Note: Formulation: Lipid-based amphotericin formulations (Abelcet) may be confused with conventional formulations (deoxycholate [Amphocin, Fungizone]) or with other lipid-based amphotericin formulations (amphotericin B liposomal [AmBisome]; 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. Premedication: To minimize infusion-related immediate reactions, premedicate with the following 30 to 60 minutes prior to administration: Acetaminophen, diphenhydramine, and/or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered (HHS [OI adult 2022]; O’Conner 2009; Sharkey 1996). Pre-infusion administration of 1 L of NS may reduce the risk of nephrotoxicity during amphotericin B treatment (HHS [OI adult 2022]).
Aspergillosis, invasive (including disseminated and extrapulmonary) (alternative agent): IV: 5 mg/kg 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. Note: Amphotericin B lipid complex should be reserved as salvage therapy for those intolerant of or refractory to preferred agents (IDSA [Patterson 2016]).
Blastomycosis, moderately severe to severe, non-CNS disease: IV: 3 to 5 mg/kg once daily for 1 to 2 weeks or until improvement, followed by oral itraconazole (IDSA [Chapman 2008]).
Candidiasis:
Candidemia (neutropenic and nonneutropenic patients), including disseminated candidiasis (alternative agent): IV: 3 to 5 mg/kg once daily. Total duration (including oral step-down therapy) is ≥14 days after first negative blood culture and continues until signs/symptoms of candidemia and neutropenia, if present, have resolved; metastatic complications warrant a longer duration (IDSA [Pappas 2016]).
Cardiac device infection (including implantable cardiac defibrillator, pacemaker, ventricular assist device): IV: 3 to 5 mg/kg once daily, with or without flucytosine; step down to azole therapy in clinically stable patients with susceptible isolates and negative repeat cultures; total antifungal duration is ≥4 weeks after device removal for isolated generator pocket infection and ≥6 weeks after device removal for wire infection (IDSA [Pappas 2016]).
Chronic disseminated (hepatosplenic): IV: 3 to 5 mg/kg once daily for several weeks, followed by oral azole step-down therapy until lesion resolution and through periods of immunosuppression (IDSA [Pappas 2016]).
Empiric therapy, suspected invasive candidiasis (nonneutropenic ICU patients) (alternative agent):
Note: Antifungal therapy is not routinely warranted for initial management of nonneutropenic patients with sepsis. Consider use for critically ill patients with unexplained fever or unexplained hypotension despite broad-spectrum antimicrobial therapy and risk factors for invasive candidiasis (eg, indwelling venous catheter, hemodialysis, trauma or burns, recent surgery, parenteral nutrition) (IDSA [Pappas 2016]; Vazquez 2022; SCC [Evans 2021]).
IV: 3 to 5 mg/kg once daily. For those who improve, continue empiric antifungal therapy for 2 weeks; consider discontinuing after 4 to 5 days in patients with no evidence of invasive candidiasis and no clinical response (IDSA [Pappas 2016]).
Endocarditis, native or prosthetic valve: IV: 3 to 5 mg/kg 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 abscesses, other complications, or a nonsurgical approach (IDSA [Pappas 2016]).
Esophageal, refractory disease (alternative agent) (off-label use): Note: Reserve use for patients who have inadequate response to or who are unable to take other agents (Kauffman 2021).
IV: 3 mg/kg/day. Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (HHS [OI adult 2020]; Kauffman 2021).
Intra-abdominal infection (eg, peritonitis, abdominal abscess) (alternative agent): IV: 3 to 5 mg/kg once daily. Duration of therapy depends on source control and clinical response (IDSA [Pappas 2016]).
Osteoarticular infection (osteomyelitis or septic arthritis) (alternative agent): IV: 3 to 5 mg/kg once daily for ≥2 weeks, followed by fluconazole. Total duration of therapy (including oral step-down therapy) is 6 to 12 months for osteomyelitis and ≥6 weeks for septic arthritis (IDSA [Pappas 2016]).
Thrombophlebitis, suppurative: IV: 3 to 5 mg/kg once daily; continue antifungal therapy until catheter removed and thrombus resolved, and for ≥2 weeks after candidemia (if present) has cleared (IDSA [Pappas 2016]).
