Major
Ciprofloxacin × Warfarin
Fluoroquinolone antibacterials×Vitamin K antagonist anticoagulants
Mechanism
Ciprofloxacin blocks CYP1A2 and, to a lesser extent, CYP3A4 – warfarin clearance routes. It also suppresses vitamin K-producing gut flora. INR rises 1.5- to 2-fold within 5–7 days of co-administration.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
During ciprofloxacin therapy, empirically reduce warfarin by 20%; check INR 3–5 days after starting and 7 days after stopping the antibiotic. Alternatives: cephalosporin or nitrofurantoin (minimal CYP impact).
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)– Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- Pharmaceutical Press: Stockley's Drug Interactions, 12th edition (2024)– Preston CL (ed.). Stockley's Drug Interactions. 12th ed. London: Pharmaceutical Press; 2024
- 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.)
- FDA: Cipro (ciprofloxacin) prescribing information (2021)
- FDA: Cipro (ciprofloxacin hydrochloride) prescribing information (2016)