Version December 2023
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 (Ref). Pre-infusion administration of 1 L of NS may reduce the risk of nephrotoxicity during amphotericin B treatment (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
Cardiac device infection (including implantable cardiac defibrillator, pacemaker, ventricular assist device): IV: 3 to 5 mg/kg once daily, with or without flucytosine; step down to azole therapy in 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 (Ref).
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 (Ref).
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) (Ref).
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 (Ref).
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 (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/day. Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
Coccidioidomycosis, severe, nonmeningeal infection: IV: 3 to 5 mg/kg once daily until clinical improvement, then switch to an oral azole (Ref). 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 (Ref).
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 (Ref).
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 (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).
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 (Ref).
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 (Ref).
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 (Ref).
Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm3): IV: 3 mg/kg every 21 days (Ref).
Immunocompetent patients: IV: 2 to 3 mg/kg once daily for 5 to 10 days (Ref).
Immunosuppressed patients: IV: 3 to 5 mg/kg once daily for 10 days (Ref).
Mucormycosis, invasive (without CNS involvement): Note: Prompt surgical debridement is often needed to achieve clinical cure (Ref).
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 (Ref).
Sporotrichosis:
Meningeal infection: IV: 5 mg/kg once daily for 4 to 6 weeks, followed by oral itraconazole (Ref).
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 (Ref).
Manufacturer's labeling: No dosage adjustment provided in manufacturer's labeling (has not been studied).
Alternate recommendations (Ref):
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).
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 (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 sparse data describing the effect of obesity on dosing requirements for polyene antifungals (Ref). 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 (Ref). 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 (Ref). There are no data supporting one weight metric over another.
Refer to adult dosing.
(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: To minimize infusion-related immediate reactions, may 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. Adequate hydration and pre-infusion 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 :
Invasive: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily; minimum duration of treatment is 6 to 12 weeks and depends on site of infection, extent of disease, and level/duration of immunosuppression (Ref).
Endocarditis: Children and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (Ref).
Blastomycosis, moderately severe to severe disease: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for 1 to 2 weeks or until improvement, followed by oral itraconazole for a total of 12 months. For CNS disease, initial IV therapy at the top end of the range (5 mg/kg/dose) is recommended for 4 to 6 weeks (Ref).
Candidiasis :
Invasive (alternative agent): Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily. Duration of therapy should be individualized based on clinical response and presence of deep-tissue foci; candidemia should be treated for ≥14 days from the first negative blood culture and clinical resolution (Ref). Note: In patients with HIV, consider doses at the higher end of the range (5 mg/kg/dose) (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).
Ventriculitis or meningitis, health care-associated: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily with or without flucytosine (Ref).
Coccidioidomycosis, severe, nonmeningeal infection: Patients with HIV:
Infants and Children: IV: 5 mg/kg/dose once daily until clinical improvement, then switch to an oral azole to complete ≥12 months of therapy. Dose may be increased to as high as 10 mg/kg/dose once daily for life-threatening infection (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 (Ref). Note: Some experts suggest initiating the oral azole in combination with the amphotericin B product and then continuing the oral azole when amphotericin B is discontinued (Ref).
Cryptococcal meningoencephalitis, disseminated disease, or severe pulmonary infection:
Infants, Children, and Adolescents: Induction therapy: IV: 5 mg/kg/dose once daily as part of appropriate combination therapy for ≥2 weeks, followed by consolidation therapy with oral fluconazole. Induction therapy duration may be extended in patients who cannot receive combination therapy, who are clinically deteriorating, if CNS cultures remain positive, or if neurological complications are present (Ref).
Histoplasmosis, moderately severe to severe pulmonary or disseminated disease (non-CNS):
Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 1 to 2 weeks and until clinical improvement, followed by oral itraconazole therapy. For patients with HIV, consider treating ≥2 weeks before transition to oral therapy (Ref).
Leishmaniasis, visceral:
Immunocompetent patients (alternative agent): Infants, Children, and Adolescents: IV: 2 to 3 mg/kg/dose once daily for 5 to 10 days (Ref).
Immunocompromised patients (alternative agent): Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for 10 days (Ref).
Patients with HIV:
Treatment (alternative agent): 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 (Ref).
Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm3): Adolescents: IV: 3 mg/kg/dose every 21 days (Ref).
