This monograph discusses amphotericin B lipid complex (ABLC); for information about other amphotericin B lipid formulations or conventional amphotericin B (amphotericin B deoxycholate) see drug specific monographs.
Amphotericin B is a polyene antifungal first isolated in 1955 from Streptomyces nodosus. In 1957, amphotericin B was approved for the treatment of progressive and potentially life threatening fungal infections. Amphotericin B maintains a broad spectrum of activity with a low potential for resistance, yet despite its efficacy, the usefulness of amphotericin B has been limited by its severe toxicities. To improve the tolerability of amphotericin B, three lipid-based formulations have been developed (amphotericin B lipid complex, amphotericin B cholesteryl sulfate complex, and amphotericin B liposomal injection). Amphotericin B lipid complex (Abelcet, ABLC) was the first lipid amphotericin B preparation available in the US. ABLC is composed of ribbon-like structures with a size ranging from 1600 to 11000 nm and a 1:1 molar ration of amphotericin B-to-phospholipid [L-alpha-dimyristoylphosphatidylcholine (DMPC) and L-alpha-dimyristoylphosphatidylglycerol (DMPG)]. Incorporating amphotericin B into a lipid complex decreases the toxicity and alters the pharmacokinetic properties of the drug without diminishing its efficacy. Data from 3 open-label studies involving patients refractory to or intolerant of conventional amphotericin B demonstrated effectiveness of ABLC in the treatment of invasive fungal infections. In addition, treatment with ABLC resulted in significantly lower incidence of nephrotoxicity when compared to conventional amphotericin B in the treatment of invasive candidiasis. ABLC was approved by the FDA in November 1995; it is indicated for the treatment of invasive fungal infections in patients who are refractory to or intolerant of conventional amphotericin B therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Amphotericin B lipid complex (ABLC) is not dosed the same as conventional amphotericin B (amphotericin B deoxycholate) or other lipid formulations (See drug specific monographs for dosing information). Further, amphotericin B lipid formulations may not be substituted for one another. The differences in the chemical composition and lipid component of these products can substantially affect their functional properties.
Route-Specific Administration
Injectable Administration
-Administer by intravenous infusion.
-Handle with aseptic technique as amphotericin B lipid complex (ABLC) does not contain any preservatives or bacteriostatic agents.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration.
Intravenous Administration
Filtration and Dilution:
-Prepare the admixture for infusion by first shaking the vial until there is no evidence of yellow sediment on the bottom of the vial.
-Transfer the appropriate amount of drug from the required number of vials into one or more sterile syringes using an 18-gauge needle.
-Attach the provided 5-micron filter needle to the syringe; inject the syringe contents through the filter needle, into the appropriate amount of 5% Dextrose injection. Each filter needle may be used on the contents of no more than four 100 mg vials.
-The suspension must be diluted with 5% Dextrose injection to a final concentration of 1 mg/mL. For pediatric patients and patients with cardiovascular disease, the final concentration may be 2 mg/mL. DO NOT USE SALINE SOLUTIONS OR MIX WITH OTHER DRUGS OR ELECTROLYTES.
-The diluted ready-for-use admixture is stable for up to 48 hours at 2-8 degrees C (36-46 degrees F) and an additional 6 hours at room temperature. Do not freeze.
Intravenous infusion:
-Flush intravenous line with D5W injection prior to infusion. If this cannot be done, then a separate IV line must be used. DO NOT USE AN IN-LINE FILTER.
-Prior to infusion, shake the bag until the contents are thoroughly mixed.
-The rate of infusion should not exceed 2.5 mg/kg/hour. If the infusion time exceeds 2 hours, mix the contents by shaking the infusion bag every 2 hours.
