Nonsteroidal Anti-inflammatory Drug (NSAID) Toxicity Follow-up

Updated: Dec 20, 2017
  • Author: Timothy J Wiegand, MD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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Further Outpatient Care

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.


Further Inpatient Care

Inpatient considerations are as follows:

  • 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.



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


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 Education

For patient education information, see the First Aid and Injuries Center, as well as Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.