Mucormycosis, invasive, without CNS involvement: Limited data available: Note: Prompt surgical debridement is often needed to achieve clinical cure (Ref).
Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily. 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, with some patients requiring lifelong therapy (Ref).
Sporotrichosis:
Meningeal infection: Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconazole (Ref).
Pulmonary, osteoarticular, and disseminated infection: Adolescents: IV: 3 to 5 mg/kg/dose once daily, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy (Ref).
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 (Ref):
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).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Nervous system: Chills (18%)
Renal: Increased serum creatinine (11%)
Miscellaneous: Fever (14%), multi-organ failure (11%)
1% to 10%:
Cardiovascular: Chest pain (3%), hypertension (5%), hypotension (8%)
Dermatologic: Skin rash (4%)
Endocrine & metabolic: Hypokalemia (5%)
Gastrointestinal: Abdominal pain (4%), diarrhea (6%), gastrointestinal hemorrhage (4%), nausea (9%), vomiting (8%)
Hematologic & oncologic: Anemia (4%), leukopenia (4%), thrombocytopenia (5%)
Hepatic: Hyperbilirubinemia (4%)
Infection: Sepsis (7%)
Nervous system: Headache (6%), pain (5%)
Renal: Renal failure syndrome (5%)
Respiratory: Dyspnea (7%), respiratory failure (8%), respiratory system disorder (4%)
<1%: Hypersensitivity: Anaphylaxis
Frequency not defined:
Cardiovascular: Acute myocardial infarction, cardiac arrhythmia (including ventricular fibrillation) cardiomyopathy, heart failure, pulmonary embolism, shock, thrombophlebitis
Dermatologic: Erythema multiforme, exfoliative dermatitis, maculopapular rash, pruritus
Endocrine & metabolic: Acidosis, hypercalcemia, hyperglycemia, hyperkalemia, hyperuricemia, hypocalcemia, hypoglycemia, hypophosphatemia, increased lactate dehydrogenase, weight loss
Gastrointestinal: Anorexia, cholangitis, cholecystitis, dyspepsia, epigastric pain, increased serum amylase, melena, stomach cramps
Genitourinary: Anuria, dysuria, impotence, oliguria
Hematologic & oncologic: Disorder of hemostatic component of blood, hematologic disease (including eosinophilia), leukocytosis
Hepatic: Acute hepatic failure, hepatic sinusoidal obstruction syndrome, hepatitis, hepatomegaly, jaundice
Hypersensitivity: Hypersensitivity reaction (including nonimmune anaphylaxis)
Local: Injection-site reaction (including inflammation at injection site)
Nervous system: Cerebrovascular accident, encephalopathy, extrapyramidal reaction, malaise, myasthenia, peripheral neuropathy, seizure, vertigo (transient)
Ophthalmic: Diplopia, visual impairment
Otic: Deafness, hearing loss, tinnitus
Renal: Increased blood urea nitrogen, renal insufficiency, renal tubular acidosis
Respiratory: Asthma, bronchospasm, hemoptysis, pleural effusion, pulmonary edema, tachypnea, wheezing
Postmarketing:
Endocrine & metabolic: Hypomagnesemia (Malani 2005)
Hepatic: Hepatotoxicity (including increased serum alanine aminotransferase, increased alkaline phosphatase, increased serum aspartate aminotransferase) (Moghnieh 2016)
Hypersensitivity: Infusion-related reaction (Moghnieh 2016)
Renal: Increased serum creatinine (Safdar 2010)
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous [preservative free]:
Abelcet: 5 mg/mL (20 mL)
No
Suspension (Abelcet Intravenous)
5 mg/mL (per mL): $6.30
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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 (Ref).
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 (Ref). 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 (Ref).
To minimize infusion-related immediate reactions, may 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. Adequate hydration and pre-infusion administration of NS may reduce the risk of nephrotoxicity during amphotericin B treatment (Ref).
Parenteral: IV: Must be diluted prior to administration. Flush line with D5W prior to infusion. Gently shake the IV container of diluted drug to ensure that contents are thoroughly mixed, then administer at a rate of 2.5 mg/kg/hour (over 2 hours for 5 mg/kg/dose). Do not use an in-line filter during administration. 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.
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
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
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
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