Lamisil and Eliquis: No Clinically Significant Interaction
Terbinafine (Lamisil) can be safely used with apixaban (Eliquis) in patients with normal liver and kidney function, as terbinafine has minimal drug-drug interactions and does not affect the CYP3A4 or P-glycoprotein pathways that are critical for apixaban metabolism. 1, 2
Why This Combination Is Safe
Terbinafine's Favorable Interaction Profile
- Terbinafine has minimal drug-drug interactions compared to azole antifungals, making it one of the safest systemic antifungals for patients on multiple medications 2, 3
- The only potentially significant interactions with terbinafine involve drugs metabolized by cytochrome P450 2D6 (certain antidepressants, beta-blockers, and antiarrhythmics), not anticoagulants 2, 4
- In a large postmarketing surveillance study of 25,884 patients, 42.8% were taking concomitant therapies with terbinafine, and no new drug-drug interactions were revealed 3
Apixaban's Critical Interaction Pathways
- Apixaban requires dose reduction or avoidance only with strong dual P-glycoprotein (P-gp) AND CYP3A4 inhibitors or inducers 1
- Strong dual inhibitors requiring dose reduction include ketoconazole, itraconazole, ritonavir, and clarithromycin 1
- Strong inducers to avoid include rifampin, carbamazepine, phenytoin, and St. John's wort 1
- Terbinafine does not inhibit or induce either P-gp or CYP3A4, which are the critical pathways for apixaban metabolism 2, 3
Practical Prescribing Guidance
Standard Dosing Without Adjustment
- Continue apixaban at the standard dose (typically 5 mg twice daily, or 2.5 mg twice daily if dose reduction criteria are met) 1
- Prescribe terbinafine 250 mg once daily for the full treatment duration: 6 weeks for fingernail onychomycosis or 12 weeks for toenail onychomycosis 2
Pre-Treatment Requirements for Terbinafine
- Obtain baseline liver function tests (ALT and AST) and complete blood count before starting terbinafine 2
- Confirm that active or chronic liver disease is absent, as this is an absolute contraindication to terbinafine 2
Monitoring Parameters
- Monitor for signs of unusual bleeding or bruising, which is standard for any patient on apixaban 1
- Monitor liver function if the patient develops symptoms suggestive of hepatotoxicity (nausea, fatigue, jaundice) while on terbinafine 2
- No additional monitoring is required specifically for drug-drug interaction between these two agents 2, 3
Important Clinical Caveats
Warfarin Is Different
- One case report documented gastrointestinal bleeding in a patient on warfarin when terbinafine was added, particularly in the context of concurrent cimetidine use 5
- This interaction is specific to warfarin (a vitamin K antagonist metabolized through hepatic pathways) and does not apply to apixaban, which has a different mechanism of action and metabolism 5
Avoid Confusion with Azole Antifungals
- Azole antifungals (itraconazole, ketoconazole, voriconazole, posaconazole) are strong CYP3A4 inhibitors and DO require apixaban dose reduction 1
- Terbinafine is an allylamine antifungal with a completely different metabolic profile than azoles 2, 3
NSAIDs Remain Problematic
- While terbinafine is safe with apixaban, oral NSAIDs should still be avoided or used with extreme caution due to increased bleeding risk 6
- If pain management is needed during terbinafine treatment, acetaminophen is the preferred first-line analgesic 7
When to Exercise Additional Caution
Renal Function Considerations
- Apixaban is contraindicated if creatinine clearance is <25 mL/min 8, 1
- Dose reduction to 2.5 mg twice daily is required if the patient meets at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1
- These criteria are independent of terbinafine use 1