Moderate
Azithromycin × Rivaroxaban
Macrolides×Direct oral anticoagulants (factor Xa inhibitors)
Mechanism
Azithromycin is a weak P-glycoprotein inhibitor; rivaroxaban is a P-glycoprotein substrate. Rivaroxaban plasma levels may rise modestly, raising bleeding risk.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools. Higher risk in older patients and chronic kidney disease.
Management
For short azithromycin courses (3–5 days), the combination is acceptable without dose change. In older patients and creatinine clearance below 50 mL/min: monitor for bleeding signs. Alternative antibiotics without P-glycoprotein effect: a cephalosporin, amoxicillin-clavulanate, doxycycline.