Amphotericin B (Liposomal)

Dosage Forms

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

Suspension Reconstituted, Intravenous [preservative free]:

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

Pharmacology

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/Pharmacodynamics

Distribution

V_d: 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)

Use: Labeled Indications

Cryptococcal meningitis in HIV-infected patients: Treatment of cryptococcal meningitis in HIV-infected patients.

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

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

Leishmaniasis (visceral): Treatment of visceral leishmaniasis.

Use: Off Label

Candidiasis, empiric therapy (non-neutropenic ICU patients)yes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, amphotericin B (liposomal) is an effective and recommended alternative agent for empiric therapy of suspected invasive candidiasis in non-neutropenic patients in the ICU.

Coccidioidomycosis in HIV-infected patientsyes

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B (liposomal) is an effective and recommended agent in the management of severe, non-meningeal coccidioidomycosis infection (ie, diffuse pulmonary or severely ill with extrathoracic, disseminated disease) in HIV-infected patients.

Fungal meningitis (secondary to contaminated [eg, Exserohilum rostratum] steroid products)c

Data from a limited number of patients studied (ie, case reports) from an outbreak of fungal infections associated with injections (epidural and intrarticular) of methylprednisolone contaminated with environmental molds (Exserohilum rostratum) suggest that amphotericin B (liposomal) in combination with voriconazole may be beneficial for the treatment of severe or refractory fungal meningitis Kauffman 2012. Additional data may be necessary to further define the role of amphotericin B (liposomal) in this condition.

Fungal osteoarticular infections (secondary to contaminated [eg, Exserohilum rostratum] steroid products)c

Data from a limited number of patients studied (ie, case reports) from an outbreak of fungal infections associated with injections (epidural and intrarticular) of methylprednisolone contaminated with environmental molds (Exserohilum rostratum) suggest that amphotericin B (liposomal) in combination with voriconazole may be beneficial for the treatment of severe fungal osteoarticular infections Kauffman 2012. Additional data may be necessary to further define the role of amphotericin B (liposomal) in this condition.

Histoplasmosis in HIV-infected patientsyes

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B (liposomal) is an effective and recommended agent for the treatment of histoplasmosis in HIV-infected patients.

Leishmaniasis (cutaneous and mucosal)yes

Based on the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) clinical practice guidelines for the diagnosis and treatment of leishmaniasis, amphotericin B (liposomal) is an effective and recommended agent for the management of cutaneous and mucosal leishmaniasis.

Leishmaniasis (cutaneous) in HIV-infected patientsyes

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B (liposomal) is an effective and recommended agent for the treatment of cutaneous leishmaniasis in HIV-infected patients.

Leishmaniasis (visceral) in HIV-infected patientsyes

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B (liposomal) is an effective and recommended agent for the treatment of visceral leishmaniasis in HIV-infected patients.

Talaromyces marneffei infection in HIV-infected patientsyes

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B (liposomal) is an effective and recommended agent for the treatment of Talaromyces marneffei infection in HIV-infected patients.

Contraindications

Hypersensitivity to amphotericin B deoxycholate or any component of the formulation

Dosage and Administration

Dosing: Adult

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

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

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

Indication-specific dosing: IV:

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

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

Candidiasis:

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

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

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

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

Empiric therapy, suspected invasive candidiasis (non-neutropenic ICU patients) (alternative agent) (off-label use): 3 to 5 mg/kg/day; treatment should continue for 14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response (IDSA [Pappas 2016]).

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

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

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

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

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

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

Coccidioidomycosis in HIV-infected patients (off-label use): Non-CNS infection, severe (ie, diffuse pulmonary or severely ill with extrathoracic, disseminated disease): 3 to 5 mg/kg/day until clinical improvement, then initiate triazole therapy (eg, fluconazole or itraconazole) (HHS [OI adult 2017])

Cryptococcosis:

Disseminated cryptococcosis (non-CNS or severe pulmonary disease) in HIV-infected patients: IV: 3 to 4 mg/kg/day with flucytosine (preferred) or fluconazole, or without a concomitant agent (HHS [OI adult 2017])

Meningitis in HIV-infected patients: 3 to 4 mg/kg/day with flucytosine (preferred) or fluconazole, or without a concomitant agent (HHS [OI adult 2017]); doses up to 6 mg/kg/dose have been reported for treatment of meningoencephalitis and may be considered for treatment failure or high fungal burden disease (IDSA [Perfect 2010])

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. 6 mg/kg/day.

