Version July 2025
Dosage guidance:
Safety: Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (eg, Abelcet, AmBisome) and amphotericin B deoxycholate (conventional amphotericin B). 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.
Candidiasis, CNS infection: Preterm and term neonates: Limited data available: IV: 5 mg/kg/dose once daily. Doses as high as 7 mg/kg/dose once daily have been reported in treatment of non-CNS invasive candidiasis (Ref). Treat for ≥3 weeks and until all signs, symptoms, and cerebrospinal fluid and radiologic abnormalities resolve. May consider addition of flucytosine as salvage therapy in patients with inadequate clinical response (Ref).
Mucormycosis, invasive: Limited data available: Note: Prompt surgical debridement is often needed to achieve clinical cure (Ref).
Neonates: IV: 5 to 10 mg/kg/dose once daily. Consider using higher end of dosing range for CNS disease. Total duration (including oral step-down therapy if possible) varies based on clinical and radiologic response and patient immune status; several months are often warranted (Ref).
Dosage guidance:
Safety: Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (eg, Abelcet, AmBisome) and amphotericin B deoxycholate (conventional amphotericin B). 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.
Clinical considerations: Premedication: To minimize infusion-related immediate reactions, may premedicate with acetaminophen, diphenhydramine, and/or hydrocortisone 30 to 60 minutes prior to administration. If the patient experiences rigors during the infusion, meperidine may be administered. Adequate hydration and preinfusion administration of NS may reduce the risk of nephrotoxicity during amphotericin B treatment (Ref).
General dosing: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily (Ref). Doses up to 10 mg/kg/dose once daily have been reported for treatment of CNS infections or mucormycosis (Ref).
Aspergillosis :
Invasive disease: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily. Minimum duration of treatment is 6 to 12 weeks and depends on site of infection, extent of disease, and level/duration of immunosuppression (Ref).
Endocarditis: Children and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (Ref).
Blastomycosis, moderately severe to severe disease: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for 1 to 2 weeks or until improvement, followed by oral itraconazole for a total of 12 months. For CNS disease, initial IV therapy at the higher end of the dosing range (5 mg/kg/dose) is recommended for 4 to 6 weeks, followed by oral itraconazole (Ref).
Candidiasis :
Invasive (alternative agent): Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily. Duration of therapy should be individualized based on clinical response and presence of deep-tissue foci; candidemia should be treated for ≥14 days from the first negative blood culture and clinical resolution (Ref).
CNS: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily with or without flucytosine. Step down to azole therapy after initial response to treatment; overall duration is until all signs, symptoms, and cerebrospinal fluid/radiologic abnormalities have resolved (Ref).
Endocarditis: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine. Step down to azole therapy in clinically stable patients with susceptible isolates and negative repeat cultures. Total antifungal duration is ≥6 weeks after valve replacement surgery, with longer duration for perivalvular abscess, other complications, or a nonsurgical approach (Ref).
Esophageal (alternative agent): Adolescents with HIV: IV: 3 to 4 mg/kg/dose once daily for 14 to 21 days (Ref).
Coccidioidomycosis, severe, nonmeningeal infection:
Patients with HIV:
Infants and Children: IV: 5 mg/kg/dose once daily; dose may be increased to as high as 10 mg/kg/dose once daily for life-threatening infection. Continue IV therapy until clinical improvement, then switch to an oral azole to complete ≥12 months of therapy (Ref).
Adolescents: IV: 3 to 5 mg/kg/dose once daily until clinical improvement, then switch to an oral azole to complete ≥12 months of therapy. May consider initiating the oral azole in combination with the amphotericin B product and then continuing the oral azole when amphotericin B is discontinued (Ref).
Cryptococcosis :
Disseminated cryptococcosis (non-CNS or severe pulmonary disease): Infants, Children, and Adolescents: Induction therapy: IV: 3 to 5 mg/kg/dose once daily as part of an appropriate combination regimen for ≥2 weeks, followed by consolidation and maintenance therapy (Ref).
Meningitis:
Patients without HIV: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily as part of an appropriate combination regimen for ≥2 weeks, followed by consolidation and maintenance therapy (Ref).
Patients with HIV:
Infants and Children: IV: 6 mg/kg/dose once daily as part of an appropriate combination regimen for ≥2 weeks, followed by consolidation and maintenance therapy (Ref).
Adolescents: IV: 3 to 4 mg/kg/dose once daily as part of an appropriate combination regimen for ≥2 weeks, followed by consolidation and maintenance therapy; doses up to 6 mg/kg/dose have been suggested for treatment of meningoencephalitis and may be considered for treatment failure or high fungal burden disease (Ref).
Febrile neutropenia, empiric therapy: Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily (Ref).
Histoplasmosis: Limited data available:
Moderately severe to severe pulmonary or disseminated disease: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for 1 to 2 weeks (≥2 weeks for patients with HIV) and until clinical improvement, followed by oral itraconazole therapy (Ref).
CNS disease: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconazole (Ref).
Leishmaniasis:
Cutaneous infection: Limited data available:
Patients without HIV: Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily on days 1 through 5, and then 3 mg/kg/dose on day 10 (for a total of 6 doses) or 3 mg/kg/dose once daily on days 1 through 7 (for a total of 7 doses). Cumulative dose administered should be 18 to 21 mg/kg to complete regimen (Ref).
Patients with HIV: Adolescents: IV: 2 to 4 mg/kg/dose once daily for 10 days (for a total of 10 doses) or an interrupted schedule of 4 mg/kg/dose on days 1 to 5 and on days 10, 17, 24, 31, and 38 (for a total of 10 doses) to achieve a cumulative dose of 20 to 60 mg/kg to complete regimen (Ref).
Mucosal infection: Limited data available: Infants, Children, and Adolescents: IV: ~3 mg/kg/dose once daily for 7 to 20 days (cumulative administered dose of ~20 to 60 mg/kg to complete regimen) (Ref).
Visceral infection:
Immunocompetent patients: Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily on days 1 through 5, and 3 mg/kg/dose on days 14 and 21; a repeat course may be given to patients who do not achieve parasitic clearance. Higher cumulative doses (ie, ≥40 mg/kg total) may be necessary if disease acquired in East Africa (Ref).
Immunocompromised patients: Infants, Children, and Adolescents: IV: Initial: 4 mg/kg/dose once daily on days 1 through 5, and 4 mg/kg/dose on days 10, 17, 24, 31, 38 (for a total of 10 doses) (Ref).
Patients with HIV:
Infants and Children: IV: Initial: 4 mg/kg/dose once daily on days 1 through 5, and 4 mg/kg/dose on days 10, 17, 24, 31, 38 (for a total of 10 doses) (Ref).
Adolescents:
Treatment: IV: 2 to 4 mg/kg/dose once daily or an interrupted schedule of 4 mg/kg/dose on days 1 through 5, and on days 10, 17, 24, 31, and 38. With either regimen, a cumulative dose of 20 to 60 mg/kg to complete regimen is recommended (Ref). Note: Higher doses (eg, cumulative dose ≥40 mg/kg to complete regimen) and/or combination therapy may be required for patients with disease acquired in East Africa or Southeast Asia (Ref).
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/dose every 2 to 4 weeks (Ref).
Mucormycosis, invasive: Limited data available: Note: Prompt surgical debridement is often needed to achieve clinical cure (Ref).
Infants, Children, and Adolescents: IV: 5 to 10 mg/kg/dose once daily. Consider using higher end of dosing range for CNS disease. Total duration (including oral step-down therapy if possible) varies based on clinical and radiologic response and patient immune status; several months are often warranted (Ref).
