What antifungal medication has a low risk of interaction with statins (HMG-CoA reductase inhibitors)?

Terbinafine is the Preferred Antifungal for Patients on Statin Therapy

Terbinafine should be used as the first-line antifungal medication in patients taking statins due to its minimal drug-drug interaction potential with HMG-CoA reductase inhibitors. 1

Antifungal-Statin Interaction Risk Assessment

Low Risk Antifungals

• Terbinafine is the safest choice for patients on statins as it:

  • Primarily affects cytochrome P450 2D6 isoenzyme, not the CYP3A4 enzyme that metabolizes most statins 1
  • Has a relatively low potential for drug interactions overall 2
  • Can be safely co-administered with statins without significant risk of increased statin concentrations 1

• Topical antifungals (regardless of class) are generally safe with statins as systemic absorption is minimal 3

High Risk Antifungals

• Azole antifungals significantly increase the risk of statin-related myopathy:
  • Fluconazole, itraconazole, and ketoconazole inhibit CYP3A4, which metabolizes most statins 3, 4
  • FDA labeling specifically warns that fluconazole increases the risk of myopathy and rhabdomyolysis when co-administered with statins 4
  • Azoles can increase statin concentrations, potentially leading to severe adverse effects 3

Clinical Decision Algorithm

1. First-line treatment: Terbinafine

   • Oral terbinafine 250mg daily for 6 weeks (fingernails) or 12-16 weeks (toenails) for dermatophyte infections 3
   • Has superior efficacy compared to itraconazole for dermatophyte onychomycosis 3
   • Minimal drug interactions with statins 1, 5

2. Second-line options (if terbinafine is contraindicated):

   • Hydrophilic statins (fluvastatin, pravastatin) with fluconazole (if azole antifungal is necessary)
     • These statins are not metabolized by CYP3A4 and may cause fewer metabolic interactions 3
     • Still requires close monitoring for myopathy symptoms 4

3. If azole antifungal is absolutely necessary:

   • Consider temporarily discontinuing statin therapy during short-term antifungal treatment 3
   • If both medications must be continued, reduce statin dose and monitor creatine kinase levels closely 4

Monitoring Recommendations

• Monitor for symptoms of myopathy (muscle soreness, tenderness, pain) at baseline and during follow-up visits 3
• Obtain creatine kinase measurements when patients report muscle symptoms 3
• Evaluate liver function (ALT/AST) initially, at 12 weeks, and then annually 3
• Be particularly vigilant in high-risk patients (elderly, frail, multisystem disease, multiple medications) 3

Important Clinical Considerations

• Terbinafine is superior to itraconazole both in vitro and in vivo for dermatophyte onychomycosis 3
• Terbinafine achieves mycological cure in >80% of patients with superficial dermatophyte infections 2
• The risk of statin-related myopathy increases significantly with azole antifungals, particularly at higher doses 3
• Patients with diabetes should especially use terbinafine over itraconazole, as itraconazole is contraindicated in congestive heart failure (more common in diabetics) 3
• Some research suggests statins themselves may have antifungal properties, but this effect occurs at supraphysiological concentrations and should not influence clinical decision-making 6, 7, 8

Common Pitfalls to Avoid

• Don't assume all antifungals have similar interaction profiles with statins
• Don't overlook the importance of monitoring for myopathy symptoms when any antifungal is used with statins
• Don't automatically discontinue beneficial statin therapy when antifungal treatment is needed - choose terbinafine instead
• Don't use itraconazole in diabetic patients on statins due to additional cardiac risks 3