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Amphotericin B

Comprehensive Guide to Amphotericin B: Uses, Dosage, Side Effects, and More

What is Amphotericin B?

Amphotericin B is a polyene antifungal medication used to treat severe fungal infections, including systemic mycoses like candidiasis, aspergillosis, and cryptococcosis. By binding to ergosterol in fungal cell membranes, this drug disrupts membrane integrity, leading to fungal cell death. Available in conventional (deoxycholate) and lipid-based formulations (e.g., liposomal, lipid complex), the antifungal is administered intravenously in hospital settings. Amphotericin B’s benefits include its broad-spectrum activity against resistant fungi, but it requires careful monitoring due to nephrotoxicity and infusion-related reactions.
A scientific diagram illustrating the complex mechanism of action of Amphotericin B (AmB) against fungal cells, showing its interaction with ergosterol, pore formation in the cell membrane, generation of reactive oxygen species (ROS), and subsequent cellular damage including membrane, DNA, protein, and mitochondrial damage.
This diagram illustrates how Amphotericin B targets fungal cell membranes by binding to ergosterol, leading to pore formation, oxidative stress, and subsequent cellular damage including membrane disruption, DNA, protein, and mitochondrial damage, ultimately causing loss of metabolic activity and cell death.

Overview of Amphotericin B

Generic Name: Amphotericin B

Brand Name: Fungizone (conventional), AmBisome (liposomal), Abelcet (lipid complex), generics

Drug Group: Polyene antifungal

Commonly Used For

  • Treat systemic fungal infections (e.g., candidemia, aspergillosis, cryptococcosis).
  • Manage severe mucocutaneous candidiasis or fungal meningitis.
  • Treat visceral leishmaniasis (liposomal form).
  • Off-label uses include fungal keratitis or prophylaxis in immunocompromised patients under specialist guidance.

Key Characteristics

Form: IV powder for reconstitution (50 mg/vial) in conventional or lipid formulations.

Mechanism: Binds to ergosterol, creating pores in fungal membranes, causing leakage and cell death.

Approval: FDA-approved (1958 for Fungizone) and EMA-approved for systemic fungal infections.

Indications and Uses of Amphotericin B

Amphotericin B is indicated for:

Systemic Fungal Infections: Treats candidiasis, aspergillosis, cryptococcosis, histoplasmosis, and mucormycosis.

Fungal Meningitis: Manages cryptococcal meningitis, often with flucytosine.

Visceral Leishmaniasis: Liposomal form is the first-line treatment.

Off-Label Uses: Prophylaxis in neutropenic patients or treatment of rare fungal infections (e.g., blastomycosis) under specialist supervision.

Note: The drug is reserved for life-threatening fungal infections due to its toxicity profile. Selection of formulation (conventional vs. lipid-based) depends on patient tolerance and infection severity.

Dosage of Amphotericin B

Important Note: Amphotericin B dosage must be prescribed and administered by a healthcare provider in a hospital setting. Dosing varies by formulation, indication, and renal function.

Dosage for Adults

Conventional (Fungizone):

  • 0.25–1 mg/kg/day IV (maximum 1.5 mg/kg/day) over 2–6 hours.
  • Initial test dose: 1 mg IV over 20–30 minutes to assess tolerance.

Liposomal (AmBisome): 3–5 mg/kg/day IV (up to 10 mg/kg/day for invasive aspergillosis or cryptococcosis).

Lipid Complex (Abelcet): 5 mg/kg/day IV.

Visceral Leishmaniasis (Liposomal): 3–5 mg/kg/day on days 1–5, then 3–5 mg/kg on days 14 and 21 (total 12–15 mg/kg).

Dosage for Children

Conventional: 0.25–1 mg/kg/day IV (maximum 1.5 mg/kg/day).

Liposomal: 3–5 mg/kg/day IV, adjusted per weight and tolerance.

Test Dose: 0.1–0.25 mg/kg (maximum 1 mg) to assess infusion reactions.

Dosage for Pregnant Women

Pregnancy Category B (Liposomal) / C (Conventional): Limited data; use only if benefits outweigh risks. Consult an infectious disease specialist.