Sporotrichosis:
Disseminated, pulmonary, or osteoarticular disease: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily, then switch to oral itraconazole after a favorable response is seen to complete ≥12 months of therapy (Ref).
Meningeal disease: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconazole to complete ≥12 months of therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: IV:
Altered kidney function:
Mild to severe impairment: Based on adult data, dosage adjustment is unlikely to be necessary because clearance by the kidney is low (Ref).
Hemodialysis, intermittent: Unlikely to be dialyzed (lipophilic and highly protein bound) (Ref). Based on adult data, no dosage adjustment or supplemental dose necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (Ref).
CRRT: Unlikely to be significantly dialyzed: Based on adult data, no dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Liposomal amphotericin B: Drug information")
Dosage guidance:
Dosage form information: 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.
Safety: For patients who experience immediate nonanaphylactic 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. Preinfusion administration of 500 mL to 1 L of NS may reduce the risk of nephrotoxicity during amphotericin treatment (Ref).
Usual dosage range: IV: 3 to 6 mg/kg once daily.
Aspergillosis, invasive (alternative agent):
Note: Guidelines recommend amphotericin B lipid formulations be considered for invasive aspergillosis only when triazoles, specifically voriconazole, are contraindicated or not tolerated (Ref).
IV: 3 to 5 mg/kg once daily (Ref); doses up to 7.5 mg/kg once daily have been recommended for CNS infection (Ref). Minimum duration of treatment is 6 to 12 weeks and depends on site of infection, extent of disease and level/duration of immunosuppression.
Candidiasis:
Candidemia (patients with neutropenia) (alternative agent): IV: 3 to 5 mg/kg once daily; may transition to fluconazole during persistent neutropenia in patients who are clinically stable, 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 (Ref).
Candidemia (patients without neutropenia) (alternative agent): IV: 3 to 5 mg/kg once daily; may transition to fluconazole (usually after 5 to 7 days) in patients who are clinically stable, 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 (Ref).
Cardiac device infection (including implantable cardiac defibrillator, pacemaker, ventricular assist device): IV: 3 to 5 mg/kg once daily, with or without flucytosine; step down to azole therapy in patients who are clinically stable with susceptible isolates and negative repeat cultures. Total antifungal duration is 4 weeks after device removal for isolated generator pocket infection and ≥6 weeks after device removal for wire infection (Ref).
Central nervous system (eg, meningitis): IV: 5 mg/kg once daily, with or without oral flucytosine; step-down to fluconazole therapy is recommended after initial response to treatment (Ref).
Chronic disseminated (hepatosplenic): IV: 3 to 5 mg/kg once daily; after several weeks, transition to oral fluconazole in patients who are clinically stable with fluconazole-susceptible isolates (Ref).
Empiric therapy, suspected invasive candidiasis (patients without neutropenia in the ICU) (alternative agent) (off-label use):
Note: Antifungal therapy is not routinely warranted for initial management of patients without neutropenia who have sepsis. Consider use for patients who are critically ill 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) (Ref).
IV: 3 to 5 mg/kg once daily; continue treatment for 14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response (Ref).
Endocarditis, native or prosthetic valve: IV: 3 to 5 mg/kg once daily, with or without flucytosine; step down to azole therapy in patients who are clinically stable with susceptible isolates and negative repeat cultures. Total antifungal duration is ≥6 weeks after valve replacement surgery, with longer duration for perivalvular abscesses, other complications, or a nonsurgical approach (Ref).
Endophthalmitis (with or without vitritis) caused by fluconazole- or voriconazole-resistant isolates: IV: 3 to 5 mg/kg once daily, 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 (Ref).
Esophageal, refractory disease (alternative agent) (off-label use):
Note: Reserve use for infections that require IV therapy and are resistant to other agents (Ref).
IV: 3 to 4 mg/kg once daily. Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (Ref).
Intra-abdominal candidiasis (alternative agent): IV: 3 to 5 mg/kg once daily; duration of therapy determined by clinical response and source control (Ref).
