Clinical Effects:

  • USES: Nonsteroidal antiinflammatory drugs (NSAIDs) are used acutely for fever and pain control and for the treatment of several rheumatologic conditions. NOTE: Salicylates, ibuprofen, naproxen, indomethacin, phenylbutazone, mefenamic acid, ketoprofen, and the COX-2 inhibitors (celecoxib, meloxicam, rofecoxib, valdecoxib) are covered under separate managements. PHARMACOLOGY: NSAIDs include at least 20 drugs that share the cyclooxygenase enzyme inhibition leading to decreased prostaglandin production and decreased pain and inflammation. TOXICOLOGY: NSAIDs cause gastrointestinal (GI) irritation directly, and by inhibiting cyclooxygenase 1 (COX-1), which is necessary for the formation of the prostaglandins PG12 and PGE2; decrease in these prostaglandins results in decreased tissue mucus and bicarbonate secretion, increased hydrochloride secretion, and decreased gastric blood flow. The acidosis associated with severe NSAID overdose appears to result from the formation acidic metabolites, and mild hypotension. Prostaglandin inhibition by NSAIDs also causes renal arteriolar constriction, reduced renal blood flow and subsequent renal insufficiency in patients with conditions characterized by high angiotensin and low intravascular volume (eg, congestive heart failure, cirrhosis, hypovolemia). COX-1 inhibition also decreases the formation of thromboxane A2 which is necessary for platelet aggregation, predisposing patients to bleeding. EPIDEMIOLOGY: NSAID overdose is common, but severe toxicity and deaths are very rare. MILD TO MODERATE TOXICITY: Most patients with an NSAID overdose are asymptomatic or have mild GI upset (ie, nausea, vomiting, abdominal pain), and sometimes hematemesis. SEVERE TOXICITY: Massive overdose can cause seizures, delirium, coma, hypotension, renal failure, hepatic dysfunction, hypoprothrombinemia, gastrointestinal bleeding, hyperkalemia and metabolic acidosis. ADVERSE EFFECTS: Dyspepsia, ulceration perforation, GI hemorrhage, acute renal failure, fluid retention, interstitial nephritis, nephrotic syndrome, asthma exacerbation, headache and aseptic meningitis may develop. Agranulocytosis, aplastic anemia, and thrombocytopenia have developed, but appear to be idiosyncratic reactions. VETERINARY/FLURBIPROFEN: Pets exposed to topical pain medications containing flurbiprofen may be at risk of developing significant illness and death. The FDA has received reports of severe illness in several households where pet owners applied the topical medication to themselves (ie, neck and feet). In these cases, it was unclear how the cats became exposed. However, 2 cats in one household developed renal failure and recovered with supportive care and 2 cats in another household developed lethargy, vomiting, melena, and anemia and died despite care.

Range of Toxicity:

  • TOXICITY: The toxic dose varies with each NSAID, but significant symptoms can occur after ingestion of 5 to 10 times the therapeutic dose. THERAPEUTIC DOSE: Varies by agent.


  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Most toxicity related to NSAID exposure resolves with supportive care; otherwise, healthy patients with a history of NSAID poisoning generally require only gastrointestinal decontamination with activated charcoal, and fluid and electrolyte replacement. SEVERE TOXICITY: Endotracheal intubation and mechanical ventilation may be necessary in patients with CNS depression or recurrent seizures. Treat seizures with benzodiazepines, and hypotension with fluids, adding adrenergic vasopressors, if necessary.
  • Decontamination: PREHOSPITAL: Activated charcoal can be given after a large overdose. HOSPITAL: Activated charcoal binds NSAIDs, but is usually not required as severe toxicity is rare. Charcoal should be administered after a large, recent overdose. Gastric lavage is generally not indicated as life threatening toxicity is very rare.
  • Airway management: Intubation and mechanical ventilation should be considered for patients who present with CNS depression.
  • Antidote: None.
  • Monitoring of patient: Measurement of serum concentrations of NSAIDs are widely available, but are not useful in guiding clinical management. Serum electrolytes, creatinine and BUN concentrations should be measured in patients with an intentional overdose. If significant CNS or respiratory toxicity is present, acid-base status should be assessed. Obtain a serum acetaminophen and salicylate concentration. Monitor vital signs.
  • Enhanced elimination procedure: NSAIDs are highly protein bound and extensively metabolized; therefore, hemodialysis is unlikely to be effective.
  • Patient disposition: HOME CRITERIA: Inadvertent exploratory ingestions in asymptomatic children can generally be managed with dilution and observation at home. OBSERVATION CRITERIA: Patients with a large or deliberate ingestion should be observed for 4 to 6 hours. If they remain asymptomatic with normal laboratory evaluation, they may be discharged after appropriate psychiatric evaluation. ADMISSION CRITERIA: Patients who may have ingested a large dose of NSAIDs and who present with CNS or cardiovascular toxicity or metabolic acidosis, or who have a known risk factor for organ system toxicity associated with NSAIDs should be considered at higher risk of complications and warrant admission.