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

Histoplasmosis treatment in HIV-infected patients (off-label use; HHS [OI adult 2017]):

Disseminated disease, moderately severe to severe: Induction therapy: 3 mg/kg/day for at least 2 weeks, followed by oral itraconazole for maintenance therapy

Histoplasma meningitis: Induction therapy: 5 mg/kg/day for 4 to 6 weeks, followed by oral itraconazole for maintenance therapy

Leishmaniasis (cutaneous) (off-label use): IV: 3 mg/kg/day on days 1 through 5, and then on day 10 or on days 1 through 7. Total dose administered should be 18 to 21 mg/kg (IDSA/ASTMH [Aronson 2016])

Leishmaniasis (cutaneous) in HIV-infected patients (off-label use): 2 to 4 mg/kg/day for 10 days or an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, 38). Total dose administered should be 20 to 60 mg/kg (HHS [OI adult 2017])

Leishmaniasis (mucosal) (off-label use): IV: ~3 mg/kg/day for a total administered dose of ~20 to 60 mg/kg (IDSA/ASTMH [Aronson 2016])

Leishmaniasis (visceral):

Immunocompetent: 3 mg/kg/day on days 1 through 5, and 3 mg/kg/day on days 14 and 21; a repeat course may be given in patients who do not achieve parasitic clearance

Immunocompromised: 4 mg/kg/day on days 1 through 5, and 4 mg/kg/day on days 10, 17, 24, 31, and 38

Leishmaniasis (visceral) in HIV-infected patients (off-label use; HHS [OI adult 2017]):

Treatment: 2 to 4 mg/kg/day or an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, and 38). Total dose administered: 20 to 60 mg/kg

Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm³): 4 mg/kg every 2 to 4 weeks

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

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

Talaromyces marneffei infection in HIV-infected patients (off-label use): 3 to 5 mg/kg/day for 2 weeks, followed by oral itraconazole for 10 weeks, followed by chronic maintenance therapy (HHS [OI adult 2015])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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

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

General dosing:

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

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

Aspergillosis, treatment:

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

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

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

Candidiasis, treatment:

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

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

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

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

Coccidioidomycosis, invasive:

Non-HIV-exposed/-positive:

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

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

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

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

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

Cryptococcosis, invasive:

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

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

Adolescents:

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

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

Meningitis:

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

HIV-exposed/-positive:

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

Alternate dosing:

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

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

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

Histoplasmosis:

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

HIV-exposed/-positive:

Disseminated infection (non-CNS disease):

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

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

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

Leishmaniasis:

Visceral infection, treatment:

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

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

HIV-exposed/-positive:

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

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

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

Sporotrichosis infection (IDSA [Kauffman 2007]):

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

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

Reconstitution

Reconstitute with 12 mL SWFI to a concentration of 4 mg/mL. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation. Shake the vial vigorously for 30 seconds, until dispersed into a translucent yellow suspension.

Filtration and dilution: Withdraw appropriate amount of reconstituted solution into a syringe, attach a 5-micron filter, and inject contents of syringe through filter needle into an appropriate amount of D₅W. Dilute to a final concentration of 1 to 2 mg/mL.

Administration

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.

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).

Storage

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.

Drug Interactions

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

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

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

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

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

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

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

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

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

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

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

Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Consider therapy modification

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Monitor therapy

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

CycloSPORINE (Systemic): Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

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

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

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

Fexinidazole [INT]: Amphotericin B may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Monitor therapy

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

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

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

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

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

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

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

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

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

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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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. Consider therapy modification

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

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

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

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

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

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

Sodium Stibogluconate: Amphotericin B may enhance the cardiotoxic effect of Sodium Stibogluconate. Consider therapy modification

Test Interactions

Falsely-elevated serum phosphate may occur when using the PHOSm assay.

Adverse Reactions

Percentage of adverse reactions is dependent upon population studied and may vary with respect to premedications and underlying illness. Incidence of decreased renal function and infusion-related events are lower than rates observed with amphotericin B deoxycholate.

