Nonsteroidal Anti-inflammatory Drug (NSAID) Toxicity

Updated: Oct 21, 2021
Author: Timothy J Wiegand, MD; Chief Editor: Gil Z Shlamovitz, MD, FACEP 


Practice Essentials

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been prescribed extensively throughout the world. More than 70 million prescriptions for NSAIDs are written each year in the United States. With over-the-counter use included, more than 30 billion doses of NSAIDs are consumed annually in the United States alone.

Most of the commonly ingested NSAIDs have few toxic effects, even when taken in significant quantities; however, with the numbers of both prescriptions and consumption of over-the-counter (OTC) NSAIDs increasing every year, so do the numbers of overdoses and NSAID-related complications reported to poison control centers around the country. Additionally, adverse events related to drug interactions, or exposure to vulnerable patients with disease states that predispose patients to NSAID toxicity, are common and may result in significant morbidity and mortality.

Most NSAID exposures are mild-to-moderate ingestions with low levels of symptom severity that include general gastrointestinal (GI) symptoms such as nausea and vomiting, and mild chemistry and electrolyte abnormalities that resolve rapidly with supportive care. In large ingestions, some patients may develop an altered level of consciousness evolving to coma with progressive and sometimes refractory metabolic acidosis and evolving multisystem organ failure. See Presentation.

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

For patient education information, see First Aid for Poisoning in Children and Child Safety Proofing.


More than 20 drugs fall under the category of NSAID. The major effect of all NSAIDs is to decrease the synthesis of prostaglandins by reversibly inhibiting cyclooxygenase (COX), an enzyme that catalyzes the formation of prostaglandins and thromboxanes from the precursor, arachidonic acid. This is in contrast to salicylates (eg, aspirin), which irreversibly bind to COX and inhibit production for the entire life of the cell, or acetaminophen, which inhibits COX centrally.

The result of NSAID-induced COX inhibition is decreased production of prostaglandins, which leads to decreased pain and inflammation. CNS, hemodynamic, pulmonary, and hepatic dysfunction may occur with certain agents, but the relationship to prostaglandin production remains uncertain. Prostaglandins are involved in maintaining GI mucosal integrity as well as regulating renal blood flow and both acute and chronic toxicity often involves the GI and renal systems.

Two isoforms of cyclooxygenase have been identified. Cyclooxygenase-1 (COX-1) has been proposed to generate prostaglandins that maintain organ function, protect the integrity of the gastric mucosa, and generate platelet-derived thromboxane responsible for platelet aggregation and vasoconstriction. COX-1 is expressed in all tissues.

Cyclooxygenase-2 (COX-2) is induced during the inflammatory response and produces prostaglandins that mediate pain and inflammation. COX-2 is also expressed in kidneys and vascular endothelium. Classic, older NSAIDs (eg, ibuprofen) inhibit COX-1 more than COX-2, whereas the newer class of NSAIDs (eg, celecoxib) inhibit COX-2 predominantly, decreasing gastrointestinal adverse effects. Selectivity of inhibition may be lost during overdose, however.


Patients who present with acute overdose and are suicidal should be chaperoned at all times while in the emergency department and never left alone for both medical and psychological reasons. A psychiatry consult should be obtained once the patient is medically stable.



United States

The American Association of Poison Control Centers National Poison Data System (AAPCC NPDS) recorded 76,411 single exposures in 2019. In the vast majority of these cases, the NSAID ingested was ibuprofen.[1]

The majority of NSAID ingestions occurred in children. There were 42,980 documented NSAID ingestions in children aged 5 years or younger. This is in contrast to only 16,332 ingestions in adults 20 years or older. Perhaps predictably, given that young children account for the majority of cases, most of the ingestions were documented as unintentional.[1]