Dosage Adjustments

Renal Impairment: Reduce dose or extend interval in conventional form (e.g., 0.5–0.7 mg/kg every 24–48 hours); liposomal forms are less nephrotoxic, so adjustments are less common.

Hepatic Impairment: No specific adjustments; monitor liver function.

Elderly: Start with lower doses; monitor for renal and infusion reactions.

Additional Considerations

  • Administer IV infusions with pre-medication (e.g., antihistamines, antipyretics) to reduce infusion reactions.
  • Monitor serum creatinine, electrolytes (potassium, magnesium), and complete blood count regularly.

How to Use Amphotericin B

Administration:

  • IV Infusion: Reconstitute powder with sterile water; dilute in 5% dextrose (not saline); infuse over 2–6 hours.
  • Test Dose: Administer 1 mg (conventional) or 0.1–0.25 mg/kg (liposomal) to assess tolerance.

Timing: Follow prescribed schedule (once daily or as adjusted).

Monitoring: Check for infusion reactions (e.g., fever, chills) and renal function during and after administration.

Additional Tips:

  • Ensure adequate hydration to protect kidney function.
  • Report symptoms like hearing loss, swelling, or severe chills immediately.

Contraindications for Amphotericin B

The antifungal is contraindicated in:

  • Patients with hypersensitivity to Amphotericin B or its components.
  • Patients with severe renal failure (unless benefits outweigh risks with lipid formulations).

Warnings & Precautions for Amphotericin B

General Warnings

Nephrotoxicity: Risk of kidney damage; monitor creatinine and urine output regularly.

Infusion Reactions: Fever, chills, or hypotension may occur; pre-medicate with antipyretics or corticosteroids.

Electrolyte Imbalance: Risk of hypokalemia or hypomagnesemia; monitor and supplement if needed.

Anemia: Bone marrow suppression may cause anemia; monitor hemoglobin.

Hepatotoxicity: Rare; monitor liver function tests.

Use in Specific Populations

Pregnancy: Category B (liposomal) or C (conventional); use cautiously with specialist consultation.

Breastfeeding: Excreted in breast milk in small amounts; weigh benefits versus risks.

Elderly: Increased risk of renal and infusion reactions; use lower doses.

Children: Approved with adjusted dosing; monitor for toxicity.

Renal Impairment: High risk with conventional form; prefer liposomal forms.

Additional Precautions

  • Inform your doctor about kidney disease, electrolyte imbalances, or previous antifungal reactions before starting the medication.
  • Avoid rapid infusion to minimize adverse reactions.

Overdose and Management of Amphotericin B

Overdose Symptoms

  • Severe hypokalemia or hypomagnesemia.
  • Acute kidney injury or renal failure.
  • Severe infusion reactions (e.g., shock, arrhythmias).

Immediate Actions

Contact Emergency Services: Stop infusion; seek immediate medical intervention.

Supportive Care: Correct electrolytes, provide hydration, and monitor renal function.

Hemodialysis: May be considered in severe cases; consult a specialist.

Additional Notes

  • Overdose is rare with proper dosing; ensure accurate weight-based calculations.
  • Report persistent symptoms promptly.

Side Effects of Amphotericin B

Common Side Effects

  • Fever or chills (20–50% during infusion)
  • Nausea or vomiting (10–20%)
  • Headache (5–10%)
  • Anemia (5–10%)

These effects may decrease with pre-medication or lipid formulations.

Serious Side Effects

Renal: Reduced urine output, swelling, or elevated creatinine.

Electrolyte: Muscle weakness or irregular heartbeat (hypokalemia).

Cardiovascular: Hypotension or arrhythmias during infusion.

Allergic Reactions: Rare; rash, anaphylaxis, or bronchospasm.

Additional Notes

  • Regular monitoring of kidney function, electrolytes, and blood counts is critical.
  • Report any unusual symptoms immediately.

