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Liposomal amphotericin B: Drug information

Liposomal amphotericin B: Drug information
(For additional information see "Liposomal amphotericin B: Patient drug information" and see "Liposomal amphotericin B: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • AmBisome
Brand Names: Canada
  • AmBisome
Pharmacologic Category
  • Antifungal Agent, Parenteral
Dosing: Adult

Note: Lipid-based amphotericin formulations (AmBisome) may be confused with conventional formulations (deoxycholate [Amphocin, Fungizone]) or with other lipid-based amphotericin formulations (amphotericin B lipid complex [Abelcet], amphotericin B cholesteryl sulfate complex [Amphotec]). Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.

Usual dosage range: IV: 3 to 6 mg/kg/day.

Note: Premedication: For patients who experience nonanaphylactic immediate infusion-related reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent ± diphenhydramine; or acetaminophen with diphenhydramine; or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

Aspergillus

Aspergillus (systemic infection) (alternative therapy) (off-label dose): IV: 3 to 5 mg/kg/day (IDSA [Patterson 2016]); doses up to 7.5 mg/kg/day have been recommended for CNS infection (IDSA [Tunkel 2017]). Minimum duration of treatment is 6 to 12 weeks and depends on site of infection, extent of disease and level/duration of immunosuppression. Note: Guidelines recommend amphotericin B lipid formulations be considered for invasive aspergillosis only when triazoles, specifically voriconazole, are contraindicated or not tolerated (IDSA [Patterson 2016]).

Aspergillosis, empiric therapy

Aspergillosis, empiric therapy (off-label dose): IV: 3 mg/kg/day. Note: Guidelines recommend amphotericin B lipid formulations be considered for invasive aspergillosis only when triazoles, specifically voriconazole, are contraindicated or not tolerated (IDSA [Patterson 2016]).

Candidiasis

Candidiasis:

Candidemia (non-neutropenic patients) (alternative agent): IV: 3 to 5 mg/kg/day; may transition to fluconazole (usually after 5 to 7 days) in clinically stable patients, with fluconazole-susceptible isolates and negative repeat cultures. Total duration of antifungal therapy is at least 2 weeks after the documented clearance of Candida from the bloodstream and resolution of candidemia-associated symptoms in patients without metastatic complications (IDSA [Pappas 2016]).

Candidemia (neutropenic patients) (alternative agent): IV: 3 to 5 mg/kg/day; may transition to fluconazole during persistent neutropenia in clinically stable patients, with fluconazole-susceptible isolates and negative repeat cultures. Total duration of antifungal therapy is at least 2 weeks after the documented clearance of Candida from the bloodstream and resolution of neutropenia and candidemia-associated symptoms in patients without metastatic complications (IDSA [Pappas 2016]).

Central nervous system (eg, meningitis): IV: 5 mg/kg/day (with or without oral flucytosine); step-down to fluconazole therapy is recommended after initial response to treatment (IDSA [Pappas 2016]).

Chronic disseminated (hepatosplenic): IV: 3 to 5 mg/kg/day; after several weeks, transition to oral fluconazole in clinically stable, fluconazole-susceptible patients (IDSA [Pappas 2016]).

Empiric therapy, suspected invasive candidiasis (non-neutropenic ICU patients) (alternative agent) (off-label use):

Note: Antifungal therapy is not routinely warranted for initial management of nonneutropenic patients with sepsis. Consider use for critically ill patients with unexplained fever or unexplained hypotension despite broad-spectrum antimicrobial therapy and risk factors for invasive candidiasis (eg, indwelling venous catheter, hemodialysis, trauma or burns, recent surgery, parenteral nutrition) (IDSA [Pappas 2016]; SSC [Evans 2021]; Vazquez 2022).

IV: 3 to 5 mg/kg/day; treatment should continue for 14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response (IDSA [Pappas 2016]).

Endocarditis (native or prosthetic valve) or infected implantable cardiac devices (eg, pacemaker, ICD, VAD): IV: 3 to 5 mg/kg/day (with or without flucytosine); for native or prosthetic valve endocarditis, therapy should continue for at least 6 weeks after valve replacement surgery (longer durations in patients with abscesses or other complications); for patients with implantable cardiac devices, therapy should continue for 4 to 6 weeks after surgery (4 for infections limited to generator pockets and at least 6 weeks for infections involving the wires). Note: May transition to fluconazole if patient clinically stable with fluconazole-susceptible isolates in whom Candida has cleared from the bloodstream; chronic or long-term suppression with fluconazole may be required (eg, prosthetic valve, valve-replacement not possible) (IDSA [Pappas 2016]).

Endophthalmitis (with or without vitritis) caused by fluconazole- or voriconazole-resistant isolates: IV: 3 to 5 mg/kg/day (with or without flucytosine) for at least 4 to 6 weeks until examination indicates resolution; for patients with vitritis or with macular involvement (with or without vitritis), an intravitreal injection of voriconazole or amphotericin B deoxycholate is also recommended (IDSA [Pappas 2016]).

Esophageal, refractory disease (alternative agent) (off-label use):

Note: Reserve use for patients who have inadequate response to or who are unable to take other agents (Kauffman 2021).

IV: 3 mg/kg/day. Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (HHS [OI adult 2021]; Kauffman 2021).

Intra-abdominal candidiasis (alternative agent): IV: 3 to 5 mg/kg/day; duration of therapy determined by clinical response and source control (IDSA [Pappas 2016]).

Osteomyelitis or septic arthritis due to Candida (alternative agent): IV: 3 to 5 mg/kg/day for at least 2 weeks, followed by fluconazole for at least 4 weeks (septic arthritis) or for 6 to 12 months (osteomyelitis) (IDSA [Pappas 2016]).

Suppurative thrombophlebitis: IV: 3 to 5 mg/kg/day; continue for at least 2 weeks after candidemia has cleared; consider transition to fluconazole in clinically stable patients with a fluconazole-susceptible isolate who have responded to initial therapy (IDSA [Pappas 2016]).

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. Empiric therapy: IV: 3 mg/kg/day; Invasive infection: 3 to 5 mg/kg/day.

Coccidioidomycosis in patients with HIV

Coccidioidomycosis in patients with HIV (off-label use): Non-CNS infection, severe (ie, diffuse pulmonary or severely ill with extrathoracic, disseminated disease): IV: 3 to 5 mg/kg/day until clinical improvement, then initiate triazole therapy (eg, fluconazole or itraconazole) (HHS [OI adult 2020]).

Cryptococcosis

Cryptococcosis:

Disseminated cryptococcosis (non-CNS or severe pulmonary disease): Induction therapy: IV: 3 to 4 mg/kg/day with flucytosine (preferred) or fluconazole, or without a concomitant agent, for 2 weeks, followed by consolidation and maintenance therapy with fluconazole (AST-IDCOP [Baddley 2019]; HHS [OI adult 2022]).

Meningitis: Induction therapy:

Resource-rich settings: IV: 3 to 4 mg/kg/day with flucytosine (preferred) or fluconazole, or without a concomitant agent, for 2 weeks (AST-IDCOP [Baddley 2019]; HHS [OI adult 2022]); doses up to 6 mg/kg/dose have been reported for treatment of meningoencephalitis and may be considered for treatment failure or high fungal burden disease (IDSA [Perfect 2010]). Induction therapy is followed by consolidation and maintenance therapy with fluconazole (AST-IDCOP [Baddley 2019]; HHS [OI adult 2022]; IDSA [Perfect 2010]).

Resource-limited settings:

Note: This regimen has only been studied in patients with HIV (Jarvis 2022).

IV: 10 mg/kg as a single dose, in combination with 14 days of fluconazole and flucytosine. Induction therapy is followed by consolidation and maintenance therapy with fluconazole (Jarvis 2022; WHO 2022a).

Fungal sinusitis

Fungal sinusitis: IV: Limited data in immunocompromised patients have shown efficacy with 3 to 10 mg/kg/day (Barron 2005; Pagano 2004; Rokicka 2006). Note: An azole antifungal is recommended if causative organism is Aspergillus spp or Pseudallescheria boydii (Scedosporium sp).

Histoplasmosis

Histoplasmosis (off-label use):

Acute pulmonary disease, moderately severe to severe: Induction therapy: IV: 3 to 5 mg/kg/day for 1 to 2 weeks, followed by itraconazole maintenance therapy (IDSA [Wheat 2007]).

Disseminated disease, moderately severe to severe: Induction therapy: IV: 3 mg/kg/day for 1 to 2 weeks (patients without HIV) or at least 2 weeks (patients with HIV), followed by itraconazole maintenance therapy (HHS [OI adult 2020]; IDSA [Wheat 2007]).

Histoplasma meningitis: Induction therapy: IV: 5 mg/kg/day for 4 to 6 weeks, followed by itraconazole maintenance therapy (HHS [OI adult 2020]; IDSA [Wheat 2007]).