Coccidioidomycosis, severe, nonmeningeal infection: IV: 3 to 5 mg/kg once daily until clinical improvement, then switch to an oral azole (AST-IDCOP [Miller 2019]; HHS [OI adult 2022]; IDSA [Galgiani 2016]). Note: Some experts suggest initiating the oral azole at the same time as amphotericin B lipid complex and continuing the oral azole when amphotericin B lipid complex is discontinued (HHS [OI adult 2022]).
Cryptococcal meningoencephalitis, disseminated disease, or severe pulmonary infection (alternative agent in patients with HIV): Induction therapy: IV: 5 mg/kg once daily in combination with flucytosine (or fluconazole if flucytosine cannot be used) for ≥2 weeks, followed by consolidation therapy with oral fluconazole. Duration of induction therapy may be extended in patients who cannot use combination therapy or who have evidence of neurological complications (Cox 2022; HHS [OI adult 2022]; IDSA [Perfect 2010]).
Fusariosis, invasive: IV: 3 to 5 mg/kg once daily; duration of treatment is often prolonged and depends on the site of infection, severity, immune status, and response to therapy (Nucci 2022; Perfect 2005). Note: Some experts suggest initial combination antifungal therapy for patients with severe immunosuppression, severe disease, or persistently positive blood cultures with monotherapy (Nucci 2022).
Histoplasmosis:
Moderately severe to severe pulmonary or disseminated disease in immunocompetent patients or solid organ transplant recipients: IV: 5 mg/kg once daily for 1 to 2 weeks, followed by oral itraconazole (AST-IDCOP [Miller 2019]; IDSA [Wheat 2007]).
Moderately severe to severe disseminated disease in patients with HIV (alternative agent): IV: 5 mg/kg once daily for ≥2 weeks, followed by oral itraconazole (HHS [OI adult 2022]).
Leishmaniasis (visceral) (off-label use):
Patients with HIV:
Treatment (alternative agent): IV: 2 to 4 mg/kg once daily or an interrupted schedule of 4 mg/kg 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 2022]).
Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm3): IV: 3 mg/kg every 21 days (HHS [OI adult 2022]).
Immunocompetent patients: IV: 2 to 3 mg/kg once daily for 5 to 10 days (IDSA/ASTMH [Aronson 2016]).
Immunosuppressed patients: IV: 3 to 5 mg/kg once daily for 10 days (IDSA/ASTMH [Aronson 2016]).
Mucormycosis, invasive (without CNS involvement): Note: Prompt surgical debridement is often needed to achieve clinical cure (ECMM/MSG-ERC [Cornely 2019]).
IV: 5 to 10 mg/kg once daily; may step down to oral therapy (eg, isavuconazole, posaconazole) based on patient response. Total duration (including oral step-down therapy) varies based on clinical and radiologic response and patient immune status; several months are often warranted, with some patients requiring lifelong therapy (ECMM/MSG-ERC [Cornely 2019]; Perfect 2005).
Neutropenic fever, empiric antifungal therapy (off-label use):
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 (IDSA [Freifeld 2011]; IDSA [Patterson 2016]).
IV: 5 mg/kg once daily (Wingard 2000).
Sporotrichosis:
Meningeal infection: IV: 5 mg/kg once daily for 4 to 6 weeks, followed by oral itraconazole (IDSA [Kauffman 2007]).
Pulmonary, osteoarticular, and disseminated infection: IV: 3 to 5 mg/kg once daily, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy (IDSA [Kauffman 2007]).
Manufacturer's labeling: No dosage adjustment provided in manufacturer's labeling (has not been studied).
Alternate recommendations (Aronoff 2007):
Intermittent hemodialysis: Not hemodialyzable; no supplemental dosage necessary.
Peritoneal dialysis: No supplemental dosage necessary.
CRRT: No supplemental dosage necessary.
No dosage adjustment provided in manufacturer's labeling (has not been studied).
(For additional information see "Amphotericin B lipid complex: Pediatric drug information")
Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (Abelcet, Amphotec, AmBisome) and conventional amphotericin B for injection. Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.
Note: 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, susceptible infections: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily.