The 2019 AAPCC NPDS Annual Report reveals that only 19,792 exposures resulted in treatment in a healthcare facility, perhaps owing to the benign nature of most NSAID adverse effects. Of these individuals who received treatment, the majority had either no significant health outcome or only minor outcomes (see below for further definition of outcomes). However, there were 1741 moderate and 152 major toxicity outcomes—mainly secondary to either naproxen or ibuprofen ingestion. Six deaths resulted from NSAID ingestion: three from colchicine, one from ibuprofen, one from indomethacin, and one from naproxen.[1]

AAPCC NPDS outcomes are defined as follows:

  • None

  • Minor: Minimally bothersome with rapid resolution (eg, self-limited GI symptoms, drowsiness, skin irritation, sinus tachycardia without hypotension)

  • Moderate: More pronounced, more prolonged, or more systemic in nature than minor symptoms; usually, some form of treatment is indicated; symptoms are not life-threatening, and the patient is without residual disability or effect (eg, acid-base disturbance, high fever, hypotension that responds to treatment, isolated brief seizures that respond to treatment)

  • Major: Potentially life-threatening or that results in significant residual disability or disfigurement (eg, seizures with status epilepticus, respiratory compromise requiring endotracheal intubation, ventricular tachycardia with hypotension, cardiac or respiratory arrest)

  • Death

Race-, Sex-, and Age-related Demographics

No scientific evidence has demonstrated that outcomes of NSAID toxicity are based on race or sex. According to the AAPCC NPDS, the majority of NSAID ingestions occur in children, typically age 5 years or younger.[1]  A review of AAPCC data from 2004 to 2013 found that of teenagers who attempted suicide by medication overdose, 9% had taken ibuprofen.[2]


Both acute and chronic poisoning with NSAIDs results in significant morbidity and mortality. The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) system has estimated that more than 100,000 hospitalizations and more than 16,000 deaths in the United States each year are due to NSAID-related complications, with costs greater than $2 billion. Gastrointestinal (GI), renal, central nervous system (CNS), hematologic, and dermatologic symptoms may ensue. Complications of NSAIDs differ with acute ingestions and long-term therapy.

Acure complications

With acute ingestion, GI symptoms typically predominate, with dyspepsia being the most common. Peptic ulceration and its complications are relatively rare. Gastrointestinal adverse effects are due to inhibitory action on cyclooxygenase. Risk of adverse GI effect increases with increased dose and duration of NSAID therapy as well as with age, history of previous GI ulcers or bleeding, presence of untreated H pylori, concurrent use of anticoagulants, SSIRs, and glucocorticoids. Hepatotoxicity is uncommon, although transient elevation of hepatic transaminase levels may occur.

Renal effects are the second most common problem.[9, 10]  Typically, these include salt and water retention. Hyperkalemia and acute kidney injury are less common and are reversible in the most instances. Acute interstitial nephritis, nephrotic syndrome, and papillary necrosis occur much less often than other renal symptoms. Elderly persons and individuals with underlying kidney problems or decreased intravascular volume from salt loss or hypoalbuminemia are at particular risk.

Concomitant use with aspirin may negate the beneficial cardiovascular effects of aspirin. NSAIDs can exacerbate underlying hypertension and heart failure.

Dermatologic lesions include generalized exanthems, pruritus, and, rarely, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Hematologic complications are rare but have been described. Accounts of patients with subsequent aplastic anemia, agranulocytosis, hemolytic anemia, neutropenia, and thrombocytopenia exist.

CNS effects are relatively common with NSAID toxicity. They include changes of mood and cognition (especially in elderly persons), seizures, headaches, and hallucinations. They are most frequent with the highly lipid-soluble NSAIDs such as ibuprofen, naproxen, and ketoprofen. With chronic use, urinary retention can occur. Aseptic meningitis has been reported secondary to NSAIDs.[11]

Adverse effects of long-term therapy

Many practitioners prescribe NSAIDs regularly for treatment of chronic conditions such as osteoarthritis and rheumatoid arthritis, and acute musculoskeletal injuries. With NSAIDs readily available in pharmacies, supermarkets, even liquor stores, many patients take these drugs assuming there is no real chance of damage.

