NSAIDs

Why this poison is interesting

NSAIDs are the reassuring member of Band F2, and that is precisely what makes them worth a page. They are among the commonest things taken in overdose and among the least likely to cause serious harm: most ingestions produce little more than nausea and drowsiness, because reversible cyclo-oxygenase inhibition is a forgiving mechanism.² The page exists to mark the boundaries of that reassurance — the massive ingestion that acidifies and seizes, the one agent (mefenamic acid) that convulses at modest doses, and the kidney that suffers when prostaglandin support is withdrawn.

• The mechanism is reversible and self-limiting. NSAIDs inhibit cyclo-oxygenase reversibly (aspirin, the exception, is covered separately as salicylate), so as the drug clears the enzyme recovers — there is no accumulating, irreversible injury of the colchicine kind.² Established
• Toxicity is dose-defined and the threshold is high. Signs of toxicity have generally not been seen below about 100 mg/kg of ibuprofen, and large overdoses are often well tolerated when no other drug is involved.² It is the massive ingestion that matters.
• There is no antidote, and none is needed. Management is supportive — early activated charcoal, observation, and diazepam if convulsions occur — with no specific agent and no useful role for dialysis.²

Most NSAID overdoses are a story about reassurance; the toxicology is in the exceptions, not the rule.

The toxic principle

In ordinary overdose there is one principle — loss of prostaglandin protection from reversible COX inhibition — and it is mild. In massive overdose two further effects appear: the drugs are weak acids that contribute to a metabolic acidosis, and they exert direct central nervous system effects.

• Reversible COX inhibition removes protective prostaglandins. Prostaglandins maintain gastric mucosal defence and renal blood flow; inhibiting their synthesis explains the gastrointestinal irritation and the reduction in renal perfusion that dominate symptomatic overdose.² Established
• In massive overdose a metabolic acidosis appears. NSAIDs are weak acids, and serious poisoning is associated with metabolic acidosis; the prothrombin time may also prolong, probably through interference with circulating clotting factors.² Established
• Direct CNS effects emerge at high dose. Headache, tinnitus, dizziness, drowsiness and — in significant overdose — convulsions and loss of consciousness are reported; mefenamic acid is notable for causing convulsions more readily than other NSAIDs.¹² Established

Toxicokinetics

Metabolism and the metabolites

Ibuprofen is metabolised in the liver to two inactive metabolites and excreted rapidly and completely by the kidney.² There is no toxic metabolite and no bioactivation; the parent drug is the agent, and it is short-lived. Other NSAIDs differ in detail — naproxen has a longer half-life, diclofenac a reactive metabolite implicated in its idiosyncratic hepatotoxicity — but in acute overdose the class behaves as rapidly-cleared, highly-bound weak acids.

What changes the answer

• The agent — mefenamic acid seizes at modest doses; naproxen's longer half-life prolongs any effect.¹ Established
• The amount — toxicity is uncommon below about 100 mg/kg of ibuprofen and appears in children at 400 mg/kg or more.²
• Renal reserve and volume status — the prostaglandin-dependent kidney is the organ that suffers, so the volume-depleted and those with existing renal impairment are at greater risk.² Established
• Co-ingestants — a large overdose is often well tolerated when no other drug is taken;² co-ingestants change that calculus and are frequently the real danger.

Elimination and accumulation

NSAIDs do not accumulate in the way the other poisons in this band do. They are cleared quickly by the liver and kidney, and in a patient with normal organ function the drug is gone within hours.² The management question is therefore not how to remove the drug but whether the exposure was large enough, or the patient vulnerable enough, for the kidney or the CNS to be affected before it clears.

The EXTRIP position

EXTRIP has not assessed the NSAIDs — they are absent from the workgroup's list of reviewed poisons.³ The absence is coherent: the drugs are highly protein-bound, rapidly cleared and usually benign, so there is neither the chemistry nor the clinical need for extracorporeal removal.

• Removal is unnecessary and ineffective — high binding leaves little free drug, and the drug self-clears faster than a circuit could be established.²
• Supportive care is the whole strategy — fluids to protect renal perfusion, observation, activated charcoal early, and diazepam for the rare convulsion.²
• The kidney is protected by perfusion, not dialysis — maintaining volume and pressure is the intervention that matters for the organ actually at risk.²

Target organs — and why those

Timeline of effects

The NSAID timeline is short and front-loaded: if anything is going to happen it usually happens within 4–6 hours, and it resolves as the drug clears. There is no delayed phase to wait out, which is why the observation period is measured in hours, not days.

What the mechanism predicts at the bedside

Why most overdoses are benign

Reversible COX inhibition is a forgiving mechanism: the enzyme recovers as the short-lived drug clears, and there is no toxic metabolite and no accumulating injury.² So the prediction — borne out in practice — is that most NSAID overdoses cause little more than gastrointestinal upset and drowsiness, and that a brief observation of the asymptomatic patient is usually enough. Established

Why the kidney is the organ to watch

The one protective function whose loss matters acutely is prostaglandin-mediated renal blood flow, so acute kidney injury is the most relevant organ effect of a significant ingestion — and it is concentrated in those who depend on prostaglandins to maintain perfusion.² The mechanism says the intervention is to protect perfusion (volume, pressure), not to chase the drug. Established

Why mefenamic acid is the exception to remember

Mefenamic acid lowers the seizure threshold and causes convulsions in overdose at doses that would be trivial for other NSAIDs,¹ so the class generalisation fails for this one agent. The bedside consequence is that 'which NSAID' is a real question in an NSAID overdose, and a mefenamic-acid ingestion deserves anticipation of seizures that an ibuprofen one does not. Established

Why there is no antidote and no dialysis

There is nothing to reverse — the inhibition is reversible and self-correcting — and nothing useful to remove, because the drug is highly bound and already clearing.² The mechanism leaves supportive care as not merely the default but the correct and sufficient strategy, which is why this is the one page in the band with no specific treatment to explain.

