AmBisome (Amphotericin B Liposomal)
amphotericin B liposomal injection
Indications for Amphotericin B Liposomal
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Empirical therapy for presumed fungal infection in febrile neutropenia | Adults and pediatrics (≥1 month) | Monotherapy | FDA Approved |
| Cryptococcal meningitis in HIV-infected patients | Adults | Induction monotherapy (followed by fluconazole consolidation) | FDA Approved |
| Invasive aspergillosis, candidiasis, or cryptococcosis refractory to conventional amphotericin B | Adults and pediatrics | Monotherapy or salvage | FDA Approved |
| Invasive fungal infection when conventional amphotericin B is contraindicated by renal impairment or toxicity | Adults and pediatrics | Alternative monotherapy | FDA Approved |
| Visceral leishmaniasis (immunocompetent patients) | Adults and pediatrics | Monotherapy | FDA Approved |
| Visceral leishmaniasis (immunocompromised patients) | Adults | Monotherapy (high relapse rate) | FDA Approved |
Amphotericin B liposomal occupies a central role in the management of life-threatening systemic fungal infections, particularly in immunocompromised hosts. The liposomal formulation delivers high tissue concentrations to organs of the reticuloendothelial system while substantially reducing the nephrotoxicity and infusion-related reactions that limit conventional amphotericin B deoxycholate. It is regarded as the preferred amphotericin B formulation in most clinical contexts where a polyene agent is warranted (FDA PI).
Mucormycosis (zygomycosis) — first-line therapy: High-dose amphotericin B liposomal (5–10 mg/kg/day) is the cornerstone of pharmacotherapy for mucormycosis. The ECMM/MSG 2019 global guideline and ESCMID 2013 guideline both strongly recommend liposomal amphotericin B as first-line treatment, combined with surgical debridement when feasible. Evidence quality: Moderate
Invasive aspergillosis — alternative first-line or salvage: When voriconazole is contraindicated or not tolerated, the IDSA 2016 guideline recommends liposomal amphotericin B (3–5 mg/kg/day) as the preferred alternative agent for invasive pulmonary aspergillosis. Evidence quality: Moderate
Invasive candidiasis in pregnancy: Amphotericin B (preferably the liposomal formulation) is regarded by the IDSA as the antifungal of choice for invasive candidiasis during pregnancy, given the teratogenic potential of azole antifungals. Evidence quality: Low
Histoplasmosis — moderate-to-severe disseminated disease: IDSA guidelines recommend liposomal amphotericin B 3 mg/kg/day as induction therapy for 1–2 weeks, followed by oral itraconazole step-down. Evidence quality: Moderate
Dosing of Amphotericin B Liposomal
Adult and Pediatric Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Febrile neutropenia — empirical antifungal therapy | 3 mg/kg IV once daily | 3 mg/kg IV once daily | 5 mg/kg/day | Continue until neutropenia resolves and fever abates for ≥4 days, or proven fungal infection treated Infuse over ~2 hours; may shorten to 1 hour if tolerated (FDA PI) |
| Cryptococcal meningitis — HIV-associated, induction | 6 mg/kg IV once daily | 6 mg/kg IV once daily | 6 mg/kg/day | Induction for 11–21 days, then transition to oral fluconazole 400 mg/day consolidation 3 mg/kg was not shown comparable to conventional amphotericin B at 10-week outcomes (FDA PI) |
| Invasive aspergillosis, candidiasis, or cryptococcosis — refractory or intolerant to conventional amphotericin B | 3 mg/kg IV once daily | 3–5 mg/kg IV once daily | 5 mg/kg/day | Treat until clinical and mycological resolution For aspergillosis, IDSA recommends 3–5 mg/kg/day; higher end for CNS disease |
| Mucormycosis — first-line (off-label) | 5 mg/kg IV once daily | 5–10 mg/kg IV once daily | 10 mg/kg/day | Higher doses (10 mg/kg) for CNS involvement; combine with surgical debridement ECMM/MSG 2019: minimum 5 mg/kg/day strongly recommended; step down to posaconazole or isavuconazole |
| Visceral leishmaniasis — immunocompetent | 3 mg/kg IV on days 1–5 | 3 mg/kg IV on days 14 and 21 | Total: 21 mg/kg | Repeat course if parasitic clearance not achieved High cure rate (96.5% at 6-month follow-up in immunocompetent patients) (FDA PI) |
