Side Effects of AmBisome (Liposomal Amphotericin B)
AmBisome causes significantly fewer infusion-related reactions and less nephrotoxicity compared to conventional amphotericin B, but still produces important adverse effects including electrolyte disturbances, hematologic toxicity, and organ dysfunction that require close monitoring.
Common Side Effects (>10% incidence)
Infusion-Related Reactions
- Chills/rigors occur in 18-48% of patients, though substantially less than the 80-90% seen with conventional amphotericin B 1
- Fever (temperature increase >1°C) affects 20-24% of patients 1
- These reactions typically occur within 1-3 hours of infusion start, last <1 hour, and decrease in frequency over time 2
- Premedication with acetaminophen or diphenhydramine can reduce these reactions 2
Acute Severe Reactions (Rare but Important)
- Approximately 20% of patients experience acute infusion-related reactions including chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, or flushing and urticaria 2
- These reactions occur within the first 5 minutes of infusion and rapidly resolve with temporary interruption and administration of IV diphenhydramine 2
- Back pain with or without chest tightness has been reported; symptoms disappear when infusion is stopped and may not recur if infusion rate is slowed 1
Nephrotoxicity (Reduced but Still Present)
AmBisome causes substantially less nephrotoxicity than conventional amphotericin B 2:
- Nephrotoxicity defined as creatinine doubling occurs in 20-22% of AmBisome patients versus 31-49% with conventional amphotericin B 1
- Manifests as azotemia from glomerular damage, often accompanied by hypokalemia from tubular damage 2
- Permanent nephrotoxicity is related to cumulative dose 2
- Nephrotoxicity can be ameliorated by hydration with 0.9% saline IV over 30 minutes before the AmBisome infusion 2
- Exacerbated by concomitant nephrotoxic drugs (particularly cyclosporine and tacrolimus) and pre-existing renal disease 2, 3
Electrolyte Disturbances
Hypokalemia (Most Common)
- Occurs in 37-50% of patients 1
- Results from renal tubular potassium wasting 2
- Requires monitoring and repletion as needed 4
Other Electrolyte Abnormalities
Hematologic Toxicity
AmBisome causes dose-dependent anemia and thrombocytopenia 5:
- Anemia occurs with 50% probability at doses ≥3.3 mg/kg/day 5
- Thrombocytopenia occurs with 50% probability at doses ≥3.0 mg/kg/day 5
- Anemia was observed in 10 of 21 adult patients in one analysis 5
- Thrombocytopenia occurred in 11 of 19 adult patients 5
Hepatotoxicity
- Elevated alkaline phosphatase: 7-22% 1
- Elevated bilirubin: 11-18% 1
- Elevated ALT/AST: 13-15% 1
- Hepatic toxicity is generally mild and reversible 2
Gastrointestinal Effects
Cardiovascular Effects
- Hypotension: 7-21% (significantly less than conventional amphotericin B at 19-22%) 1
- Hypertension: 8-23% 1
- Tachycardia: 9-23% 1
- Rare idiosyncratic reactions include arrhythmias and allergic reactions including anaphylaxis 2
Neurologic Toxicity (Rare but Documented)
- Confusion, headache, anxiety occur in 7-20% 1
- Rarely, neurotoxicity manifests as confusion, delirium, hearing loss, blurred vision, or seizures 2
- Memory difficulties and cognitive issues have been reported in otherwise healthy patients, resolving over weeks after discontinuation 6
Respiratory Effects
Important Clinical Considerations
Pediatric Patients
Children tolerate AmBisome better than adults 2:
- Lower incidence of hypokalemia (37% vs 55% with conventional amphotericin B)
- Lower incidence of chills (29% vs 68%)
- Lower incidence of vomiting (27% vs 55%)
- More tolerance for nephrotoxic effects than older individuals
Monitoring Requirements
Based on the toxicity profile, monitor:
- Serum electrolytes (potassium, magnesium, calcium)
- Renal function (creatinine, BUN)
- Complete blood count
- Liver function tests
- Vital signs during and after infusion
Dose-Related Toxicity
Higher doses (>6 mg/kg/day) increase risk without clear survival benefit 7:
- Saturable pharmacokinetics at doses >10 mg/kg/day may explain lack of additional benefit
- Consistently higher nephrotoxicity rates with high-dose regimens
- Routine escalation beyond 5-6 mg/kg/day not supported by evidence