Pyrazinamide and Drug-induced liver injury: is the FAERS signal real?
Pyrazinamide ↔ Drug-induced liver injury
Pyrazinamide is a first-line antituberculosis drug and the most hepatotoxic of the standard regimen; drug-induced liver injury appears at 655 co-reports here (PRR 48.7), and its use is limited by that risk. Hyperuricaemia and gout are also common because the drug raises urate, and the label advises monitoring liver enzymes, especially when combined with isoniazid and rifampicin.
Regulatory basis: pyrazinamide prescribing information — hepatotoxicity; hyperuricaemia; monitoring during combination therapy.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Onset within weeks |
| Strength | met | PRR 48.7, large |
| Consistency | met | Reproduced across case series |
| Specificity | met | Fairly specific within the regimen |
| Biological gradient | met | Dose-related |
| Plausibility | met | Metabolite-driven hepatocellular injury |
| Coherence | met | Fits the DILI picture |
| Experiment | n/a | Too rare for trial detection |
| Analogy | met | Analogous to isoniazid hepatotoxicity |
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.
✓ Trial evidence found — Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy (NCT00042289)
| Adverse event | ABC 300mg b.i.d. MOTHER (n=26) · ATV/COBI 300/150 mg q.d. INFANT (n=12) · ATV/COBI 300/150 mg q.d. MOTHER (n=12) · ATV/RTV 300/100mg q.d. INFANT (n=22) | |||
|---|---|---|---|---|
| Drug-induced liver injury | 0/26 | 0/12 | 0/12 | 0/22 |
| Hepatitis | 0/26 | 0/12 | 0/12 | 0/22 |
| Hepatitis fulminant | 0/26 | 0/12 | 0/12 | 0/22 |
Post-marketing signal terms appear in this trial's posted adverse-event tables; per-arm counts shown as affected/at-risk. View on ClinicalTrials.gov →