Infusion-related reactions have been reported with the administration of amphotericin B lipid complex (ABLC). Infusion-related reactions are toxicities occurring during or shortly after (within 1-2 hours) administration of ABLC and include symptoms such as chills (18%), fever (14%), rigors, decreased blood pressure, bronchospasms, arrhythmias, and shock. The severity with which these reactions occur is usually most intense during the first administration and decrease in strength with subsequent doses. The mechanism for this adverse event is unknown; however, the infusion-related reactions may be a result of prostaglandin synthesis stimulated by amphotericin B. The incidence of infusion-related reactions associated with ABLC has been shown to be higher than with amphotericin B liposomal injection (LAmB). In a clinical study of adult and pediatric febrile neutropenic patients, 5 mg/kg/day of ABLC resulted in an 88% incidence of infusion-related reactions with the first dose of treatment. In this same study, patients receiving LAmB at 3 mg/kg/day and 5 mg/kg/day experienced infusion-related reactions at a rate of 51% and 48% respectively. Although several medications frequently are prescribed to suppress these reactions prior to administration of an amphotericin B dose, only hydrocortisone, meperidine, and ibuprofen have been shown to be effective. Slowing the rate of infusion is not helpful. Infusion-related reactions can be more severe if administration occurs shortly after platelet or granulocyte transfusions.
Anaphylaxis or anaphylactoid reactions (< 0.1%), bronchospasm, dyspnea (7%), and wheezing have been reported in patients receiving treatment with amphotericin B lipid complex (ABLC). If severe respiratory distress, anaphylaxis or an anaphylactoid reaction occurs, the drug should be discontinued immediately and the patient given appropriate therapy as indicated. Cases of anaphylaxis have been reported when patients are switched from conventional amphotericin B to lipid formulations or when patients are switched between different amphotericin B lipid formulations.
Amphotericin B lipid complex (ABLC) is associated with a lower risk of nephrotoxicity (up to 42%) when compared to conventional amphotericin B and has been used in patients with preexisting renal impairment. Nephrotoxicity is manifest in many forms including azotemia, hypokalemia, renal tubular acidosis (RTA), and frank renal failure. Renal tubular acidosis may be present without concurrent systemic acidosis. The mechanism is due, in part, to lysis of cholesterol-rich lysosomal membranes of renal tubular cells, causing renal tubular necrosis. Tubuloglomerular feedback (TGF) provokes constriction of the afferent arteriole, which, in turn, causes azotemia. It is believed that TGF is augmented by renal electrolyte loss during a hyponatremic state and that sodium 'loading' prior to administering ABLC may attenuate the process. Azotemia can develop after only a few doses. Although renal function can return to baseline in several days if ABLC therapy is held, irreversible renal tubular necrosis can develop, especially after prolonged therapy, large cumulative doses, or concomitant therapy with other nephrotoxic drugs. It appears that patients with higher serum low-density lipoprotein (LDL) concentrations are more susceptible to ABLC-induced nephrotoxicity than those with lower concentrations. Cases of azotemia, increased serum creatinine (11%), hyperuricemia, hypokalemia (5%), hyperkalemia, hypomagnesemia, hypophosphatemia, hypercalcemia, and hypocalcemia have been reported in patients receiving ABLC. Other adverse renal effects reported in patients receiving ABLC include anuria, decreased renal function, dysuria, oliguria, and renal failure (unspecified) (5%). In a clinical study of febrile neutropenic patients receiving ABLC the incidence of nephrotoxicity, defined as a 100% increase in baseline serum creatinine, was 42%. Health care providers are advised to monitor renal function and serum electrolytes concentrations (particularly potassium and magnesium) in patients receiving treatment with ABLC.
A normocytic, normochromic anemia occurs in most patients receiving conventional amphotericin B. This reaction is believed to be caused by a suppressive effect on erythropoietin production. Usually, this condition does not require transfusions and generally returns to baseline within several months following discontinuation of therapy. Anemia has also been reported in 4% of patients receiving amphotericin B lipid complex (ABLC) during clinical trials. Other hematologic effects include leukopenia (4%) and thrombocytopenia (5%). Cases of coagulopathy, eosinophilia, and leukocytosis were reported during open-label, uncontrolled clinical trials; the frequency and causal association between these adverse events and ABLC can not be established.