Aspergillosis , treatment:
Invasive: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily; duration of treatment depends on site of infection, extent of disease, and level of immunosuppression (IDSA [Walsh 2008])
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 usually for 1 to 2 weeks, if CNS infection 4 to 6 weeks may be needed; follow with oral itraconazole for a total of 12 months (IDSA [Chapman 2008])
Candidiasis , treatment:
Invasive (Independent of HIV status): Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily (IDSA [Pappas 2016]); Note: In HIV-exposed/-infected patients, doses at the higher end of the range may be considered (5 mg/kg/day) (HHS [OI pediatric 2013]).
Endocarditis: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015]; IDSA [Pappas 2016])
Esophageal: HIV-exposed/-infected: Adolescents: IV: 3 to 4 mg/kg/dose once daily for 14 to 21 days (HHS [OI adult 2016])
Coccidioidomycosis , invasive:
Non-HIV-exposed/-infected:
Disseminated infection, nonpulmonary: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily with or without concomitant azole antifungal therapy (IDSA [Galgiani 2005])
Pulmonary infection, diffuse: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily for several weeks, followed by an oral azole antifungal for a total length of therapy ≥12 months (IDSA [Galgiani 2005])
HIV-exposed/-infected: Non-CNS infection, severe (ie, diffuse pulmonary or severely ill with extrathoracic, disseminated disease):
Infants and Children: IV: 5 mg/kg/dose once daily until clinical improvement; dose may be increased to as high as 10 mg/kg/dose once daily for life-threatening infection (HHS [OI pediatric 2013])
Adolescents: IV: 3 to 5 mg/kg/dose once daily until clinical improvement, then switch to fluconazole or itraconazole (HHS [OI adult 2016])
Cryptococcosis:
Disseminated (non-CNS or severe pulmonary disease):
Infants and Children (independent of HIV status): IV: 5 mg/kg/dose once daily; for severe infection in HIV-exposed/-infected patients, may consider the addition of flucytosine (HHS [OI pediatric 2013]; IDSA [Perfect 2010])
Adolescents:
Non-HIV-exposed: IV: 5 mg/kg/dose once daily (with flucytosine) for ≥4 weeks may be used for severe pulmonary cryptococcosis or for cryptococcemia with evidence of high fungal burden, followed by oral fluconazole. Note: If flucytosine is not given or treatment is interrupted, consider prolonging induction therapy for an additional 2 weeks (IDSA [Perfect 2010]).
HIV-exposed/-infected: IV: Induction therapy: 5 mg/kg/dose once daily with flucytosine for at least 2 weeks, followed by oral fluconazole or itraconazole (HHS [OI adult 2016]).
Meningitis:
Infants and Children:
Non-HIV-exposed/-infected: IV: 5 mg/kg/dose once daily with or without oral flucytosine for a minimum 2-week induction; combination with flucytosine is the preferred treatment (IDSA [Perfect 2010])
HIV-exposed/-infected: IV: 5 mg/kg/dose once daily plus flucytosine or fluconazole; 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 2013])
Adolescents:
Non-HIV-exposed/-infected; nontransplant recipients: IV: Induction therapy: 5 mg/kg/dose once daily (with flucytosine) for ≥4 weeks followed by oral fluconazole; should be used as an alternative to conventional amphotericin B in patients with renal concerns. Note: If flucytosine is not given or treatment is interrupted, consider prolonging induction therapy for an additional 2 weeks (IDSA [Perfect 2010]).
HIV-exposed/-infected: IV: Induction therapy: 5 mg/kg/dose once daily with flucytosine for at least 2 weeks, followed by fluconazole for consolidation therapy (HHS [OI adult 2016]; IDSA [Perfect 2010]). Note: If flucytosine is not given due to intolerance, duration of amphotericin B lipid complex therapy should be 4 to 6 weeks (IDSA [Perfect 2010]).
Transplant recipients: Induction therapy: IV: 5 mg/kg/dose once daily (with flucytosine) for at least 2 weeks followed by oral fluconazole. Note: If flucytosine is not given, duration of therapy should be 4 to 6 weeks (IDSA [Perfect 2010]).
