Clarithromycin × Dabigatran

Clarithromycin inhibits P-glycoprotein (P-gp), the efflux transporter for dabigatran. In healthy volunteers, clarithromycin 500 mg twice daily increased dabigatran AUC about 1.19-fold and Cmax about 1.15-fold (EMA SmPC). The increase alone is small, but P-gp inhibition and impaired renal function are the two major independent factors that raise dabigatran exposure (FDA label), and their effects add up.

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.

With creatinine clearance (CrCl) of 50 mL/min or more, keep the dabigatran dose. In atrial fibrillation the dose also stays the same at CrCl 30–50 mL/min: the FDA label lists clarithromycin among P-gp inhibitors that need no dabigatran dose adjustment. Per the FDA label, avoid the combination in two cases: CrCl below 50 mL/min when dabigatran is used to treat or prevent deep vein thrombosis and pulmonary embolism, and CrCl 15–30 mL/min in atrial fibrillation. Calculate CrCl with the Cockcroft–Gault formula before the course. During the course, watch for signs of bleeding and anaemia, especially with reduced renal function (EMA SmPC). If the combination is unsuitable, choose an antibiotic that is not listed as a P-gp inhibitor in the dabigatran label.