Antifungal drugs

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Joanna Breems
MD, FACP · Clinical Assistant Professor
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Table of Contents

Amphotericin B

Ampho B

  • Broad spectrum, little resistance
  • GI and renal toxicity limit dose
  • Binds ergosterol causing cytoplasmic membrane holes

Azoles

Fluconazole, Miconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole

  • Inhibits ergosterol synthesis in cytoplasmic membrane
  • Topical Rx for dermatophytes and skin
  • Candida (clotrimazole, miconazole)
  • Systemic Rx specific to different fungi
  • Voriconazole is best for aspergillus

Echinocandins

Caspofungin, Micafungin, Anidulafungin

  • Inhibit glucan synthesis in cell wall

Flucytosine

5-FC

  • Inhibits DNA and RNA
  • Easily induces resistance so always combine with another drug, especially Ampho B

Griseofulvin and Terbinafine

  • Used orally for dermatophytes

Nystatin

  • Topical Rx for oral or cutaneous Candida

Terbinafine (Lamisil, Lamisil AT)

  • Class(es)

    Antifungal

  • Clinical use(s)

    FDA approved: Dermal mycosis, onychomycosis due to dermatophyte, Tinea capitis.

  • Mechanism(s) of action

    Inhibits the biosynthesis of ergosterol, an integral component of fungal cell membrane.

  • Key adverse effects

    Nasopharyngitis (oral granules, 10% ), increased liver enzymes (oral tablets, 3.3% ), Terbinafine 1% topical cream or gel has been associated with local burning, pruritus, skin discoloration, or erythema (2%).

  • Key drug/food interactions

    Strong CYP2D6 inhibitor. Avoid drugs primarily metabolized by CYP2D6 (e.g., codeine, tramadol, metoclopramide).

  • Special considerations

    Available orally and topically only. Contraindicated in chronic or active liver disease.

Nystatin (Mycostatin)

  • Class(es)

    Polyene antifungal

  • Clinical use(s)

    FDA approved: Candidiasis infection treatment.
    Off-label/clinical use: Candidiasis infection prophylaxis.

  • Mechanism(s) of action

    Binds to sterols in the fungal cell membrane leading to loss of membrane barrier selectivity.

  • Key adverse effects

    Skin irritation.

  • Key drug/food interactions

    None significant.

  • Special considerations

    Powder: Very moist lesions are best treated with topical powder.
    Oral suspension: For oropharyngeal and esophageal candidiasis, have patients swish and swallow. For oral thrush, have patients swish and spit.

Fluconazole (Diflucan)

  • Class(es)

    Triazole/Antifungal

  • Clinical use(s)

    FDA approved: Candidiasis, cryptococcal meningitis, antifungal prophylaxis in allogenic bone marrow transplant patients.
    Off-label/clinical use: Coccidioidomycosis, cryptococcal pneumonia, primary antifungal prophylaxis in pediatric oncology.

  • Mechanism(s) of action

    Interferes with fungal cytochrome P450 activity decreasing ergosterol synthesis and inhibiting cell membrane formation.

  • Key adverse effects

    Nausea, headache, elevated liver enzymes.

  • Key drug/food interactions

    QT prolonging medications, warfarin, carbamazepine.

  • Special considerations

    Risk QT prolongation.
    Renally adjusted: CrCl < 50 ml/min.

Voriconazole (Vfend)

  • Class(es)

    Triazoles/Antifungal

  • Clinical use(s)

    FDA approved: Aspergillosis, candidemia, candidiasis of the esophagus, invasive candidiasis, mycosis, serious infections due to scedosporium apiospermum and fusarium spp.
    Off-label/clinical use: blastomycosis, candida endophthalmitis, febrile neutropenia, mycosis due to scedosporium prolificans, oropharyngeal candidiasis, pulmonary aspergillosis.

  • Mechanism(s) of action

    Inhibits fungal cytochrome P450-dependent ergosterol synthesis resulting in loss of ergosterol in the fungal cell wall.

  • Key adverse effects

    Hallucinations, nausea, diarrhea, vomiting.

  • Key drug/food interactions

    QT prolonging medications, St. Johns Wort, food (may ↓ voriconazole absorption).

  • Special considerations

    Risk of QT prolongation.

Amphotericin B (Amphocin, Fungizone)

  • Class(es)

    Antifungal

  • Clinical use(s)

    FDA approved: Aspergillosis (invasive), candidemia and other candida infections, candidiasis esophageal, fungal infections, empiric therapy.
    Off-label/clinical use: Candidiasis oropharyngeal, other candida infections.

  • Mechanism(s) of action

    Inhibits synthesis of β(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi.

  • Key adverse effects

    Elevated liver enzymes, hypotension, tachycardia, elevated serum creatinine.

  • Key drug/food interactions

    Cyclosporine, rifampin, tacrolimus.

  • Special considerations

    Hepatically adjusted: Moderate-severe hepatic impairment (Child-Pugh class B/C).
    Black box warning: Should not be used in noninvasive forms of fungal infections.

Caspofungin (Cancidas)

  • Class(es)

    Echinocandin/Antifungal

  • Clinical use(s)

    FDA approved: Aspergillus, candidemia, candidiasis of esophagus, febrile neutropenia (empiric antifungal), invasive candidiasis.
    Off-label/clinical use: Aspergillosis, candida endophthalmitis, candidiasis (cardiovascular/osteoarticular), oropharyngeal candidiasis, pulmonary aspergillosis.

  • Mechanism(s) of action

    Inhibits synthesis of β(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi.

  • Key adverse effects

    Hypotension, diarrhea, elevated liver enzymes.

  • Key drug/food interactions

    Cyclosporine, tacrolimus, rifampin.

  • Special considerations

    Hepatically adjusted: Moderate-severe hepatic impairment (Child-Pugh class B/C).