Major
Apixaban × Clarithromycin
Direct oral anticoagulants (factor Xa inhibitors)×Macrolide antibiotic
Mechanism
Clarithromycin blocks CYP3A4 and P-glycoprotein – two apixaban clearance routes. Apixaban levels rise by about 60%, and bleeding risk increases.
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
Avoid where possible. Alternative antibiotics: azithromycin or doxycycline. If clarithromycin is required, reduce apixaban to 2.5 mg twice daily only when at least two of these apply: age ≥80, weight ≤60 kg, serum creatinine ≥133 µmol/L.