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Causality: well established
Causality assessment · Causality: well established
Propylthiouracil and Hepatotoxicity / acute liver failure: 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.
Propylthiouracil ↔ Hepatotoxicity / acute liver failure
n=46 co-reports · PRR 34.7 · ROR 35.5
Propylthiouracil, an antithyroid drug, carries a boxed warning for severe liver injury that can progress to acute liver failure and even require transplantation — a risk serious enough that its use is now largely limited to the first trimester of pregnancy and to thyroid storm, with methimazole preferred otherwise. The injury is idiosyncratic and can be sudden. The 46 co-reports (PRR 34.7) reflect a rare but regulatorily prominent and potentially fatal effect.
Regulatory basis: propylthiouracil prescribing information (boxed warning for hepatotoxicity/liver failure). Established propylthiouracil-hepatotoxicity literature.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Liver injury develops during therapy and can be fulminant |
| Strength | met | PRR 35 on a small co-report count — a strong relative signal for a rare event |
| Consistency | met | Reproduced across case series and pharmacovigilance analyses |
| Specificity | met | A distinctive propylthiouracil toxicity, less typical of methimazole |
| Biological gradient | partial | Largely idiosyncratic rather than simply dose-related |
| Plausibility | met | Immune/metabolic hepatocellular injury is proposed |
| Coherence | met | Coheres with the boxed warning and restricted-use recommendations |
| Experiment | partial | Dechallenge (withdrawal) is essential and can be life-saving; no randomized trial |
| Analogy | met | Analogous to severe drug-induced liver injury from other drugs |
This page's own qualitative read, not an automated/citation-gated assessment.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for propylthiouracil captured hepatotoxicity or liver failure; it is rare and idiosyncratic, identified through case series and regulatory review rather than a trial AE table.