Histoplasmosis:
Non-HIV-exposed/-infected: Disseminated (non-CNS) or pulmonary disease: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 1 to 2 weeks followed by oral itraconazole for a total of 12 weeks; conventional amphotericin B typically preferred (IDSA [Wheat 2007])
HIV-exposed/-infected: Disseminated disease (moderately severe to severe): Adolescents: IV: 3 mg/kg/dose once daily for at least 2-week induction, followed by oral itraconazole (HHS [OI adult 2016])
Leishmaniasis, visceral, HIV-exposed/-infected (HHS [OI adult 2016]):
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
Chronic maintenance: Adolescents: IV: 3 mg/kg/dose every 21 days; Note: Use reserved for patients with visceral infection and CD4 count <200 cells/mm3
Sporotrichosis infection (IDSA [Kauffman 2007]): Adolescents:
Meningeal: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconazole
Pulmonary, osteoarticular, and disseminated: IV: 3 to 5 mg/kg/dose once daily, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy
Infants, Children, and Adolescents:
Manufacturer’s recommendations: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
Alternate recommendations: The following adjustments have been recommended (Aronoff 2007):
Hemodialysis: No supplemental dosage necessary
Peritoneal dialysis: No supplemental dosage necessary
Continuous renal replacement therapy (CRRT): No supplemental dosage necessary
There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
Refer to adult dosing.
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 500 mg is recommended (recommendation extrapolated from a study of a similar product [Wasmann 2020; expert opinion]). Due to higher doses, dosing using actual body weight may be associated with increased toxicity (Amsden 2011). Refer to adult dosing for indication-specific doses.
Rationale for recommendations: There are sparse data describing the effect of obesity on dosing requirements for polyene antifungals (Amsden 2011). There are no human pharmacokinetic studies for amphotericin B (lipid complex) in subjects with obesity. Amphotericin B (lipid complex) has a high Vd (131 to 147 L/kg), although distribution into adipose tissue is likely limited (Amsden 2011; Dupont 2002). There are no data correlating Vd with body weight, and one pharmacokinetic study with a different lipid formulation of amphotericin B found no relationship between clearance and weight (Wasmann 2020). There are no data supporting one weight metric over another.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous [preservative free]:
Abelcet: 5 mg/mL (20 mL)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Abelcet: 5 mg/mL (20 mL)
IV: To minimize infusion-related immediate reactions, premedicate with the following 30 to 60 minutes prior to administration: Acetaminophen, diphenhydramine, and/or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered (HHS [OI adult 2022]; O’Conner 2009; Sharkey 1996).
Administer at an infusion rate of 2.5 mg/kg/hour (eg, over 2 hours for 5 mg/kg). May prolong infusion over >2 hours if necessary to reduce infusion-related reaction (Bassetti 2011). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours. Do not use an in-line filter during administration. Flush line with dextrose; normal saline may cause precipitate.
Pre-infusion administration of 1 L of NS may reduce the risk of nephrotoxicity during amphotericin B treatment (HHS [OI adult 2022]).
Parenteral: IV: Prior to administration, amphotericin B lipid complex 5 mg/mL concentrated suspension must be diluted. Flush line with D5W prior to infusion. Gently shake the IV container of diluted drug to insure that contents are thoroughly mixed then administer at a rate of 2.5 mg/kg/hour (over 2 hours). The manufacturer recommends that an in-line filter should not be used during administration of amphotericin B lipid complex. If infusion time exceeds 2 hours, mix the contents by gently rotating the infusion bag every 2 hours.
Fungal infection, invasive: Treatment of invasive fungal infection in patients who are refractory to or intolerant of amphotericin B deoxycholate.
Candidiasis, esophageal, refractory disease; Leishmaniasis, visceral; Neutropenic fever, empiric antifungal therapy
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.
Lipid-based amphotericin formulations (Abelcet) may be confused with conventional formulations (Fungizone) or with other lipid-based amphotericin formulations (amphotericin B liposomal [AmBisome]; amphotericin B cholesteryl sulfate complex [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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.