| Visceral leishmaniasis — immunocompromised | 4 mg/kg IV on days 1–5 | 4 mg/kg IV on days 10, 17, 24, 31, 38 | Total: 40 mg/kg | Relapse rate is very high (>88%) in immunocompromised patients; consult ID specialist Maintenance or suppressive therapy may be required; no standard regimen established (FDA PI) |
| Histoplasmosis — moderate-to-severe disseminated (off-label) | 3 mg/kg IV once daily | 3 mg/kg IV once daily | 5 mg/kg/day | Induction for 1–2 weeks, then step down to oral itraconazole IDSA guideline recommendation for moderate-to-severe or CNS histoplasmosis |
Amphotericin B liposomal (AmBisome) is not interchangeable on a mg-per-mg basis with amphotericin B deoxycholate, amphotericin B lipid complex (Abelcet), or amphotericin B cholesteryl sulfate (Amphotec). These formulations differ in pharmacokinetics, dosing, and toxicity profiles. Medication errors involving formulation confusion have caused serious nephrotoxicity and death. Always verify the specific amphotericin B product before administration.
Reconstitute each 50 mg vial with 12 mL Sterile Water for Injection (yields 4 mg/mL). Shake vigorously for 30 seconds. Filter through the provided 5-micron filter into D5W to a final concentration of 1–2 mg/mL (0.2–0.5 mg/mL for infants/small children). Infuse over approximately 2 hours. Do NOT use saline for reconstitution or dilution, as precipitation will occur. Flush existing IV lines with D5W before infusion (FDA PI).
Pharmacology of Amphotericin B Liposomal
Mechanism of Action
Amphotericin B liposomal exerts its antifungal activity through binding to ergosterol, the principal sterol in fungal cell membranes. This binding creates transmembrane pores that allow leakage of essential monovalent ions (potassium, sodium, hydrogen, chloride), disrupting electrochemical gradients and ultimately causing fungal cell death. The liposomal delivery system encapsulates amphotericin B within unilamellar bilayer liposomes less than 100 nm in diameter, which preferentially target fungal cells and reticuloendothelial tissues. This targeted delivery achieves high tissue concentrations in the liver, spleen, and lungs while reducing the direct binding to mammalian cholesterol-containing membranes that drives nephrotoxicity. The liposomal carrier also reduces uptake by renal tubular cells, which accounts for the improved renal safety profile compared with conventional amphotericin B deoxycholate. Amphotericin B retains broad-spectrum activity against Aspergillus, Candida, Cryptococcus, Blastomyces, Histoplasma, and Mucorales species.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV administration only; 100% bioavailability | No oral formulation exists; amphotericin B is not absorbed from the GI tract |
| Distribution | Vss 0.10–0.44 L/kg (dose-dependent); concentrates in liver, spleen, lungs; nonlinear PK with greater than proportional increase in Cmax and AUC from 1–5 mg/kg/day; steady state by day 4 | Low volume of distribution reflects liposomal sequestration in the reticuloendothelial system; high tissue penetration despite low serum Vd; serum levels do not reflect tissue activity |
| Metabolism | Metabolic pathways not characterized; not a CYP substrate, inducer, or inhibitor | Minimal hepatic drug-drug interaction risk via CYP pathways; no dose adjustment for hepatic impairment formally studied |
| Elimination | Initial t½ 7–10 h; terminal t½ 100–153 h (tissue redistribution); clearance at steady state 11–22 mL/hr/kg (dose-independent); excretion pathway not fully characterized | Long terminal half-life due to slow redistribution from tissues, not renal elimination; neither hemodialysis nor peritoneal dialysis removes amphotericin B liposomal effectively |
Side Effects of Amphotericin B Liposomal
Adverse event data are derived primarily from Study 94-0-002, a randomized double-blind trial of 687 febrile neutropenic patients comparing amphotericin B liposomal 3 mg/kg/day (n=343) with conventional amphotericin B 0.6 mg/kg/day (n=344), and from Study 94-0-013 in HIV-associated cryptococcal meningitis (n=267). Amphotericin B liposomal demonstrated a significantly lower incidence of nephrotoxicity and infusion-related reactions compared with conventional amphotericin B (FDA PI).