>10%:

Cardiovascular: Hypertension (8% to 20%), tachycardia (9% to 19%), peripheral edema (15%), edema (12% to 14%), hypotension (7% to 14%), chest pain (8% to 12%), localized phlebitis (9% to 11%)

Central nervous system: Chills (29% to 48%), insomnia (17% to 22%), headache (9% to 20%), pain (14%), anxiety (7% to 14%), confusion (9% to 13%)

Dermatologic: Skin rash (5% to 25%), pruritus (11%)

Endocrine & metabolic: Hypokalemia (31% to 51%), hypomagnesemia (15% to 50%), hyperglycemia (8% to 23%), hypocalcemia (5% to 18%), hyponatremia (9% to 12%), hypervolemia (8% to 12%)

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

Genitourinary: Nephrotoxicity (14% to 47%), hematuria (14%)

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

Hepatic: Increased serum alkaline phosphatase (7% to 22%), hyperbilirubinemia (≤18%), increased serum ALT (15%), increased serum AST (13%), abnormal hepatic function tests (not specified) (4% to 13%)

Hypersensitivity: Transfusion reaction (9% to 18%)

Infection: Sepsis (7% to 14%), infection (11% to 13%)

Neuromuscular & skeletal: Weakness (6% to 13%), back pain (12%)

Renal: Increased serum creatinine (18% to 40%), increased blood urea nitrogen (7% to 21%)

Respiratory: Dyspnea (18% to 23%), pulmonary disease (14% to 18%), cough (2% to 18%), epistaxis (9% to 15%), pleural effusion (13%), rhinitis (11%)

Miscellaneous: Infusion related reactions (4% to 21%; fever [7% to 24%], chills [6% to 24%], vomiting [4% to 16%], nausea [8% to 14%], dyspnea [5% to 10%], tachycardia [2% to 10%], hypertension [2% to 9%], vasodilation [5%], hypotension [4%], hyperventilation [1%], hypoxia [≤1%])

2% to 10%:

Cardiovascular: Atrial fibrillation, bradycardia, cardiac arrest, cardiac arrhythmia, cardiomegaly, facial edema, flushing, heart valve disease, orthostatic hypotension, vascular disorder, vasodilation

Central nervous system: Dizziness (7% to 9%), abnormality in thinking, agitation, coma, depression, drowsiness, dysesthesia, dystonia, hallucination, malaise, nervousness, paresthesia, rigors, seizure

Dermatologic: Diaphoresis (7%), alopecia, cellulitis, dermal ulcer, dermatological reaction, maculopapular rash, skin discoloration, urticaria, vesiculobullous dermatitis, xeroderma

Endocrine & metabolic: Hypernatremia (4%), acidosis, hyperchloremia, hyperkalemia, hypermagnesemia, hyperphosphatemia, hypophosphatemia, increased lactate dehydrogenase, increased nonprotein nitrogen

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

Genitourinary: Dysuria, toxic nephrosis, urinary incontence, vaginal hemorrhage

Hematologic & oncologic: Blood coagulation disorder, bruise, decreased prothrombin time, hemophthalmos, hemorrhage, hypoproteinemia, increased prothrombin time, oral hemorrhage, petechia, purpura

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

Hypersensitivity: Delayed hypersensitivity, hypersensitivity reaction

Immunologic: Graft versus host disease

Infection: Herpes simplex infection

Local: Inflammation at injection site

Neuromuscular & skeletal: Arthralgia, myalgia, neck pain, ostealgia, tremor

Ophthalmic: Conjunctivitis, dry eyes

Renal: Acute renal failure, renal failure, renal function abnormality

Respiratory: Hypoxia (6% to 8%), asthma, atelectasis, dry nose, flu-like symptoms, hemoptysis, hyperventilation, pharyngitis, pneumonia, pulmonary edema, respiratory alkalosis, respiratory failure, respiratory insufficiency, sinusitis

Miscellaneous: Procedural complication (8% to 10%)

Postmarketing and/or case reports: Agranulocytosis, angioedema, bronchospasm, cyanosis, erythema, hemorrhagic cystitis, hypoventilation, rhabdomyolysis

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued; the patient should not receive further infusions. Administer under close clinical observation during initial dosing.
• Infusion reactions: Acute reactions (including fever and chills) may occur 1 to 3 hours after starting infusions; reactions are more common with the first few doses and generally diminish with subsequent doses. Immediately discontinue infusion if a severe anaphylactic reaction occurs; the patient should not receive further infusions.

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]).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

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

Monitoring Parameters

Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, hematocrit, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc); monitor cardiac function if used concurrently with corticosteroids

Pregnancy

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. 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).

Patient Education

What is this drug used for?

• It is used to treat fungal infections.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Lack of appetite
• Trouble sleeping
• Back pain
• Abdominal pain
• Cough
• Anxiety
• Runny nose
• Sweating a lot

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Chest pain
• Blood in the urine
• Fast heartbeat
• Black, tarry, or bloody stools
• Vomiting blood
• Shortness of breath
• Edema
• Severe dizziness
• Passing out
• Severe headache
• Vision changes
• Chills
• Sore throat
• Severe loss of strength and energy
• Confusion
• Bruising
• Bleeding
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.