Cases of cardiac arrest (6%), respiratory failure (8%), chest pain (unspecified) (3%), hypertension (5%), and hypotension (8%) have been associated with the use of amphotericin B lipid complex (ABLC) during clinical trials. Other cardiorespiratory adverse events reported during open-label, uncontrolled clinical trials include heart failure, pulmonary edema, shock, myocardial infarction, hemoptysis, tachypnea, pulmonary embolism, cardiomyopathy, pleural effusion, and arrhythmia exacerbation including ventricular fibrillation; however, because these events occurred in uncontrolled trials, neither a frequency nor a definitive causal relationship can be established. Health care providers are advised of the potential for increased pulmonary toxicities in patients receiving leukocyte transfusions with amphotericin B infusions (see Precautions).
Intravenous administration of amphotericin B lipid complex (ABLC) can cause an injection site reaction that includes symptoms such as pain and inflammation at the injection site. Phlebitis has also been associated with ABLC treatment during uncontrolled clinical trials. Take precautions to avoid extravasation of ABLC as this may result in local irritation.
Gastrointestinal (GI) adverse reactions, such as abdominal pain (4%), anorexia, abdominal cramping, diarrhea (6%), dyspepsia, epigastric pain, GI bleeding (4%), melena, nausea (3-9%), vomiting (3-8%), and weight loss, have occurred in patients receiving amphotericin B lipid complex (ABLC) during clinical trials.
Hepatotoxicity has been associated with amphotericin B lipid complex (ABLC) therapy. During clinical trials, recipients of ABLC experienced elevated bilirubin concentrations or hyperbilirubinemia (4%), elevated hepatic enzymes, elevated alkaline phosphatase and lactate dehydrogenase, acute hepatic failure, hepatitis, jaundice, hepatomegaly, and hepatic veno-occlusive disease (VOD). Additionally, biliary disorders, such as cholangitis and cholecystitis, have developed in ABLC treated patients. Health care providers are advised to monitor hepatic function in patients receiving treatment with ABLC.
Adverse neurologic reactions have been reported in patients receiving amphotericin B lipid complex (ABLC). Headache, noted in 6% of ABLC recipients, was the most frequently reported neurologic event during clinical trials. Other events observed in open-label, uncontrolled clinical trials included cerebral vascular accident (stroke), diplopia, encephalopathy, extrapyramidal syndrome, hearing loss, malaise, peripheral neuropathy, seizures, tinnitus, transient vertigo, and visual impairment; however, because these events occurred in uncontrolled trials, neither a frequency nor a definitive causal relationship can be established.
Rash (unspecified) was reported by 4% of amphotericin B lipid complex (ABLC) recipients during clinical trials. Other dermatologic adverse events reported during open-label, uncontrolled trials included maculopapular rash, pruritus, exfoliative dermatitis, and erythema multiforme; the frequency and causal associated between these adverse events and ABLC has not been established.
Generalized pain was experienced by 5% of amphotericin B lipid complex (ABLC) recipients during clinical trials. Other adverse events developing in ABLC treated patients included arthralgia, bone pain, musculoskeletal pain, and myasthenia.
Metabolic adverse events associated with amphotericin B lipid complex (ABLC) therapy during open-label, uncontrolled clinical trials include metabolic acidosis, hyperamylasemia, hyperglycemia, and hypoglycemia; the frequency and causal relationship between these adverse events and ABLC has not been established.
Adverse events experienced by recipients of amphotericin B lipid complex (ABLC) during clinical trials include multiple organ failure (11%), infection and sepsis (5-7%), asthma, and impotence (erectile dysfunction).
Amphotericin B lipid complex (ABLC) is contraindicated in patients with a known hypersensitivity to amphotericin B or any other component in the formulation. Anaphylaxis has been reported with the use of ABLC; thus, administer ABLC only under close observation by medically trained personnel. If a severe anaphylactic reaction occurs during administration of ABLC, the drug should be immediately discontinued and the patient should not receive further doses of amphotericin B.
Cardiorespiratory arrest has been reported in patients receiving an overdose of amphotericin B. When administering ABLC, exercise caution to prevent inadvertent overdose; if an overdose occurs, discontinue therapy and administer supportive measures.
Acute pulmonary toxicity has been reported in patients receiving amphotericin B and leukocyte transfusions; concomitant use of leukocyte transfusions and amphotericin B lipid complex (ABLC) should be avoided.