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Chills / rigors | 47.5% | Most common infusion-related reaction; significantly less than conventional amphotericin B (75.9%); premedication with acetaminophen and diphenhydramine reduces severity |
| Hypokalemia | 42.9% | Dose-related renal potassium wasting; monitor electrolytes daily; supplement aggressively to maintain K+ >3.5 mmol/L |
| Nausea | 39.7% | Usually mild to moderate; antiemetic premedication may help |
| Diarrhea | 30.3% | Generally self-limiting; assess for C. difficile if prolonged |
| Vomiting | 31.8% | Often infusion-related; consider slowing infusion rate |
| Rash | 24.8% | Non-specific; differentiate from anaphylaxis |
| Hyperglycemia | 23.0% | Monitor blood glucose; may reflect steroid co-administration |
| Dyspnea | 23.0% | Distinguish from infusion-related respiratory distress vs. underlying disease |
| Creatinine increased | 22.4% | Lower than conventional amphotericin B (42.2%); nephrotoxicity defined as doubling of baseline creatinine: 18.7% vs. 33.7% |
| Alkaline phosphatase increased | 22.2% | Monitor hepatic function panel; generally transient |
| BUN increased | 21.0% | Part of nephrotoxicity profile; usually reversible on discontinuation |
| Hypomagnesemia | 20.4% | Co-occurs with hypokalemia; supplement both electrolytes simultaneously |
| Abdominal pain | 19.8% | Evaluate for GI pathology if severe |
| Headache | 19.8% | Common; rule out meningeal disease in relevant populations |
| Blood product transfusion reaction | 18.4% | Reflects underlying hematological condition rather than direct drug effect |
| Bilirubinemia | 18.1% | Monitor LFTs; usually cholestatic pattern |
| Insomnia | 17.2% | Steroid premedication may contribute |
| Hypotension | 14.3% | Lower than conventional amphotericin B (21.5%); monitor vitals during infusion |
| Sepsis | 14.0% | Reflects underlying immunocompromised state |
| ALT increased | 14.6% | Monitor hepatic panel; hepatotoxicity generally reversible |
| Epistaxis | 14.9% | Associated with thrombocytopenia from underlying disease |
| Tachycardia | 13.4% | Lower than conventional amphotericin B (20.9%); infusion-related |
| Asthenia | 13.1% | Multifactorial in critically ill patients |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Edema / peripheral edema | 14.3% / 14.6% | Monitor fluid balance; adjust IV fluid administration |
| Anxiety | 13.7% | Often situational in hospitalized immunocompromised patients |
| AST increased | 12.8% | Usually mild; hepatocellular injury rare |
| Chest pain | 12.0% | Differentiate infusion-related chest tightness from cardiac events |
| Confusion | 11.4% | Consider metabolic causes including electrolyte disturbance |
| Infection | 11.1% | Superinfection or new infection in immunocompromised host |
| Pruritus | 10.8% | Usually mild; may be infusion-related |
| GI hemorrhage | 9.9% | Monitor in thrombocytopenic patients |
| Hypertension | 7.9% | Lower than conventional amphotericin B (16.3%); infusion-related |
| Back pain / flushing reaction | 2–10% | Acute back pain with chest tightness can occur minutes after infusion start; resolves rapidly when infusion stopped; may not recur at slower rate |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Nephrotoxicity (doubling of serum creatinine) | 18.7% | Within first 1–2 weeks; cumulative | Monitor creatinine daily; aggressive saline loading (500–1000 mL NS before infusion) reduces risk; consider dose reduction if creatinine doubles; do not switch to conventional amphotericin B |