Leishmaniasis

Leishmaniasis:

Cutaneous (off-label use):

Patients without HIV: IV: 3 mg/kg/day on days 1 through 5, and then on day 10 or on days 1 through 7. Total dose administered should be 18 to 21 mg/kg (IDSA/ASTMH [Aronson 2016]).

Patients with HIV: IV: 2 to 4 mg/kg/day for 10 days or an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, 38). Total dose administered should be 20 to 60 mg/kg (HHS [OI adult 2020]).

Mucosal (off-label use):

Patients without HIV: IV: ~3 mg/kg/day for a cumulative total administered dose of ~20 to 60 mg/kg (IDSA/ASTMH [Aronson 2016]).

Patients with HIV: IV: 2 to 4 mg/kg/day for 10 days or an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, 38). Total dose administered should be 20 to 60 mg/kg (HHS [OI adult 2020]).

Visceral:

Immunocompetent: IV: 3 mg/kg/day on days 1 through 5, and 3 mg/kg/day on days 14 and 21; a repeat course may be given in patients who do not achieve parasitic clearance (manufacturer's labeling).

Immunocompromised, including patients with HIV:

Treatment, monotherapy: IV: 2 to 4 mg/kg/day or an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, and 38). Total dose administered: 20 to 60 mg/kg (HHS [OI adult 2022]; manufacturer’s labeling).

Treatment, combination therapy: Note: For patients with HIV and visceral leishmaniasis acquired in East Africa or Southeast Asia (WHO 2022b).

IV: 5 mg/kg on days 1, 3, 5, 7, 9, and 11 (total dose administered: 30 mg/kg) in combination with miltefosine (Abongomera 2018; Burza 2022; Diro 2019; Mahajan 2015; WHO 2022b).

Secondary prophylaxis (chronic maintenance therapy) for patients with HIV and high risk of visceral leishmaniasis relapse (eg, CD4 count <200 cells/mm3): IV: 4 mg/kg once every 2 to 4 weeks (HHS [OI adult 2022]). For patients with visceral leishmaniasis acquired in Southeast Asia, 3 to 5 mg/kg once every 3 to 4 weeks is recommended (WHO 2022b).

Meningitis, severe or in patients not improving with voriconazole monotherapy

Meningitis (secondary to contaminated [eg, Exserohilum rostratum] steroid products), severe or in patients not improving with voriconazole monotherapy (off-label use) (CDC 2013; Kauffman 2012): IV: 5 to 6 mg/kg/day in combination with voriconazole for ≥3 months; a higher dose (7.5 mg/kg/day) may be considered in patients who are not improving. Note: Consult an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

Mucormycosis

Mucormycosis (off-label use): IV: 5 to 10 mg/kg/day (ECMM/MSG-ERC [Cornely 2019]; Lanternier 2015). Note: 10 mg/kg/day recommended for patients with CNS disease or solid organ transplant recipients. Treatment duration is typically weeks to months depending on response and host immunosuppression (ECMM/MSG-ERC [Cornely 2019]).

Osteoarticular infection, severe or in patients with clinical instability

Osteoarticular infection (secondary to contaminated [eg, Exserohilum rostratum] steroid products), severe or in patients with clinical instability (off-label use) (CDC 2013; Kauffman 2012): IV: 5 mg/kg/day in combination with voriconazole for ≥3 months. Note: Consult an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

Talaromycosis in patients with HIV

Talaromycosis (formerly Penicillinosis) in patients with HIV (off-label use): IV: 3 to 5 mg/kg/day for 2 weeks, followed by oral itraconazole for 10 weeks, followed by chronic maintenance therapy (HHS [OI adult 2020]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (clearance by the kidney is only 5% of total clearance [Bekersky 2002]) (Nemecek 2019; expert opinion).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (lipophilic and highly protein bound [Gussak 2001]): No supplemental dose or dosage adjustment necessary (Heintz 2009; Obata 2020; expert opinion).

Peritoneal dialysis: Unlikely to be dialyzed (lipophilic and highly protein bound): No dosage adjustment necessary (expert opinion).

CRRT: Unlikely to be significantly dialyzed: No dosage adjustment necessary (Bellmann 2003; Heintz 2009; Obata 2020).

PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzed: No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Pediatric

(For additional information see "Liposomal amphotericin B: Pediatric drug information")

Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (Abelcet, Amphotec, AmBisome) and conventional amphotericin B for injection. Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.

Note: Premedication: For patients who experience nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

General dosing:

Empiric therapy: Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily

Treatment, susceptible systemic infection: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily

Aspergillosis, treatment

Aspergillosis , treatment:

Invasive: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily (IDSA [Patterson 2016])

Endocarditis: Children and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015])

Blastomycosis, invasive

Blastomycosis , invasive: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for initial therapy, if CNS infection 4 to 6 weeks may be needed; followed by oral itraconazole for a total of 12 months (IDSA [Chapman 2008])

Candidiasis, treatment

Candidiasis , treatment:

Invasive (Independent of HIV status): Infant, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily (Filioti 2007; IDSA [Pappas 2016]); Note: In HIV-exposed/-infected patients, doses at the higher end of the range may be considered (5 mg/kg/day) (HHS [OI pediatric 2016]).

CNS infection: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily with or without flucytosine (IDSA [Pappas 2016])

Endocarditis: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015]; IDSA [Pappas 2016])

Esophageal: HIV-exposed/-infected: Adolescents: IV: 3 to 4 mg/kg/dose once daily for 14 to 21 days (HHS [OI adult 2016])

Coccidioidomycosis, invasive

Coccidioidomycosis , invasive:

Non-HIV-exposed/-infected:

Disseminated infection, nonpulmonary: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily with or without concomitant azole antifungal (IDSA [Galgiani 2005])

Pulmonary infection, diffuse: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily for several weeks, followed by an oral azole antifungal for a total length of therapy ≥12 months (IDSA [Galgiani 2005])

HIV-exposed/-infected: Non-CNS infection, severe (ie, diffuse pulmonary or severely ill with extrathoracic, disseminated disease):

Infants and Children: IV: 5 mg/kg/dose once daily until clinical improvement (minimum of several weeks of therapy), then initiate triazole therapy (eg, fluconazole or itraconazole); dose may be increased to as high as 10 mg/kg/dose once daily for life-threatening infection (HHS [OI pediatric 2016])

Adolescents: IV: 3 to 5 mg/kg/dose once daily until clinical improvement, then switch to fluconazole or itraconazole (HHS [OI adult 2016])

Cryptococcosis, invasive

Cryptococcosis , invasive:

Disseminated cryptococcosis (non-CNS or severe pulmonary disease):

Infants and Children (independent of HIV status): IV: 3 to 5 mg/kg/dose once daily with oral flucytosine; if flucytosine unavailable or not tolerated, may administer alone or in combination with high-dose fluconazole in HIV-exposed/-infected patients (HHS [OI pediatric 2016]; IDSA [Perfect 2010])

Adolescents:

Non-HIV-exposed/-infected: IV: 3 to 4 mg/kg/dose once daily for at least 14 days; may consider addition of oral flucytosine (IDSA [Perfect 2010])

HIV-exposed/-infected: IV: 3 to 4 mg/kg/dose once daily with or without flucytosine or fluconazole (HHS [OI adult 2016])

Meningitis:

Non-HIV-exposed/-infected: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily with flucytosine (IDSA [Perfect 2010])

HIV-exposed/-infected:

Manufacturer’s labeling: Infants, Children, and Adolescents: IV: 6 mg/kg/dose once daily

Alternate dosing:

Infants and Children: IV: 6 mg/kg/dose once daily with or without oral flucytosine or high dose fluconazole for a minimum 2-week induction; Note: Minimum 2-week induction, followed by consolidation and chronic suppressive therapy; a longer duration of induction therapy may be necessary if CSF is not negative or lack of clinical improvement (HHS [OI pediatric 2016])

Adolescents: IV: 3 to 4 mg/kg/dose once daily with or without oral flucytosine or fluconazole (HHS [OI adult 2016]); doses up to 6 mg/kg/dose have been reported for treatment of meningoencephalitis and may be considered for treatment failure or high fungal burden disease (IDSA [Perfect 2010])

Febrile neutropenia, empiric therapy

Febrile neutropenia, empiric therapy: Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily (Caselli 2012; IDSA [Patterson 2016])

Histoplasmosis

Histoplasmosis:

Non-HIV-exposed/-infected: Acute pulmonary disease or disseminated (non-CNS): Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily for 1 to 2 weeks followed by oral itraconazole for a total of 12 weeks; conventional amphotericin B typically preferred (IDSA [Wheat 2007])

HIV-exposed/-infected:

Disseminated infection (non-CNS disease):

Infants and Children: IV: 3 to 5 mg/kg/dose once daily for at least 2 weeks for induction; if itraconazole not tolerated for consolidation therapy, may continue for 4 to 6 weeks (HHS [OI pediatric 2016])

Adolescents: IV: 3 mg/kg/dose once daily for at least 2 weeks for induction (HHS [OI adult 2016])

CNS disease: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks for induction, followed by consolidation therapy (HHS [OI adult 2016]; HHS [OI pediatric 2016])

Leishmaniasis

Leishmaniasis:

Visceral infection, treatment:

Immunocompetent patients: Infants, Children, and Adolescents: IV: Initial: 3 mg/kg/dose once daily on days 1 to 5 and 3 mg/kg/dose on days 14 and 21. Note: Repeat course may be given to patients who do not achieve parasitic clearance.

