Clarithromycin × Rivaroxaban

Rivaroxaban is cleared partly through the CYP3A4 enzyme and the P-glycoprotein (P-gp) transporter. The European Medicines Agency (EMA) classes clarithromycin as a strong CYP3A4 inhibitor and a moderate P-gp inhibitor: at 500 mg twice daily it raised the rivaroxaban area under the curve 1.5-fold and peak concentration 1.4-fold (rivaroxaban SmPC, EMA). In severe kidney impairment, rivaroxaban levels are higher even without interacting drugs, on average 1.6-fold (rivaroxaban SmPC, EMA).

Bleeding gums, nosebleeds, bruising without injury, blood in the urine or stool, heavy periods. In severe cases, gastrointestinal or intracranial bleeding. The risk is higher in patients aged 75 or over, with chronic kidney disease, previous bleeding or anaemia, and with concomitant antiplatelet drugs, non-steroidal anti-inflammatory drugs or systemic corticosteroids.

The combination can be used with caution. The European Medicines Agency (EMA) considers the interaction clinically irrelevant for most patients but potentially significant in high-risk patients (rivaroxaban SmPC, EMA). The US Food and Drug Administration (FDA) requires no special measures (rivaroxaban FDA label). Caution matters most in patients at high risk of bleeding (clarithromycin SmPC) and in those with reduced kidney function: rivaroxaban is used with caution in patients with renal impairment who take drugs that raise its levels (rivaroxaban SmPC, EMA), and the European Society of Cardiology (ESC) flags clarithromycin specifically when kidney function is impaired (ESC 2024). The European Heart Rhythm Association (EHRA) advises particular caution with polypharmacy and when two or more risk factors are present, such as age 75 or over, chronic kidney disease, antiplatelet drugs, non-steroidal anti-inflammatory drugs, systemic corticosteroids or previous bleeding; in that case, first consider whether another anticoagulant or antibiotic with fewer interactions is suitable (EHRA 2021). Watch the patient for signs of bleeding and stop rivaroxaban if severe bleeding occurs (rivaroxaban SmPC, EMA).