Administer amphotericin B lipid complex (ABLC) with caution to patients with preexisting renal impairment or renal failure. Although ABLC has an improved safety profile when compared to conventional amphotericin B, nephrotoxicity can still develop. In a study of febrile neutropenic patients receiving ABLC, the incidence of renal toxicity, defined as a 100% increase in baseline serum creatinine, was 42%. According to the manufacturer, ABLC has been successfully administered to patients with preexisting renal disease; no dose adjustment recommendations are given. However, renal function should be monitored during ABLC therapy.
Amphotericin B lipid complex (ABLC) has not been studied in patients with hepatic disease; administer the drug with caution in patients with preexisting hepatic impairment or hepatic failure. Monitor liver function tests during ABLC therapy.
Amphotericin B lipid complex (ABLC) has been shown to cause anemia, leukopenia, and thrombocytopenia in clinical trails. Administer ABLC with caution in patients with preexisting hematological disease including anemia, leukopenia, and thrombocytopenia. In addition, monitor CBC and platelets during ABLC therapy.
Use caution when administering amphotericin B lipid complex (ABLC) to patients with an electrolyte imbalance including hyperkalemia, hypokalemia, hypomagnesemia, hypercalcemia, and hypocalcemia. Serum electrolyte abnormalities may occur after administration of ABLC. Monitor serum electrolytes during ABLC therapy.
Administer amphotericin B lipid complex (ABLC) with caution to patients with preexisting cardiac disease including patients with preexisting hypotension and hypertension. In clinical studies patients have experienced cardiac arrest, chest pain, hypotension, and hypertension after ABLC infusions.
The pharmacokinetic properties of amphotericin B lipid complex (ABLC) have not been studied in the geriatric population; however, the drug has been used effectively in this population to treat systemic fungal infections. No serious unexpected adverse effects have been reported in elderly patients who have received ABLC in dosages similar to those used in younger patients. Closely monitor the use of ABLC in elderly patients.
The pharmacokinetic properties of amphotericin B lipid complex (ABLC) have not been studied in neonates, infants, children and adolescents <= 16 years of age; however, the drug has been used effectively in this population to treat systemic fungal infections. No serious unexpected adverse effects have been reported in pediatric patients who have received ABLC in dosages similar to those used in adults. Closely monitor the use of ABLC in pediatric patients.
Use amphotericin B lipid complex (ABLC) during pregnancy only after taking into account the importance of the drug to the mother. Adequate and well-controlled studies have not been conducted in pregnant women. Reproductive studies in rats and rabbits at doses of ABLC up to 0.64 times the human dose revealed no harm to the fetus.
It is not known whether amphotericin B lipid complex (ABLC) is excreted in human milk. Because of the potential for serious adverse reactions in breast-fed infants from ABLC, discontinue breast-feeding or discontinue ABLC, taking into account the importance of the drug to the mother. Fluconazole or ketoconazole may be potential alternatives to consider during breast-feeding. Assess site of infection, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent.
Infusion-related reactions have been reported with the administration of amphotericin B lipid complex (ABLC). Acute reactions may include fever, chills, rigors, decreased blood pressure, bronchospasm, arrhythmias, and shock and usually occur during or shortly after (within 1-2 hours) administration of ABLC. The severity with which these reactions occur is usually most intense during the first administration and decreases in strength with subsequent doses. Although several medications frequently are prescribed to suppress these reactions prior to administration of an amphotericin B dose, only hydrocortisone, meperidine, and ibuprofen have been shown to be effective. Slowing the rate of infusion is not helpful. Infusion-related reactions can be more severe if administration occurs shortly after platelet or granulocyte transfusions.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Aspergillus fumigatus, Aspergillus sp., Blastomyces dermatitidis, Candida albicans, Candida guilliermondii, Candida sp., Candida stellatoidea, Candida tropicalis, Coccidioides immitis, Cryptococcus sp., Histoplasma sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of CNS infections, including meningitis:
NOTE: For CNS infections caused by Cryptococcus, see Cryptococcus meningitis.