The most common complications of chronic therapy with NSAIDs are gastrointestinal.[12]  Most of the deaths reported by the ARAMIS group involved GI bleeding.[13]  Most of the remainder involved renal complications. Other considerations are as follows:

  • NSAIDS should be used with caution in older patients and in those with chronic medical problems, such as diabetes and congestive heart failure, due to a significantly increased risk of serious side effects.[14]

  • Elderly individuals are at particular risk for the adverse effects of NSAIDs. One study showed that 30-40% of all elderly persons use NSAIDs and that 10-13% of elderly persons take NSAIDs every day..

  • Serious, potentially fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur, and are most likely during the first 2 weeks of therapy but can happen at any time. Medication should be stopped immediately at the first sign of rash, mouth sores, or allergic reaction (eg, swelling, itching, shortness of breath).

  • With long-term use, neurologic symptoms and urinary retention can occur. Renal effects, such as interstitial nephritis, can occur both in acute and long-term use.

  • Histamine-2 (H2) blockers and prostaglandins have been proposed to be used concomitantly with NSAIDs to block the irritating effects on the gastric mucosa; however, no substantial studies have shown any real protection, and, in fact, use of H2 blockers can possibly increase the risk of subsequent serious GI complications.




Patient history

In nonsteroidal anti-inflammatory drug (NSAID) exposures, the clinician should elicit information on the agent ingested, the amount ingested, and the time of ingestion. The most toxic effects are reported after ingestion of phenylbutazone (Butazolidin; no longer available for human use in the United States), mefenamic acid (Ponstel), and meclofenamate sodium (Meclomen); however, all NSAIDS can have untoward effects.

Amount ingested

Most NSAID exposures are mild-to-moderate ingestions with low levels of symptom severity that include general gastrointestinal (GI) symptoms such as nausea and vomiting, and mild chemistry and electrolyte abnormalities that resolve rapidly with supportive care.

In large ingestions, some patients may develop an altered level of consciousness evolving to coma with progressive and sometimes refractory metabolic acidosis and evolving multisystem organ failure. Seizures may be involved and are seen with increased frequency in certain classes of NSAIDs such as the pyrazolones and fenamates (eg, phenylbutazone and mefenamic acid, respectively).

Other NSAIDs are usually less toxic than those mentioned above. Doses of 100 mg/kg or less of ibuprofen, the most widely used NSAID, generally cause minimal symptoms; life-threatening situations do not typically occur until ingestions of 400 mg/kg or more.

Time of ingestion

Nomograms that correlate time and amount of drug ingested are not reliable for predicting outcome. Patients with recent significant ingestion of anthranilic acids derivatives (fenamates), as well as pyrazolones, require close observation for approximately 24 hours for signs of early severe poisoning.

NSAIDs and adverse drug reactions (ADRs) and drug interactions

NSAIDs are implicated in nearly 25% of all adverse drug reactions, with the most commonly reported effects being GI irritation. NSAIDs increase the relative risk of GI hemorrhage by approximately three-fold, although estimations as high as 10-fold have been reported in the literature.[3]

The second most common type of adverse effect occurring with NSAID use involves the renal system. In the setting of high angiotensin and low intravascular flow (eg, congestive heart failure, cirrhosis, or dehydration), NSAID-induced decrease in prostaglandins leads to a decrease in renal blood flow and subsequently the glomerular filtration rate. Retention of salt, water, and potassium may ensue. Congestive heart failure may be exacerbated by concomitant use of NSAIDs.[4]

Considerable toxicity may result from interactions between NSAIDs and the following drugs:

  • Oral anticoagulants

  • Lithium

  • Oral hypoglycemic agents

  • Phenytoin

  • Methotrexate

  • Digoxin

  • Aminoglycosides


The possibility of co-ingestants should always be considered and is based on the history and examination findings. In general, patients with isolated NSAID overdose are asymptomatic or have mild GI upset (dyspepsia, nausea, vomiting, and abdominal pain). At higher doses, patients may exhibit CNS symptoms, including drowsiness, lethargy, ataxia, and nystagmus. Massive overdoses may cause the patient to present comatose with refractory acidosis and multisystem organ failure. Co-ingestants should be considered in any drug overdose.