Immunocompromised patients: Infants, Children, and Adolescents: IV: Initial: 4 mg/kg/dose once daily on days 1 to 5 and 4 mg/kg/dose on days 10, 17, 24, 31, 38

HIV-exposed/-infected:

Treatment: Adolescents: IV: 2 to 4 mg/kg/dose once daily or an interrupted schedule of 4 mg/kg/dose on days 1 to 5, and on days 10, 17, 24, 31, and 38 to achieve a total dose of 20 to 60 mg/kg (HHS [OI adult 2016])

Chronic maintenance therapy: Adolescents: IV: 4 mg/kg/dose every 2 to 4 weeks; Note: Use reserved for patients with visceral infection and CD4 count <200 cells/mm3 (HHS [OI adult 2016])

Cutaneous infection, treatment; HIV-exposed/-infected: Adolescents: IV: 2 to 4 mg/kg/dose once daily for 10 days or an interrupted schedule of 4 mg/kg/dose on days 1 to 5, and on days 10, 17, 24, 31, and 38 to achieve a total dose of 20 to 60 mg/kg (HHS [OI adult 2016])

Sporotrichosis infection

Sporotrichosis infection (IDSA [Kauffman 2007]):

Disseminated, pulmonary or osteoarticular disease: Adolescents: IV: 3 to 5 mg/kg/dose once daily, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy

Meningeal: Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconazole

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

End-stage renal disease (ESRD) on intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Poorly dialyzed.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):

IV: No dosage adjustment necessary. Use actual body weight for weight-based dose calculations; however, a maximum daily dose of 600 mg is recommended (Wasmann 2020; expert opinion). Due to higher doses, dosing using actual body weight may be associated with increased toxicity (Amsden 2011). Refer to adult dosing for indication-specific doses.

Rationale for recommendations: There are limited data describing the effect of obesity on dosing requirements for polyene antifungals (Amsden 2011). Amphotericin B (liposomal) has a low Vd (0.11 to 0.42 L/kg), suggesting limited distribution in adipose tissue (Amsden 2011; Dupont 2002). Based on one pharmacokinetic study of amphotericin B (liposomal) in 16 patients with morbid obesity, body size had no effect on drug clearance (Wasmann 2020). There are no data supporting one weight metric over another.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted, Intravenous:

Generic: 50 mg (1 ea)

Suspension Reconstituted, Intravenous [preservative free]:

AmBisome: 50 mg (1 ea) [contains cholesterol, distearoyl phosphatidylglycerol, hydrogenated soy phosphatidylcholine, sodium succinate hexahydrate, sucrose, tocopherol, dl-alpha (vit e)]

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted, Intravenous:

AmBisome: 50 mg (1 ea) [contains cholesterol, distearoyl phosphatidylglycerol, hydrogenated soy phosphatidylcholine, sodium succinate hexahydrate, sucrose, tocopherol, dl-alpha (vit e)]

Administration: Adult

IV: Administer via intravenous infusion, over a period of approximately 2 hours. Infusion time may be reduced to approximately 1 hour in patients in whom the treatment is well-tolerated. If the patient experiences discomfort during infusion, the duration of infusion may be increased. Existing intravenous line should be flushed with D5W before and after infusion (if not feasible, administer through a separate line). An in-line membrane filter (not less than 1 micron) may be used.

For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic immediate infusion-related reactions, premedicate with the following drugs, 30 to 60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) ± diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

Preinfusion administration of NS 500 to 1,000 mL IV appears to reduce the risk of nephrotoxicity during amphotericin B treatment (HHS [OI adult 2020]).

Administration: Pediatric

Parenteral: IV: Do not use in-line filter less than 1 micron to administer AmBisome. Flush line with D5W prior to infusion; infusion of diluted AmBisome should start within 6 hours of preparation; infuse over 2 hours; infusion time may be reduced to 1 hour in patients who tolerate the treatment. If the patient experiences discomfort during infusion, the duration of infusion may be increased. Discontinue if severe respiratory distress occurs.

For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs, 30 to 60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen,) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

Use: Labeled Indications

Cryptococcal meningitis in patients with HIV: Treatment of cryptococcal meningitis in patients with HIV.

Fungal infections, empiric therapy: Empiric treatment in febrile neutropenic patients with presumed fungal infection.

Fungal infections, systemic therapy: Treatment of systemic infections caused by Aspergillus sp, Candida sp, and/or Cryptococcus sp in patients refractory to conventional amphotericin B deoxycholate therapy or when renal impairment or unacceptable toxicity precludes the use of the deoxycholate formulation.

Leishmaniasis (visceral): Treatment of visceral leishmaniasis.

Use: Off-Label: Adult

Candidiasis, empiric therapy (non-neutropenic ICU patients); Candidiasis, esophageal, refractory disease; Coccidioidomycosis in patients with HIV; Fungal meningitis (secondary to contaminated [eg, Exserohilum rostratum] steroid products); Fungal osteoarticular infections (secondary to contaminated [eg, E. rostratum] steroid products); Histoplasmosis; Leishmaniasis (cutaneous and mucosal); Mucormycoses; Talaromycosis (formerly Penicillinois) in patients with HIV

Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Sound-alike/look-alike issues:

AmBisome may be confused with Ambisolm, Ambisom

Amphotericin B liposomal may be confused with amphotericin B

Other safety concerns:

Lipid-based amphotericin formulations (AmBisome) may be confused with conventional formulations (Amphocin, Fungizone) or with other lipid-based amphotericin formulations (Abelcet, Amphotec)

Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.

Adverse Reactions (Significant): Considerations
Electrolyte abnormalities

Amphotericin B (liposomal) is associated with hypocalcemia, hypokalemia, hypomagnesemia, and hyponatremia. Depletion of these electrolytes can predispose the patient to severe adverse reactions (asthenia, rhabdomyolysis, and cardiac arrhythmias). Compared with conventional amphotericin, liposomal amphotericin is associated with fewer cases of hypokalemia and hypomagnesemia (Ref). No significant differences in frequency of hypokalemia have been observed between patients who received liposomal amphotericin and amphotericin B lipid complex at a dose of 5 mg/kg/day (Ref). Electrolyte abnormalities may continue for weeks after dose reduction or discontinuation (Ref).

Mechanism: Alters cell membrane permeability leading to intracellular leakage and various tubular defects, causing electrolyte abnormalities (Ref).

Onset: Varied; in one study, hypokalemia occurred with a median onset of 10 days (range: 3 to 54 days) (Ref).

Risk factors:

• Baseline albumin level (Ref)

• Baseline electrolyte levels (Ref)

• History of hypokalemia (Ref)

Hypersensitivity reactions

Amphotericin B (liposomal) is associated with a variety of hypersensitivity reactions, including immediate (eg, infusion-related reaction, anaphylaxis) (Ref) and type IV hypersensitivity reactions, ranging from skin rash, with or without accompanying symptoms (Ref) to drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref). Acute infusion-related reactions can include fever, chills or rigors, dyspnea, hypotension, tachycardia, hypertension, hypoxia, and chest pain (Ref); symptoms generally resolve after discontinuation of the infusion and administration of an antihistamine (Ref). Based on symptom presentation, it is difficult to differentiate between anaphylaxis and infusion-related reactions, although infusion-related reactions generally occur with the first dose without previous exposure to amphotericin B compounds (Ref).

Mechanism:

Immediate hypersensitivity reactions: Dose-related, non-immunologic. Possibly related to liposomal complement activation leading to development of complement activation-related pseudoallergy (Ref) or to release of IL-1 beta, TNF-alpha, and prostaglandin E2 (Ref). Liposome rather than the amphotericin B component is likely the key factor in inducing immediate reactions (Ref). Although there are numerous case reports of anaphylaxis related to liposomal amphotericin B in the literature, none have shown an IgE-mechanism; most of the reported reactions are likely infusion-related reactions.

Type IV hypersensitivity reactions: Non–dose-related, immunologic. Maculopapular eruptions and DRESS are T-cell-mediated (Ref).