-for the treatment of CNS infections due to Aspergillus sp. in patients refractory to or intolerant of amphotericin B deoxycholate:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Guidelines suggest amphotericin B lipid complex as salvage therapy.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Guidelines suggest amphotericin B lipid complex as salvage therapy.
Neonates: 5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B lipid complex as salvage therapy.
-for the treatment of CNS infections due to Blastomyces dermatitidis*:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with an oral azole for at least 12 months and until resolution of CSF abnormalities.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with an oral azole for at least 12 months and until resolution of CSF abnormalities.
-for the treatment of CNS infections due to Histoplasma capsulatum*:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with itraconazole for at least 12 months and until resolution of abnormal cerebrospinal fluid (CSF) findings. Guidelines suggest liposomal amphotericin B as preferred treatment.
Adolescents: 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with itraconazole for at least 12 months and until resolution of abnormal cerebrospinal fluid (CSF) findings. Guidelines suggest liposomal amphotericin B as preferred treatment.
Infants and Children: 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with itraconazole for at least 12 months and until resolution of cerebrospinal fluid (CSF) abnormalities. Guidelines suggest liposomal amphotericin B as preferred treatment.
-for the treatment of meningitis due to Sporothrix schenckii*:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours for at least 4 to 6 weeks. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy.
For the treatment of candidemia and invasive candidiasis (non-CNS), including chronic disseminated (hepatosplenic candidiasis), in patients refractory to or intolerant of amphotericin B deoxycholate:
NOTE: For CNS disease, see meningitis indication.
-for the treatment of candidemia and invasive candidiasis (non-CNS):
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates: 3 to 5 mg/kg/dose IV every 24 hours as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours.
-for the treatment of chronic disseminated (hepatosplenic candidiasis):
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours for several weeks, followed by oral fluconazole.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for several weeks, followed by oral fluconazole.
For the treatment of invasive aspergillosis in patients who are refractory to or intolerant of amphotericin B deoxycholate:
NOTE: For CNS disease, see meningitis indication.
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
For the treatment of fungal ophthalmic infection, including endophthalmitis, caused by Aspergillus sp. in patients who are refractory to or intolerant of amphotericin B deoxycholate:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
For the treatment of esophageal candidiasis* in persons living with HIV:
Intravenous dosage:
Adults: 3 to 4 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative.
Adolescents: 3 to 4 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative.
For the treatment of cardiovascular system infections, including endocarditis, myocarditis, pericarditis, suppurative thrombophlebitis*, and infected pacemaker*, implantable cardiac defibrillator (ICD)*, or ventricular assist devices (VAD)* in patients who are refractory to or intolerant of other antifungal therapies:
-for the treatment of Candida cardiovascular system infections:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates: 3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Guidelines suggest a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
-for the treatment of Aspergillus cardiovascular system infections:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. After surgical replacement of an infected valve, consider lifelong antifungal therapy.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. After surgical replacement of an infected valve, consider lifelong antifungal therapy. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%.
Neonates: 5 mg/kg/dose IV every 24 hours. Specific neonatal recommendations are not available. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. After surgical replacement of an infected valve, consider lifelong antifungal therapy.
For the treatment of respiratory infections (i.e., pneumonia, tracheobronchitis, sinusitis) in patients who are refractory to or intolerant of amphotericin B deoxycholate:
-for the treatment of Candida pneumonia:
Intravenous dosage:
Adults: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 3 to 5 mg/kg/dose IV every 24 hours.
Infants, Children, and Adolescents: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 3 to 5 mg/kg/dose IV every 24 hours.
Neonates: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. 3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to amphotericin B deoxycholate or fluconazole for neonatal candidiasis. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement.
