Summary for UKPID

    Mefenamic acid

    Dr Alan Worsley Bsc(hons) PhD MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information


    Mefenamic acid

    Type of product

         A non steroidal anti-inflammatory drug.


    Mefenamic acid      Tablets 500mg
                        Capsules 250mg & 500mg
                        Paediatric Suspension 50mg/5ml


         The fatal dose is not known. The minimum amount which has been
         reported to cause convulsions is 2.5g in a 12 year old girl.


         Convulsions are the main feature of acute overdosage. Most
         patients have only one fit but some have several. Convulsions may
         be preceeded by agitation and twitching.

         Vomiting and diarrhoea may occur but are seldom a serious
         problem. In most cases all features of acute toxicity will have
         been resolved with 12 hours.

         Rarely, acute renal failure and hypoprothrombinaemia may develop.


    1.   Give oral activated charcoal to adults who have ingested more
         than 2.5g

    2.   Do not use emetics due to the possible rapid onset of

    3.   Children who have ingested more than 25mg/kg should be given
         activated charcoal.

    4.   Single, brief convulsions do not require treatment, but if they
         are prolonged or recurrent, they should be controlled with
         intravenous diazepam.

    5.   Observe the patients for at least 12 hours.

    6.   Other measures as indicated by the patients clinical conditions.


    Smolinske SC et al
    Toxic effects of non steroidal anti-inflammatory drugs in overdose.
    Drug safety (1990) 5: 252-274

    McKillop G & Canning GP
    A case of intravenous and oral mefenamic acid poisoning.
    Scot Med J (1987) 32 : 81-82

    Shipton EA & Muller FO
    Severe mefenamic acid poisoning. A case report.
    SA Med J (1985) 67: 823-4

    Court H & Volans GN
    Poisoning after overdosage with non steroidal anti-inflammatory drugs.
    Adv Drug. React. Pois. Rev. (1984) 3: 1-21

    Gossinger H et al
    Coma in mefenamic acid poisoning
    Lancet (1982) 2: 384

    Balali-Mood et al
    Mefenamic acid overdosage
    Lancet (1981) 1: 1354-6


         proprietary name:- Ponstan, Ponstan Forte

    Chemical group/family

         Non steroidal Anti-inflamatory
         BNF 10.1.1

    Reference Number1

         (CAS) 61-68-7 (mefenamic acid)


         Lambert Court,
         Chestnut Ave,
         SO53 3ZQ

         Tel 01703 620500


         mefenamic acid 250mg, 500mg tablets
         mefenamic acid 50mg/5ml oral suspension

    Physico-chemical properties: (Dollery)3

         N-(2,3-Xylyl) anthranilic acid

    Molecular weight:        241.3

    pKa                      4.2

         in alcohol          1 in 185
         in water            practically insoluble

    Hazard /risk classification




         Mild to moderate pain in rheumatoid arthritis (including juvenile
         arthritis), osteoarthritis, and related conditions.

         Dysmenorrhoea and menorrhagia.

    Therapeutic Dosage (BNF)6


    Adults                   500mg three times daily

    Child over 6 months      25mg/kg daily in divided doses for not longer
                             than 7 days except in juvenile arthritis.


    Gastro-intestinal ulceration or bleeding.
    History of hypersensitivity precipitated by aspirin or other NSAIDs.
    Also specifically inflamatory bowel disease; blood tests required
    during long term treatment.


    Caution should be used in patients with GI upset/ bleeding, asthma and
    patients with renal and hepatic impairment.


    Oral absorption               >90%
    Presystemic metabolism        0
    Volume of distribution        1.3l/kg
    Plasma half life
         range                    3-4h
    plasma protein binding        99%

    Adverse effects

    Drowsiness, dizziness, skin rashes, diarrhoea, thrombocytopaenia,
    haemolytic anaemia.


    Mefenamic acid was used as a tocolytic in a double blinded randomised
    human study. Compared to controls, preterm delivery occured less in
    the mefenamic acid group (15% vs 40% p<0.005), and birth weights were
    higher. No adverse effects were observed in the newborns exposed in
    utero to mefenamic acid (Mital P et al J R Soc Health 1992 ;112:

    Constriction of the ductus arteriosus in utero is a pharmacological
    consequence arising from the use of prostaglandin synthesis inhibitors
    during pregnancy, as is inhibition of labour, prolongation of
    pregnancy, and suppression of renal function. Persisitent pulmonary
    hypertension of the newborn may occur if these agents are used in the
    3rd trimester close to delivery ( Levin DL Semin.Perinatol.
    1980;4:35-44). Women attempting to conceive should not use any
    prostaglandin synthetase inhibitor, including mefenamic acid , because
    of the findings in a variety of animal models that indicate these
    agents block blastocyst implantation (Matt DW et al. Reproductive
    toxicology. 2nd Edn. New York Raven Press.1995:175-93, Dawood MY. Am J
    Obstet Gynecol. 1993; 169:1255-65 )

    Breast Milk4

    Small amounts of mefenamic acid are excreted into breast milk and
    absorbed by the nursing infant (Buchanan RA et al. Curr Ther Res Clin
    Exp. 1968;10:592-6). Ten nursing mothers were given mefenamic acid
    500mg oral loading dose, followed by 250mg three times daily. The
    averages of mean daily concentrations of mefenamic acid in maternal
    plasma and milk were 0.94 microg/ml and 0.17microg/ml, respectively,
    corresponding to a milk:plasma ration of 0.18. The mean infant blood
    concentration of mefenamic acid was 0.08 microg/ml.



