What is the recommended dose of liposomal amphotericin B (AmBisome) for patients with Chronic Kidney Disease (CKD)?

Liposomal Amphotericin B Dosing in Chronic Kidney Disease

No dose adjustment of liposomal amphotericin B is required for patients with chronic kidney disease, including those with severe renal impairment or on dialysis. 1

Standard Dosing Recommendations by Indication

The dosing of liposomal amphotericin B in CKD patients follows the same weight-based regimens used in patients with normal renal function, as the drug does not require renal dose adjustment:

For Invasive Candidiasis

• CNS candidiasis (meningitis): 5 mg/kg IV daily 1
• Candida chorioretinitis/endophthalmitis (fluconazole-resistant isolates): 3-5 mg/kg IV daily 1
• Candidemia in critically ill patients: Standard echinocandin dosing is preferred first-line, but liposomal amphotericin B at 3-5 mg/kg IV daily is an alternative 1

For Endemic Mycoses

• Disseminated histoplasmosis (moderately severe to severe): 3 mg/kg IV daily for 1-2 weeks, followed by oral itraconazole 1
• Acute pulmonary histoplasmosis with respiratory complications: 3 mg/kg IV daily (historical guideline recommended this dose for patients with renal impairment specifically) 1

For Mucormycosis

• Without CNS involvement: 5 mg/kg IV daily 1
• With CNS involvement: 10 mg/kg IV daily 1

Rationale for No Dose Adjustment in CKD

Liposomal amphotericin B is specifically recommended as the preferred amphotericin B formulation when patients have renal impairment or develop nephrotoxicity. 1 The key pharmacologic principles supporting this approach include:

• Minimal renal excretion: Amphotericin B is not significantly eliminated by the kidneys, so reduced renal function does not lead to drug accumulation 2
• Not removed by dialysis: The drug is not dialyzable, so no supplemental dosing is needed post-hemodialysis 1
• Reduced nephrotoxicity profile: Liposomal amphotericin B causes significantly less nephrotoxicity than conventional amphotericin B deoxycholate, making it the formulation of choice when creatinine is elevated above 2.5 mg/dL 1, 3

Evidence Supporting Safety in Renal Impairment

In critically ill patients with baseline serum creatinine >1.5 mg/dL who received liposomal amphotericin B, renal function actually improved during treatment. 4 This multicenter study demonstrated:

• Mean decrease in creatinine of 1.08 mg/dL from baseline (p<0.001) 4
• 50% of patients returned to normal creatinine levels 4
• Only 6.25% experienced worsening renal function 4
• No patients required treatment discontinuation or initiation of dialysis due to the drug 4

Comparative trials have consistently shown liposomal amphotericin B produces significantly less nephrotoxicity than conventional amphotericin B, with fewer patients experiencing creatinine doubling even when receiving concomitant nephrotoxic agents. 3, 5

Practical Dosing Considerations

Dose Selection

• Use the indication-specific dose (3-10 mg/kg/day) regardless of baseline renal function 1
• Higher doses (5-10 mg/kg/day) have been associated with increased nephrotoxicity risk, but this remains substantially lower than conventional amphotericin B 1, 6
• Lower doses (1-1.5 mg/kg/day) may be equally effective for some indications and offer cost savings, though this is not guideline-recommended 6

Monitoring

• Monitor serum creatinine, potassium, and magnesium levels during therapy 1, 3
• Electrolyte abnormalities (hypokalemia, hypomagnesemia) can still occur with liposomal formulations, though less frequently than with conventional amphotericin B 3
• Ensure adequate hydration during therapy 1

Common Pitfalls to Avoid

• Do not reduce the dose based solely on CKD stage or elevated baseline creatinine - this is unnecessary and may compromise efficacy 1, 4
• Do not confuse liposomal amphotericin B with conventional amphotericin B deoxycholate - the latter does require extreme caution in renal impairment and is associated with nephrotoxicity in up to 80% of patients 1, 3
• Do not assume all lipid formulations are equivalent - amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) have different pharmacokinetics and toxicity profiles than liposomal amphotericin B 5
• Avoid concomitant nephrotoxic medications when possible (aminoglycosides, vancomycin, NSAIDs, contrast agents), as these increase the risk of additive renal injury even with the liposomal formulation 1, 4