Any individual presenting with a history of NSAID overdose should have a serum acetaminophen level obtained.

Physical Examination

In a retrospective case series of 126 patients with ibuprofen overdose, 19% of patients developed symptoms, predominantly CNS depression and GI upset, typically within 4 hours. In a prospective study of 45 adults and 39 pediatric patients, all patients who became ill did so within 4 hours. In this study, coma, apnea, and/or metabolic acidosis occurred in 9% of adults and 5% of children. Ingestions of more than 400 mg/kg of ibuprofen are associated with seizures, apnea, hypotension, bradycardia, metabolic acidosis, and renal and hepatic dysfunction.[5]

Vital signs

Bradypnea or tachypnea may suggest early respiratory or metabolic acidosis. NSAIDs can promote salt and water retention and can antagonize beta-blockers, diuretics, and angiotensin-converting enzyme (ACE) inhibitors, resulting in an elevated blood pressure.

An S3 gallop or marked dysrhythmia may be noted if the patient presents with worsening heart failure.

Central nervous system (CNS) findings

Myoclonus, muscle twitching, or seizures are characteristic (but not specific) of symptomatic massive overdose. Seizures may be focal or general. Tremors or muscle twitching may portend seizures or coma. Analysis of  NSAID overdose cases reported to the United Kingdom National Poisons Information Service, which included 10,398 single-drug exposures, found that mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of ibuprofen, diclofenac, or naproxen.[6]

Mild CNS symptoms may be nonspecific (eg, headache). Subtle mental status changes, such as difficulty concentrating or mild anxiety, may be observed. Patients with severe toxicity may be agitated and delirious, or they may be comatose to the point of requiring endotracheal intubation.

Case reports have also described tinnitus and transient hearing loss after NSAID use.

Pulmonary findings

Aspirin-sensitive individuals with asthma who ingest NSAIDs may present with wheezing or respiratory arrest. The reaction may also include flushed face and/or neck, conjunctivitis, rhinorrhea, and possibly angioedema.

Gastrointestinal findings

Although ulcers are unlikely and perforations very rare in acute overdose, patients with gastrointestinal symptoms require thorough abdominal examination.

A rectal examination may reveal evidence of gastrointestinal bleeding and is mandatory in any patient who presents with acute or chronic toxicity.

Delayed manifestations

Delayed effects of severe poisonings include renal failure, hepatic failure, and platelet dysfunction. Look for generalized weakness, a sallow complexion, acidosis, heart failure, jaundice, liver tenderness, petechiae, and other signs of bleeding disorders.

Manifestations by NSAID class

Poisoning by acute overdose of specific NSAIDs is best addressed by considering each of the seven chemical classifications (including salicylates). Fenamates and pyrazolones (eg, phenylbutazone) are the most toxic and should be managed most aggressively.

Table 1. Chemical Classifications of NSAIDs (Open Table in a new window)

NSAID Drug Class

Maximum Daily Dose



Clinical Symptoms


Examples: Aspirin and other salicylates, eg, sodium or magnesium salicylate (not covered in this article), diflunisal (Dolobid) – not metabolized to salicylic acid

1500 mg

8-12 h

Salicylates: See Toxicity, Salicylate for discussion of acetylsalicylic acid toxicity

Salicylates: See Toxicity, Salicylate

Diflunisal: This NSAID commonly causes drowsiness, vomiting, and diarrhea.

Hyperventilation, tachycardia, diaphoresis, tinnitus, disorientation, stupor, coma, cardiopulmonary arrest, and fatality are rarely observed and occur only with doses exceeding 15 g.

The lowest reported dose resulting in fatality is 15 g.