Drug Interactions with Amphotericin B

The medication may interact with:

  • Nephrotoxic Drugs (e.g., Vancomycin, NSAIDs): Increase kidney damage risk; avoid or monitor closely.
  • Corticosteroids: May enhance hypokalemia; monitor electrolytes.
  • Digoxin: Risk of toxicity with hypokalemia; monitor levels.
  • Flucytosine: Synergistic antifungal effect; adjust doses to avoid toxicity.
Action: Provide your healthcare provider with a complete list of medications and supplements.

Patient Education or Lifestyle

Medication Adherence: Amphotericin B is administered by professionals; follow hospital treatment protocols and attend follow-up visits.

Monitoring: Report symptoms like fever, swelling, or hearing changes immediately. Regular blood tests are required.

Lifestyle: Stay hydrated to support kidney function; practice infection control to prevent fungal spread.

Diet: Maintain a balanced diet; avoid excessive potassium or magnesium unless prescribed.

Emergency Awareness: Know signs of renal failure (e.g., low urine output) or severe infusion reactions; seek immediate care.

Follow-Up: Schedule post-treatment tests to assess kidney and liver function.

Pharmacokinetics of Amphotericin B

Absorption: Not absorbed orally; administered IV for systemic effect.

Distribution: Volume of distribution ~4 L/kg; penetrates poorly into cerebrospinal fluid.

Metabolism: Not significantly metabolized; excreted unchanged.

Excretion: Primarily renal (<5% unchanged); some biliary excretion.

Half-Life: 15–24 hours (prolonged in renal impairment).

Pharmacodynamics of Amphotericin B

The antifungal exerts its effects by:

  • Binding to ergosterol in fungal membranes, forming pores that cause leakage.
  • Exhibiting broad-spectrum activity against yeasts and molds (e.g., Candida, Aspergillus).
  • Demonstrating concentration-dependent killing, optimized with sustained levels.
  • Effective against resistant fungi when susceptibility is confirmed.

Storage of Amphotericin B

Temperature: Store at 2–8°C (36–46°F); protect from light and freezing.

Reconstituted Solution: Use within 24 hours if refrigerated; do not freeze.

Safety: Store out of reach of children; restricted to hospital use.

Disposal: Dispose of unused vials per hospital protocols and local regulations.

Frequently Asked Questions (FAQs)

Q: What does Amphotericin B treat?
A: The drug treats severe fungal infections like candidiasis or cryptococcosis.

Q: Can Amphotericin B cause kidney damage?
A: Yes, nephrotoxicity is a risk; report reduced urine output immediately.

Q: Is Amphotericin B safe for children?
A: Approved with adjusted dosing; monitor for toxicity.

Q: How is Amphotericin B administered?
A: Via IV infusion in a hospital by trained professionals.

Q: How long is Amphotericin B treatment?
A: Typically 2–6 weeks, depending on infection severity and response.

Regulatory Information

The medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in 1958 (Fungizone); later for lipid formulations.

European Medicines Agency (EMA): Approved for systemic fungal infections.

Other Agencies: Approved globally for equivalent uses; consult local guidelines.

References

  1. U.S. Food and Drug Administration (FDA). (2023). Fungizone (Amphotericin B) Prescribing Information.
    • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
  2. European Medicines Agency (EMA). (2023). Amphotericin B Summary of Product Characteristics.
    • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
  3. National Institutes of Health (NIH). (2023). Amphotericin B: MedlinePlus Drug Information.
    • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
  4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Amphotericin B.
    • WHO’s inclusion of Amphotericin B for fungal infections.
  5. Clinical Infectious Diseases. (2020). Amphotericin B in Invasive Fungal Infections.
    • Peer-reviewed article on Amphotericin B efficacy (note: access may require a subscription).
Disclaimer: This article provides general information about Amphotericin B for educational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare provider, such as an infectious disease specialist, before using this drug or making any medical decisions. Improper use of this medication can lead to serious health risks, including kidney damage, infusion reactions, or electrolyte imbalances.

 

Dr. Andrew Parker is a board-certified internal medicine physician with over 10 years of clinical experience. He earned his medical degree from the University of California, San Francisco (UCSF), and has worked at leading hospitals including St. Mary’s Medical Center. Dr. Parker specializes in patient education and digital health communication. He now focuses on creating clear, accessible, and evidence-based medical content for the public.

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