Tamiflu and Eliquis Interaction Assessment
Direct Answer
There is no clinically significant pharmacokinetic or pharmacodynamic interaction between Tamiflu (oseltamivir) and Eliquis (apixaban), and these medications can be safely co-administered without dose adjustment.
Mechanistic Analysis
The lack of interaction between these agents is explained by their distinct metabolic and elimination pathways:
Oseltamivir Metabolism and Excretion
- Oseltamivir is primarily metabolized by hepatic esterases (not CYP450 enzymes) to its active form, oseltamivir carboxylate 1, 2
- Approximately 80% is absorbed systemically and excreted renally via glomerular filtration and tubular secretion through the anionic pathway 1
- The drug has minimal CYP450 involvement in its metabolism 1
Apixaban Metabolism and Excretion
- Apixaban is primarily metabolized via hepatic CYP3A4-dependent pathways 1
- Only 27% undergoes renal elimination 1
- The drug is a substrate for P-glycoprotein (P-gp) transporter 1
- Apixaban has an apparent half-life of approximately 12 hours 1
Why No Interaction Occurs
- Oseltamivir does not inhibit or induce CYP3A4, which is the primary metabolic pathway for apixaban 1
- Oseltamivir is not a P-gp inhibitor or inducer, so it does not affect apixaban transport 1
- The renal excretion pathways differ: oseltamivir uses the anionic tubular secretion pathway, while apixaban undergoes minimal renal clearance 1
Known Drug Interactions to Consider
Oseltamivir Interactions
- Probenecid is the only documented interaction, reducing oseltamivir carboxylate clearance by ~50% through competition for renal tubular secretion 1
- Warfarin interaction: Case reports document INR elevation when oseltamivir is added to warfarin therapy, requiring close INR monitoring 3, 4
- Live attenuated influenza vaccine (LAIV): Avoid oseltamivir within 48 hours before LAIV and for 14 days after LAIV 5
Apixaban Interactions Requiring Dose Adjustment
- Strong dual CYP3A4 and P-gp inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): Reduce apixaban dose by 50% if on 5-10 mg twice daily; avoid if on 2.5 mg twice daily 1
- Strong dual CYP3A4 and P-gp inducers (e.g., rifampin, carbamazepine, phenytoin): Avoid concomitant use due to reduced apixaban efficacy 1
Clinical Management Recommendations
No special monitoring or dose adjustments are required when prescribing oseltamivir to patients taking apixaban 1. However, consider these practical points:
Renal function assessment: Both drugs require dose adjustment in renal impairment, though for different reasons 1, 5
Gastrointestinal tolerability: Oseltamivir causes nausea/vomiting in ~10% of adults; administering with food improves tolerability without affecting absorption 1, 5, 6
Bleeding risk considerations: While oseltamivir does not increase apixaban levels, monitor for bleeding if the patient develops severe influenza-related complications (thrombocytopenia, hepatic dysfunction) that could independently affect coagulation 1
Common Pitfall to Avoid
Do not confuse the warfarin-oseltamivir interaction with apixaban-oseltamivir co-administration. The documented INR elevation with warfarin 3, 4 does not apply to direct oral anticoagulants like apixaban, which have predictable pharmacokinetics independent of vitamin K-dependent clotting factors 1.