Major
Clarithromycin × Dabigatran
Macrolide antibiotic×Direct thrombin inhibitor
Mechanism
Clarithromycin blocks intestinal P-glycoprotein, the main transporter of dabigatran. Dabigatran plasma levels rise by 49–60%, and bleeding risk becomes clinically significant.
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 the combination if creatinine clearance is below 50 mL/min. During clarithromycin therapy, reduce dabigatran to 110 mg twice daily. Alternative antibiotic: azithromycin (minimal P-glycoprotein interaction).