Osteomyelitis or septic arthritis due to Candida (alternative agent): IV: 3 to 5 mg/kg once daily for at least 2 weeks, followed by fluconazole for at least 4 weeks (septic arthritis) or for 6 to 12 months (osteomyelitis) (Ref).
Suppurative thrombophlebitis: IV: 3 to 5 mg/kg once daily; continue for at least 2 weeks after candidemia has cleared; consider transition to fluconazole in patients who are clinically stable with a fluconazole-susceptible isolate who have responded to initial therapy (Ref).
Coccidioidomycosis, severe, nonmeningeal infection (off-label use): IV: 3 to 5 mg/kg once daily until clinical improvement, then switch to an oral azole (eg, fluconazole or itraconazole). Note: Some experts suggest initiating the oral azole at the same time as amphotericin B liposomal and continuing the oral azole when amphotericin B liposomal is discontinued (Ref).
Cryptococcosis:
Disseminated cryptococcosis (non-CNS or severe pulmonary disease): Induction therapy: IV: 3 to 4 mg/kg once daily with flucytosine (preferred) or fluconazole, or without a concomitant agent, for 2 weeks, followed by consolidation and maintenance therapy with fluconazole (Ref).
Meningitis: Induction therapy:
Resource-abundant settings: IV: 3 to 4 mg/kg once daily with flucytosine (preferred) or fluconazole, or without a concomitant agent, for 2 weeks (Ref); 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 (Ref). Induction therapy is followed by consolidation and maintenance therapy with fluconazole (Ref).
Resource-limited settings:
Note: This regimen has only been studied in patients with HIV (Ref).
IV: 10 mg/kg as a single dose, followed by 14 days of fluconazole and flucytosine. Induction therapy is followed by consolidation and maintenance therapy with fluconazole (Ref).
Fungal infection, pulmonary, prophylaxis in lung transplant recipients (alternative agent) (off-label use): Note: Optimal dose, frequency, and duration are not defined and are patient and center dependent; an example is provided, refer to institutional protocols. Some transplant centers administer in combination with a systemic antifungal to prevent systemic infection (Ref).
Inhalation for nebulization (off-label route): 25 mg three times weekly for 60 days post-transplant, then 25 mg once weekly from day 61 to 180 days post-transplant, then 25 mg every 2 weeks thereafter based on center-specific protocols (Ref).
Fungal sinusitis: IV: Limited data in patients who are immunocompromised have shown efficacy with 3 to 10 mg/kg once daily (Ref). Note: An azole antifungal is recommended if causative organism is Aspergillus spp or Pseudallescheria boydii (Scedosporium sp).
Fusariosis, invasive (off-label use):
Non-CNS infection: IV: 3 to 5 mg/kg once daily. Note: Some experts suggest combination antifungal therapy for patients with severe immunosuppression, severe disease, or increasing skin lesions or persistently positive blood cultures with monotherapy (Ref).
CNS infection: IV: Initial: 5 mg/kg once daily in combination with voriconazole; dose escalation to 7.5 to 10 mg/kg once daily may be considered for insufficient response (Ref).
Duration:Duration of therapy is often prolonged and depends on site of infection, severity, immune status, and response to therapy (Ref).
Histoplasmosis (off-label use):
Acute pulmonary disease, moderately severe to severe: Induction therapy: IV: 3 to 5 mg/kg once daily for 1 to 2 weeks, followed by itraconazole maintenance therapy (Ref).
Disseminated disease, moderately severe to severe:Induction therapy: IV: 3 mg/kg once daily for 1 to 2 weeks (patients without HIV) or at least 2 weeks or until clinically improved (patients with HIV), followed by itraconazole maintenance therapy (Ref).
Histoplasma meningitis: Induction therapy: IV: 5 mg/kg once daily for 4 to 6 weeks depending on symptom resolution and improved CSF findings, followed by itraconazole maintenance therapy (Ref).
