Is it safe for an adult patient with a history of cardiovascular disease to take ELIQUIS (apixaban), BENZONATATE ( Tessalon), and AUGMENTIN (amoxicillin/clavulanate) together?

Safety of Concurrent ELIQUIS, Benzonatate, and Augmentin Use

Yes, it is safe to take ELIQUIS (apixaban), benzonatate, and Augmentin (amoxicillin/clavulanate) together, as there are no clinically significant drug-drug interactions between these three medications.

Mechanism and Interaction Analysis

ELIQUIS (Apixaban) Metabolism

• Apixaban is primarily metabolized through CYP3A4 and P-glycoprotein (P-gp) pathways 1
• Clinically significant interactions occur only with strong dual CYP3A4 and P-gp inhibitors or inducers 1
• Dose reduction by 50% is required only when combining apixaban with strong dual CYP3A4/P-gp inhibitors (such as ketoconazole, clarithromycin, or ritonavir) 1

Augmentin (Amoxicillin/Clavulanate) Profile

• Augmentin is a beta-lactam antibiotic that does not significantly inhibit or induce CYP3A4 or P-gp 1
• Unlike clarithromycin (a strong CYP3A4/P-gp inhibitor that increases bleeding risk with apixaban), amoxicillin/clavulanate has no documented interaction with direct oral anticoagulants 1
• The combination of antibiotics with anticoagulants is commonly used in clinical practice without dose adjustment requirements 1

Benzonatate Characteristics

• Benzonatate is a non-narcotic cough suppressant with local anesthetic properties that works peripherally on stretch receptors in the respiratory tract
• It has no known interactions with CYP450 enzymes or P-gp transporters
• No documented interactions exist between benzonatate and anticoagulants or antibiotics

Monitoring Recommendations

Bleeding Risk Assessment

• Monitor for signs and symptoms of bleeding (bruising, blood in urine/stool, prolonged bleeding from cuts, unusual fatigue) during antibiotic therapy 1
• The baseline bleeding risk with apixaban remains unchanged by this combination, but patients should be counseled on recognition of bleeding symptoms 1

Renal Function Considerations

• If the patient has chronic kidney disease (CrCl <30 mL/min), apixaban dosing may need adjustment independent of these drug interactions 1, 2
• Augmentin requires dose adjustment in severe renal impairment, but this does not affect apixaban dosing decisions 1

Common Pitfalls to Avoid

Antibiotic Selection Errors

• Do not substitute Augmentin with clarithromycin or erythromycin while on apixaban, as macrolide antibiotics are strong CYP3A4/P-gp inhibitors that significantly increase apixaban levels and bleeding risk 1
• Azithromycin is a safer macrolide alternative if needed, as it only inhibits P-gp without strong CYP3A4 inhibition 1

Antiplatelet Combination Warning

• Avoid adding aspirin or NSAIDs (ibuprofen, naproxen) during this treatment period, as the combination of anticoagulants with antiplatelets significantly increases bleeding risk 1
• If the patient requires pain management, acetaminophen is the preferred analgesic 3

Duration of Therapy

• Complete the full course of Augmentin as prescribed (typically 7-14 days depending on infection)
• Benzonatate should be used only as needed for cough suppression and discontinued when symptoms resolve
• Continue apixaban without interruption unless bleeding occurs 1, 4

Clinical Context for Cardiovascular Patients

Heart Failure Considerations

• If the patient has heart failure, ensure they are not on multiple interacting medications that could complicate anticoagulation management 1
• The polypharmacy burden in cardiovascular patients increases interaction risk, but this specific three-drug combination remains safe 1

Infection Management Priority

• Treating acute bacterial infections with Augmentin takes precedence and should not be delayed due to anticoagulation concerns 5
• The short duration of antibiotic therapy (typically 5-14 days) minimizes any theoretical interaction risk 5