Presentation
A 68-year-old woman with non-valvular atrial fibrillation, maintained on warfarin 5 mg daily with a stable INR (2.0-3.0) over the preceding six months, reported gum bleeding on brushing and two episodes of mild epistaxis over 48 hours. Five days earlier she had been prescribed clarithromycin 500 mg twice daily by her primary-care physician for a lower respiratory tract infection. She denied trauma, melena, haematuria, or any change to diet, alcohol intake, or other medicines. (Patient details are fictional and provided for demonstration.)
Investigations
Point-of-care INR was 6.8 (target 2.0-3.0). Full blood count showed haemoglobin 12.4 g/dL with a normal platelet count. There was no clinical evidence of major or life-threatening bleeding, and renal and hepatic function were within normal limits. Figure 1 shows the INR trend before and after intervention.
Diagnosis
Supratherapeutic INR secondary to a pharmacokinetic drug-drug interaction between warfarin and clarithromycin, with associated minor mucosal bleeding. Clarithromycin inhibits CYP3A4, reducing warfarin metabolism and potentiating its anticoagulant effect.
Treatment
Warfarin was withheld. In keeping with guidance for an INR of 6.0-8.0 without major bleeding, 1 mg of oral phytomenadione (vitamin K1) was given and the antibiotic was switched to an agent with lower interaction potential. The patient was counselled on bleeding precautions, with the INR rechecked at 48 hours.
Outcome narrative
The INR fell to 3.1 at 48 hours; warfarin was resumed at a reduced dose with close monitoring and returned to target within a week. Bleeding resolved completely with no further complications. The patient was reminded to inform every prescriber of her warfarin therapy and to request INR review whenever a new medicine is started.
Learning points
- Macrolides (especially clarithromycin and erythromycin) inhibit CYP3A4 and can raise the INR sharply within days in patients on warfarin. - For an INR of 6.0-8.0 without major bleeding, withhold warfarin and consider low-dose oral vitamin K1, following local anticoagulation guidance. - Screen for interactions before co-prescribing antibiotics with warfarin; consider lower-risk options (e.g., doxycycline) where clinically appropriate. - Patient counselling and timely INR rechecking are central to safe anticoagulation. - This is an illustrative example case included to demonstrate the Clinical Case Library submission and display format.
References
1. Keeling D, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol. 2011;154(3):311-324. 2. Holbrook AM, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095-1106. 3. Baillargeon J, et al. Concurrent use of warfarin and antibiotics and risk of bleeding in older adults. Am J Med. 2012;125(2):183-189.