Warfarin and INR increased: is the FAERS signal real?
Warfarin ↔ INR increased
Warfarin's effect is measured by the INR, and the INR is the test used to dose it; a report of "international normalised ratio increased" is therefore partly a description of the drug working and partly of the monitoring built around it, not a discrete adverse event in the usual sense. The over-representation of INR terms for warfarin is expected: the test is nearly exclusive to vitamin-K-antagonist therapy, which guarantees disproportionality by construction. Genuine supratherapeutic INR with bleeding is a real and important warfarin hazard, but the raw "INR increased" signal is a monitoring/coding artifact rather than a novel safety finding. Tellingly, INR terms also appear in the comparator arm of a modern anticoagulant trial (below).
Methodological note, not a regulatory finding: INR is the monitoring parameter used to dose vitamin-K antagonists; its over-representation is a coding/monitoring artifact. Supratherapeutic INR with bleeding remains a real, labeled warfarin risk (warfarin prescribing information).
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | n/a | The INR is the measurement, not a biological event |
| Strength | met | PRR 93 — but this measures the exclusivity of the test, not harm |
| Consistency | met | Consistent wherever warfarin is monitored |
| Specificity | not established | The term reflects a required test, not a distinct clinical effect |
| Biological gradient | n/a | — |
| Plausibility | n/a | INR rises because that is the drug's intended pharmacology, not an adverse reaction |
| Coherence | not established | Fails coherence as an adverse-reaction concept; it is a monitoring value |
| Experiment | n/a | — |
| Analogy | met | Directly analogous to other lab-monitoring artifacts (e.g. thalidomide ↔ hCG) |
This page's own qualitative read, not an automated/citation-gated assessment.
✓ Trial evidence found — warfarin vs apixaban in atrial fibrillation (NCT00412984, ARISTOTLE)
| Term (as recorded) | Warfarin (n=9,088) | Apixaban (n=9,052) |
|---|---|---|
| International normalised ratio increased (serious) | 3 | 5 |
| International normalised ratio abnormal (serious) | 5 | 5 |
INR terms were recorded in both arms — even the apixaban arm, which does not require INR dosing — confirming that these entries track the monitoring/recording process rather than a drug-specific effect. View on ClinicalTrials.gov →