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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 once daily.

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 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. Note: Guidelines recommend amphotericin B lipid formulations be considered for invasive aspergillosis only when triazoles, specifically voriconazole, are contraindicated or not tolerated (Ref).

Candidiasis

Candidiasis:

Candidemia (non-neutropenic patients) (alternative agent): IV: 3 to 5 mg/kg once daily; 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 (Ref).

Candidemia (neutropenic patients) (alternative agent): IV: 3 to 5 mg/kg once daily; 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 (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 clinically stable, fluconazole-susceptible patients (Ref).

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) (Ref).

IV: 3 to 5 mg/kg once daily; treatment should continue 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) or infected implantable cardiac devices (eg, pacemaker, ICD, VAD): IV: 3 to 5 mg/kg once daily (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) (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 patients who have inadequate response to or who are unable to take other agents (Ref).

IV: 3 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 clinically stable patients with a fluconazole-susceptible isolate who have responded to initial therapy (Ref).

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 once daily until clinical improvement, then initiate triazole therapy (eg, fluconazole or itraconazole) (Ref).

Cryptococcosis

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-rich 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, in combination with 14 days of fluconazole and flucytosine. Induction therapy is followed by consolidation and maintenance therapy with fluconazole (Ref).

Fungal sinusitis

Fungal sinusitis: IV: Limited data in immunocompromised patients 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

Fusariosis, invasive (off-label use):

IV: 3 to 5 mg/kg once daily; duration of treatment is often prolonged and depends on site of infection, severity, immune status, and response to therapy (Ref). 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: 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).

Histoplasmosis

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 (patients with HIV), followed by itraconazole maintenance therapy (Ref).

Histoplasma meningitis: Induction therapy: IV: 5 mg/kg once daily for 4 to 6 weeks, followed by itraconazole maintenance therapy (Ref).

Leishmaniasis

Leishmaniasis:

Cutaneous (off-label use):

Patients without HIV: 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).

Patients with HIV: IV: 2 to 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). Total dose administered should be 20 to 60 mg/kg (Ref).

Mucosal (off-label use):

Patients without HIV: IV: ~3 mg/kg once daily for a cumulative total administered dose of ~20 to 60 mg/kg (Ref).

Patients with HIV: IV: 2 to 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). Total dose administered should be 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:

Treatment, monotherapy: IV: 2 to 4 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). Total dose administered: 20 to 60 mg/kg (Ref).

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

IV: 5 mg/kg as a single dose on days 1, 3, 5, 7, 9, and 11 (total dose administered: 30 mg/kg) in combination with miltefosine (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).

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) (Ref): IV: 5 to 6 mg/kg once daily in combination with voriconazole for ≥3 months; a higher dose (7.5 mg/kg once daily) 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 once daily (Ref). Note: 10 mg/kg once daily recommended for patients with CNS disease or solid organ transplant recipients. Treatment duration is typically weeks to months depending on response and host immunosuppression (Ref).

Neutropenic fever, empirical antifungal therapy

Neutropenic fever, empirical antifungal therapy:

Note: Recommended for patients with persistent or recurrent fever after ≥4 days of antimicrobial therapy when the duration of neutropenia is expected to exceed 7 days (Ref).

IV: 3 to 5 mg/kg once daily (Ref).

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) (Ref): IV: 5 mg/kg once daily 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 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.

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 (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).

Dosing: Hepatic Impairment: Adult

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

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 (Ref). Due to higher doses, dosing using actual body weight may be associated with increased toxicity (Ref). 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 (Ref). Amphotericin B (liposomal) has a low Vd (0.11 to 0.42 L/kg), suggesting limited distribution in adipose tissue (Ref). Based on one pharmacokinetic study of amphotericin B (liposomal) in 16 patients with morbid obesity, body size had no effect on drug clearance (Ref). There are no data supporting one weight metric over another.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

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

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).

Aspergillosis

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

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

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

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

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

Febrile neutropenia, empiric therapy: Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily (Ref).

Histoplasmosis

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

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

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

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.

Dosing: Kidney Impairment: Pediatric

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).

Dosing: Hepatic Impairment: Pediatric

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

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.

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: 50 mg (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Suspension (reconstituted) (AmBisome Intravenous)

50 mg (per each): $370.85

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.

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 (Ref).

Administration: Pediatric

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.

Use: Labeled Indications

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

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

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); Fusariosis, invasive; 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.

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

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

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. 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 and Oral [Non-Absorbable]) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination

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

Tacrolimus (Systemic): Amphotericin B may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Vancomycin: May enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy

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 (Adult Data Unless Noted)

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)

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