Onset:

Infusion-related reactions: Rapid; can occur with the initial dose, often within the first 5 minutes of infusion (Ref); tolerance to infusion-related reactions usually develops during therapy (Ref).

Type IV hypersensitivity reactions: Varied; maculopapular rash usually occurs 5 to 7 days after initiation (Ref) and DRESS usually occurs 1 to 8 weeks after initiation (Ref).

Risk factors:

• Although slowing the rate of infusion reduces risk of developing infusion-related events for conventional amphotericin B deoxycholate, this strategy may not be necessary for liposomal amphotericin B (Ref)

• Decreased risk of infusion-related adverse reactions with liposomal amphotericin B compared to other amphotericin B formulations, including conventional amphotericin and amphotericin B lipid complex, in adults (Ref) but not in children (Ref)

• Most patients who develop a severe infusion reaction to liposomal or amphotericin can tolerate alternative formulations (Ref); although, some patients develop reactions on multiple lipid formulations (Ref)

Nephrotoxicity

Clinical manifestations of amphotericin B (liposomal) nephrotoxicity may range from increased serum creatinine to acute kidney injury (occasionally leading to chronic kidney disease) (Ref). Compared with amphotericin deoxycholate, liposomal amphotericin is associated with fewer nephrotoxic events (Ref). Differences between amphotericin B lipid complex and liposomal amphotericin are unclear (Ref). Liposomal amphotericin nephrotoxicity is considered reversible, but cases of persistent damage have been observed. About 30% of patients with liposomal amphotericin-associated nephrotoxicity will have complete renal recovery within 10 days of onset (Ref).

Mechanism: Dose- and time-related; may be related to maximum daily dose and/or cumulative dose. Amphotericin alters cell membrane permeability, causing alterations in tubular and vascular smooth muscle cell function; decreased renal blood flow results in reduced glomerular filtration rate and direct renal tubular toxicity (Ref).

Onset: Varied; duration of therapy prior to development of nephrotoxicity typically ranges from 3 to 21 days (Ref); median duration to onset ~3 to 4 days (Ref).

Risk factors:

• Higher daily dose (Ref)

• Longer duration of therapy (Ref)

• Baseline albumin level and albumin supplementation (Ref)

• Concurrent nephrotoxic drugs (Ref)

• Higher weight and baseline body surface area (Ref)

• Older patients (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics.

>10%:

Cardiovascular: Chest pain (8% to 12%), edema (12% to 14%), hypertension (8% to 20%), hypotension (7% to 14%), peripheral edema (15%), tachycardia (9% to 19%)

Dermatologic: Pruritus (11%), skin rash (5% to 25%) (table 1)

Amphotericin B (Liposomal): Adverse Reaction: Skin Rash

Drug (Amphotericin B [Liposomal])

Comparator

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Comparator)

Comments

12%

5%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

Comparator: Amphotericin B deoxycholate

5%

5%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

Comparator: Amphotericin B deoxycholate

25%

24%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Comparator: Amphotericin B deoxycholate

24%

14%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

Comparator: Amphotericin B lipid complex

22%

14%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

Comparator: Amphotericin B lipid complex

Endocrine & metabolic: Hyperglycemia (8% to 23%), hypervolemia (8% to 12%), hypocalcemia (5% to 18%) (table 2), hypokalemia (31% to 51%) (table 3), hypomagnesemia (15% to 49%) (table 4), hyponatremia (9% to 12%) (table 5)

Amphotericin B (Liposomal): Adverse Reaction: Hypocalcemia

Drug (Amphotericin B [Liposomal])

Comparator

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Comparator)

Comments

17%

14%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

Comparator: Amphotericin B deoxycholate

13%

14%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

Comparator: Amphotericin B deoxycholate

18%

21%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Comparator: Amphotericin B deoxycholate

11%

5%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

Comparator: Amphotericin B lipid complex

5%

5%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

Comparator: Amphotericin B lipid complex

Amphotericin B (Liposomal): Adverse Reaction: Hypokalemia

Drug (Amphotericin B [Liposomal])

Comparator

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Comparator)

Comments

51%

48%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

Comparator: Amphotericin B deoxycholate

31%

48%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

Comparator: Amphotericin B deoxycholate

43%

51%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Comparator: Amphotericin B deoxycholate

43%

40%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

Comparator: Amphotericin B lipid complex

38%

40%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

Comparator: Amphotericin B lipid complex

Amphotericin B (Liposomal): Adverse Reaction: Hypomagnesemia

Drug (Amphotericin B [Liposomal])

Comparator

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Comparator)

Comments

49%

40%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

Comparator: Amphotericin B deoxycholate

29%

40%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

Comparator: Amphotericin B deoxycholate

26%

15%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

Comparator: Amphotericin B lipid complex

20%

26%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Comparator: Amphotericin B deoxycholate

15%

15%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

Comparator: Amphotericin B lipid complex

Amphotericin B (Liposomal): Adverse Reaction: Hyponatremia

Drug (Amphotericin B [Liposomal])

Comparator (Amphotericin B Deoxycholate)

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Amphotericin B Deoxycholate)

Comments

12%

9%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

Comparator: Amphotericin B deoxycholate

9%

9%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

Comparator: Amphotericin B deoxycholate

Gastrointestinal: Abdominal pain (7% to 20%), anorexia (10% to 14%), constipation (15%), diarrhea (11% to 30%), nausea (16% to 40%), vomiting (11% to 32%)

Genitourinary: Hematuria (14%)

Hematologic & oncologic: Anemia (27% to 48%), leukopenia (15% to 17%), thrombocytopenia (6% to 13%)

Hepatic: Hyperbilirubinemia (9% to 18%), increased serum alanine aminotransferase (15%), increased serum alkaline phosphatase (7% to 22%), increased serum aspartate aminotransferase (13%)

Hypersensitivity: Infusion-related reaction (≤24%)

Local: Localized phlebitis (9% to 11%)

Nervous system: Anxiety (7% to 14%), asthenia (6% to 13%) (table 6), chills (≤48%), confusion (9% to 13%), headache (9% to 20%), insomnia (17% to 22%), pain (14%), rigors (≤48%)

Amphotericin B (Liposomal): Adverse Reaction: Asthenia

Drug (Amphotericin B [Liposomal])

Comparator

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Comparator)

Comments

13%

11%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Comparator: Amphotericin B deoxycholate

8%

12%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

Comparator: Amphotericin B lipid complex

6%

12%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

Comparator: Amphotericin B lipid complex

Neuromuscular & skeletal: Back pain (12%)

Renal: Increased blood urea nitrogen (7% to 21%), increased serum creatinine (14% to 47%) (table 7), nephrotoxicity (19%) (table 8)

Amphotericin B (Liposomal): Adverse Reaction: Increased Serum Creatinine

Drug (Amphotericin B [Liposomal])

Comparator

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Comparator)

Comments

47%

60%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

1.5 × baseline serum creatinine; comparator: Amphotericin B deoxycholate

39%

44%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

Comparator: Amphotericin B deoxycholate

35%

60%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

1.5 × baseline serum creatinine; comparator: Amphotericin B deoxycholate

35%

60%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

1.5 × baseline serum creatinine; comparator: Amphotericin B deoxycholate

21%

33%

6 mg/kg/day

Cryptococcal meningitis in patients with HIV

94

87

2 × baseline serum creatinine; comparator: Amphotericin B deoxycholate

19%

44%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

Comparator: Amphotericin B deoxycholate

14%

33%

3 mg/kg/day

Cryptococcal meningitis in patients with HIV

86

87

2 × baseline serum creatinine; comparator: Amphotericin B deoxycholate

29%

63%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

1.5 × baseline serum creatinine; comparator: Amphotericin B lipid complex

26%

63%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

1.5 × baseline serum creatinine; comparator: Amphotericin B lipid complex

22%

42%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Comparator: Amphotericin B deoxycholate

20%

49%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

Comparator: Amphotericin B lipid complex

19%

49%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

Comparator: Amphotericin B lipid complex

15%

42%

5 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

81

78

2 × baseline serum creatinine; comparator: Amphotericin B lipid complex

14%

42%

3 mg/kg/day

Fungal infection, empiric therapy in febrile neutropenic patients

85

78

2 × baseline serum creatinine; comparator: Amphotericin B lipid complex

Amphotericin B (Liposomal): Adverse Reaction: Nephrotoxicity

Drug (Amphotericin B [Liposomal])

Comparator (Amphotericin B Deoxycholate)

Dose

Indication

Number of Patients (Amphotericin B [Liposomal])

Number of Patients (Amphotericin B Deoxycholate)

19%

34%

N/A

Fungal infection, empiric therapy in febrile neutropenic patients

343

344

Respiratory: Cough (2% to 18%), dyspnea (18% to 23%), epistaxis (9% to 15%), pleural effusion (13%), rhinitis (11%)

1% to 10%:

Cardiovascular: Atrial fibrillation (2% to 10%), bradycardia (2% to 10%), cardiac arrhythmia (2% to 10%), cardiomegaly (2% to 10%), flushing (2% to 10%), heart valve disease (2% to 10%), orthostatic hypotension (2% to 10%), vascular disease (2% to 10%), vasodilation (2% to 10%)

Dermatologic: Alopecia (2% to 10%), cellulitis (2% to 10%), dermal ulcer (2% to 10%), diaphoresis (7%), maculopapular rash (2% to 10%), skin discoloration (2% to 10%), urticaria (2% to 10%), vesiculobullous dermatitis (2% to 10%), xeroderma (2% to 10%)

Endocrine & metabolic: Acidosis (2% to 10%), hyperchloremia (2% to 10%), hyperkalemia (2% to 10%), hypermagnesemia (2% to 10%), hypernatremia (4%), hyperphosphatemia (2% to 10%), hypophosphatemia (2% to 10%), increased lactate dehydrogenase (2% to 10%), increased nonprotein nitrogen (2% to 10%), respiratory alkalosis (2% to 10%)

Gastrointestinal: Aphthous stomatitis (2% to 10%), dyspepsia (2% to 10%), dysphagia (2% to 10%), enlargement of abdomen (2% to 10%), eructation (2% to 10%), fecal incontinence (2% to 10%), flatulence (2% to 10%), gastrointestinal hemorrhage (10%), gingival hemorrhage (2% to 10%), hematemesis (2% to 10%), hemorrhoids (2% to 10%), hiccups (2% to 10%), increased serum amylase (2% to 10%), intestinal obstruction (2% to 10%), oral hemorrhage (2% to 10%), rectal disease (2% to 10%), stomatitis (2% to 10%), xerostomia (2% to 10%)

Genitourinary: Dysuria (2% to 10%), toxic nephrosis (2% to 10%), urinary incontinence (2% to 10%), vaginal hemorrhage (2% to 10%)

Hematologic & oncologic: Bruise (2% to 10%), decreased prothrombin time (2% to 10%), disorder of hemostatic components of blood (2% to 10%), hemophthalmos (2% to 10%), hemorrhage (2% to 10%), hypoproteinemia (2% to 10%), petechia (2% to 10%), prolonged prothrombin time (2% to 10%), purpuric disease (2% to 10%)

Hepatic: Hepatic injury (2% to 10%), hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease) (2% to 10%), hepatomegaly (2% to 10%)

Hypersensitivity: Facial edema (2% to 10%), hypersensitivity reaction (2% to 10%), type IV hypersensitivity reaction (2% to 10%)

Local: Inflammation at injection site (2% to 10%)

Nervous system: Abnormality in thinking (2% to 10%), agitation (2% to 10%), coma (2% to 10%), depression (2% to 10%), dizziness (7% to 9%), drowsiness (2% to 10%), dysesthesia (2% to 10%), dystonia (2% to 10%), hallucination (2% to 10%), malaise (2% to 10%), nervousness (2% to 10%), paresthesia (2% to 10%), seizure (2% to 10%), tremor (2% to 10%)

Neuromuscular & skeletal: Arthralgia (2% to 10%), myalgia (2% to 10%), neck pain (2% to 10%), ostealgia (2% to 10%)

Ophthalmic: Conjunctivitis (2% to 10%), dry eye syndrome (2% to 10%)

Renal: Acute kidney injury (2% to 10%), renal failure syndrome (2% to 10%), renal function abnormality (2% to 10%)

Respiratory: Asthma (2% to 10%), atelectasis (2% to 10%), dry nose (2% to 10%), flu-like symptoms (2% to 10%), hemoptysis (2% to 10%), hyperventilation (2% to 10%), hypoxia (6% to 8%), pharyngitis (2% to 10%), pneumonia (2% to 10%), pulmonary edema (2% to 10%), respiratory failure (2% to 10%), respiratory insufficiency (2% to 10%), sinusitis (2% to 10%)

Postmarketing:

Dermatologic: Erythema of skin

Genitourinary: Hemorrhagic cystitis

Hematologic & oncologic: Agranulocytosis

Hypersensitivity: Anaphylaxis (Bates 1995, Laing 1994, Schenider 1998), angioedema (Nath 2014), drug reaction with eosinophilia and systemic symptoms (Hagihara 2015)

Neuromuscular & skeletal: Rhabdomyolysis (Marking 2014)

Respiratory: Bronchospasm, cyanosis, hypoventilation

Contraindications

Hypersensitivity to amphotericin B deoxycholate or any component of the formulation

Warnings/Precautions

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, amphotericin has been determined to be an agent that may cause direct myocardial toxicity (magnitude: moderate/major) (AHA [Page 2016]).

Other warnings/precautions:

• Leukocyte transfusions: Acute pulmonary toxicity has been reported in patients receiving simultaneous leukocyte transfusions and amphotericin B.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arsenic Trioxide: Amphotericin B may enhance the hypotensive effect of Arsenic Trioxide. Amphotericin B may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as amphotericin B. Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Cardiac Glycosides: Amphotericin B may enhance the adverse/toxic effect of Cardiac Glycosides. Risk C: Monitor therapy

Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and amphotericin B whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification

Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy

CycloSPORINE (Systemic): Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Amphotericin B may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dichlorphenamide: Amphotericin B may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dronabinol: May increase the serum concentration of Amphotericin B. Specifically, dronabinol may displace amphotericin B from its protein-binding sites, leading to an increased concentration of active, unbound drug. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. Amphotericin B may increase the serum concentration of Flucytosine. Risk C: Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination

Ganciclovir-Valganciclovir: May enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methoxyflurane: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination

Pregnancy Considerations

Amphotericin crosses the placenta and enters the fetal circulation. Amphotericin B is recommended for the treatment of serious systemic fungal diseases in pregnant women; refer to current guidelines (IDSA [Pappas 2016]; King 1998; Pilmis 2015).

Breastfeeding Considerations

It is not known if amphotericin is excreted into breast milk. Due to its poor oral absorption, systemic exposure to the nursing infant is expected to be decreased; however, because of the potential for toxicity, breast-feeding is not recommended by the manufacturer (Mactal-Haaf 2001).

Dietary Considerations

If on parenteral nutrition, may need to adjust the amount of lipid infused. The lipid portion of amphotericin B (liposomal) formulation contains 0.27 kcal per 5 mg (Sacks 1997).

Monitoring Parameters

Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, CBC, temperature; monitor input and output; monitor for signs of hypokalemia (eg, muscle weakness, cramping, drowsiness, ECG changes); monitor cardiac function if used concurrently with corticosteroids; hypersensitivity reactions, including immediate (eg, infusion-related reaction, anaphylaxis) and type IV hypersensitivity reactions (eg, skin rash, DRESS).

Mechanism of Action

Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman 1992).

Pharmacokinetics

Note: Exhibits nonlinear kinetics (greater than proportional increase in serum concentration with an increase in dose)

Distribution: Vd: 0.1 to 0.16 L/kg

Half-life elimination: 7 to 10 hours (following a single 24-hour dosing interval); Terminal half life: 100 to 153 hours (following multiple dosing up to 49 days)

Pricing: US

Suspension (reconstituted) (AmBisome Intravenous)

50 mg (per each): $339.66

Suspension (reconstituted) (Amphotericin B Liposome Intravenous)

50 mg (per each): $305.69

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • AmBisome (AE, AR, AT, AU, BE, CH, CR, CY, DE, DK, DO, EG, ES, ET, FI, FR, GB, GR, GT, HK, HN, IE, IL, IT, JP, KR, KW, LB, LU, LV, MT, NI, NL, NO, PA, PL, PT, PY, QA, SA, SE, SG, SV, TH, TR, TW);
  • Ambisome (BB, BR, HU, IS, SI);
  • Amfostat (MX);
  • Amphotec (CN);
  • Fengkesong (CN)