| Severe hypokalemia (≤2.5 mmol/L) | 6.7% | Days to weeks of therapy | Monitor potassium at least daily; supplement IV potassium aggressively; concurrent magnesium repletion essential for refractory hypokalemia; cardiac monitoring if K+ <3.0 |
| Anaphylaxis / severe hypersensitivity | Rare (post-marketing) | During or shortly after infusion | Stop infusion immediately; treat with epinephrine and supportive care; permanently discontinue amphotericin B liposomal; test dose not reliably predictive |
| Acute pulmonary toxicity (with leukocyte transfusions) | Rare | During concurrent leukocyte infusion | Separate leukocyte transfusions from amphotericin B infusion by as long as possible; monitor respiratory status closely |
| Cardiac arrest / arrhythmia | 2–10% (arrhythmia); rare (arrest) | Variable; often linked to electrolyte disturbance | Maintain potassium >3.5 and magnesium >1.5 mg/dL; cardiac monitoring in patients on digoxin or with pre-existing cardiac disease |
| Acute kidney failure | 2–10% | Days to weeks; cumulative dose-related | Volume expansion; avoid concurrent nephrotoxins; may require dose reduction or temporary discontinuation; renal function often recovers after stopping therapy |
| Hepatocellular damage / veno-occlusive liver disease | 2–10% | Variable | Monitor LFTs; discontinue if severe hepatotoxicity develops |
| Rhabdomyolysis | Very rare (post-marketing) | Variable | Monitor CK if myalgia develops; aggressive hydration; discontinue if confirmed |
| Agranulocytosis | Very rare (post-marketing) | Variable | Monitor CBC; difficult to distinguish from underlying disease in neutropenic patients |
| Reason for Discontinuation | AmBisome | Context |
|---|---|---|
| Nephrotoxicity | 18.7% (2x creatinine) | vs 33.7% conventional amphotericin B in Study 94-0-002 |
| Infusion-related reactions | Lower than comparators | Nearly 3x fewer patients required dose reduction for toxicity vs conventional amphotericin B |
| Overall toxicity-related discontinuation | 14.3% | Study 94-0-002; includes all causes |
Premedicate with acetaminophen 650 mg, diphenhydramine 25–50 mg, and optionally hydrocortisone 25–50 mg IV 30 minutes before infusion. If chills/rigors occur, meperidine 25–50 mg IV is effective for acute rigors. Slow the infusion rate if reactions occur; the infusion may be extended beyond 2 hours. Most infusion-related reactions diminish with subsequent doses. On Day 1 without premedication, fever occurred in 17% of AmBisome patients vs 44% with conventional amphotericin B (FDA PI).
Drug Interactions with Amphotericin B Liposomal
No formal clinical drug interaction studies have been conducted with amphotericin B liposomal. Because amphotericin B is not metabolized through cytochrome P450 enzymes, pharmacokinetic interactions are uncommon. However, pharmacodynamic interactions are clinically important, particularly those that compound nephrotoxicity or electrolyte disturbances. The interactions below are based on the known interaction profile of amphotericin B and the specific warnings in the AmBisome prescribing information.
The PHOSm assay (used in some Beckman Coulter analyzers) may report falsely elevated serum phosphate levels in patients receiving amphotericin B liposomal. If hyperphosphatemia appears inconsistent with the clinical picture, confirm with an alternative assay method before initiating treatment for hyperphosphatemia (FDA PI).