    Excretion of lithium may be reduced by concurrent use of mefenamic

    Oral anticoagulants

    Slight potentiation of oral anticoagulants is documented but rarely

    Albumen bound drugs
    Mefenamic acid binds strongly to plasma proteins and competition for
    non-specific binding sites on plasma albumen may occur.


    NSAIDs probably act by inhibiting prostaglandin synthesis.
    Prostaglandins (Pgs) are believed to cause vasodilation, increased
    vascular permeability, and increased sensitivity of nerve endings to
    other inflammatory mediators. By reversible inhibitio of the enzyme
    cyclo-oxygenase, NSAIDs block the conversion of the arachidonic acid
    found in the cell membrane phospholipids into various PGs.
    Since PGs appear to maintain the gastric mucosal barrier, NSAID
    inhibition of PG synthesis may be the cause of the gastritis, peptic
    ulceration, and gastrointestinal bleeding observed with NSAIDs.

    NSAIDs cause sodium retention, especially in patients with underlying
    sodium retaining states such as congestive heart failure. Although the
    mechanism is not entirely clear, the inhibition of PG synthesis plays
    a leading role. These compounds redistribute renal blood flow away
    from the superficial cortical glomeruli to the juxtamedullary
    glomeruli, which have a greater capacity to absorb sodium.


    There are no data available on the epidemiology of poisoning with
    mefanamic acid. Cumulative data is available on the non steroidal
    anti-inflammatory drugs in general. Mefanamic acid is often prescribed
    to adolescent women for gynaecological problems, endometreosis etc.
    Overdose with this drug has often been associated with this section of
    the population.


    Range of toxicity (Poisindex)

    Toxic Levels

    Mean plasma mefenamic acid levels at hospital admission were higher in
    patients with seizures (73+/- 46mcg/mL) than in patients without
    seizures (38+/-24mcg/mL)

    Fatal Level

    Not Known



    Acute overdose

    Most cases of NSAID overdose develop no effects or mild effects
    consisting of lethargy and gastrointestinal upset. However convulsions
    are a feature of acute overdosage with mefenamic acid and occur in
    about one third of cases.

    Low gradew fever, hypotension, and sinus tachycardia have been noted
    in both overdose, and therapeutic use of NSAIDs.

    Metabolic acidosis occurs rarely in overdose, usually in conjunction
    with seizures.


    A 4 year old, concurrently taking cephalexin, noscapine, and mefenamic
    acid, experienced hypothermia to 34.8 degrees C, and irregular
    respirations 3 hours after ingesting 4ml of mefenamic syrup. rewarming
    with an electric blanket resulted in a temperature of 36 degrees C 7
    hours later (Anon 1989).


    Seizures have been reported in up to 38% of cases, with a mean onset
    of 4.4hours (range 0.5 to 12 hours), often preceded by muscle
    twitching. The lowest dose reported to cause seizures was 2.5g, and
    the lowest plasma level reported was 46mcg/ml. Other neurological
    findings include dyskinesias (one case), agitation and restlessness
    (one case ), altered mental status, and coma (two cases).
    The mean time from ingestion to seizures is 4.4 hours, with a range of
    0.56 to 12 hours.


    1. Incidence. In 29 patients with significant ingestion i.e plasma
    concentration greater than 10mcg/ml, seizures occured in 11 (38%)7.

    2. Onset. The mean time from ingestion to seizure is 4.4hours, witha
    range of 0.56 to 12hours8.

    3. Dose. Lowest dose ingested to cause seizures was 2.5g in a 12yr
    old. Four patients ingesting 5g or less had seizures8.


    Nausea, vomiting, epigastric pain, erosive oesophagitis, pancreatitis
    and gastrointestinal bleeding have been associated with therapeutic
    and/or overdose of NSAIDs10.


    Case report 1. Haematemesis, vomiting and diarrhoea were reported
    folowing oral ingestion of 20 tablet (5 g) in a 22 year old, followed
    by an intravenous injection of 2.25g mefenamic acid mixed with

    Case report 2. Vomiting, abdominal pain and diarrhoea lasted 18 hours
    in a 30 yr old patient after ingesting 12.5g mefenamic acid12.


    Diarrhoea and steatorrhoea have been reported with chronic therapeutic
    Diarrhoea due to proctitis or ileocolitis was reported in 4 patients
    taking mefenamic acid in doses of 500mg two to three times daily for 6
    weeks or longer 14,15.


