Side Effects of Liposomal Amphotericin B
Liposomal amphotericin B is substantially better tolerated than conventional amphotericin B deoxycholate, with significantly reduced nephrotoxicity and fewer infusion-related reactions, though these adverse events still occur and require monitoring. 1
Infusion-Related Reactions
Acute infusion-related reactions occur in approximately 20% of patients receiving liposomal amphotericin B, which is significantly lower than the 44-54% seen with conventional amphotericin B. 1, 2
Common infusion-related symptoms include:
- Fever (17% vs 44% with conventional formulation) 2
- Chills or rigors (18% vs 54% with conventional formulation) 2
- Headache 1
- Nausea and vomiting 1
- Hypotension 1, 2
- Tachypnea 1
Severe acute reactions can include chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria. 1 The majority (85%) of these reactions occur within the first 5 minutes of infusion and rapidly resolve with temporary interruption of the infusion and administration of intravenous diphenhydramine. 1
Liposome-induced complement activation-related pseudoallergy (CARPA) is a specific mechanism causing infusion reactions unique to liposomal formulations. 1
Management of Infusion Reactions:
- Premedication with diphenhydramine can reduce incidence 1
- Infuse over minimum of 1 hour (typically 2 hours) 1
- Temporarily interrupt infusion if reactions occur 1
- Administer IV diphenhydramine for acute reactions 1
Nephrotoxicity
Nephrotoxicity occurs in 19% of patients receiving liposomal amphotericin B, which is significantly less than the 34% seen with conventional amphotericin B. 2 However, this remains a clinically important adverse effect requiring vigilant monitoring. 1
Renal toxicity manifests as:
- Electrolyte abnormalities, particularly hypokalemia and hypomagnesemia 1, 3
- Elevated serum creatinine (defined as doubling of baseline or exceeding 2 times upper limit of normal) 2
- Azotemia from glomerular damage 4
- Renal tubular acidosis from distal tubular epithelial toxicity 3
Hypokalemia occurs in up to 80% of patients receiving amphotericin B formulations, though less frequently with liposomal preparations. 3 This results from selective distal tubular damage causing potassium wasting. 3
Nephrotoxicity Prevention and Monitoring:
- Baseline and frequent (once or twice weekly) serum chemistry monitoring including creatinine, BUN, potassium, and magnesium 1, 4
- Hydration with 0.9% saline IV 30 minutes before infusion 1, 3, 4
- Avoid concomitant nephrotoxic agents (NSAIDs, other nephrotoxic drugs) 1, 5
- Electrolyte supplementation as needed 1, 3
- Consider increased intervals between doses or drug holidays if toxicity develops 1
Hematologic Effects
- Anemia can occur with liposomal amphotericin B therapy 1
- Less frequent than with conventional formulations 6
- Regular CBC monitoring is recommended 1, 4
Hepatotoxicity
- Elevated aminotransferase levels may occur 4
- Regular liver function monitoring is advised 4
- Generally less severe than renal toxicity 7
Comparative Toxicity Profile
Liposomal amphotericin B demonstrates superior tolerability compared to other amphotericin B formulations:
- Versus conventional amphotericin B deoxycholate: Significantly fewer infusion reactions (17% vs 44% fever; 18% vs 54% chills), less nephrotoxicity (19% vs 34%) 2, 6, 7
- Versus amphotericin B lipid complex (ABLC): Significantly lower infusion-related events and nephrotoxicity 8
- Versus echinocandins: More infusion-related events and nephrotoxicity than caspofungin or micafungin 7
Dosage-Related Toxicity
Higher doses of liposomal amphotericin B (10 mg/kg/day) are associated with increased nephrotoxicity compared to standard dosing (3 mg/kg/day), though infusion-related reactions remain similar. 7 The standard 3 mg/kg/day dosage provides optimal balance of efficacy and tolerability. 7
Special Populations
Pregnancy: FDA pregnancy category B - liposomal amphotericin B is considered probably compatible during pregnancy and breastfeeding, though interruption of breastfeeding may be prudent. 1
Pediatric patients: Similar adverse event profile to adults, with generally good tolerability 7
Critical Monitoring Requirements
Baseline and ongoing laboratory monitoring must include: