← All causality assessments
Causality: well established
Causality assessment · Causality: well established
Ketoconazole (oral) and Hepatotoxicity: 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.
Ketoconazole (oral) ↔ Hepatotoxicity
n=64 co-reports · PRR 3.5 · ROR 3.5
Oral ketoconazole can cause serious liver injury, ranging from asymptomatic transaminase rises to fatal hepatitis, which is why it was withdrawn from the market for oral use in the EU in 2013 and is now largely restricted to topical application. The injury is idiosyncratic rather than simply dose-related, can occur at any point during treatment, and is the reason liver function was monitored during the drug's oral era. The 64 co-reports (PRR 3.5) reflect a genuine, historically significant hepatotoxicity.
Regulatory basis: oral ketoconazole withdrawal in the EU (2013) and FDA restrictions (2013) over hepatotoxicity; ketoconazole prescribing information.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Liver injury occurs during therapy and generally improves after withdrawal |
| Strength | partial | PRR 4 on a small co-report count — a modest statistical signal |
| Consistency | met | Reproduced across decades of case reports and reviews |
| Specificity | met | A recognised idiosyncratic drug-induced liver injury |
| Biological gradient | met | Not clearly dose-related; idiosyncratic |
| Plausibility | met | Metabolic and immune-mediated liver injury are proposed mechanisms |
| Coherence | met | Coheres with the market withdrawal and current restrictions |
| Experiment | partial | Dechallenge (withdrawal) usually improves liver tests; no randomized trial |
| Analogy | met | Analogous to hepatotoxicity from other azoles and 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 oral ketoconazole captured hepatotoxicity; the injury is idiosyncratic and was characterised through case series and regulatory review, not a trial AE table.