It is important that the recommended dose is not exceeded and the regime adhered to since some reports have involved daily dosages under 3g.
(a) Symptoms
Symptoms include headache, nausea, vomiting epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, tinnitus, fainting, occasionally convulsions [Mefenamic acid has a tendency to induce tonic-clonic (grand mal) convulsions in overdose]. In 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
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.
Haemodialysis is of little value since mefenamic acid and its metabolites are firmly bound to plasma proteins.
36 months for amber polystyrene bottle
48 months for blister and HDPE DUMA and polypropylene container
Lactose, pregelatinised starch, maize starch, povidone, silicon dioxide, talc, magnesium stearate, croscarmellose sodium type A, sodium laurilsulfate, purified water*, Opadry OY-LS-22808 (H.P.M.C.2910 15cP, lactose, polyethylene glycol 4000, vanillin, E104, E110, E171), Opaglos AG7350 (purified water, beeswax white, carnauba wax yellow, polysorbate 20, sorbic acid).
*not detectable
The most frequently reported side effects associated with mefenamic acid involve the gastrointestinal tract.
Diarrhoea occasionally occurs following the use of mefenamic acid. Although this may occur soon after starting treatment, it may also occur after several months of continuous use. The diarrhoea has been investigated in some patients who have continued this drug in spite of its continued presence. These patients were found to have associated proctocolitis. If diarrhoea does develop the drug should be withdrawn immediately and this patient should not receive mefenamic acid again.
Frequencies are not known for the following adverse reactions:
Blood and the lymphatic system disorders
Haemolytic anaemia*, 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.Agranulocytosis, aplastic anaemia, eosinophilia, neutropenia, pancytopenia, thrombocytopenia.
*reversible when mefenamic acid is stopped
Immune system disorders
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 and erythema multiforme).Metabolism and nutritional disorders
Glucose intolerance in diabetic patients, hyponatraemia.Pyschiatric disorders
Confusion, depression, hallucinations, nervousness.Nervous system disorders
Optic neuritis, headaches, paraesthesia, dizziness, drowsiness, reports of 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.Blurred vision, convulsions, insomnia.
Eye disorders
Eye irritation, reversible loss of colour vision, visual disturbances.Ear and labyrinth disorders
Ear pain, tinnitus, vertigo.Cardiac / Vascular disorders
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).
Palpitations.
Hypotension.
Respiratory, thoracic and mediastinal disorders
Asthma, dyspnoea.Gastrointestinal disorders
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. 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.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.
Anorexia, colitis, enterocolitis, gastric ulceration with or without haemorrhage, pancreatitis, steatorrhea.
Hepato-bilary disorders
Borderline elevations of one or more liver function tests, cholestatic jaundice.Mild hepatotoxicity, hepatitis, hepatorenal syndrome.
Skin and subcutaneous tissue disorders
Angioedema, laryngeal oedema, erythema multiforme, face oedema, bullous reactions including Lyell's syndrome (toxic epidermal necrolysis) and Stevens-Johnson syndrome, perspiration, rash, photosensitivity reaction, pruritus and urticaria.Renal and urinary disorders
Allergic glomerulonephritis, acute interstitial nephritis, dysuria, haematuria, nephrotic syndrome, non-oliguric renal failure (particularly in dehydration), proteinuria, renal failure including renal papillary necrosis.General disorders
Fatigue, malaise, multi-organ failure, pyrexia.Investigations
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.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.
Preclinical safety data does not add anything of further significance to the prescriber.
ANIMAL MODELS
Mefenamic acid is non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic properties.
Its anti-inflammatory effect was first established in the UV erythema model of inflammation. Further studies included inhibition of granulation tissue growth into subcutaneous cotton pellets in rats and carrageenin induced rat paw oedema tests.
Antipyretic activity was demonstrated in yeast-induced pyresis in rats. In this model its antipyretic activity was roughly equal to that of phenylbutazone and flufenamic acid, but less than that of indomethacin.
Analgesic activity was demonstrated in tests involving pain sensitivity of rats paws inflamed by brewers yeast. Mefenamic acid was less potent than flufenamic acid in this model.
Prostaglandins are implicated in a number of disease processes including inflammation, modulation of the pain response, dysmenorrhoea, menorrhagia and pyrexia.
In common with most NSAIDs mefenamic acid inhibits the action of prostaglandin synthetase (cyclo oxygenase). This results in a reduction in the rate of prostaglandin synthesis and reduced prostaglandin levels.
The anti-inflammatory activity of NSAIDs in the rat paw oedema test has been correlated with their ability to inhibit prostaglandin synthetase. When mefenamic acid is ranked in both these tests it falls between indomethacin and phenylbutazone and it is probable that inhibition of prostaglandin synthesis contributes to the pharmacological activity and clinical efficacy of mefenamic acid.
There is also considerable evidence that the fenamates inhibit the action of prostaglandins after they have been formed. They therefore both inhibit the synthesis and response to prostaglandins. This double blockade may well be important in their mode of action.
Absorption and Distribution
Mefenamic acid is absorbed from the gastro intestinal tract. Peak levels of 10 mg/l occur two hours after the administration of a 1g oral dose to adults.
Metabolism
Mefenamic acid is predominantly metabolised by cytochrome P450 enzyme CYP2C9 in the liver, first to a 3 hydroxymethyl derivative (metabolite I) and then a 3 carboxyl derivative (metabolite II). Both metabolites undergo secondary conjugation to form glucuronides.
Therefore in patients who are known or suspected to be poor CYP2C9 metabolisers based on previous history/experience with other CYP2C9 substrates, mefenamic acid should be administered with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.
Elimination
Fifty two percent of a dose is recovered from the urine, 6% as mefenamic acid, 25% as metabolite I and 21% as metabolite II. Assay of stools over a 3 day period accounted for 10-20 % of the dose chiefly as unconjugated metabolite II.
The plasma levels of unconjugated mefenamic acid decline with a half life of approximately two hours.
12/07/2015
Chemidex Pharma Limited
Chemidex House
Egham Business Village
Crabtree Road
Egham
Surrey TW20 8RB
United Kingdom
Store below 30°C.
a) Aluminium foil/pvc blister pack in cardboard carton. Pack sizes: 100
b) HDPE DUMA and polypropylene container. Pack sizes: 100 and 500
c) Amber polystyrene bottle with a high density polyethene anti-arthritic closure. Pack sizes: 6, 12, 84, 100 and 500.
PL 17736/0007
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
Not applicable
10/10/2005