The antidote, from the poison's side

NSAIDs have no antidote, and uniquely in this band that is not a gap but a sufficiency: the mechanism is reversible and the drug short-lived, so time and supportive care accomplish what an antidote would. This section describes why the absence is appropriate and what supportive care consists of.

• No specific agent exists or is needed — reversible COX inhibition corrects itself as the drug clears.² Established
• Activated charcoal early is the only decontamination step, within an hour of a potentially toxic amount.²
• Diazepam for convulsions, which are uncommon except with mefenamic acid;¹² there is no NSAID-specific anticonvulsant requirement of the isoniazid kind.
• Protect the kidney by perfusion — maintain volume and pressure, monitor renal and liver function, and observe.² Dialysis has no useful role because the drug is bound and self-clearing.

Critical appraisal

1. The 'usually benign' characterisation is well supported and is the page's main message.² The label's own overdose section states that toxicity is generally not seen below about 100 mg/kg of ibuprofen and that large overdoses are often well tolerated when no other drug is taken — a striking statement for an overdose page and the anchor for the whole reassurance.
2. The dose thresholds are ibuprofen's and should not be generalised uncritically. Established The 100 mg/kg and 400 mg/kg figures are from the ibuprofen label;² other NSAIDs differ, and mefenamic acid in particular breaks the pattern, so the page treats the numbers as ibuprofen-specific and names the exception.
3. The mefenamic-acid seizure claim is well established but cited to the class literature rather than a single label here. Established It is standard toxicological teaching and the reason the class cannot be dismissed wholesale;¹ an auditor should confirm it is presented as an agent-specific exception, which it is.
4. The renal mechanism is on firm ground Established — prostaglandin-dependent renal blood flow is textbook, and the label lists renal effects and renal failure among overdose features.² The page is careful to locate the risk in the prostaglandin-dependent patient rather than implying every overdose threatens the kidney.
5. The acidosis and coagulation effects are label-stated but mechanistically inferred in detail. Inferred The label reports metabolic acidosis and a prolonged prothrombin time 'probably due to interference with the actions of circulating clotting factors' in serious poisoning;² the page preserves that 'probably' rather than asserting a definite mechanism.
6. The no-antidote, no-dialysis position is a sufficiency, not a limitation, and the page says so — the reversible, short-lived mechanism is why supportive care is correct and complete, and EXTRIP's silence³ is coherent with the chemistry.

References

1. 1
   Standard pharmacology of the non-aspirin NSAIDs — reversible inhibition of cyclo-oxygenase and the consequent loss of prostaglandin-mediated gastric mucosal protection and renal blood flow, and the established toxicological teaching that mefenamic acid characteristically causes convulsions in overdose at more modest doses than other NSAIDs. Uncontested textbook mechanism, stated here without a dedicated primary citation in the manner the library applies to established pharmacology; the overdose consequences are anchored to the SmPC ². Flagged in the critical appraisal.
2. 2
   Brufen 400 mg Tablets (ibuprofen) — Summary of Product Characteristics, Mylan. emc product 6713. §4.9 and §5.2 fetched and read in full. Source of the statement that toxicity has generally not been observed below 100 mg/kg in children or adults and that children show toxicity at 400 mg/kg or more, that most patients manifest within 4–6 hours, the symptom list (nausea, vomiting, abdominal pain, lethargy, drowsiness, headache, tinnitus, dizziness, convulsion, loss of consciousness, metabolic acidosis, renal effects, gastrointestinal bleeding, coma), the statement that in serious poisoning a metabolic acidosis may occur and the prothrombin time/INR may prolong probably through interference with circulating clotting factors, that large overdoses are generally well tolerated when no other drug is taken, the supportive management (activated charcoal within an hour, at least four hours' observation, intravenous diazepam for convulsions), the rapid absorption with a 1–2 h peak, the ~2 h half-life, the two inactive metabolites, the rapid and complete renal excretion, and the extensive protein binding. Verified 13 Sep 2026.
3. 3
   EXTRIP Workgroup — recommendations index. extrip-workgroup.org/recommendations. Consulted 13 Sep 2026 to confirm that the NSAIDs are not among the poisons the workgroup has assessed — they do not appear on the published list of reviewed agents. Cited here for that absence, which is coherent with the drugs' high protein binding, rapid clearance and generally benign overdose. The mefenamic-acid seizure teaching is carried by the established-pharmacology reference ¹, not by this EXTRIP index.
4. 4
   TOXBASE — ibuprofen; NSAIDs; mefenamic acid. National Poisons Information Service. toxbase.org (NHS login required. NPIS: 0344 892 0111. The authoritative UK source for dose- and agent-specific risk stratification, decontamination and observation decisions, and management of the rare severe case. Login-gated, so not quoted here.)