Which Antibiotics Can Be Taken with Eliquis (Apixaban)
Most commonly prescribed antibiotics are safe to use with apixaban, but you must avoid rifampin and nafcillin, exercise caution with erythromycin and clarithromycin, and monitor kidney function when using trimethoprim-sulfamethoxazole. 1
Antibiotics to Avoid Completely
Rifampin is contraindicated with apixaban because it is a strong combined P-gp and CYP3A4 inducer that dramatically reduces apixaban blood levels by accelerating its metabolism, thereby increasing the risk of stroke and blood clots 1, 2
Nafcillin should be avoided as it reduces apixaban effectiveness over time through enzyme induction 1
Antibiotics Requiring Dose Adjustment or Close Monitoring
Clarithromycin does NOT require apixaban dose adjustment despite being a combined P-gp and strong CYP3A4 inhibitor, as pharmacokinetic data demonstrate no clinically significant interaction 2
Erythromycin (a moderate CYP3A4 inhibitor) requires closer bleeding monitoring when combined with apixaban, though no formal dose adjustment is mandated 1
Trimethoprim-sulfamethoxazole may affect kidney function, which compounds bleeding risk in patients taking apixaban, particularly in those with baseline renal impairment 1
Safe Antibiotics (No Interaction)
Most commonly prescribed antibiotics have no significant interaction with apixaban, including:
- Penicillins (amoxicillin, ampicillin) - no CYP3A4 or P-gp effects
- Cephalosporins (cephalexin, ceftriaxone) - no metabolic interaction
- Fluoroquinolones (ciprofloxacin, levofloxacin) - minimal interaction risk
- Tetracyclines (doxycycline) - no significant interaction
- Azithromycin - unlike clarithromycin, has minimal CYP3A4 inhibition
Understanding the Mechanism
Apixaban is eliminated through multiple pathways: renal excretion (27%), metabolism by CYP3A4, and direct intestinal excretion via P-glycoprotein (P-gp) 2, 3
Strong dual inhibitors of both CYP3A4 AND P-gp (like ketoconazole) increase apixaban exposure by approximately 2-fold, significantly raising bleeding risk 2, 3
Strong inducers of CYP3A4 and P-gp (like rifampin, carbamazepine, phenytoin) decrease apixaban exposure by accelerating its elimination, increasing stroke risk 2
High-Risk Patient Populations Requiring Extra Caution
Elderly patients (>75 years), those with kidney impairment (CrCl 30-50 mL/min), and patients weighing <50 kg face compounded bleeding risk with any interacting antibiotic, as even moderate CYP3A4/P-gp inhibitors can cause clinically significant bleeding in these populations 1
Patients with renal impairment have prolonged apixaban half-life (17 hours versus 12 hours in normal function), increasing bleeding risk with any medication that further elevates apixaban levels 4
Monitoring Recommendations When Using Antibiotics with Apixaban
Monitor for bleeding signs including unusual bruising, blood in urine or stool, prolonged bleeding from cuts, or unexplained bleeding when starting any antibiotic 1
Assess kidney function before initiating trimethoprim-sulfamethoxazole and monitor for deterioration, as this combination can compound renal effects 1
Avoid adding NSAIDs or aspirin during antibiotic treatment, as the combination of apixaban with antiplatelet agents significantly increases bleeding risk 2