Data for a common clinical dilemma.

Apatient receivingwarfarin for atrial fibrillation experiences worsening of her chronic obstructive pulmonarydiseasewith purulent sputum. You want to start an antibiotic. Her international normalized ratio (INR) has been rock stable at 2.5. Shouldyouadjust thedoseof warfarin? Would the answer be different if she was just ill andyouwerenotgoing touse an antibiotic? Does it depend on the antibiotic? This is a common medicine (warfarin) and a common situation (upper respiratory tract infection), and yet there are no easy real-world answers. Harnessing the power of linked medical, pharmacy, and laboratory records and an anticoagulation database, Clark and coauthors show that upper respiratory tract infection increases the risk of excessive anticoagulation evenwithout antibiotics,probablybecauseofacombinationofeating less,using acetaminophen-containing medications, and developing fever. With antibiotics, the risk increases a bit more, but the differenceisnotstatisticallysignificant.Antibiotics interferingwith warfarin metabolism (metronidazole and trimethoprimsulfamethoxazole) were more likely to result in clinically concerning increases in INR (≥5.0). Of importance to us as clinicians is that most patients had minimal changes in the INR with antibiotics, indicating that we should not lower warfarin dosages preemptively. On the other hand, we can take from this study that patients with respiratory tract illness, especially those receiving an antibiotic that interferes with warfarin metabolism, as well as women, patients with cancer, and those with an elevated baseline INR, are at higher risk for excessive anticoagulation and should have additional INR monitoring. Related article page 409 Research Original Investigation Warfarin InteractionsWith Antibiotics