Major
Clarithromycin × Rivaroxaban
Macrolide antibiotic×Direct oral anticoagulants (factor Xa inhibitors)
Mechanism
Clarithromycin blocks CYP3A4 and P-glycoprotein – the two main rivaroxaban clearance routes. Rivaroxaban levels rise by roughly 50%, and bleeding risk grows in patients with renal impairment.
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. Do not prescribe if creatinine clearance is below 30 mL/min. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 and P-glycoprotein interaction).