Antifungals

Amphotericin

Rapid Review

  • Mechanism of Action: Anti-fungal; binds to ergosterol in fungal membranes and causes intracellular contents to leak out.
  • Indications: used for severe or disseminated fungal infections (invasive aspergillosis, cryptococcal meningitis, blastomycosis, coccidiomycosis)
  • Contraindications: allergy to class/drug
  • Dosage: Dosage varies significantly based on formulation. Generally, a single test dosage (1 mg in 20 mL of 5% dextrose) is infused over 20-30 minutes with close monitoring. If tolerated, then give a single daily dosage of 0.25mg/kg.
  • Half-life: Up to 14 days; depending on dosage
  • Adverse Reactions: Associated with significant renal toxicity. May also cause fever, chills, muscle rigor, and hypotension
  • Special Considerations: May cause hypokalemia and hypomagnesemia. Should be supplemented with potassium and magnesium. IV fluids help minimize nephrotoxicity.

Pearls

  • Amphotericin is notorious for it’s frequency of side effects. Approximately 80% of patients will have some infusion related or renal toxicity. Always consult pharmacy when possible prior to administering this medication to avoid drug-drug interactions.
  • Hypokalemia and hypomagnesemia are also common side effects. Supplement with potassium and magnesium as needed. 
Video Credit: Medicosis

Clotrimazole

Rapid Review

  • Mechanism of Action: Azole antifungal; inhibits 14-alpha demethylase and reduces fungal cell membrane synthesis.
  • Indications: Tinea infections (ringworm, jock itch, athletes foot), pityriasis versicolor, oropharyngeal candidiasis, vulvovaginal candidiasis
  • Contraindications: Allergy to drug/class
  • Dosage:
    • Tinea infections: Topical 1% cream applied bid x 2-4 weeks
    • Oropharyngeal infection: 10mg PO 5 times daily x 14 days
    • Vulvovaginal infection: 1 applicator 2% PV qhs x 3 days
  • Half-life: Unknown
  • Adverse Reactions: Itching, nausea, vomiting.
  • Special Considerations: Oral formulations may cause abnormal liver function tests in 10% of patients.

Pearls

  • Clotrimazole is useful for minor infections, such as ringwor, athlete’s foot, or vaginal yeast infections. However, for more severe or refractory infections, PO fluconazole is often needed.
  • Some clotrimazole formulations have a corticosteroid (betamethasone) mixed with it to treat specific inflammatory tinea infections (ex. Epidermophyton or Trichophyton). However, this may exacerbate or worsen other common fungal infections
Video Credit: Drug Talk

Fluconazole

Rapid Review

  • Mechanism of Action: Triazole antifungal; inhibits cytochrome P450 to prevent egosterol synthesis to increase cellular permeability.
  • Indications: Vaginal, oropharyngeal, or esophageal candidiasis. Systemic candida infections.
  • Contraindications: Allergy to drug/class, coadministration with drugs that prolong QT intervals
  • Dosage:
    • Vaginal candidiasis: Single 150mg dose PO
    • Esophageal/oropharyngeal candidiasis: 100mg PO q daily x 2 weeks
  • Half-life: 24 hours
  • Adverse Reactions: GI symptoms (nausea, abdominal pain, diarrhea), anaphylaxis, hepatotoxicity, QT prolongation
  • Special Considerations: 
  • Fluconazole is an antifungal medication used to treat candidal infections (e.g. vaginal yeast infection), tinea as well as invasive fungal infections.

Pearls

  • Fluconazole may care a wide array of adverse dermatologic skin reactions, ranging from alopecia to Steven-Johnson/Toxic epidermal necrolysis. 
  • Although high doses of fluconazole (> 400 mg per day) has been shown to be harmful to fetuses, a single dose of fluconazole for vaginal candidiasis is likely safe. 
Video Credit: Drug Talk