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Causality: well established
Causality assessment · Causality: well established
Benzocaine and Methaemoglobinaemia: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Benzocaine ↔ Methaemoglobinaemia
n=35 co-reports · PRR 46.5 · ROR 48.2
Benzocaine is a topical anaesthetic; its metabolite oxidises haemoglobin, and methaemoglobinaemia (reported here as cyanosis, 35 co-reports, PRR 46.5) is a rare but potentially fatal effect, most often with sprays used for procedures in children. The FDA issued a warning specifically about benzocaine sprays in infants, and the reaction is dose- and patient-related.
Regulatory basis: benzocaine labelling — FDA warning on methaemoglobinaemia with benzocaine sprays; oxidant-haemolysis literature.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Onset within an hour |
| Strength | met | PRR 46.5, very large |
| Consistency | met | Reproduced across case reports |
| Specificity | met | Highly specific to oxidant anaesthetics |
| Biological gradient | met | Dose-related |
| Plausibility | met | Oxidative haemoglobin modification |
| Coherence | met | Fits the mechanism |
| Experiment | n/a | Not a trial endpoint |
| Analogy | met | Analogous to prilocaine methaemoglobinaemia |
This table is this page's own qualitative read of the literature cited above, not an automated or citation-gated assessment — see the note at the bottom of this page.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for benzocaine captured methaemoglobinaemia as a tracked adverse event in a usable structure. Methaemoglobinaemia is rare and typically procedure-related, so trials did not report it as a coded event.