Examples: Phenylbutazone

600 mg

50-100 h

Pyrazolones: Phenylbutazone (Butazolidin), one of the most toxic NSAIDs

Symptoms of mild poisoning include nausea, abdominal pain, and drowsiness; no longer approved for human use in the US.

Severe poisoning has multisystem effects that, early on, include the GI system (eg, nausea, vomiting, diarrhea), CNS (eg, dizziness, seizures, coma), the cardiovascular system (eg, pulmonary edema, arrest), metabolic and respiratory acidosis, and electrolyte abnormalities.

Delayed severe toxicity (2-7 d) includes renal, hepatic, and hematologic dysfunction.

Although the pyrazolones have been withdrawn from the market, phenylbutazone is available from veterinary sources and from other countries (eg, it has presented in southwestern United States)

Fenamates (anthranilic acids)

Examples: Meclofenamate (Meclomen), mefenamic acid (Ponstel)

1000 mg

2 h

These drugs have not been studied thoroughly, but they have caused vomiting, diarrhea, muscle twitching, and seizures. Most patients recover completely within 24 h.

Myoclonus, muscle twitching, or seizures are characteristic of symptomatic overdose. Seizures may be focal or general. In one series, 20% of 54 patients who developed abnormal neuromuscular activity described as, "twitching" developed seizures (generalized, grand mal, tonic-clonic).






Acetic acids


Diclofenac (Voltaren),


indomethacin (Indocin),

ketorolac (Toradol, Sprix),

sulindac (Clinoril)

PO ketorolac daily dosage limit is 40 mg. Not to exceed daily dose of 126 mg for intranasal ketorolac (63 mg/24 h if older than 65 y). Total cumulative ketorolac (any administration route) should not exceed 5 days in a row.

Typically 8-30 h

Sulindac is a prodrug. Peak concentrations may be delayed 2-5 h.

Sulindac overdoses are very rare, but case reports have shown effects on renal function. Indomethacin poisoning can cause headache, lethargy, disorientation, seizure, nausea, vomiting, and GI bleeding. Seizures were reported in the case of a 6-year-old who ingested, "a bottle" of indomethacin.

Diclofenac can cause nausea, vomiting, tinnitus, hallucinations, and acute renal failure (3 cases).

COX-2 inhibitors

Examples: Celecoxib

400 mg -celecoxib

3-11 h

Considered to be relatively safe

Only available Cox-2 inhibitor in the US

Propionic acids Examples:

Ibuprofen (Motrin, Advil), naproxen (Naprosyn, Anaprox), carprofen (Rimadyl), ketoprofen (Orudis)

For ibuprofen- 3200 mg and T1/2 3 h

For naproxen-

1500 mg and T1/2 12-17 h


Severe toxicity reported mainly in children and can occur in ingestions of 400 mg/kg or more; symptoms include seizures, apnea, hypertension, and renal and hepatic dysfunction

Headache, tinnitus, drowsiness, nausea, vomiting, and abdominal pain are the most common symptoms, and commonly appear within 4 h of ingestion.

In a retrospective case series of 126 patients with ibuprofen overdose, 19% of patients developed symptoms, predominantly CNS depression and GI upset, typically within 4 h. In a prospective study of 45 adults and 39 pediatric patients, all patients who became ill did so within 4 h. In this study, coma, apnea, and/or metabolic acidosis occurred in 9% of adults and 5% of children. Ingestions of more than 400 mg/kg of ibuprofen are associated with seizures, apnea, hypotension, bradycardia, metabolic acidosis, and renal and hepatic dysfunction.

Oxicams Examples:

Piroxicam (Feldene)

20 mg

45-50 h


Occasionally, these NSAIDs can cause dizziness, blurred vision, seizures, and coma.