    Case report. Pancreatitis was reported in a 32 year old after use of  
    mefanamic acid 250mg four times daily16.


    Acute renal failure, uraemia and nephrotic syndrome have occurred with
    both acute overdose and chronic ingestion of most NSAIDs.

    Renal failure.

    Renal failure is not a prominent acute overdose symptom 17,18,19,
    however it has been reported in one case12.

    Reversible renal failure (non-oliguric) has been reported with
    administration of 12 to 15 g of mefenamic acid over 4 to 5 days 7,20.

    Irreversible renal interstitial nephritis has occured with chronic use

    Renal Papillary Necrosis.

    Case report. Renal papillary necrosis has been described in a 47 yr
    old who ingested mefenamic acid for 10 years and a 58 year old who
    took 10 capsules per week for 10 years 22.

    Interstitial Fibrosis.

    Case report. A child aged 13 with a history of focal segmental
    glomerulosclerosis developed renal impairment 8 months after mefenamic
    acid 750mg per day. Fibrosis was suspected, but not confirmed by
    biopsy 23.


    Anaphylactoid reactions have been associated with therapeutic
    ingestion of mefenamic acid, tolmetin, sulindac, ketorolac,
    fenoxopren, naproxen, but have not bee reported following acute


    1.   Dose of activated charcoal within 1-2 hours of ingestion, or
         empty the stomach.

    2.   Treatment is systematic and supportive.

    3.   Seizures-administer diazepam 5-10mg I/V every 15minutes PRN up to

    4.   Monitor vital signs

    5.   Hypotension- administer IV fluids

    6.   Monitor for sins of gastrointestinal ulceration and haemorrhage.

    7.   There is no evidence to suggest that enhanced elimination is of


    Plasma NSAID levels are insufficiently studied to be clinically
    useful. Monitor the patients acid-base balance. Fluid and electrolyte
    imbalances have been reported.


    Case Reports

    1.   A 19yr old female took 12.5g mefenamic acid and developed status
         epilepticus three hours later. She received 10ml paraldehyde i/m
         and recovered 24.

    2.   A study of 54 patients who ingested 1.5g to 50g mefenamic acid 1
         to 18 hours prior to hospital admission, reported that of the 29
         patients whose plasma concentrations were greater than 10mcg/ml,
         14 were symptom free. Muscle twitching was observed in 15
         patients and grand mal seizure in 11 patients. One to eleven
         hours after ingestion the plasma concentration of mefenamic acid
         ranged from 11 to 148mcg/ml. Patients with twitching and seizures
         generally had concentrations above a line joining 100mcg/ml at 2
         hour post ingestion and 15mcg/ml at 15hours. Three patients had
         seizures at serum levels below this line.


    Dr Alan Worsley Bsc(hons) PhD MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph was produced by the staff of the Newcastle Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Peer review was undertaken by the Directors of the UK National Poisons
    Information Service.

    Last updated September 1997


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    2.   ABPI data sheet Compendium. Datapharm publications Ltd. 1995-6

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    4.   Briggs G G et al. Drugs in pregnancy and lactation. Update Vol 8
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    5.   British National Formulary. No32 (sept 1996) section 10.1

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         overdose. Lancet (1981); 1:1354-56

    8.   Court H et Volans GN. Poisoning after overdose with non-steroidal
         and anti-inflammatory drugs. Adv Drug React Ac Pois

    9.   Gossinger H, Hruby K, Haubenstock A et al. Coma in mefenamic acid
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    10.  De Caestecker JS et Heading RC. Iatrogenic oesophageal ulceration
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    12.  Turnbull AJ, Campbell P et Hughes JA . Mefenamic acid
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    14.  Phillips MS, Fehilly B Stewart S et al. Enteritis and colitis
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    16.  Van Walraven AA, Edels M et Fong S. Pancreatitis caused by
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    17.  Venning V, Dixon AJ et Oliver DO. Mefenamic acid nephropathy.
         Lancet (1980);2:745-746

    18.  Malik S, Arthurton I, Griffith ID. Mefenamic acid nephropathy.
         Lancet (1980);2:746

    19.  Robertson CE, Ford MJ et Van Someren V. Mefenamic acid
         nephropathy. Lancet (19800;2:232-233

    20.  Reynolds JEF (Ed);Martindale:The Extra Pharmacopoeia(1990)

    21.  Boletis J, Williams AJ, Shortland JR et al. Irreversible renal
         failure following mefenamic acid. Nephron(1989);51:575-576

    22.  Segasothy M, Thyaparan A, Kamal A et al. Mefenamic acid
         nephropathy. Nephron(19870;45;156-157

    23.  Itami N, Akutsu Y, Yasoshima K et al. Progressive renal failure
         despite discontinuation of mefenamic acid. Nephron

    24.  Young R J. Mefenamic acid poisoning and epilepsy. BMJ (1979); 2:

    See Also:
       Toxicological Abbreviations