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Causality: well established
Causality assessment · Causality: well established
Phenytoin and Stevens–Johnson syndrome / TEN: 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.
Phenytoin ↔ Stevens–Johnson syndrome / TEN
n=771 co-reports · PRR 36.2 · ROR 37.6
Phenytoin, an older antiepileptic also used in some cardiac and neurosurgical settings, is another leading cause of Stevens–Johnson syndrome and toxic epidermal necrolysis, with the same aromatic-antiepileptic, HLA-linked pattern seen with carbamazepine. The reaction usually appears within the first weeks of therapy and requires immediate withdrawal. The 771 co-reports (PRR 36.2) reflect both the severity of the reaction and the drug's continued use worldwide.
Regulatory basis: phenytoin prescribing information (SJS/TEN warning; HLA-B*15:02 caution). Established phenytoin-HLA pharmacogenomics.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Skin reaction appears early in therapy and is managed by immediate withdrawal |
| Strength | met | PRR 36 on a large co-report count |
| Consistency | met | Reproduced across populations and linked to HLA-B*15:02 |
| Specificity | partial | Shared with other aromatic antiepileptics, a class pattern |
| Biological gradient | partial | Linked more to genetic risk than to a simple dose gradient |
| Plausibility | met | Immune-mediated keratinocyte death, often HLA-restricted, is the mechanism |
| Coherence | met | Coheres with the labelled warnings and genetic-screening advice |
| Experiment | partial | Dechallenge (immediate withdrawal) is essential and can be life-saving; no randomized trial |
| Analogy | met | Analogous to SJS/TEN from carbamazepine, lamotrigine, and allopurinol |
This page's own qualitative read, not an automated/citation-gated assessment.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for phenytoin captured SJS/TEN; it is a rare, severe idiosyncratic reaction identified through case series and pharmacogenetics rather than a trial AE table.