Formulary
Amphotericin B: Uses, Dosing, Side Effects and Indian Brand Names
Amphotericin B is the broadest-spectrum antifungal available and the only reliable treatment for mucormycosis, but its use is limited by significant nephrotoxicity that mandates pre-hydration and electrolyte monitoring.
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Clinically reviewed by Awaiting clinical review
Amphotericin B: Uses, Dosing, Side Effects and Indian Brand Names
Amphotericin B is the broadest-spectrum antifungal available and the only reliable treatment for mucormycosis, but its use is limited by significant nephrotoxicity that mandates pre-hydration and electrolyte monitoring.
NEET PG High-Yield: Binds ergosterol (fungal) > cholesterol (mammalian) -- basis of selectivity. Pore formation in fungal membrane. Broadest spectrum antifungal (covers Mucor, which azoles and echinocandins do NOT). Only drug for mucormycosis. Nephrotoxicity: type 1 (distal) RTA + hypokalaemia + hypomagnesaemia. Pre-hydrate with NS. 'Shake and bake' reactions. Liposomal formulation: less toxic, much more expensive. Must infuse in D5W, never saline. First-line for kala-azar in India (liposomal). Anaemia from reduced EPO. COVID-associated mucormycosis in India (2021).
Clinical overview
Amphotericin B is the oldest systemic antifungal and remains the broadest-spectrum antifungal available, earning the title 'gold standard' for life-threatening invasive fungal infections. It covers virtually all pathogenic fungi: Candida species (including fluconazole-resistant C. krusei and C. glabrata), Cryptococcus neoformans, Aspergillus species, dimorphic fungi (Histoplasma, Blastomyces, Coccidioides), Mucorales (the ONLY reliable drug for mucormycosis), and Sporothrix. Mucormycosis (zygomycosis) became devastatingly relevant in India during the COVID-19 pandemic (COVID-associated mucormycosis or CAM), where amphotericin B was the only effective treatment and supplies became critically short. The conventional formulation (amphotericin B deoxycholate) is notoriously nephrotoxic -- it reduces renal blood flow (afferent arteriolar vasoconstriction) and causes direct tubular toxicity, producing a characteristic distal renal tubular acidosis (type 1 RTA), hypokalaemia, and hypomagnesaemia. Infusion-related reactions (fever, chills, rigors -- 'shake and bake') are so common that premedication with paracetamol, diphenhydramine, and hydrocortisone is standard. The liposomal formulation (AmBisome) significantly reduces nephrotoxicity and infusion reactions but is substantially more expensive. In Indian practice, both deoxycholate and liposomal formulations are used, with the choice often driven by availability and cost. Adequate pre-hydration with normal saline before each dose is essential to mitigate nephrotoxicity.
Pharmacological class
Amphotericin B belongs to the Polyene Antifungal Antibiotics class. Binds to ergosterol in the fungal cell membrane, forming transmembrane channels (pores) that increase membrane permeability to monovalent ions (K+, Na+, H+). This causes leakage of intracellular contents and cell death. Amphotericin B also induces oxidative damage through generation of free radicals. Selectivity is based on higher affinity for ergosterol (fungal) than cholesterol (mammalian), though this selectivity is imperfect, accounting for its significant toxicity.
Indian brand names and formulations
Available as: Fungizone (Bristol-Myers Squibb), Amphotret (Bharat Serums), AmBisome (Gilead -- liposomal), Amphomul (Bharat Serums -- lipid emulsion).
IV powder for reconstitution (deoxycholate): 50 mg vial (reconstitute with sterile water, then dilute in D5W only). Liposomal (AmBisome): 50 mg vial. Lipid complex (Abelcet): 50 mg/10 mL, 100 mg/20 mL. Lipid emulsion formulations (Indian generics): available as a cost-effective alternative to liposomal. Oral suspension and topical formulations: not systemically absorbed, used for oropharyngeal candidiasis (limited availability in India).
Regulatory status
Amphotericin B is classified under Schedule H in India under the Drugs and Cosmetics Act, 1940. Prescription-only. Hospital use only (IV administration). Liposomal formulation included in NLEM after the COVID-associated mucormycosis crisis.
Indications
- Mucormycosis/zygomycosis (drug of choice -- no alternative has comparable efficacy)
- Invasive aspergillosis (alternative to voriconazole in intolerant patients)
- Cryptococcal meningitis (induction phase with flucytosine)
- Invasive candidiasis (resistant species or critically ill)
- Visceral leishmaniasis/kala-azar (liposomal formulation -- WHO-recommended first-line in India)
- Histoplasmosis, blastomycosis, coccidioidomycosis (severe/disseminated)
- Empiric antifungal therapy in persistent febrile neutropenia
Dosing
Deoxycholate: Test dose 1 mg in 20 mL D5W over 20-30 min, then start 0.5-1.0 mg/kg/day, titrated to 1.0-1.5 mg/kg/day. Infuse over 4-6 hours. Liposomal (AmBisome): 3-5 mg/kg/day (can give over 2 hours). Mucormycosis: high-dose liposomal 5-10 mg/kg/day. Visceral leishmaniasis: liposomal 10 mg/kg total dose over 4-5 days (WHO regimen for India). Pre-hydrate with 500-1000 mL normal saline before each dose.