Monitoring for Amphotericin B Liposomal
-
Serum Creatinine & BUN
Baseline, then daily
Routine Nephrotoxicity occurs in ~19% of patients (doubling creatinine). Trend creatinine daily; if doubling occurs, consider dose reduction or temporary hold. Pre-hydration with 500–1000 mL normal saline is protective. -
Serum Potassium
Baseline, then daily
Routine Hypokalemia (≤2.5 mmol/L) occurs in ~7% of patients. Renal potassium wasting is the primary mechanism. Supplement aggressively; refractory hypokalemia often reflects concurrent hypomagnesemia. -
Serum Magnesium
Baseline, then daily
Routine Hypomagnesemia occurs in ~20% of patients. Must be repleted alongside potassium; magnesium depletion impairs potassium conservation. -
Hepatic Function Panel
Baseline, then 2–3x/week
Routine Elevated alkaline phosphatase (~22%), bilirubin (~18%), and transaminases (~13–15%) are common. Hepatotoxicity is generally reversible but monitor for veno-occlusive disease in transplant recipients. -
Complete Blood Count
Baseline, then 2x/week
Routine Anemia occurs in 27–48% (dose-dependent); thrombocytopenia in 6–13%. Monitor for hematologic recovery in neutropenic patients. -
Vital Signs During Infusion
Every infusion, especially first doses
Routine Monitor temperature, blood pressure, heart rate, respiratory rate, and SpO2 during infusion. Infusion-related fever (17%), chills (18%), hypotension (3.5%), and tachycardia (2.3%) were reported on Day 1. -
Serum Phosphate
If hyperphosphatemia reported
Trigger-based False elevation possible with PHOSm assay on Beckman Coulter analyzers. Confirm with alternative assay if result is clinically unexpected. -
Blood Glucose
Daily during therapy
Routine Hyperglycemia (~23%); may be compounded by concurrent corticosteroid use. Adjust insulin as needed.
Contraindications & Cautions for Amphotericin B Liposomal
Absolute Contraindications
- Known hypersensitivity to amphotericin B deoxycholate or any component of the liposomal formulation (phospholipids, cholesterol, alpha-tocopherol, sucrose) — unless the treating physician determines that the benefit of therapy outweighs the risk of a hypersensitivity reaction (FDA PI)
Relative Contraindications (Specialist Input Recommended)
- Pre-existing severe renal impairment (CrCl <10 mL/min): While amphotericin B liposomal is significantly less nephrotoxic than conventional amphotericin B and has been used successfully in patients with pre-existing renal impairment, risk-benefit assessment and nephrologist consultation are warranted. Dialysis does not effectively remove the drug.
- Concurrent use with other nephrotoxic agents: If avoidable, defer concurrent nephrotoxic drug therapy; if unavoidable, intensive renal monitoring and pre-hydration are essential.
- Patients with non-invasive fungal infections: Amphotericin B liposomal should not be used for non-invasive fungal infections (e.g., oral thrush, vaginal candidiasis, esophageal candidiasis) in patients with normal neutrophil counts. The toxicity profile does not justify use for these indications.
Use with Caution
- Pregnancy: No adequate controlled studies in pregnant women. Animal studies showed no teratogenicity in rats (up to 5 mg/kg) or rabbits (up to 3 mg/kg), but higher doses in rabbits were associated with increased spontaneous abortions. Use only if the potential benefit justifies the potential risk to the fetus.
- Lactation: It is unknown whether amphotericin B liposomal is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision must be made whether to discontinue nursing or the drug.
- Pediatric patients <1 month of age: Safety and effectiveness not established in neonates under 1 month.
- Elderly patients (≥65 years): Limited experience (72 patients in clinical program); no dose adjustment required, but monitor renal function closely.
- Hepatic impairment: The effect of hepatic impairment on the disposition of amphotericin B liposomal is unknown. Monitor hepatic function.
- Patients on concurrent digitalis glycosides: Hypokalemia potentiates digitalis toxicity; maintain potassium levels meticulously.
Amphotericin B liposomal (AmBisome) is NOT interchangeable with other amphotericin B-containing products on a mg-per-mg basis. Conventional amphotericin B deoxycholate, amphotericin B lipid complex (Abelcet), and amphotericin B cholesteryl sulfate (Amphotec) differ substantially in pharmacokinetics, dosing, and toxicity. Overdosage due to formulation confusion may result in severe nephrotoxicity and death. Always verify the specific amphotericin B formulation before prescribing and dispensing.
Anaphylaxis has been reported with amphotericin B-containing drugs, including AmBisome. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusions of amphotericin B liposomal. During the initial dosing period, patients should be under close clinical observation by medically trained personnel.
Patient Counselling for Amphotericin B Liposomal
Purpose of Therapy
Amphotericin B liposomal is a powerful antifungal medication used to treat serious, potentially life-threatening fungal infections. It is given by intravenous infusion in a hospital or supervised clinical setting. The liposomal formulation is designed to be gentler on the kidneys than older versions of the same medication, but close monitoring is still essential throughout the course of treatment.
