Oral Mild to moderate pain, Osteoarthritis, Rheumatoid arthritis
Adult: 500 mg tid. Alternatively, initiate at 500 mg, followed by 250 mg 6 hourly as necessary, usually not more than 1 week. Use the lowest effective dose for the shortest possible duration. Child: As oral susp: >6 months to <2 years 25 mg/kg daily in divided doses or 50 mg 1-3 times daily; 2-<5 years 100 mg 1-3 times daily; 5-<9 years 150 mg 1-3 times daily; 9-<12 years 200 mg 1-3 times daily. As tab or cap: ≥12 years Same as adult dose. Use the lowest effective dose for the shortest possible duration. Max treatment duration: 7 days (except in the treatment of systemic onset juvenile chronic arthritis). Treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Elderly: Use the lowest effective dose for the shortest possible duration.
Oral Menorrhagia, Primary dysmenorrhoea
Adult: 500 mg tid. Alternatively, initiate at 500 mg, followed by 250 mg 6 hourly. Start treatment at the onset of excessive bleeding or menstrual pain. Use the lowest effective dose for the shortest possible duration.
Oral Fever
Child: As oral susp: >6 months 25 mg/kg daily in divided doses. Use the lowest effective dose for the shortest possible duration. Max treatment duration: 7 days. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Hypersensitivity to mefenamic acid; history of hypersensitivity reaction (e.g. asthma, rhinitis, angioedema, urticaria) to aspirin or other NSAIDs. Inflammatory bowel disease, history of gastrointestinal bleeding or perforation related to previous NSAID therapy, active gastrointestinal ulceration or bleeding, history of recurrent peptic ulcer disease or haemorrhage (≥2 distinct episodes of proven ulceration or bleeding), severe heart failure. Use in the setting of CABG surgery. Severe renal and hepatic impairment. Pregnancy (3rd trimester).
Special Precautions
Patient with risk factors for CV disease (e.g. hyperlipidaemia, diabetes mellitus, smoking), hypertension, CHF, established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, other forms of asthma, oedema, coagulation disorder, intracranial haemorrhage, history of ulcer (particularly if complicated with haemorrhage or perforation), SLE, mixed connective tissue disorder, epilepsy, hypovolaemia. Patient undergoing surgery or dental procedures. Dehydrated and debilitated patients. Concomitant use with oral corticosteroids, SSRIs, antiplatelets, anticoagulants, diuretics, or ACE inhibitors. Consider discontinuation in women who have difficulties conceiving or those undergoing investigation of infertility. May mask signs and symptoms of infection. Mild to moderate renal and hepatic impairment. Children and elderly. Pregnancy (1st and 2nd trimester) and lactation.
Adverse Reactions
Significant: Na and fluid retention, diarrhoea, new-onset or worsening of hypertension, hyperkalaemia; renal papillary necrosis and other renal injury (prolonged use); may impair female fertility (prolonged use); aseptic meningitis (particularly in patients with autoimmune disorders), decreased platelet adhesion and aggregation, anaemia. Rarely, potentially severe blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia). Cardiac disorders: Cardiac failure, palpitations. Ear and labyrinth disorders: Ear pain, vertigo, tinnitus. Eye disorders: Blurred vision, reversible loss of colour vision, eye irritation. Gastrointestinal disorders: Nausea, vomiting, dyspepsia, constipation, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of Crohn's disease and colitis, pancreatitis, steatorrhoea, enterocolitis. General disorders and administration site conditions: Fatigue, malaise, pyrexia. Investigations: Elevated LFTs. Metabolism and nutrition disorders: Glucose intolerance (in diabetic patients), hyponatraemia, anorexia. Nervous system disorders: Headache, dizziness, drowsiness, paraesthesia, convulsions. Psychiatric disorders: Depression, confusion, hallucinations, nervousness, insomnia. Renal and urinary disorders: Dysuria, haematuria, cystitis. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, photosensitivity reaction, alopecia, perspiration. Vascular disorders: Hypotension. Potentially Fatal: CV thrombotic events (including MI and stroke), gastrointestinal inflammation, bleeding, ulceration, or perforation; bronchospasm (in patients with aspirin-sensitive asthma). Rarely, severe anaphylactic-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) or multiorgan hypersensitivity reactions, exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis or failure).
PO: C, Z (NSAIDs caused foetal ductus arteriosus premature closure, foetal renal impairment and persistent pulmonary hypertension. Avoid near term, else use lowest dose for shortest time.)
Patient Counseling Information
This drug may cause drowsiness, dizziness, and blurred vision, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor CBC, occult blood loss, chemistry profile, and LFTs (periodically); renal function (urine output, serum BUN and creatinine). Closely monitor blood pressure during initiation and throughout treatment. Observe for signs and symptoms of gastrointestinal bleeding.
Overdosage
Symptoms: Lethargy, drowsiness, headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding. Rarely, diarrhoea, disorientation, excitation, tinnitus, fainting, hypertension, respiratory depression, acute renal failure, and coma; occasionally, convulsions. Management: Symptomatic and supportive treatment. Induce emesis or perform gastric lavage, then administer activated charcoal. Ensure good urine output. Closely monitor renal and hepatic function. Observe for at least 4 hours following ingestion. In case of frequent or prolonged convulsions, administer IV diazepam.
Drug Interactions
May increase the risk of bleeding with other NSAIDs or salicylates (e.g. aspirin), anticoagulants (e.g. warfarin), antiplatelet agents, corticosteroids, and SSRIs. May enhance the nephrotoxic effect of ciclosporin or tacrolimus. May reduce the effects of antihypertensive agents (e.g. ACE inhibitors, angiotensin II antagonists, β-blockers), diuretics (e.g. furosemide, thiazides), and mifepristone (consider avoiding mefenamic acid for at least 8-12 days after mifepristone use). May increase the plasma concentration of cardiac glycosides, lithium, aminoglycosides, and methotrexate. May prolong the half-life of oral hypoglycaemic agents, increasing the risk of hypoglycaemia. Metabolism and elimination may be reduced with probenecid. May increase the risk of haematological toxicity with zidovudine.
Food Interaction
May increase the risk of gastrointestinal bleeding, ulceration, or perforation with alcohol.
Lab Interference
May give a false-positive result in urinary bilirubin using the diazo tab test. May result in a false-positive aldosterone/renin ratio (ARR).
Action
Description: Mefenamic acid, an anthranilic acid derivative, is an NSAID with analgesic and antipyretic properties. It reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes resulting in decreased formation of prostaglandin precursors. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: 2-4 hours. Distribution: Enters breast milk (small amounts). Volume of distribution: 1.06 L/kg. Plasma protein binding: >90% to albumin. Metabolism: Predominantly metabolised in the liver by CYP2C9 isoenzyme into 3-hydroxymethyl mefenamic acid, which may be oxidised further into 3-carboxymefenamic acid; both metabolites undergo secondary conjugation to form glucuronides. Excretion: Via urine (approx 52%; 6% as unchanged drug, 25% as 3-hydroxymethyl mefenamic acid, 21% as 3-carboxymefenamic acid); faeces (approx 20%, mainly as unconjugated 3-carboxymefenamic acid). Elimination half-life: Approx 2-4 hours.
Chemical Structure
Mefenamic acid Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4044, Mefenamic acid. https://pubchem.ncbi.nlm.nih.gov/compound/Mefenamic-acid. Accessed Sept. 27, 2022.
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