- USES: Mefenamic acid is a nonsteroidal antiinflammatory drug (NSAID) used for dysmenorrhea, pain control and various rheumatological conditions. PHARMACOLOGY: Mefenamic acid inhibits the cyclooxygenase enzyme, leading to decreased prostaglandin production and decreased pain and inflammation. TOXICOLOGY: Gastrointestinal (GI) symptoms are due to both local irritant effects and the inhibition of prostaglandins (PG), which are responsible in part for maintaining the GI mucosal barrier. Inhibition of thromboxane A2 production in platelets prolongs bleeding time and contributes to GI bleeding. Inhibition of PGI2 and PGE2, which have vasodilatory and natriuretic activity in the kidney, can be linked to sodium and water retention and occasional acute renal failure. The specific mechanism of mefenamic acid-induced seizures is unknown. EPIDEMIOLOGY: Due to its poor safety profile, mefenamic acid has largely been replaced with safer NSAIDs. Therefore, overdose is rare; however, severe toxicity may result from overdose. MILD TO MODERATE TOXICITY: In general, patients are asymptomatic or have mild gastrointestinal upset (ie, nausea, vomiting, abdominal pain). Symptoms typically occur within 4 to 6 hours of ingestion. SEVERE TOXICITY: With severe overdose, coma, renal failure, and, rarely, cardiopulmonary arrest may occur. Seizures are a common finding (38%) following overdose (mean onset is 4.4 hours [range 0.5 to 12 hours]); muscle twitching (usually precedes seizures), gastrointestinal effects (vomiting, hematemesis, diarrhea, and abdominal pain), dyskinesias, agitation, coma, and restlessness may occur. Hypertension, acute lung injury, and metabolic acidosis have also developed. Symptoms typically occur within 4 to 6 hours of ingestion. ADVERSE EFFECTS: Nausea, vomiting, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, GI ulcer, abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headache, increased bleeding time, pruritus, rashes, and tinnitus have been reported in up to 10% of patients taking mefenamic acid or other NSAIDs. Cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, and acute renal failure have rarely been reported. Other rare effects include anaphylactoid reactions, cardiovascular effects, respiratory depression, pneumonia, various dermatological effects (eg, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria, angioedema, fixed drug eruption, pseudoporphyria, and toxic epidermal necrolysis), and hematologic abnormalities (eg, hemolytic anemia, agranulocytosis, pancytopenia, thrombocytopenic purpura, bone marrow aplasia). One case of pancreatitis has been reported after therapeutic use.
Range of Toxicity:
- TOXICITY: ACUTE: CHILD: lowest dose reported to cause seizures was 2.5 grams in a 12-year-old; ADULT: lowest dose to cause coma and seizures was 3.5 grams. CHRONIC: ADULT: renal failure occurred following 12 to 15 grams over 4 to 5 days. THERAPEUTIC DOSES: Initial dose, 500 mg, followed by 250 mg every 6 hours. CHILDREN: Safety and efficacy for children younger than 14 years have not been established. For age 14 years and older, initial dose, 500 mg, followed by 250 mg every 6 hours.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Most NSAID toxicity resolves with supportive care to include fluid and electrolyte replacement. MANAGEMENT OF SEVERE TOXICITY: Maintain an open airway and support ventilation. Treat seizures with benzodiazepines, hypotension with fluids and adrenergic vasopressors, and coma with intubation. Monitor the patient’s CNS, renal, and acid/base function following a significant overdose.
- Decontamination: PREHOSPITAL: Activated charcoal can be given to patients with significant overdose who are alert and can protect their airway. HOSPITAL: Activated charcoal binds mefenamic acid and should be administered after significant overdose. Gastric lavage is generally not indicated, as this drug is absorbed rapidly and severe toxicity is exceedingly rare.
- Airway management: Endotracheal intubation should be considered for patients who develop CNS depression or recurrent seizures (rare).
- Antidote: None.
- Enhanced elimination procedure: Mefenamic acid is highly protein-bound; hemodialysis is unlikely to be effective.
- Monitoring of patient: Plasma concentrations are not readily available or clinically useful in the management of overdose. Monitor serum electrolytes in patients with significant vomiting and/or diarrhea. Monitor vital signs and mental status. Monitor liver enzymes and renal function following significant overdose. Monitor patients for gastrointestinal bleeding. If significant CNS or respiratory toxicity is present, assess acid-base status.
- Patient disposition: HOME CRITERIA: Asymptomatic patients with inadvertent ingestions of therapeutic or near-therapeutic doses can be managed at home with mild or water dilution and observation. OBSERVATION CRITERIA: Symptomatic children or adults and adults with deliberate ingestion should be referred to a healthcare facility for observation and treatment. Most patients who have ingested significant amounts of mefenamic acid will manifest symptoms within 4 to 6 hours. ADMISSION CRITERIA: Patients who develop CNS depression, seizures, hypotension, acidosis, or gastrointestinal bleeding should be admitted. CONSULT CRITERIA: Consultation with a medical toxicologist or poison center should be considered for any patient with significant symptoms, renal failure, GI bleeding, acidosis, or seizures.