How Treatment Is Given
The medication is infused through a vein over approximately 2 hours, typically once daily. Treatment duration varies by the type and severity of infection and may last from several days to several weeks. Blood tests will be performed frequently during treatment to check kidney function, electrolyte levels, and blood counts.
Sources
- AmBisome (amphotericin B) liposome for injection. Full Prescribing Information. Astellas Pharma US, Inc. / Gilead Sciences, Inc. Revised 2024. FDA Label (PDF) Primary source for all FDA-approved dosing, indications, adverse events, and pharmacokinetic data presented in this monograph.
- DailyMed. Amphotericin B liposome — amphotericin B injection, powder, lyophilized, for solution. U.S. National Library of Medicine. DailyMed Continuously updated FDA label database for the most current prescribing information.
- Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999;340(10):764–771. doi:10.1056/NEJM199903113401004 Landmark RCT (Study 94-0-002) establishing equivalence of AmBisome to conventional amphotericin B in febrile neutropenia with superior safety.
- Leenders AC, Reiss P, Portegies P, et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS. 1997;11(12):1463–1471. doi:10.1097/00002030-199712000-00010 Pivotal trial comparing AmBisome dosing regimens (3 and 6 mg/kg) to conventional amphotericin B for HIV-associated cryptococcal meningitis.
- Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–415. doi:10.1056/NEJMoa020191 Established voriconazole as preferred first-line for invasive aspergillosis; positions liposomal amphotericin B as alternative.
- Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis. 2007;44(10):1289–1297. doi:10.1086/514341 Showed no benefit of 10 mg/kg loading dose over standard 3 mg/kg for invasive mold infections, with increased nephrotoxicity at higher doses.
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60. doi:10.1093/cid/ciw326 IDSA guideline positioning liposomal amphotericin B as alternative first-line therapy for invasive aspergillosis when voriconazole is contraindicated.
- Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the ECMM in cooperation with the MSG ERC. Lancet Infect Dis. 2019;19(12):e405–e421. doi:10.1016/S1473-3099(19)30312-3 Global consensus guideline strongly recommending high-dose liposomal amphotericin B (minimum 5 mg/kg/day) as first-line treatment for mucormycosis.
- Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–e50. doi:10.1093/cid/civ933 IDSA candidiasis guideline recommending amphotericin B as the preferred antifungal in pregnancy and as salvage therapy for invasive candidiasis.
- Skiada A, Lanternier F, Groll AH, et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013;98(4):492–504. doi:10.3324/haematol.2012.065110 ECIL guidelines recommending liposomal amphotericin B at 5 mg/kg/day minimum with surgical debridement for mucormycosis.
- Laniado-Laborin R, Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009;26(4):223–227. doi:10.1016/j.riam.2009.06.003 Review of the mechanistic basis for amphotericin B toxicity, including ergosterol-binding selectivity and renal tubular injury pathways.
- Adler-Moore J, Proffitt RT. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience. J Antimicrob Chemother. 2002;49(Suppl 1):21–30. doi:10.1093/jac/49.suppl_1.21 Detailed review of the liposomal delivery system, explaining the mechanism by which the unilamellar lipid bilayer reduces toxicity while preserving antifungal activity.
- Heinemann V, Bosse D, Jehn U, et al. Pharmacokinetics of liposomal amphotericin B (AmBisome) in critically ill patients. Antimicrob Agents Chemother. 1997;41(6):1275–1280. doi:10.1128/AAC.41.6.1275 Characterization of nonlinear pharmacokinetics and dose-dependent volume of distribution in critically ill patients.
- Groll AH, Piscitelli SC, Walsh TJ. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol. 1998;44:343–500. doi:10.1016/S1054-3589(08)60129-5 Comprehensive pharmacological review covering amphotericin B formulations, with detailed tissue distribution and elimination data relevant to dose selection.
- Hamill RJ. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs. 2013;73(9):919–934. doi:10.1007/s40265-013-0069-4 Comparative review of nephrotoxicity rates and clinical outcomes across amphotericin B formulations, supporting preferential use of liposomal form.