Does Ceftriaxone Lower INR?
No, ceftriaxone does not lower INR—it actually increases INR and potentiates warfarin's anticoagulant effect, increasing bleeding risk.
Mechanism of Interaction
Ceftriaxone, like all antibiotics, can elevate INR in patients on warfarin through multiple mechanisms 1:
- Gut microbiome disruption: All antibiotics alter the gut flora, which is a rich source of vitamin K production, thereby potentiating warfarin's anticoagulant effects 1
- Direct pharmacokinetic effects: While ceftriaxone is not specifically listed as a CYP2C9 inhibitor (unlike sulfonamides or metronidazole), the general antibiotic effect on vitamin K availability remains clinically significant 1
Clinical Evidence
A case report documented a 67-year-old woman on stable long-term warfarin therapy (INR consistently 1.9-3.0) who experienced dramatic INR elevations on two separate occasions after receiving ceftriaxone 1g intramuscularly 2:
- First episode: INR increased to 10.74 four days after ceftriaxone administration
- Second episode: INR increased to 16.99 four days after ceftriaxone administration
- Both episodes required phytonadione (vitamin K) administration and warfarin dose adjustments 2
This pattern of INR elevation (not reduction) is consistent with the broader evidence on antibiotic-warfarin interactions 3.
Clinical Management Recommendations
When prescribing ceftriaxone to warfarin patients:
- Increase INR monitoring frequency: Check INR closely whenever antibiotics are initiated in patients on chronic warfarin therapy 1
- Expect INR elevation, not reduction: The typical pattern is INR increase occurring 2-8 days after antibiotic initiation 2, 3
- Monitor for bleeding complications: A large database analysis showed that acute upper respiratory tract infection with antibiotic use increases the risk of excessive anticoagulation (INR ≥5.0) to 3.2% compared to 2.6% in stable controls 3
Common pitfall to avoid: Do not assume ceftriaxone will lower INR. The opposite occurs—INR rises, increasing bleeding risk. The case report demonstrates INR values reaching dangerous levels (>10) requiring urgent reversal 2.
Context: General Antibiotic-Warfarin Interactions
While specific high-risk antibiotics like sulfamethoxazole and metronidazole warrant preemptive warfarin dose reductions of 25-33% 1, ceftriaxone's interaction appears less predictable but still clinically significant. The illness itself (upper respiratory tract infection) also independently increases INR, separate from antibiotic effects 3.
Bottom line: Ceftriaxone raises INR rather than lowering it, requiring vigilant monitoring and potential warfarin dose reduction to prevent bleeding complications 1, 2.