Which antibiotics have a high enough risk of interacting with warfarin to warrant pre-emptive adjustments in warfarin dosage?

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I have several patients that are on long-term coumadin management. When treating mild acute infections in these patients with antibiotics, are certain antibiotics preferred? Also, which antibiotics need a pre-emptive adjustment in coumadin dose?

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Antibiotics that are less likely to affect the INR are Penicillin, Clindamycin and first- and fourth-generation cephalosporins.


Empiric adjustment should be considered with the use of Bactrim, Rifampin, Fluconazole and Metronidazole. See the chart below for adjustment recommendations for each:


Source: https://pubmed.ncbi.nlm.nih.gov/31038898/


Other antibiotics such as fluoroquinolones (Ciprofloxacin, Levofloxacin) and macrolides (Azithromycin, Clarithromycin and Erythromycin) may affect the INR, but the effect is variable and patient specific. 


To put it into clinical practice:

  1. Choose antibiotics with less likelihood to affect the INR such as PCN G, Cindamycin  or cephalosporins

  2. If Bactrim or Flagyl can’t be avoided, adjust warfarin dose pre-emptively, and recheck INR 3- 5 days after starting the antibiotics and 3-5 days after discontinuing the antibiotics

  3. When prescribing fluoroquinolones, macrolides, and tetracyclines, do not adjust warfarin dose preemptively with a plan to check INR 5 days after starting the course. 


https://pubmed.ncbi.nlm.nih.gov/27565097/

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