Leishmaniasis:
Cutaneous (off-label use):
Immunocompetent: IV: 3 mg/kg once daily 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 (Ref).
Immunocompromised, including patients with HIV: IV: 4 mg/kg once daily for 10 days or an interrupted schedule (eg, 4 mg/kg once daily on days 1 through 5, and then on days 10, 17, 24, 31, 38) for a cumulative total dose administered of 20 to 60 mg/kg (Ref).
Mucosal (off-label use):
Immunocompetent: IV: ~3 mg/kg once daily for a cumulative total administered dose of ~20 to 60 mg/kg (Ref).
Immunocompromised, including patients with HIV: IV: 4 mg/kg once daily for 10 days or an interrupted schedule (eg, 4 mg/kg once daily on days 1 through 5, and then on days 10, 17, 24, 31, 38) for a cumulative total dose administered of 20 to 60 mg/kg (Ref).
Visceral:
Immunocompetent: IV: 3 mg/kg once daily on days 1 through 5, and 3 mg/kg once daily on days 14 and 21; a repeat course may be given in patients who do not achieve parasitic clearance (Ref).
Immunocompromised, including patients with HIV:
Leishmania infantum/chagasi: IV: 3 to 5 mg/kg once daily or an interrupted schedule (eg, 4 mg/kg once daily on days 1 through 5, and then on days 10, 17, 24, 31, and 38) for a cumulative total dose administered of 20 to 60 mg/kg (Ref).
Leishmania donovani:
Combination therapy: IV: 5 mg/kg once daily on days 1, 3, 5, 7, 9, and 11 (total cumulative dose administered: 30 mg/kg) in combination with miltefosine (Ref).
Monotherapy (alternative regimen): IV: 3 to 5 mg/kg once daily or an interrupted schedule (eg, 4 mg/kg once daily on days 1 through 5, and then on days 10, 17, 24, 31, and 38) for a cumulative total dose administered of 20 to 60 mg/kg (Ref).
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 (Ref). For patients with visceral leishmaniasis acquired in Southeast Asia, 3 to 5 mg/kg once every 3 to 4 weeks is recommended (Ref). Continue until CD4 count is ≥350 cells/mm3, HIV viral load undetectable for 6 months, and no symptoms of relapse (Ref).
Talaromycosis (formerly Penicillinosis) in patients with HIV (off-label use): IV: 3 to 5 mg/kg once daily for 2 weeks, followed by oral itraconazole for 10 weeks, followed by chronic maintenance therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (Ref)) (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (lipophilic and highly protein bound (Ref)): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (lipophilic and highly protein bound): No dosage adjustment necessary (Ref).
CRRT: Unlikely to be significantly dialyzed: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzed: No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
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)
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)
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)
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)
|
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)
|
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 |
|
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 |
|
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 |
|
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%)
|
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)
|
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 |
|
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
Hypersensitivity to amphotericin B deoxycholate or any component of the formulation
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.
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: 50 mg (1 ea)
Yes
Suspension (reconstituted) (AmBisome Intravenous)
50 mg (per each): $381.97
Suspension (reconstituted) (Amphotericin B Liposome Intravenous)
50 mg (per each): $305.69 - $305.70
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.
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)]
The lipid portion of amphotericin B (liposomal) formulation contains 0.27 kcal per 5 mg; for patients receiving parenteral nutrition, adjustment to the amount of lipids may be necessary (Sacks 1997).
To minimize infusion-related immediate reactions, may premedicate with acetaminophen, diphenhydramine, and/or hydrocortisone 30 to 60 minutes prior to administration. If the patient experiences rigors during the infusion, meperidine may be administered. Adequate hydration and preinfusion administration of NS may reduce the risk of nephrotoxicity during amphotericin B treatment (Ref).
