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Causality: well established
Causality assessment · Causality: well established
Methadone and QT prolongation / torsades: 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.
Methadone ↔ QT prolongation / torsades
n=862 co-reports · PRR 12.1 · ROR 12.3
Methadone prolongs the cardiac QT interval and can cause torsades de pointes, particularly at higher doses, when combined with other QT-prolonging drugs, or in patients with electrolyte disturbance. This is why ECG monitoring is advised during methadone initiation and dose increases for opioid-use disorder. The effect is a genuine, dose-related cardiac toxicity rather than an idiosyncratic one. The 862 co-reports (PRR 12.1) reflect the drug's wide use in addiction treatment and pain.
Regulatory basis: methadone prescribing information (QT prolongation and torsades warning; ECG monitoring advice).
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | QT prolongation is measured during therapy and resolves after withdrawal |
| Strength | met | PRR 12 on a large co-report count |
| Consistency | met | Reproduced across ECG studies and case series |
| Specificity | met | A recognised opioid effect, strongest for methadone |
| Biological gradient | partial | Dose-related, especially above ~100 mg/day |
| Plausibility | met | hERG-channel blockade delays cardiac repolarisation |
| Coherence | met | Coheres with the labelled ECG-monitoring advice |
| Experiment | partial | Dechallenge (withdrawal/dose reduction) reverses it; no randomized trial |
| Analogy | met | Analogous to QT risk with other QT-prolonging opioids 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 methadone captured QT prolongation or torsades; the risk was characterised through ECG studies and the labelled monitoring advice rather than a trial AE table.