Ciprofloxacin × Warfarin

Ciprofloxacin inhibits CYP1A2 and CYP3A4, the enzymes that clear the less potent of the two forms of warfarin (US warfarin label, FDA), and increases the anticoagulant effect. How far the international normalised ratio (INR) will rise is hard to predict: the contribution of ciprofloxacin depends on the infection itself, the patient's age and general condition (ciprofloxacin SmPC). Infections and changes in gut flora also alter the response to warfarin on their own (warfarin SmPC).

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.

The combination is not prohibited but needs frequent monitoring. Check the international normalised ratio (INR) frequently during the ciprofloxacin course and shortly after it ends (ciprofloxacin SmPC; US ciprofloxacin label, FDA). Monitor coagulation closely whenever a drug is added to or withdrawn from warfarin therapy (warfarin SmPC); the FDA also advises close INR monitoring when any antibiotic is started or stopped (US warfarin label). Adjust the warfarin dose to the INR if needed (US warfarin label). Ask the patient to report bleeding gums, nosebleeds, bruising, red or dark brown urine and black stools straight away (US warfarin label).