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Causality: well established
Causality assessment · Causality: well established
Bosentan 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.
Bosentan ↔ Hepatotoxicity
n=258 co-reports · PRR 2.9 · ROR 2.9
Bosentan, used for pulmonary arterial hypertension, causes a dose-related rise in liver enzymes that can occasionally amount to clinically significant liver injury, and it carries a boxed warning requiring monthly liver-function testing for the whole duration of treatment. Because the effect appears during therapy and usually reverses when the drug is stopped, monitoring is the key safety measure. The 258 co-reports (PRR 2.9) reflect both the real effect and the drug's specialised use in a narrow patient group.
Regulatory basis: bosentan prescribing information (boxed warning for hepatotoxicity; mandatory monthly liver-function testing).
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Liver enzymes rise during therapy and fall after withdrawal |
| Strength | partial | PRR 3 on a modest co-report count |
| Consistency | met | Reproduced across the bosentan trial programme |
| Specificity | met | A recognised bosentan effect, uncommon with many drugs |
| Biological gradient | met | Dose-related |
| Plausibility | met | Direct hepatotoxicity (with some evidence of immune involvement) is proposed |
| Coherence | met | Coheres with the boxed warning and monthly monitoring requirement |
| Experiment | partial | Dechallenge (withdrawal) reverses the enzyme rise; no randomized trial |
| Analogy | met | Analogous to hepatotoxicity from other endothelin-receptor antagonists |
This page's own qualitative read, not an automated/citation-gated assessment.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for bosentan captured abnormal liver function as a coded event; the hepatotoxicity is captured through the mandatory monthly monitoring programme rather than a trial AE table.