Major
ciprofloxacin × warfarin
Fluoroquinolone antibacterials×Vitamin K antagonist anticoagulants
Mechanism
Dual mechanism: 1) ciprofloxacin is a moderate CYP1A2 inhibitor and weak CYP3A4 inhibitor, raising R-warfarin concentration; 2) elimination of gut flora reduces vitamin K2 synthesis. INR rises 3–7 days after antibiotic initiation; in some patients by 1–2 units or more (Stockley's Drug Interactions; review by Glasheen et al., J Gen Intern Med, 2005).
Management
Check INR on days 3 and 7 of the course and again 7–10 days after completion. For courses ≥ 5 days, pre-emptively reduce the warfarin dose by 15–25 %. If feasible, choose an antibiotic with less INR impact (e.g. a cephalosporin where susceptibility allows).
Sources
- Journal of General Internal Medicine: Impact of fluoroquinolones on the CYP450 system and the international normalized ratio: case reports and review (2005)— J Gen Intern Med 2005;20(8):761–765 (Glasheen JJ et al.)
- Pharmaceutical Press: Stockley's Drug Interactions, 12th edition (2024)— Preston CL (ed.). Stockley's Drug Interactions. 12th ed. London: Pharmaceutical Press; 2024
- Lexicomp: Lexicomp Drug Interactions (2024)— Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- FDA: Cipro (ciprofloxacin) prescribing information (2021)