-for the treatment of invasive pulmonary, sinus, or tracheobronchial aspergillosis:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. In lung transplant recipients with tracheobronchial aspergillosis (TBA) associated with anastomotic endobronchial ischemia or ischemic reperfusion injury, inhaled amphotericin B is suggested in addition to systemic therapy; treat for at least 3 months or until TBA is resolved, whichever is longer. Surgery alone may be used to treat Aspergillus fungal ball of the paranasal sinus.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. In lung transplant recipients with tracheobronchial aspergillosis (TBA) associated with anastomotic endobronchial ischemia or ischemic reperfusion injury, inhaled amphotericin B is suggested in addition to systemic therapy; treat for at least 3 months or until TBA is resolved, whichever is longer. Surgery alone may be used to treat Aspergillus fungal ball of the paranasal sinus.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. In lung transplant recipients with tracheobronchial aspergillosis (TBA) associated with anastomotic endobronchial ischemia or ischemic reperfusion injury, inhaled amphotericin B is suggested in addition to systemic therapy; treat for at least 3 months or until TBA is resolved, whichever is longer. Surgery alone may be used to treat Aspergillus fungal ball of the paranasal sinus.
For the treatment of intraabdominal infections due to candidiasis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours as an alternative.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours as an alternative.
Neonates: 3 to 5 mg/kg/dose IV every 24 hours as an alternative.
For the treatment of bone and joint infections, including osteomyelitis and infectious arthritis, in patients who are refractory to or intolerant of amphotericin B deoxycholate:
-for the treatment of Candida osteomyelitis or infectious arthritis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to fluconazole. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to fluconazole. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.
Neonates: 3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest 3 to 5 mg/kg/dose IV every 24 hours as an alternative to amphotericin B deoxycholate or fluconazole for neonatal candidiasis. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.
-for the treatment of Aspergillus osteomyelitis or infectious arthritis:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 8 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Longer courses (greater than 6 months) are frequently necessary.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 8 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Longer courses (greater than 6 months) are frequently necessary.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 8 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Longer courses (greater than 6 months) are frequently necessary.
For empirical therapy for presumed fungal infection in patients with febrile neutropenia* or non-neutropenic patients at high risk for fungal infection* (e.g., critically ill patients with risk factors for invasive candidiasis and no other known cause of fever):
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines for candidiasis suggest 3 to 5 mg/kg/day IV of a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Aspergillosis clinical practice guidelines suggest empirical therapy for high-risk patients with prolonged neutropenia who remain persistently febrile despite broad-spectrum antibiotic therapy. In neutropenic patients with cancer, empiric antifungal therapy is suggested for patients with persistent or recurrent fever after 4 to 7 days of antibiotics and whose overall duration of neutropenia is expected to be more than 7 days. If already receiving antifungal prophylaxis, consider switching to a different class of mold active agent.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines for candidiasis suggest 3 to 5 mg/kg/day IV of a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Aspergillosis clinical practice guidelines suggest empirical therapy for high-risk patients with prolonged neutropenia who remain persistently febrile despite broad-spectrum antibiotic therapy. In neutropenic patients with cancer, empiric antifungal therapy is suggested for patients with persistent or recurrent fever after 4 to 7 days of antibiotics and whose overall duration of neutropenia is expected to be more than 7 days. If already receiving antifungal prophylaxis, consider switching to a different class of mold active agent. Caspofungin or liposomal amphotericin B is a preferred agent for empiric antifungal therapy in children with cancer and/or undergoing hematopoietic stem cell transplantation.
For the treatment of CNS cryptococcal infections, including cryptococcal meningitis and cerebral cryptococcomas, in patients who are refractory to or intolerant of amphotericin B deoxycholate:
-Persons living with HIV:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as an alternative induction therapy. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Adolescents: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as an alternative induction therapy. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants and Children: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
-Organ transplant recipients:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent for 4 to 6 weeks for patients unable to tolerate flucytosine. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent for 4 to 6 weeks for patients unable to tolerate flucytosine. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B lipid complex in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent for 4 to 6 weeks for patients unable to tolerate flucytosine. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
-Non-HIV, nontransplant patients:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours with flucytosine for at least 4 weeks as an alternative induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, extend induction therapy for a total of 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours with flucytosine for at least 4 weeks as an alternative induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, extend induction therapy for a total of 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B lipid complex with flucytosine for at least 4 weeks as an alternative induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, extend induction therapy for a total of 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
For the treatment of moderately severe to severe blastomycosis:
NOTE: For CNS disease, see meningitis indication.
