amphotericin B
Brand: Fungizone (conventional), AmBisome (liposomal), Abelcet (lipid complex)
Prototype Drug
Drug Class: polyene antifungal antibiotic
Drug Family: antifungal
Subclass: broad-spectrum polyene macrolide antifungal
Organ Systems: infectious-disease
Mechanism of Action
Binds ergosterol in the fungal cell membrane, creating pores that increase membrane permeability; loss of potassium, protons, and small molecules causes fungal cell death; the selectivity of amphotericin B for ergosterol over cholesterol explains its antifungal vs. mammalian toxicity.
ergosterol (fungal cell membrane)
Indications
- invasive aspergillosis (primary or salvage)
- invasive candidiasis
- cryptococcal meningitis (in HIV — with flucytosine)
- mucormycosis (liposomal preferred)
- histoplasmosis and other endemic mycoses (severe or disseminated)
- empiric antifungal therapy in febrile neutropenia
Contraindications
- amphotericin B hypersensitivity (conventional formulation)
Adverse Effects
Common
- infusion reactions (fever, chills, rigors, headache, nausea — conventional > liposomal)
- nephrotoxicity (most clinically significant)
- electrolyte wasting (hypokalemia, hypomagnesemia)
Serious
- nephrotoxicity (dose-dependent; 80% with conventional formulation; significantly less with liposomal)
- severe hypokalemia and hypomagnesemia
- normochromic normocytic anemia
- cardiovascular collapse (with rapid infusion of conventional formulation)
- hepatotoxicity (rare)
Pharmacokinetics (ADME)
| Absorption | IV only (negligible oral absorption) |
| Distribution | binds to serum lipoproteins and tissues; liposomal formulation reduces tissue binding and nephrotoxicity |
| Metabolism | not significantly metabolized |
| Excretion | renal and biliary (extremely slow elimination); detectable for weeks after discontinuation |
| Half-life | 15 days (terminal) |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | once-daily |
| Protein Binding | 91–95% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| nephrotoxic agents (aminoglycosides, cyclosporine, tacrolimus) | additive nephrotoxicity — avoid or use with extreme caution | major |
| fluconazole and azoles | pharmacodynamic antagonism — azoles inhibit ergosterol synthesis (target of amphotericin); may reduce amphotericin efficacy; clinical significance controversial | moderate |
| digoxin | amphotericin-induced hypokalemia potentiates digoxin toxicity | major |
Nursing Considerations
- Pre-medicate for infusion reactions: acetaminophen 650 mg + diphenhydramine 25 mg 30 minutes before conventional amphotericin; meperidine 25–50 mg or hydrocortisone IV is used for severe rigors.
- Infuse conventional amphotericin over 4–6 hours; NEVER infuse rapidly — cardiovascular collapse can result from potassium efflux with rapid infusion.
- Electrolyte replacement is essential: monitor potassium and magnesium daily and replace aggressively; hypokalemia from potassium wasting predisposes to fatal arrhythmias.
- Liposomal amphotericin (AmBisome) is preferred over conventional for most indications due to significantly reduced nephrotoxicity and infusion reactions at equivalent efficacy.
Clinical Pearls
- Amphotericin B has been the 'gold standard' antifungal for decades — broad spectrum, fungicidal activity, and minimal resistance — but its toxicity burden earned it the nickname 'ampho-terrible' in clinical settings; liposomal formulations maintain the efficacy while dramatically reducing nephrotoxicity.
- The combination of amphotericin B deoxycholate + flucytosine for cryptococcal meningitis is the induction regimen of choice due to synergistic fungicidal activity; flucytosine penetrates the CNS and provides rapid CSF sterilization.
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.