Pharmacology · Polyene antifungals
Amphotericin B !
Polyene antifungal given by vein for life-threatening fungal infections. It opens pores in the fungal membrane but can harm the kidneys.
Updated 2026-11-01
Also called: amphotericin B deoxycholate (conventional), liposomal amphotericin B, amphotericin B lipid complex
Mechanism of action
Amphotericin B binds ergosterol in the fungal cell membrane and forms transmembrane channels through which potassium, sodium, hydrogen and chloride ions leak out, killing the cell. It has a higher affinity for ergosterol than for cholesterol, but binding to human cholesterol, especially in the kidney, causes its toxicity. Lipid formulations (liposomal, lipid complex) carry the same drug with fewer infusion and kidney adverse events than the conventional deoxycholate form.
- Amphotericin B binds ergosterol in the fungal membrane
- Its molecules group into pores across the membrane
- K⁺ and other ions leak out and the fungus dies
- Some binding to human cholesterol injures the kidney
Pharmacokinetics
- Absorption
- Given by vein for systemic infections.
- Distribution
- Highly bound to plasma proteins; reaches inflamed pleura, peritoneum and joints, but very little reaches the CSF.
- Elimination
- Very slow, through the kidneys over weeks to months; haemodialysis does not remove it.
- Half-life
- Conventional form: an initial phase of about a day, then a terminal half-life of about 15 days.
Indications
- Invasive aspergillosis. Aspergillosis →
- Cryptococcal meningitis, as induction together with flucytosine; the liposomal form is labelled for it in people with HIV. Cryptococcal meningitis →
- Invasive and systemic candidiasis. Candidiasis: oral, oesophageal and invasive →
- Severe or progressive histoplasmosis. Histoplasmosis →
- Severe paracoccidioidomycosis, an endemic mycosis of Latin America. Paracoccidioidomycosis →
- Blastomycosis and rapidly progressing coccidioidomycosis. Endemic mycoses: blastomycosis and coccidioidomycosis →
- Mucormycosis (zygomycosis).
- Empirical therapy of presumed fungal infection in febrile neutropenic patients (liposomal form). Febrile neutropenia →
- Visceral leishmaniasis (liposomal form); the conventional form may be used in American mucocutaneous leishmaniasis, though it is not the first choice. Leishmaniasis →
Adverse effects
Common
- Fever, shaking chills, nausea, vomiting and headache, usually 1 to 3 hours after starting the infusion and worse with the first doses
- Hypotension and fast breathing during the infusion
- Low potassium and low magnesium
- Normochromic, normocytic anaemia
- Pain and phlebitis at the infusion site
Contraindications
- Known hypersensitivity, unless the infection is life-threatening and only amphotericin B can treat it
- Conventional form: not for non-invasive infections (thrush, vaginal or oesophageal candidiasis) in patients with normal neutrophil counts
Key interactions
- Other nephrotoxic drugs (aminoglycosides, cyclosporine, pentamidine)
- Add kidney damage; renal function is monitored intensively.
- Corticosteroids and corticotropin
- Worsen hypokalaemia and its cardiac risk.
- Digoxin and other digitalis glycosides
- Amphotericin-induced hypokalaemia raises digitalis toxicity.
- Flucytosine
- Synergistic antifungal effect, but amphotericin B may raise flucytosine toxicity by reducing its renal excretion.
- Skeletal muscle relaxants
- Hypokalaemia may strengthen their effect.
- Leukocyte transfusions
- Acute pulmonary toxicity; the two are separated as much as possible.
What is monitored
- Serum creatinine and urea, frequently
- Potassium and magnesium (also calcium)
- Liver tests, blood count and haemoglobin
- Vital signs during the infusion, closely with the first doses
Administration and safety
- Look-alike risk: conventional (deoxycholate), liposomal and lipid-complex products are not interchangeable mg for mg; confusing them has caused fatal overdoses. Check the exact product name and the order before preparing it.
- Reconstitute with sterile water without preservative and dilute only in dextrose: saline or bacteriostatic diluents make it precipitate. Flush an existing line with dextrose before and after, or use a separate line.
- Give as a slow intravenous infusion over hours; a rapid infusion has caused hypotension, hypokalaemia, arrhythmias and shock.
- Do not mix with other drugs in the same bag or line. If an in-line filter is used, its pore must be wide enough to let the drug pass.
- Store the conventional powder refrigerated and protected from light; strict aseptic technique, as it has no preservative.
Nursing care
- Before each dose: creatinine, potassium and magnesium; report rising creatinine or falling electrolytes.
- During the infusion: temperature, pulse, breathing and blood pressure, closely with the first doses; stop the infusion and call for help if anaphylaxis appears.
- Premedication (antipyretic, antihistamine) and saline hydration before the dose, when ordered, reduce infusion reactions and kidney injury.
- Fluid balance and daily weight; watch for weakness, cramps or palpitations from low potassium.
- Check the IV site for phlebitis and extravasation, which irritates tissue.
Pregnancy and breastfeeding
Animal studies showed no fetal harm and serious fungal infections in pregnancy have been treated with it, though human data are few; it is used when clearly needed.
Test yourself
Think of the answer, then tap the question to see it.
Why is a mix-up between conventional and liposomal amphotericin B so dangerous?
They are dosed very differently and are not interchangeable mg for mg; giving a lipid-formulation amount of the conventional drug has caused fatal cardiac or cardiopulmonary arrest.
Which solution is used to dilute amphotericin B, and which must never be used?
Dextrose. Saline makes the drug precipitate, so it is not used to dilute it or to flush the line.
Why is amphotericin B combined with flucytosine in cryptococcal meningitis?
The two are synergistic, flucytosine reaches the CSF well while amphotericin B reaches it poorly, and the combination prevents the fast resistance seen with flucytosine alone.
A patient on amphotericin B and digoxin develops palpitations. What laboratory value is checked first?
Potassium (and magnesium): amphotericin-induced hypokalaemia increases digoxin toxicity and arrhythmia risk.
Related drugs
Related conditions
- Aspergillosis
- Cryptococcal meningitis
- Candidiasis: oral, oesophageal and invasive
- Histoplasmosis
- Paracoccidioidomycosis
- Endemic mycoses: blastomycosis and coccidioidomycosis
- Febrile neutropenia
- Leishmaniasis
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - AMPHOTERICIN B injection, powder, lyophilized, for solution (DailyMed (U.S. National Library of Medicine), 2022); DailyMed - AMPHOTERICIN B injectable, liposomal (DailyMed (U.S. National Library of Medicine), 2026); Amphotericin B Liposomal Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 61 (McGraw Hill, 2023).
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