>10%:
Central nervous system: Chills (18%)
Renal: Increased serum creatinine (11%)
Miscellaneous: Fever (14%), multi-organ failure (11%)
1% to 10%:
Cardiovascular: Hypotension (8%), cardiac arrest (6%), hypertension (5%), chest pain (3%)
Central nervous system: Headache (6%), pain (5%)
Dermatologic: Skin rash (4%)
Endocrine & metabolic: Hypokalemia (5%)
Gastrointestinal: Nausea (9%), vomiting (8%), diarrhea (6%), abdominal pain (4%), gastrointestinal hemorrhage (4%)
Hematologic & oncologic: Thrombocytopenia (5%), anemia (4%), leukopenia (4%)
Hepatic: Hyperbilirubinemia (4%)
Infection: Sepsis (7%), infection (5%)
Renal: Renal failure (5%)
Respiratory: Respiratory failure (8%), dyspnea (6%), respiratory tract disease (4%)
<1%, postmarketing, and/or case reports: Acute hepatic failure, anaphylactoid reaction, anuria, asthma, blood coagulation disorder, brain disease, bronchospasm, cardiac arrhythmia, cardiomyopathy, cerebrovascular accident, cholangitis, cholecystitis, deafness, dysuria, eosinophilia, erythema multiforme, exfoliative dermatitis, extrapyramidal reaction, hearing loss, hematologic disease, hemoptysis, hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease), hepatitis, hepatomegaly, hepatotoxicity, hypercalcemia, hyperkalemia, hypersensitivity reaction, hypocalcemia, hypomagnesemia, increased blood urea nitrogen, increased serum transaminases, injection site reaction, jaundice, leukocytosis, myasthenia, myocardial infarction, oliguria, peripheral neuropathy, pleural effusion, pulmonary edema, pulmonary embolism, renal insufficiency, renal tubular acidosis, seizure, shock, tachycardia, thrombophlebitis, ventricular fibrillation, vertigo (transient), visual impairment
Hypersensitivity to amphotericin or any component of the formulation
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 severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation.
• Infusion reactions: Acute reactions (including fever and chills) may occur 1-2 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses. Infusion has been rarely associated with hypotension, bronchospasm, arrhythmias, and shock.
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:
• Antineoplastics: Concurrent use with antineoplastic agents may enhance the potential for renal toxicity, bronchospasm or hypotension; use with caution.
• Nephrotoxic drugs: Concurrent use of amphotericin B with other nephrotoxic drugs may enhance the potential for drug-induced renal toxicity.
Other warnings/precautions:
• Leukocyte transfusions: Acute pulmonary toxicity has been reported in patients receiving leukocyte transfusions and amphotericin B; amphotericin B lipid complex and concurrent leukocyte transfusions are not recommended.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arsenic Trioxide: Amphotericin B may enhance the hypotensive effect of Arsenic Trioxide. Amphotericin B may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as amphotericin B. Risk D: Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Cardiac Glycosides: Amphotericin B may enhance the adverse/toxic effect of Cardiac Glycosides. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and amphotericin B whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE (Systemic): Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Amphotericin B may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dichlorphenamide: Amphotericin B may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Dronabinol: May increase the serum concentration of Amphotericin B. Specifically, dronabinol may displace amphotericin B from its protein-binding sites, leading to an increased concentration of active, unbound drug. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. Amphotericin B may increase the serum concentration of Flucytosine. Risk C: Monitor therapy
Foscarnet: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methoxyflurane: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination
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; Pilmus 2015).
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, breastfeeding is not recommended by the manufacturer (Mactal-Haaf 2001).
If on parenteral nutrition, may need to adjust the amount of lipid infused. The lipid portion of amphotericin B (lipid complex) formulation contains 0.045 kcal per 5 mg (Sacks 1997).
BUN and serum creatinine levels should be determined every other day while therapy is increased and at least weekly thereafter. Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
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.
Note: Exhibits nonlinear kinetics; volume of distribution and clearance from blood increases with increasing dose.
Distribution: High tissue concentration found in the liver, spleen, and lung ; Vd: Increases with higher doses (likely reflects increased uptake by tissues); 131 L/kg with 5 mg/kg/day
Half-life elimination: 173 hours following multiple doses
Excretion: 0.9% of dose excreted in urine over 24 hours; effects of hepatic and renal impairment on drug disposition are unknown
Suspension (Abelcet Intravenous)
5 mg/mL (per mL): $6.30
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