Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Chemidex Pharma Limited, Chemidex House, Egham Business Village, Crabtree Road, Egham, Surrey TW20 8RB, United Kingdom
Hypersensitivity to mefenamic acid or any of the other ingredients.
Inflammatory bowel disease.
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Severe heart failure, hepatic failure and renal failure (see section 4.4).
Because the potential exists for cross-sensitivity to aspirin, ibuprofen, or other non-steroidal anti-inflammatory drugs, mefenamic acid must not be given to patients who have previously shown hypersensitivity reaction (e.g. asthma, bronchospasm, rhinitis, angioedema or urticaria) to these medicines.
During the last trimester of pregnancy (see section 4.6).
Treatment of pain after coronary artery bypass graft (CABG) surgery.
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).
Patients on prolonged therapy should be kept under regular surveillance with particular attention to liver dysfunction, rash, blood dyscrasias or development of diarrhoea.
Appearance of any of these symptoms should be regarded as an indication to stop therapy immediately (see section 4.8).
Use with concomitant NSAIDs including cyclooxygenase 2 specific inhibitors (see section 4.5).
Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of ‘Medication Overuse Headache’ should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.
Precaution should be taken in patients suffering from dehydration and renal disease, particularly the elderly.
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).
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.
The administration of an NSAID may cause a dose dependant 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).
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 some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for mefenamic acid.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with mefenamic acid after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
As NSAIDs can interfere with platelet function, they should be used in caution in patients with intracranial haemorrhage and bleeding diathesis.
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. Smoking and alcohol use are added risk factors.
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. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for patients at risk of GI bleeding such as the elderly, 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 could increase the risk of gastrotoxicity or bleeding such as corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving mefenamic acid the treatment should be withdrawn.
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).
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with use of NSAIDs (see section 4.8). Patients appear to be at 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. Mefenamic acid should be stopped at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
The use of mefenamic acid 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 mefenamic acid should be considered.
In dysmenorrhoea and menorrhagia lack of response should alert the physician to investigate other causes.
Caution should be exercised when treating patients suffering from epilepsy.
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 (see section 5.2).
Concomitant consumption of alcohol with mefenamic acid may increase the risk of gastrointestinal bleeding, ulceration and perforation.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sunset yellow may cause allergic-type reactions.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Concurrent therapy with other plasma protein binding drugs may necessitate a modification in dosage.
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4). Concurrent administration of mefenamic acid with oral anti-coagulant drugs requires careful prothrombin time monitoring.
It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct medical supervision.
Lithium: a reduction in renal lithium clearance and elevation of plasma lithium levels. Patients should be observed carefully for signs of lithium toxicity.
The following interactions have been reported with NSAIDs but have not necessarily been associated with Ponstan Capsules:
Other analgesics including cyclooxygenase-2 selective inhibitors: avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).
Antidepressants: selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Antihypertensives and diuretics: a reduction in antihypertensive and diuretic effect has been observed. Diuretics can increase the nephrotoxicity of NSAIDs.
ACE inhibitors and angiotensin-II-receptor antagonists: a reduction in antihypertensive effect and an increased risk of renal impairment especially in elderly patients. Patients should be adequately hydrated and the renal function assessed in the beginning and during concomitant therapy.
Aminoglycosides: reduction in renal function in susceptible individuals, decreased elimination of aminoglycoside and increased plasma concentrations.
Anti-platelet agents: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Acetylsalicylic Acid: experimental data implies that mefenamic acid interferes with the anti-platelet effect of low-dose aspirin when given concomitantly, and thus may interfere with aspirin’s prophylactic treatment of cardiovascular disease. However, the limitations of this experimental data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular mefenamic acid use.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Ciclosporin: the risk of nephrotoxicity of ciclosporin may be increased with NSAIDs.
Corticosteroids: concomitant use may increase the risk of gastrointestinal ulceration or bleeding (see section 4.4).
Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia.
Methotrexate: elimination of the drug can be reduced, resulting in increased plasma levels.
Mifepristone: NSAIDs should not be taken for 8-12 days after mifepristone administration, NSAIDs can reduce the effects of mifepristone.
Probenecid: reduction in metabolism and elimination of NSAIDs and metabolites.
Quinolone antibiotics: animal data indicates that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Tacrolimus: possible increased risk of nephrotoxicity when NSAIDS are given with tacrolimus.
Zidovudine: increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV haemaophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.
Trace amounts of mefenamic acid may be present in breast milk and transmitted to the nursing infant. Therefore, mefenamic acid should not be taken by nursing mothers.
The use of mefenamic acid 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 mefenamic acid should be considered (see section 4.4).
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
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 (see section 4.4). 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) (see section 4.4). 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 (see section 4.4). 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 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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