For country code abbreviations (show table)
  1. Abongomera C, Diro E, de Lima Pereira A, et al. The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral Leishmaniasis in HIV co-infected patients in Ethiopia: a retrospective cohort study. PLoS Negl Trop Dis. 2018;12(5):e0006527. doi:10.1371/journal.pntd.0006527 [PubMed 29799869]
  2. AmBisome (amphotericin B [liposomal]) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; May 2020.
  3. American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.
  4. Amsden JR, Slain D. Antifungal dosing in obesity: a review of the literature. Curr Fungal Infect Rep. 2011;5:83-91. doi:10.1007/s12281-011-0049-7
  5. Anderson CM. Sodium chloride treatment of amphotericin B nephrotoxicity. Standard of care? West J Med. 1995;162(4):313-317. [PubMed 7747495]
  6. Andrew EC, Curtis N, Coghlan B, Cranswick N, Gwee A. Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations. Br J Clin Pharmacol. 2018;84(5):1006-1012. doi:10.1111/bcp.13521 [PubMed 29352486]
  7. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of Leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016;63(12):1539-1557. doi:10.1093/cid/ciw742. [PubMed 27941143]
  8. Baddley JW, Forrest GN; AST Infectious Diseases Community of Practice. Cryptococcosis in solid organ transplantation-guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13543. doi:10.1111/ctr.13543 [PubMed 30900315]
  9. Baltimore RS, Gewitz M, Baddour LM, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young and the Council on Cardiovascular and Stroke Nursing. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation. 2015;132(15):1487-1515. doi:10.1161/CIR.0000000000000298 [PubMed 26373317]
  10. Barron MA, Lay M, Madinger NE. Surgery and treatment with high-dose liposomal amphotericin B for eradication of craniofacial zygomycosis in a patient with Hodgkin’s Disease who had undergone allogeneic hematopoietic stem cell transplantation. J Clin Microbiol. 2005;43(4):2012-2014. doi:10.1128/JCM.43.4.2012-2014.2005 [PubMed 15815047]
  11. Bates CM, Carey PB, Hind CR. Anaphylaxis due to liposomal amphotericin (AmBisome). Genitourin Med. 1995;71(6):414. doi:10.1136/sti.71.6.414 [PubMed 8566990]
  12. Bates DW, Su L, Yu DT, et al. Correlates of acute renal failure in patients receiving parenteral amphotericin B. Kidney Int. 2001;60(4):1452-1459. doi:10.1046/j.1523-1755.2001.00948.x [PubMed 11576359]
  13. Bekersky I, Fielding RM, Dressler DE, Lee JW, Buell DN, Walsh TJ. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans. Antimicrob Agents Chemother. 2002;46(3):828-833. doi:10.1128/aac.46.3.828-833.2002 [PubMed 11850268]
  14. Bellmann R, Egger P, Gritsch W, et al. Amphotericin B lipid formulations in critically ill patients on continuous veno-venous haemofiltration. J Antimicrob Chemother. 2003;51(3):671-681. doi:10.1093/jac/dkg139 [PubMed 12615870]
  15. Bicanic T, Bottomley C, Loyse A, et al. Toxicity of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated cryptococcal meningitis. Antimicrob Agents Chemother. 2015;59(12):7224-7231. doi:10.1128/AAC.01698-15 [PubMed 26349818]
  16. Bishara J, Weinberger M, Lin AY, Pitlik S. Amphotericin B--not so terrible. Ann Pharmacother. 2001;35(3):308-310. doi:10.1345/aph.10240 [PubMed 11261528]
  17. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  18. Buckley MS, Anderson CS, Patel SA, Yerondopoulos MJ, Wicks LM, Martin MT. Apparent lack of cross-reactivity for infusion-related reactions between two forms of lipid-based amphotericin B. Am J Health Syst Pharm. 2013;70(12):1047-1051. doi:10.2146/ajhp120530 [PubMed 23719882]
  19. Burza S, Mahajan R, Kazmi S, et al. AmBisome monotherapy and combination AmBisome-miltefosine therapy for the treatment of visceral Leishmaniasis in patients coinfected with human immunodeficiency virus in India: a randomized open-label, parallel-arm, phase 3 trial. Clin Infect Dis. 2022;75(8):1423-1432. doi:10.1093/cid/ciac127 [PubMed 35147680]
  20. Candidiasis (Mucocutaneous). In: US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated May 26, 2020. Accessed June 16, 2021. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf.
  21. Cannon JP, Garey KW, Danziger LH. A prospective and retrospective analysis of the nephrotoxicity and efficacy of lipid-based amphotericin B formulations. Pharmacotherapy. 2001;21(9):1107-14. doi:10.1592/phco.21.13.1107.34613 [PubMed 11560200]
  22. Caselli D, Cesaro S, Ziino O, et al. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children. Br J Haematol. 2012;158(2):249-255. doi:10.1111/j.1365-2141.2012.09156.x [PubMed 22571507]
  23. Cesaro S, Calore E, Messina C, Zanesco L. Allergic reaction to the liposomal component of liposomal amphotericin B. Support Care Cancer. 1999;7(4):284-286. doi:10.1007/s005200050262 [PubMed 10423056]
  24. Centers for Disease Control and Prevention. Interim treatment guidance for central nervous system (CNS) and parameningeal infections associated with injection of contaminated steroid products. October 23, 2013. http://www.cdc.gov/hai/outbreaks/clinicians/index.html
  25. Cetin H, Yalaz M, Akisu M, Hilmioglu S, Metin D, Kultursay N. The efficacy of two different lipid-based amphotericin B in neonatal Candida septicemia. Pediatr Int. 2005;47(6):676-680. doi:10.1111/j.1442-200x.2005.02135.x [PubMed 16354223]
  26. Chapman SW, Dismukes WE, Proia LA, et al; Infectious Diseases Society of America. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Jun 15;46(12):1801-12. doi: 10.1086/588300 [PubMed 18462107]
  27. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12):e405‐e421. doi:10.1016/S1473-3099(19)30312-3 [PubMed 31699664]
  28. Cronin JE, Barron RL. Anaphylaxis upon switching lipid-containing amphotericin B formulation. Clin Infect Dis. 1999;28(6):1342. doi:10.1086/517799 [PubMed 10451192]
  29. Diro E, Blesson S, Edwards T, et al. A randomized trial of AmBisome monotherapy and AmBisome and miltefosine combination to treat visceral Leishmaniasis in HIV co-infected patients in Ethiopia. PLoS Negl Trop Dis. 2019;13(1):e0006988. doi:10.1371/journal.pntd.0006988 [PubMed 30653490]
  30. Drewett GP, Copaescu A, DeLuca J, Holmes NE, Trubiano JA. Asystolic cardiac arrest following liposomal amphotericin B infusion: anaphylaxis or compliment activation-related pseudoallergy? Allergy Asthma Clin Immunol. 2021;17(1):80. doi:10.1186/s13223-021-00582-x [PubMed 34325715]
  31. Dupont B. Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother. 2002;49(suppl 1):31-36. doi:10.1093/jac/49.suppl_1.31 [PubMed 11801578]
  32. Edwards JE Jr, Bodey GP, Bowden RA, et al. International conference for the development of a consensus on the management and prevention of severe candidal infections. Clin Infect Dis. 1997;25(1):43-59. doi:10.1086/514504. [PubMed 9243032]
  33. Eggimann P, Francioli P, Bille J, et al. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med. 1999;27(6):1066-1072. doi:10.1097/00003246-199906000-00019 [PubMed 10397206]
  34. Emminger W, Graninger W, Emminger-Schmidmeier W, et al. Tolerance of high doses of amphotericin B by infusion of a liposomal formulation in children with cancer. Ann Hematol. 1994;68(1):27-31. doi:10.1007/BF01695916 [PubMed 8110875]
  35. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y [PubMed 34599691]
  36. Farmakiotis D, Tverdek FP, Kontoyiannis DP. The safety of amphotericin B lipid complex in patients with prior severe intolerance to liposomal amphotericin B. Clin Infect Dis. 2013;56(5):701-703. doi:10.1093/cid/cis972 [PubMed 23166189]
  37. Fichtenbaum CJ, Zackin R, Rajicic N, Powderly WG, Wheat LJ, Zingman BS. Amphotericin B oral suspension for fluconazole-refractory oral candidiasis in persons with HIV infection. Adult AIDS Clinical Trials Group Study Team 295. AIDS. 2000;14(7):845-852. doi:10.1097/00002030-200005050-00011 [PubMed 10839593]
  38. Filioti J, Spiroglou K, Panteliadis CP, Roilides E. Invasive candidiasis in pediatric intensive care patients: epidemiology, risk factors, management, and outcome. Intensive Care Med. 2007;33(7):1272-1283. doi:10.1007/s00134-007-0672-5. [PubMed 17503015]
  39. Galgiani JN, Ampel NM, Blair JE, et al; Infectious Diseases Society of America. Coccidioidomycosis. Clin Infect Dis. 2005;41(9):1217-1223. doi:10.1086/496991. [PubMed 16206093]
