ); uncommon ( ≥1/1000 to ≤1/100 ); rare ( ≥1/10,000 to ≤ 1/1000 ); very rare ( ≤1/10,000 ), not known (cannot be estimated from the available data).
Blood and the lymphatic system disorders
Frequency not known: autoimmune haemolytic anaemia (see section c, Information characterising individual serious and/or frequently occurring adverse reactions), anaemia, hypoplasia bone marrow, haematocrit decreased, thrombocytopenic purpura, temporary lowering of the white blood cell count (leukopenia) with a risk of infection, sepsis, and disseminated intravascular coagulation.Rare: agranulocytosis, aplastic anaemia, eosinophilia, neutropenia, pancytopenia
Immune system disorders
Frequency not known: anaphylaxis
Metabolism and nutritional disorders
Frequency not known: glucose intolerance in diabetic patients, hyponatraemia
Frequency not known: nervousness
Nervous system disorders
Frequency not known: aseptic meningitis, blurred vision, convulsions, dizziness, drowsiness, headache and insomnia
Frequency not known: eye irritation, reversible loss of colour vision
Ear and labyrinth disorders
Frequency not known: ear pain
Frequency not known: palpitations
Frequency not known: hypotension
Respiratory, thoracic and mediastinal disorders
Frequency not known: asthma, dyspnoea
Frequency not known: abdominal pain, diarrhoea (see section c, Information characterising individual serious and/or frequency occurring adverse reactions) and nausea with or without vomiting.Less frequent: anorexia, colitis, constipation, dyspepsia, enterocolitis, flatulence, gastric ulceration with or without haemorrhage, pancreatitis, steatorrhoea
Frequency not known: borderline elevations of one or more liver function tests, cholestatic jaundice.Less frequent: mild hepatotoxicity, hepatitis, hepatorenal syndrome
Skin and subcutaneous tissue disorders
Frequency not known: angioedema, laryngeal oedema, erythema multiforme, face oedema, Lyell's syndrome (toxic epidermal necrolysis), perspiration, rash, Stevens-Johnson syndrome, photosensitivity reaction and urticaria
Renal and urinary disorders
Frequency not known: allergic glomerulonephritis, acute interstitial nephritis, dysuria, haematuria, nephrotic syndrome, non-oliguric renal failure (particularly in dehydration), proteinuria, renal failure including renal papillary necrosis
Very rare: multi-organ failure, pyrexia
c) Information characterising individual serious and/or frequently occurring adverse reactions
Reversible haemolytic anaemia: Reports are associated with ≥12 months of mefenamic acid therapy and the anaemia is reversible with discontinuation of treatment.Diarrhoea: Although this may occur soon after starting treatment, it may also occur after several months of continuous use. If diarrhoea persists then inflammatory bowel disease should be excluded; if present mefenamic acid must be stopped.Note: A positive reaction in certain tests for bile in the urine of patients receiving mefenamic acid has been demonstrated to be due to the presence of the drug and its metabolites and not to the presence of bile.
d) Adverse reactions which may not have been observed but which are generally accepted as being attributable to other NSAIDs
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm, or dyspnoea or (c) assorted skin disorders including rashes of various types, pruritus, urticaria, purpura, angioedema, and more rarely exfoliative or bullous dermatoses, including epidermal necrolysis, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme and Stevens-Johnson syndrome.Neurological and special senses: Visual disturbances, optic neuritis, paraesthesia, reports of aseptic meningitis (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 (see section 4.4, Special warnings and precautions for use), depression, confusion, hallucinations, tinnitus, vertigo, malaise, fatigue and drowsiness.Cardiovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4, Special warnings and precautions for use).Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4, Special warnings and precautions for use). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed.
Additional information on special populations
Elderly or debilitated patients seem to tolerate gastrointestinal ulceration or bleeding less well than other individuals and most spontaneous reports of fatal GI events are in this population. Renal toxicity has been seen in patients with pre-renal conditions leading to a reduction in renal blood flow or blood volume. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and the elderly.
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
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