What is the difference between amphotericin B and amphotericin B liposomal in terms of formulation, efficacy, and toxicity, particularly for patients with severe fungal infections and impaired renal function?

Key Differences Between Amphotericin B and Amphotericin B Liposomal

Yes, there are critical differences between conventional amphotericin B deoxycholate and liposomal amphotericin B—they differ fundamentally in formulation, dosing, toxicity profile, and cost, and should never be interchanged without careful consideration. 1

Formulation Differences

Three distinct lipid-associated formulations exist and are NOT interchangeable:

• Amphotericin B deoxycholate (conventional): The classic preparation with amphotericin B bound to deoxycholate 1
• Liposomal amphotericin B (AmBisome): The only true liposomal formulation, where amphotericin B is encapsulated in small unilamellar liposomes 1, 2
• Amphotericin B lipid complex (ABLC/Abelcet): Ribbon-like lipid structure 1, 2
• Amphotericin B colloidal dispersion (ABCD/Amphotec/Amphocil): Disc-like structures 1, 2

The lipid formulations have different pharmacological properties, rates of adverse events, shape, size, reticuloendothelial clearance, and visceral diffusion patterns. 1, 2

Dosing Differences

Critical dosing distinction that prevents medication errors:

• Conventional amphotericin B deoxycholate: 0.6–1.0 mg/kg per day 1
• Lipid-associated formulations (including liposomal): 3–5 mg/kg per day 1

The lipid formulation reduces direct exposure of renal tubular cells to free amphotericin B, allowing for higher doses while maintaining improved safety. 3, 4

Toxicity Profile: The Most Clinically Significant Difference

Nephrotoxicity

Liposomal amphotericin B is significantly less nephrotoxic than conventional amphotericin B deoxycholate, though 19-50% of patients still experience some degree of renal injury. 3, 4

• Conventional amphotericin B causes nephrotoxicity in the majority of patients 4
• The KDIGO guidelines provide a Grade 1A recommendation to use azole antifungals and/or echinocandins rather than conventional amphotericin B when equal therapeutic efficacy can be assumed 4
• Lipid formulations are particularly important for patients at high risk for renal failure, including those with pre-existing renal disease, transplant recipients, and patients receiving other nephrotoxic agents 1

Infusion-Related Reactions

• Liposomal amphotericin B has the lowest infusion-related events among all formulations 5, 2
• Conventional amphotericin B and ABCD have similar rates of immediate infusion reactions 6
• In a randomized double-blind trial, liposomal amphotericin B had significantly fewer infusion-related events than ABLC 6, 2

Efficacy Comparison

Both formulations are equally effective when used at appropriate dosages for invasive fungal infections. 1

• Clinical studies indicate lipid formulations are "as effective as amphotericin B deoxycholate when used in appropriate dosages" 1
• Response rates for liposomal amphotericin B: 66% in aspergillosis and 81% in candidiasis 6
• Several comparative studies confirmed similar or superior efficacy relative to conventional amphotericin B 6, 7

FDA Approval Status

Only ABLC and liposomal amphotericin B are FDA-approved for proven candidiasis cases. 1

These approvals are specifically for second-line therapy in patients who:

• Are intolerant of conventional amphotericin B deoxycholate 1
• Have infection refractory to conventional therapy 1
• Have initial renal insufficiency (creatinine ≥2.5 mg/dL or creatinine clearance <25 mL/min) 1
• Experience significant creatinine increase (up to 2.5 mg/dL in adults or 1.5 mg/dL in children) 1
• Have severe, acute, administration-related toxicity 1

Liposomal amphotericin B has an additional indication for empirical therapy of suspected fungal infections in febrile neutropenic patients, giving it an advantage over other formulations. 5, 7

Cost Considerations

Lipid formulations are extremely expensive compared to conventional amphotericin B. 5, 2

• Higher acquisition costs limit front-line use despite superior safety profile 1
• The decreased incidence of acute kidney injury and associated reduction in hospitalization costs makes lipid formulations cost-effective compared to conventional amphotericin B despite higher acquisition costs 4
• Use is often restricted to patients intolerant of, or refractory to, conventional amphotericin B 2

Clinical Recommendations

When lipid formulations are used, liposomal amphotericin B (AmBisome) is preferred over other lipid formulations when available. 1

The NCCN guidelines state that amphotericin B lipid complex and liposomal amphotericin B are preferred over conventional amphotericin B deoxycholate when available. 1

Prevention Strategies Apply to Both Formulations

• Hydration with 0.9% saline intravenously 30 minutes before infusion ameliorates nephrotoxicity 3, 8, 4
• Monitor serum creatinine and electrolytes at minimum once or twice weekly 3, 4
• Avoid concomitant nephrotoxic medications 4
• Use the lowest effective dose and shortest duration of therapy 3, 8

Important Caveat on Renal Replacement Therapy

Neither dialysis nor hemofiltration significantly reduces amphotericin B serum concentrations, so dose adjustment for renal replacement therapy is not required for either formulation. 3, 4