  40. Girois SB, Chapuis F, Decullier E, Revol BG. Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2006;25(2):138-149. doi:10.1007/s10096-005-0080-0 [PubMed 16622909]
  41. Gould FK, Denning DW, Elliott TS, et al; Working Party of the British Society for Antimicrobial Chemotherapy. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy [published correction in J Antimicrob Chemother. 2012;67(5):1304]. J Antimicrob Chemother. 2012;67(2):269-289. doi:10.1093/jac/dkr450. [PubMed 22086858]
  42. Gussak HM, Rahman S, Bastani B. Administration and clearance of amphotericin B during high-efficiency or high-efficiency/high-flux dialysis. Am J Kidney Dis. 2001;37(6):E45. doi:10.1053/ajkd.2001.24545 [PubMed 11382716]
  43. Hagihara M, Yamagishi Y, Hirai J, et al. Drug-induced hypersensitivity syndrome by liposomal amphotericin-B: a case report. BMC Res Notes. 2015;8:510. doi:10.1186/s13104-015-1486-0 [PubMed 26420570]
  44. HHS Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Department of Health and Human Services. 2016. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf.
  45. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562-577. doi:10.1592/phco.29.5.562 [PubMed 19397464]
  46. Hiemenz JW, Walsh TJ. Lipid formulations of amphotericin B: recent progress and future directions. Clin Infect Dis. 1996;22(suppl 2):S133-S144. doi:10.1093/clinids/22.supplement_2.s133 [PubMed 8722841]
  47. Hoetzenecker W, Nägeli M, Mehra ET, et al. Adverse cutaneous drug eruptions: current understanding. Semin Immunopathol. 2016;38(1):75-86. doi:10.1007/s00281-015-0540-2 [PubMed 26553194]
  48. Jarvis JN, Lawrence DS, Meya DB, et al; Ambition Study Group. Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. N Engl J Med. 2022;386(12):1109-1120. doi:10.1056/NEJMoa2111904 [PubMed 35320642]
  49. Jarvis JN, Leeme TB, Molefi M, et al. Short-course high-dose liposomal amphotericin B for human immunodeficiency virus-associated cryptococcal meningitis: a phase 2 randomized controlled trial. Clin Infect Dis. 2019;68(3):393-401. doi:10.1093/cid/ciy515 [PubMed 29945252]
  50. Johnson MD, Drew RH, Perfect JR. Chest discomfort associated with liposomal amphotericin B: report of three cases and review of the literature. Pharmacotherapy. 1998;18(5):1053-1061. [PubMed 9758315]
  51. Juster-Reicher A, Flidel-Rimon O, Amitay M, Even-Tov S, Shinwell E, Leibovitz E. High-dose liposomal amphotericin B in the therapy of systemic candidiasis in neonates. Eur J Clin Microbiol Infect Dis. 2003;22(10):603-607. doi:10.1007/s10096-003-0993-4 [PubMed 13680398]
  52. Kauffman CA, Bustamante B, Chapman SW, Pappas PG; Infectious Diseases Society of America. Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(10):1255-1265. doi:10.1086/522765 [PubMed 17968818]
  53. Kauffman CA. Esophageal candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed September 23, 2021.
  54. Kauffman CA, Pappas PG, Patterson TF. Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2013;368(26):2495-500. doi:10.1056/NEJMra1212617 [PubMed 23083312]
  55. King CT, Rogers PD, Cleary JD, Chapman SW. Antifungal therapy during pregnancy. Clin Infect Dis. 1998;27(5):1151-1160. doi: 10.1086/514977 [PubMed 9827262]
  56. Kobayashi R, Keino D, Hori D, et al. Analysis of hypokalemia as a side effect of liposomal amphotericin in pediatric patients. Pediatr Infect Dis J. 2018;37(5):447-450. doi:10.1097/INF.0000000000001802 [PubMed 28945677]
  57. Laing RB, Milne LJ, Leen CL, Malcolm GP, Steers AJ. Anaphylactic reactions to liposomal amphotericin. Lancet. 1994;344(8923):682. doi:10.1016/s0140-6736(94)92116-4 [PubMed 7915365]
  58. Lanternier F, Poiree S, Elie C, et al. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J Antimicrob Chemother. 2015;70(11):3116‐3123. doi:10.1093/jac/dkv236 [PubMed 26316385]
  59. Leenders AC, Daenen S, Jansen RL, et al. Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections. Br J Haematol. 1998;103(1):205-212. doi:10.1046/j.1365-2141.1998.00944.x [PubMed 9792309]
  60. Lehrnbecher T, Robinson P, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol. 2017;35(18):2082-2094. doi:10.1200/JCO.2016.71.7017 [PubMed 28459614]
  61. Loo AS, Muhsin SA, Walsh TJ. Toxicokinetic and mechanistic basis for the safety and tolerability of liposomal amphotericin B. Expert Opin Drug Saf. 2013;12(6):881-895. doi:10.1517/14740338.2013.827168 [PubMed 23931455]
  62. Lowery MM, Greenberger PA. Amphotericin-induced stridor: a review of stridor, amphotericin preparations, and their immunoregulatory effects. Ann Allergy Asthma Immunol. 2003;91(5):460-466. doi:10.1016/S1081-1206(10)61514-1 [PubMed 14692429]
  63. Lyman CA, Walsh TJ. Systemically administered antifungal agents. A review of their clinical pharmacology and therapeutic applications. Drugs. 1992;44(1):9-35. doi:10.2165/00003495-199244010-00002 [PubMed 1379913]
  64. Mactal-Haaf C, Hoffman M, Kuchta A. Use of anti-infective agents during lactation, Part 3: Antivirals, antifungals, and urinary antiseptics. J Hum Lact. 2001;17(2):160-166. doi:10.1177/089033440101700214 [PubMed 11847833]
  65. Mahajan R, Das P, Isaakidis P, et al. Combination treatment for visceral Leishmaniasis patients coinfected with human immunodeficiency virus in India. Clin Infect Dis. 2015;61(8):1255-1262. doi:10.1093/cid/civ530 [PubMed 26129756]
  66. Marking U, den Boer M, Das AK, et al. Hypokalaemia-induced rhabdomyolysis after treatment of post-Kala-azar dermal Leishmaniasis (PKDL) with high-dose AmBisome in Bangladesh-a case report. PLoS Negl Trop Dis. 2014;8(6):e2864. doi:10.1371/journal.pntd.0002864 [PubMed 24922279]
  67. Matsuoka T, Usami E, Yoshimura T, Takada H, Yasuda T. (2011) Risk factors contributing to occurrence of hypokalemia after liposomal-amphotericin B administration. Iryo Yakugaku (Japanese J Pharm Heal Care Sci). 2011;37:487-493.
  68. Milosevits G, Mészáros T, Őrfi E, et al. Complement-mediated hypersensitivity reactions to an amphotericin B-containing lipid complex (Abelcet) in pediatric patients and anesthetized rats: Benefits of slow infusion. Nanomedicine. 2021;34:102366. doi:10.1016/j.nano.2021.102366 [PubMed 33549818]
  69. Mistro S, Maciel Ide M, de Menezes RG, Maia ZP, Schooley RT, Badaró R. Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis. Clin Infect Dis. 2012;54(12):1774-1777. doi:10.1093/cid/cis290 [PubMed 22491505]
  70. Mora-Duarte J, Betts R, Rotstein C, et al; Caspofungin Invasive Candidiasis Study Group. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020-2029. doi:10.1056/NEJMoa021585 [PubMed 12490683]
  71. Mukhtar M, Aboud M, Kheir M, et al. First report on Ambisome-associated allergic reaction in two Sudanese leishmaniasis patients. Am J Trop Med Hyg. 2011;85(4):644-6445. doi:10.4269/ajtmh.2011.10-0511 [PubMed 21976565]
  72. Nath P, Basher A, Harada M, et al. Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion. Trop Doct. 2014;44(4):241-242. doi:10.1177/0049475514543655 [PubMed 25139411]
  73. Nemecek BD, Hammond DA, eds. Demystifying Drug Dosing in Renal Dysfunction. American Society of Health-System Pharmacists; 2019.
  74. Obata Y, Takazono T, Tashiro M, et al. The clinical usage of liposomal amphotericin B in patients receiving renal replacement therapy in Japan: a nationwide observational study. Clin Exp Nephrol. 2021;25(3):279-287. doi:10.1007/s10157-020-01989-3 [PubMed 33179180]
  75. Pagano L, Offidani M, Fianchi L, et al; GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Infection Program. Mucormycosis in hematologic patients. Haematologica. 2004 ;89(2):207-214. [PubMed 15003897]
  76. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association [published correction appears in Circulation. 2016;134(12):e261]. Circulation. 2016;134(6):e32-e69. [PubMed 27400984]
  77. 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 [PubMed 26679628]10.1093/cid/civ933
  78. Patel R. Antifungal agents. Part I. Amphotericin B preparations and flucytosine. Mayo Clin Proc. 1998;73(12):1205-1225. doi:10.4065/73.12.1205 [PubMed 9868423]
  79. 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. Accessed August 8, 2016. http://cid.oxfordjournals.org/content/early/2016/06/22/cid.ciw326.full.pdf+html. [PubMed 27365388]
  80. Patterson TF, Thompson GR 3rd, Denning DW, et al. Executive summary: Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;63(4):433-442. doi:10.1093/cid/ciw444 [PubMed 27481947]