Diagnostic Considerations

Other problems to consider in the differential diagnosis include the following:

  • Ingestions - Acetaminophen, salicylate, other co-ingestants

  • Agitated delirium

  • Seizure

  • Coma

  • Metabolic acidosis

  • Electrolyte abnormalities -Hyperkalemia, hypophosphatemia, hypocalcemia, hypernatremia

  • Dyspepsia

  • Gastrointestinal bleed

  • Renal insufficiency

  • Congestive heart failure

Differential Diagnoses



Laboratory Studies

Routine determination of the specific plasma nonsteroidal anti-inflammatory drug (NSAID) concentration is not clinically useful in patients with NSAID toxicity; however, serum levels may be of use to establish diagnosis or for academic purposes. Although a nomogram has been developed for ibuprofen, it is not clinically useful since serum levels do not correlate with clinical symptoms. A typical therapeutic ibuprofen level is 3 mg/dL.

Obtain a serum acetaminophen (APAP) level, in view of the possibility of co-ingestion. In acute overdose, asymptomatic patients with no co-ingestions may not require specific serum or urine studies other than a serum acetaminophen level. A 4-hour acetaminophen level should be ordered in every patient with suspected ingestion due to the notorious lack of signs and symptoms in the initial 24 hours after acetaminophen ingestion. Consider obtaining baseline renal and hepatic function tests in patients with asymptomatic ingestions of phenylbutazone, mefenamic acid, and meclofenamate.

In symptomatic patients, obtain the following:

  • Serum electrolytes
  • Renal function studies
  • Liver function tests
  • Coagulation studies, including a prothrombin time with international normalized ratio (INR)
  • Complete blood count (CBC)

In any patient with a low bicarbonate level on the chemistry panel, or an anion gap (see the Anion Gap calculator), and in patients with progressive decline in mental status or seizures, an arterial blood gas (ABG) and plasma lactate should be obtained. Additional electrolyte assays, including magnesium and phosphorus, should be considered in symptomatic patients because hypomagnesemia and hypophosphatemia may develop within a day or two after significant NSAID ingestion.

Obtain a serum salicylate level in any patient with drug overdose and an anion gap acidosis (see Salicylate Toxicity).

Many of the NSAIDs are acidic compounds (carboxylic acids such as diclofenac, ibuprofen, and indomethacin) or are metabolized to acidic compounds (ibuprofen). An anion gap acidosis may be discovered in the setting of NSAID overdose simply due to parent and metabolite compound accumulation. Additionally, in severe overdoses, coma, multisystem organ failure, and refractory lactic acidosis have been reported. The etiology of this acidosis is likely due to both accumulation of parent compound and metabolites as well as inhibition of mitochondrial respiration and distributive shock in the setting of progressive acidosis.

Imaging Studies

A computed tomography (CT) scan of the head may be warranted for workup of patients with any of the following:

  • Seizure
  • Altered mental status
  • Coma

Chest radiography or abdominal plain films are rarely indicated. Although NSAIDs may cause GI irritation, no imaging tests are necessary unless there is consideration for a perforated viscus (as in a patient with nausea and vomiting after acute ingestion).

Other Tests

An electrocardiogram (ECG) is required in hyperkalemic patients and should be obtained in any patient who presents with an acute overdose to help exclude cyclic antidepressant toxicity or exposure to cardioactive drugs.


Lumbar puncture should be performed in patients with altered mental state and symptoms suggestive of CNS infection.



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


Medication Summary

The goals of pharmacotherapy are to reduce morbidity, prevent complications, and reduce the toxic levels of drug. No specific antidotes for nonsteroidal anti-inflammatory drug (NSAID) poisoning exist.

GI decontaminant

Class Summary

These agents may bind and limit absorption of NSAIDs from the GI tract.

Activated charcoal (Liqui-Char)

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.

For maximum effect, administer within 30 min of ingesting poison. Risk/benefit assessment may be favorable for AC up to 4 hours after exposure. Consult with poison control center.

Alkalinizing agents

Class Summary

These agents are used to accelerate excretion of the drug.

Sodium bicarbonate (Neut)

Sodium bicarbonate is indicated for the treatment of recalcitrant acidosis (pH < 7).