Parenteral: IV: An in-line filter (≥1 micron) may be used. Flush line with D5W prior to infusion; infuse over 2 hours; if infusion is well-tolerated, infusion time may be reduced to 1 hour. If the patient experiences discomfort during infusion, the duration of infusion may be increased.
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) ± 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 may reduce the risk of nephrotoxicity during amphotericin B treatment (Ref).
Inhalation (off-label route): Obtain appropriate volume to administer prescribed dose (eg, 25 mg dose is equivalent to ~6 mL of reconstituted solution) (Ref). Use with jet nebulizer; refer to nebulizer manufacturer's information for usage instructions and volume specifications (Ref).
Store intact vials at ≤25°C (≤77°F). Reconstituted vials are stable at 2°C to 8°C (36°F to 46°F) for 24 hours. Do not freeze. Begin infusion within 6 hours of dilution with D5W. Extended storage information may be available; contact product manufacturer to obtain current recommendations.
Empirical therapy for presumed fungal infection in febrile, neutropenic patients; treatment of patients with Aspergillus species, Candida species, and/or Cryptococcus species infections refractory to amphotericin B deoxycholate (conventional amphotericin), or in patients for whom renal impairment or unacceptable toxicity precludes the use of amphotericin B deoxycholate; treatment of cryptococcal meningitis in patients with HIV; treatment of visceral leishmaniasis (all indications: FDA approved in ages ≥1 month and adults); has also been used for treatment of blastomycosis, histoplasmosis infection, coccidioidomycosis, mucormycosis, and sporotrichosis.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (liposomal forms with conventional counterparts) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
AmBisome may be confused with Ambisolm, Ambisom.
Amphotericin B liposomal may be confused with amphotericin B or amphotericin B lipid complex.
Lipid-based amphotericin formulations (AmBisome) may be confused with conventional formulations (Amphocin, Fungizone) or with the other lipid-based amphotericin formulation (Abelcet).
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.
None known.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects 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 increase nephrotoxic effects of Aminoglycosides. Amphotericin B may increase neurotoxic effects of Aminoglycosides. Risk C: Monitor
Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Arsenic Trioxide: Amphotericin B may increase hypotensive effects of Arsenic Trioxide. Amphotericin B may increase QTc-prolonging effects 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Cardiac Glycosides: Amphotericin B may increase adverse/toxic effects of Cardiac Glycosides. Risk C: Monitor
Colistimethate: Amphotericin B may increase nephrotoxic effects 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 increase hypokalemic effects of Amphotericin B. Risk C: Monitor
CycloSPORINE (Systemic): Amphotericin B may increase nephrotoxic effects of CycloSPORINE (Systemic). Amphotericin B may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dichlorphenamide: Amphotericin B may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
DroNABinol: May increase 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
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Flucytosine: Amphotericin B may increase adverse/toxic effects of Flucytosine. Amphotericin B may increase serum concentration of Flucytosine. Risk C: Monitor
Foscarnet: May increase nephrotoxic effects of Amphotericin B. Management: Avoid concomitant use of foscarnet and amphotericin B, unless the expected benefits of combined treatment outweigh the risks. If combined, monitor renal function closely. Risk D: Consider Therapy Modification
Ganciclovir-Valganciclovir: May increase nephrotoxic effects of Amphotericin B. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methoxyflurane: May increase nephrotoxic effects of Amphotericin B. Risk X: Avoid
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Saccharomyces boulardii: Antifungal Agents (Systemic and Oral [Non-Absorbable]) may decrease therapeutic effects of Saccharomyces boulardii. Risk X: Avoid
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Tacrolimus (Systemic): Amphotericin B may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor
Vancomycin: May increase nephrotoxic effects of Amphotericin B. Risk C: Monitor
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).
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).
BUN, serum creatinine, ins & outs, liver function tests, serum electrolytes (particularly magnesium and potassium), CBC, vital signs; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes) and infusion-related reactions.
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).
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)