  81. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291-322. doi:10.1086/649858 [PubMed 20047480]
  82. Personett HA, Kayhart BM, Barreto EF, et al. Renal recovery following liposomal amphotericin B-induced nephrotoxicity. Int J Nephrol. 2019;2019:8629891. doi:10.1155/2019/8629891 [PubMed 30809394]
  83. Pilmis B, Jullien V, Sobel J, et al. Lecuit M, Lortholary O, Charlier C. Antifungal drugs during pregnancy: an updated review. J Antimicrob Chemother. 2015;70(1):14-22. doi:10.1093/jac/dku355 [PubMed 25204341]
  84. Prentice HG, Hann IM, Herbrecht R, et al. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol. 1997;98(3):711-7118. doi:10.1046/j.1365-2141.1997.2473063.x [PubMed 9332329]
  85. Queiroz-Telles F, Berezin E, Leverger G, et al; Micafungin Invasive Candidiasis Study Group. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J. 2008;27(9):820-826. doi:10.1097/INF.0b013e31817275e6 [PubMed 18679151]
  86. Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute. N Engl J Med. 1994;331(20):1325-1330. doi:10.1056/NEJM199411173312001 [PubMed 7935701]
  87. Rex JH, Pappas PG, Karchmer AW, et al; National Institute of Allergy and Infectious Diseases Mycoses Study Group. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis. 2003;36(10):1221-1228. doi:10.1086/374850 [PubMed 12746765]
  88. Rex JH, Walsh TJ, Sobel JD, et al. Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30(4):662-678. doi:10.1086/313749 [PubMed 10770728]
  89. Ringdén O, Andström E, Remberger M, Svahn BM, Tollemar J. Safety of liposomal amphotericin B (AmBisome) in 187 transplant recipients treated with cyclosporin. Bone Marrow Transplant. 1994;14(suppl 5):S10-S14. [PubMed 7703925]
  90. Rocha PN, Kobayashi CD, de Carvalho Almeida L, de Oliveira Dos Reis C, Santos BM, Glesby MJ. Incidence, predictors, and impact on hospital mortality of amphotericin B nephrotoxicity defined using newer acute kidney injury diagnostic criteria. Antimicrob Agents Chemother. 2015;59(8):4759-4769. doi:10.1128/AAC.00525-15 [PubMed 26014956]
  91. Roden MM, Nelson LD, Knudsen TA, et al. Triad of acute infusion-related reactions associated with liposomal amphotericin B: analysis of clinical and epidemiological characteristics. Clin Infect Dis. 2003;36(10):1213-1220. doi:10.1086/374553 [PubMed 12746764]
  92. Rokicka M. AmBisome treatment of fungal sinusitis in severe immunocompromised patient with acute lymphoblastic leukemia relapsed after autologous peripheral blood transplantation. Acta Biomed. 2006;77(suppl 2):26-27. [PubMed 16918064]
  93. Sacks GS, Cleary JD. Nutritional impact of lipid-associated amphotericin B formulations. Ann Pharmacother. 1997;31(1):121-122. doi:10.1177/106002809703100124 [PubMed 8997484]
  94. Safdar A, Ma J, Saliba F, et al. Drug-induced nephrotoxicity caused by amphotericin B lipid complex and liposomal amphotericin B: a review and meta-analysis. Medicine (Baltimore). 2010;89(4):236-244. doi:10.1097/MD.0b013e3181e9441b [PubMed 20616663]
  95. Sawaya BP, Briggs JP, Schnermann J. Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties. J Am Soc Nephrol. 1995;6(2):154-164. doi:10.1681/ASN.V62154 [PubMed 7579079]
  96. Scarcella A, Pasquariello MB, Giugliano B, Vendemmia M, de Lucia A. Liposomal amphotericin B treatment for neonatal fungal infections. Pediatr Infect Dis J. 1998;17(2):146-148. doi:10.1097/00006454-199802000-00013 [PubMed 9493812]
  97. Scardina T, Fawcett AJ, Patel SJ. Amphotericin-associated infusion-related reactions: A narrative review of pre-medications. Clin Ther. 2021;43(10):1689-1704. doi:10.1016/j.clinthera.2021.09.011 [PubMed 34696915]
  98. Schneider P, Klein RM, Dietze L, Söhngen D, Leschke M, Heyll A. Anaphylactic reaction to liposomal amphotericin (AmBisome). Br J Haematol. 1998;102(4):1108-1109. doi:10.1046/j.1365-2141.1998.0952a.x [PubMed 9734666]
  99. Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]
  100. Shadur B, Trahair TN, O'Brien T, Russell SJ, Ziegler JB. Desensitisation to liposomal amphotericin B. J Allergy Clin Immunol Pract. 2017;5(1):181-183. doi:10.1016/j.jaip.2016.08.006 [PubMed 27743834]
  101. Slain D. Lipid-based amphotericin B for the treatment of fungal infections. Pharmacotherapy. 1999;19(3):306-323. doi:10.1592/phco.19.4.306.30934 [PubMed 10221369]
  102. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America [published online June 18, 2014]. Clin Infect Dis. 2014;59(2):e10-e52. doi:10.1093/cid/ciu296. [PubMed 24947530]
  103. Tiphine M, Letscher-Bru V, Herbrecht R. Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability. Transpl Infect Dis. 1999;1(4):273-283. doi:10.1034/j.1399-3062.1999.010406.x [PubMed 11428998]
  104. Tunkel AR, Glaser CA, Bloch KC, et al; Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47(3):303-327. doi:10.1086/589747 [PubMed 18582201]
  105. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's dlinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64(6):e34-e65. doi:10.1093/cid/ciw861 [PubMed 28203777]
  106. Turkova A, Roilides E, Sharland M. Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy - is there a 'right' choice? Curr Opin Infect Dis. 2011;24(2):163-171. doi:10.1097/QCO.0b013e328343614e [PubMed 21301335]
  107. Usami E, Kimura M, Kanematsu T, et al. Evaluation of hypokalemia and potassium supplementation during administration of liposomal-amphotericin B. Exp Ther Med. 2014;7(4):941-946. doi:10.3892/etm.2014.1534 [PubMed 24669255]
  108. US Department of Health and Human Services Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. Accessed May 12, 2022. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/whats-new.
  109. US Department of Health and Human Services Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed October 5, 2022. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/whats-new-guidelines.
  110. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed May 12, 2022. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/whats-new-guidelines
  111. Vaidya SJ, Seydel C, Patel SR, Ortin M. Anaphylactic reaction to liposomal amphotericin B. Ann Pharmacother. 2002;36(9):1480-1481. doi:10.1345/aph.1C001 [PubMed 12196074]
  112. Vazquez JA. Management of candidemia and invasive candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed July 18, 2022.
  113. Wade RL, Chaudhari P, Natoli JL, Taylor RJ, Nathanson BH, Horn DL. Nephrotoxicity and other adverse events among inpatients receiving liposomal amphotericin B or amphotericin B lipid complex. Diagn Microbiol Infect Dis. 2013;76(3):361-367. doi:10.1016/j.diagmicrobio.2013.04.001 [PubMed 23774005]
  114. Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med. 1999;340(10):764-771. doi:10.1056/NEJM199903113401004 [PubMed 10072411]
  115. Wasmann RE, Smit C, van Dongen EPH, et al. Fixed dosing of liposomal amphotericin B in morbidly obese individuals. Clin Infect Dis. 2020;70(10):2213-2215. doi:10.1093/cid/ciz885 [PubMed 31588493]
  116. Wazny LD, Brophy DF. Amiloride for the prevention of amphotericin B-induced hypokalemia and hypomagnesemia. Ann Pharmacother. 2000;34(1):94-97. doi:10.1345/aph.19127 [PubMed 10669191]
  117. Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807‐825. doi:10.1086/521259 [PubMed 17806045]
  118. Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A; L Amph/ABLC Collaborative Study Group. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis. 2000;31(5):1155-1163. doi:10.1086/317451 [PubMed 11073745]
  119. World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. Geneva: World Health Organization; 2022. https://www.who.int/publications/i/item/9789240052178. Accessed October 5, 2022a.
  120. World Health Organization. WHO guidelines for the treatment of visceral Leishmaniasis in HIV co-infected patients in East Africa and South-East Asia. Geneva: World Health Organization; 2022. https://www.who.int/publications/i/item/9789240048294. Accessed September 26, 2022b.
  121. Yokota T, Yoshikawa N, Arimori K, Ikeda R. Retrospective analysis of risk factors for liposomal amphotericin B-associated nephrotoxicity. Pharmazie. 2020;75(11):599-601. doi:10.1691/ph.2020.0731 [PubMed 33239137]
  122. Zhang B, Li Q, Shi C, Zhang X. Drug-induced pseudoallergy: A review of the causes and mechanisms. Pharmacology. 2018;101(1-2):104-110. doi:10.1159/000479878 [PubMed 29136631]
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