Table 1.
Similarities and differences between drug-induced torsade de pointes and drug-induced liver injury
| DITdP | DILI | |
| Endpoint/biomarker | Surrogate, but well defined biomarker of risk (QT prolongation with specific thresholds) | Surrogate, but well defined biomarker of risk (transaminase elevation with specific thresholds) |
| Key mechanism | Largely described (dose-dependent hERG K+ channel inhibition) | Only partially understood (different hypotheses) |
| Dose-response relationship | Dose dependent (with only a few exceptions) | Idiosyncratic, although dose-dependence exists |
| Regulatory impact | Pre-clinical and clinical guidelines (pre-marketing) | Clinical guideline (pre-marketing) |
| Clinical impact | Significant (a leading cause of drug withdrawal worldwide) | Significant (a leading cause of drug withdrawal worldwide) |
| Predictivity of pre-clinical assays | Reasonably good (new models under investigation) | Sub-optimal (especially for in vivo models) |
| Predictivity of clinical studies | Good (thorough QT study), albeit imperfect | Good (Hy’s law), albeit imperfect |
| Role of genetics | Important (long QT syndrome) | Partially defined (only for some drugs) |
| Awareness (clinicians, regulators, drug developers, researchers) | Significant at all levels | Significant at some levels (drug developers, researchers) |
| Risk assessment tools (clinical) | Drug- and patient-related risk factors are well recognized (https://www.crediblemeds.org/); CDSSs are under implementation | Drug- and patient-related risk factors are only partially recognized (https://livertox.nlm.nih.gov/) |
| Causality assessment tools (clinical) | Not present, but the majority of TdP cases are drug induced (the so-called designated medical event); phenotype standardized | Specific, but challenging (several differential diagnoses) |
| Therapy | Magnesium sulphate, electrical cardioversion or isoproterenol (isoprenaline) or transvenous pacing (refractory TdP cases); removal or correction of precipitants, including drugs | No specific treatment other than drug discontinuation; liver transplantation may be required in acute liver failure cases |