What antifungal medication does not interact with Plaquenil (hydroxychloroquine)?

Antifungal Selection to Avoid Interactions with Plaquenil (Hydroxychloroquine)

Echinocandins (micafungin, anidulafungin, caspofungin) and amphotericin B formulations are the safest antifungal choices when avoiding drug interactions with hydroxychloroquine, as they do not interact through cytochrome P450 pathways.

Primary Recommendations by Drug Class

Echinocandins - First Choice for Minimal Interactions

• Micafungin is the echinocandin with the fewest drug interactions and requires no dosage adjustment, making it an excellent choice when hydroxychloroquine is being used 1
• Anidulafungin also lacks relevant interactions and can be used safely in combination with hydroxychloroquine 1
• Caspofungin has more interactions than other echinocandins but still significantly fewer than azoles 1
• Standard dosing: Micafungin 100 mg daily, anidulafungin 200 mg loading then 100 mg daily, caspofungin 70 mg loading then 50 mg daily 2

Amphotericin B Formulations - Second Choice

• Amphotericin B (both deoxycholate and lipid formulations) lacks cytochrome P450-mediated drug interactions, making it compatible with hydroxychloroquine 3, 1
• The primary concern with amphotericin B is nephrotoxicity and electrolyte disturbances, not drug-drug interactions through metabolic pathways 3, 4
• Liposomal amphotericin B (L-AmB) has significantly lower nephrotoxicity than deoxycholate formulation 1

Antifungals to AVOID with Hydroxychloroquine

Azole Antifungals - High Interaction Risk

• All azole antifungals (fluconazole, itraconazole, voriconazole, posaconazole) inhibit cytochrome P450 enzymes, particularly CYP3A4, creating potential for significant drug interactions 3, 5
• Itraconazole and posaconazole are also substrates and inhibitors of P-glycoprotein transporter protein, adding another layer of interaction potential 5
• While fluconazole has the fewest interactions among azoles, it still modifies drug metabolism through CYP450 inhibition 1, 5

Additional Concern: QT Prolongation

• Both hydroxychloroquine and azole antifungals can prolong the QT interval, creating additive risk for dangerous arrhythmias including torsades de pointes 3
• This pharmacodynamic interaction is particularly concerning when azoles are combined with other QT-prolonging medications 3

Clinical Algorithm for Selection

For invasive candidiasis:

• Use echinocandins (micafungin or anidulafungin preferred) as first-line therapy 2, 6, 1
• Amphotericin B formulations are acceptable alternatives 2, 6

For invasive aspergillosis:

• Use liposomal amphotericin B or echinocandins 2, 6
• Avoid voriconazole (standard first-line) due to CYP450 interactions 5

For cryptococcosis:

• Use amphotericin B deoxycholate plus flucytosine as induction therapy 2, 6
• Avoid fluconazole consolidation therapy if possible; consider extended amphotericin B 2

For mucormycosis:

• Use liposomal amphotericin B (drug of choice with no interaction concerns) 2, 6

Important Caveats

• Therapeutic drug monitoring is not required for echinocandins, simplifying management compared to azoles 1
• Amphotericin B may cause renal dysfunction leading to accumulation of renally metabolized drugs, though this is not a direct drug-drug interaction 1
• If azole therapy is absolutely necessary, fluconazole has the lowest interaction potential among azoles, but ECG monitoring for QT prolongation is essential 1, 5
• Topical antifungals have minimal systemic exposure and essentially no interaction risk for superficial infections 7