Nonsteroidal Anti-inflammatory Drug (NSAID) Toxicity Treatment & Management

Updated: Oct 21, 2021
  • Author: Timothy J Wiegand, MD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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Approach Considerations

Management of acute nonsteroidal anti-inflammatory drug (NSAID) poisoning is essentially supportive and symptomatic. Initial stabilization consists of securing the airway, breathing, and circulation (ABCs).

For gastrointestinal (GI) decontamination, syrup of ipecac is no longer recommended and should not be administered for NSAID overdose in any circumstances. If the patient has no clinical evidence of a perforated viscous, decontaminate with activated charcoal (AC). The patient should be able to protect airway (eg, normal mental status, preserved gag reflex, absence of vomiting) in order to prevent aspiration of charcoal.

Activated charcoal may not be warranted in patients presenting later than 1-4 hours post ingestion. No evidence exists that empiric administration of activated charcoal in drug overdose improves clinical outcome.

Orogastric lavage may be indicated in massive overdoses after recent exposure, especially in the patients that are intubated.

No specific antidotes for NSAID poisoning exist. Patients with significant toxicity who develop severe acidosis may require supportive treatment with intravenous sodium bicarbonate.

Hemodialysis may be considered for the correction of severe acidosis. Because NSAIDs are highly protein bound, hemodialysis may not help clear the drug from the blood, but it may be indicated in patients who develop acute kidney injury as a complication of the ingestion. Acute renal failure is usually corrected after a few days.

There is no role for urinary alkalinization or forced diuresis in the setting of NSAID toxicity or overdose. Use of sodium bicarbonate to treat metabolic acidosis depends upon the etiology and patient characteristics. Careful attention to the patient’s volume status and renal function during hydration is essential to avoid iatrogenic complications, particularly in patients with adverse drug reactions and medical comorbidities that may have predisposed them to NSAID toxicity such as congestive heart failure.

Sodium bicarbonate is not a specific antidote for NSAID toxicity; however, it should be considered in addition to other supportive cares in an acidotic patient. Transient acidosis in mild-moderate NSAID toxicity typically is self-limited and improves rapidly. Lactic acidosis in the setting of tissue hypoperfusion and multisystem organ failure may be refractory to bicarbonate administration and aggressive supportive cares aimed at restoring normal tissue oxygenation and perfusion are key. Hemodialysis against an alkaline bath may facilitate correction of acid-base and electrolyte abnormalities as well as facilitate management of volume status in the critically ill patient.

Extracorporeal membrane oxygenation (ECMO) has been used successfully to treat refractory hypotension from massive ibuprofen overdose. [7]

Seizures induced by NSAIDs tend to be short lived. Seizures should be treated with benzodiazepines or with other GABAergic drugs such as barbiturates or propofol.

Consider admission for all significant ingestions of mefenamic acid (Ponstel) or meclofenamate (Meclomen), whether the patient is symptomatic or not. Symptomatic patients with ingestion of the less toxic NSAIDs (eg, ibuprofen) should be observed for 6 hours and may be safely discharged (or cleared for psychiatric assessment in cases of intentional overdose) if there is no evidence of toxicity (eg, GI symptoms, change of mental status, acidosis).

Patients with signs of GI bleeding, such as hematemesis, or guaiac-positive stools, may require endoscopic evaluation.

Significant alteration in level of consciousness may require endotracheal intubation and admission to a critical care unit. Significant metabolic acidosis and episodes of acute renal failure have been reported.

Psychiatric evaluation is necessary for intentional ingestions.

Asymptomatic patients who have ingested a less-toxic NSAID may be discharged and followed on an outpatient basis if they are reliable. Psychiatric evaluation is necessary for intentional ingestions.



Consult the regional poison control center (800-222-1222) for additional information and patient care recommendations. Medical toxicologists – ABMS (American Board of Medical Subspecialties) certified physicians are on-call to assist with patient management through the regional poison control center.



Practitioners should avoid prescribing high-dose NSAIDs to patients at high risk of complications. Risk factors include the following:

  • Advanced age
  • Alcoholism, diabetes, or other chronic medical conditions
  • Active gastric ulcer disease
  • Use of medications that may impair renal flow (eg, ACE inhibitors, cotrimoxazole)

Practitioners can also prevent toxic effects of NSAIDs by searching for alternative medications for relief of pain and inflammation or suggesting alternative methods of pain relief, such as acupuncture or other physical/rehabilitation therapies. The American College of Rheumatology recommends acetaminophen for the treatment of mild to moderate osteoarthritis pain. Other alternatives are topical capsaicin or topical NSAIDs (for hand arthritis) and tramadol.

Patients should be advised to consult product labels when using over-the-counter analgesics, in order to avoid exceeding recommended doses, which could occur when using two products containing the same ingredients or the same class of drug at the same time. As with paracetamol in the United Kingdom, limits on amount of NSAID purchased at one time and differences in packaging can possibly prevent toxicity from acute ingestion of NSAIDs.

A meta-analysis of strategies for preventing gastrointestinal toxicity from NSAIDs found that the risk ratio (RR) for each approach was as follows [8] :

  • Selective cyclooxygenase 2 (COX-2) inhibitor plus proton pump inhibitor (PPI): Ulcer complications RR, 0.07
  • Selective COX-2 inhibitor: Ulcer complications RR, 0.25; symptomatic ulcer RR, 0.12
  • Nonselective NSAID plus PPI: Ulcer complications 0.28,; symptomatic ulcer 0.11
  • Nonselective NSAID plus misoprostol: Ulcer complications RR, 0.47; symptomatic ulcer RR, 0.41