Contraindications
- Known hypersensitivity to amphotericin B
- Severe renal impairment (relative -- may be necessary for life-threatening infections; use liposomal formulation)
- Note: amphotericin B in D5W (dextrose 5%) ONLY -- never in saline (causes precipitation)
Adverse effects
- Nephrotoxicity (dose-limiting; afferent arteriolar vasoconstriction + direct tubular damage; manifests as rising creatinine, distal RTA type 1, hypokalaemia, hypomagnesaemia; partially prevented by saline pre-loading)
- Infusion-related reactions ('shake and bake': fever, rigors, chills, nausea, vomiting, headache -- premedicate with paracetamol, diphenhydramine, +/- hydrocortisone; meperidine 25-50 mg IV for severe rigors)
- Hypokalaemia (due to increased renal potassium wasting -- can cause arrhythmias; supplement aggressively)
- Hypomagnesaemia
- Normocytic normochromic anaemia (suppression of erythropoietin production)
- Thrombophlebitis (use central line when possible)
Drug interactions
- Nephrotoxic drugs (aminoglycosides, ciclosporin, tacrolimus, cisplatin, NSAIDs): additive nephrotoxicity; avoid if possible, monitor creatinine daily
- Digoxin: amphotericin-induced hypokalaemia potentiates digoxin toxicity
- Flucytosine: amphotericin increases flucytosine entry into fungal cells (synergy), but also reduces renal clearance of flucytosine (monitor levels to avoid bone marrow toxicity)
- Corticosteroids: may worsen amphotericin-induced hypokalaemia
- Diuretics (loop and thiazide): additive hypokalaemia and nephrotoxicity
Pregnancy and lactation
Category B. Despite its toxicity, amphotericin B is the preferred antifungal for life-threatening fungal infections during pregnancy because it has the longest safety record and no teratogenic effects have been demonstrated. Azoles (fluconazole, itraconazole) are more teratogenic at high doses.
Exam-style clinical scenario
A poorly controlled diabetic (HbA1c 12%) post-COVID patient presents with facial pain, unilateral proptosis, black eschar on the palate, and CT showing erosion of maxillary sinus walls extending into the orbit. Diagnosis and treatment? Rhino-orbital-cerebral mucormycosis. Treatment: IV liposomal amphotericin B 5-10 mg/kg/day + urgent surgical debridement + glycaemic control. This is a surgical AND medical emergency.
Cost in India
Deoxycholate: Rs 150-300 per 50 mg vial. Liposomal (AmBisome): Rs 3,000-7,000 per 50 mg vial (significantly more expensive). A full course of mucormycosis treatment may cost Rs 3-7 lakhs for the liposomal formulation alone.
Clinical governance
Author: MedNext Editorial Team. Clinical reviewer: Awaiting clinical review. Jurisdiction: India (Drugs and Cosmetics Act, 1940). Sources: CIMS India, Indian Pharmacopoeia. Publication state: Awaiting clinical review. Correction: Report errors at support@mednext.academy.
Frequently Asked Questions
Why must amphotericin B be infused in D5W and never in saline?
Amphotericin B deoxycholate forms a colloidal suspension stabilised by deoxycholate micelles. Sodium chloride (saline) disrupts these micelles, causing the drug to aggregate and precipitate out of solution. This produces visible turbidity and can cause infusion of particulate matter, potentially causing embolism. Always reconstitute in sterile water and dilute in D5W (dextrose 5% in water). This is NOT true for lipid formulations (liposomal, lipid complex), which have their own lipid carrier systems.
How does the liposomal formulation reduce toxicity?
In liposomal amphotericin B (AmBisome), the drug is encapsulated in small unilamellar liposomes (~80 nm). These liposomes preferentially accumulate at sites of fungal infection (where the reticuloendothelial system is activated) and release amphotericin B directly at the fungal cell membrane. The liposomal carrier reduces binding to mammalian cholesterol-containing membranes (especially renal tubular cells), markedly reducing nephrotoxicity. It also reduces the interaction with mast cells that causes infusion reactions.
Why was mucormycosis so devastating in India during COVID-19?
COVID-associated mucormycosis (CAM) arose from a 'perfect storm': (1) uncontrolled diabetes (hyperglycaemia and diabetic ketoacidosis provide iron for Rhizopus growth), (2) corticosteroid use for COVID pneumonia (immunosuppression), (3) possibly COVID-mediated immune dysregulation, and (4) industrial oxygen contamination (unproven). India reported over 45,000 cases in the 2021 wave. Amphotericin B was the only effective treatment, and the sudden demand created severe shortages. The government declared it a notifiable disease and ramped up production.
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