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Causality: well established
Causality assessment · Causality: well established
Valproate and Hyperammonaemia: 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.
Valproate ↔ Hyperammonaemia
n=298 co-reports · PRR 64.7 · ROR 65.7
Valproate can raise blood ammonia even when liver enzymes are normal, occasionally causing encephalopathy; 298 co-reports give an extreme PRR of 64.7. The label warns of hyperammonaemic encephalopathy, especially with concomitant topiramate or in urea-cycle disorders.
Regulatory basis: valproate prescribing information — hyperammonaemia and hyperammonaemic encephalopathy warning.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Hours to days |
| Strength | met | PRR 64.7, an extreme signal |
| Consistency | met | Reproduced across cohorts |
| Specificity | met | Fairly specific to valproate |
| Biological gradient | met | Dose-related |
| Plausibility | met | Known urea-cycle interference |
| Coherence | met | Fits valproate's metabolic effects |
| Experiment | n/a | Too specific for routine trial capture |
| Analogy | met | Analogous to topiramate interaction |
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 valproate captured hyperammonaemia as a tracked adverse event in a usable structure. Ammonia is not a standard safety endpoint in epilepsy trials.