-for the treatment of moderately severe to severe pulmonary blastomycosis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of 6 to 12 months of therapy.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of 12 months of therapy.
Neonates: 5 mg/kg/dose IV every 24 hours.
-for the treatment of moderately severe to severe disseminated extrapulmonary blastomycosis, including osteoarticular blastomycosis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of 12 months of therapy.
Neonates: 5 mg/kg/dose IV every 24 hours.
-for the treatment of blastomycosis in immunosuppressed patients:
Intravenous dosage:
Immunosuppressed Adults: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. Lifelong suppressive therapy may be required.
Immunosuppressed Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. Lifelong suppressive therapy may be required.
Immunosuppressed Neonates: 5 mg/kg/dose IV every 24 hours.
For the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis:
-for the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis in persons without HIV who are refractory to or intolerant of other therapies:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Neonates: 5 mg/kg/dose IV every 24 hours.
-for the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis in persons living with HIV:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole for at least 12 months then long-term suppressive therapy; discontinuation is dependent on clinical and serological response. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Adolescents: 3 to 5 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole for at least 12 months then long-term suppressive therapy; discontinuation is dependent on clinical and serological response. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Infants and Children: 5 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole for at least 12 months then long-term suppressive therapy. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
For the treatment of moderately severe to severe pulmonary or disseminated histoplasmosis in patients refractory to or intolerant of amphotericin B deoxycholate:
-for the treatment of pulmonary histoplasmosis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks. Continue step-down therapy with itraconazole for a total of 12 weeks. Guidelines suggest a lipid formulation amphotericin B as a preferred treatment.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks. Continue step-down therapy with itraconazole for a total of 12 weeks. Guidelines suggest amphotericin B lipid complex as alternate therapy in patients unable to tolerate amphotericin B deoxycholate.
Neonates: 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks. Continue step-down therapy with itraconazole for a total of 12 weeks. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B lipid complex as alternate therapy in patients unable to tolerate amphotericin B deoxycholate.
-for the treatment of disseminated histoplasmosis:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks. For HIV-infected patients, continue step-down therapy with itraconazole for at least 12 months. Longer treatment may be required in patients with persistent immunodeficiency. Guidelines suggest amphotericin B lipid complex as an alternate treatment to liposomal amphotericin B.
Adolescents: 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks. For HIV-infected patients, continue step-down therapy with itraconazole for at least 12 months. Longer treatment may be required in patients with persistent immunodeficiency. Guidelines suggest amphotericin B lipid complex as an alternate treatment to liposomal amphotericin B.
Infants and Children: 5 mg/kg/dose IV every 24 hours for for at least 2 weeks or longer if clinical improvement is delayed. Continue step-down therapy with itraconazole for 12 months for HIV-infected patients. Guidelines suggest liposomal amphotericin B as the preferred treatment in HIV-infected children and amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.
Neonates: 5 mg/kg/dose IV every 24 hours for for at least 2 weeks or longer if clinical improvement is delayed. Continue step-down therapy with itraconazole for 12 months for HIV-infected patients. Although specific neonatal recommendations are not available, guidelines suggest liposomal amphotericin B as the preferred treatment in HIV-infected children and amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.
For the treatment of visceral leishmaniasis*:
Intravenous dosage:
Immunocompetent Adults: 2 to 3 mg/kg/dose IV every 24 hours for 5 to 10 days as an alternative to liposomal amphotericin B. In general, this formulation is not recommended, but may be considered with patients who develop liposome-induced complement activation-related pseudoallergy (CARPA).
Immunocompromised Adults: 2 to 5 mg/kg/dose IV every 24 hours for 10 days or 4 mg/kg/dose IV on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38, for a cumulative total of 20 to 60 mg/kg, as an alternative to liposomal amphotericin B. In general, this formulation is not recommended, but may be considered with patients who develop liposome-induced complement activation-related pseudoallergy (CARPA). Chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is recommended in HIV-infected patients.
Immunocompetent Infants, Children, and Adolescents: 2 to 3 mg/kg/dose IV every 24 hours for 5 to 10 days as an alternative to liposomal amphotericin B. In general, this formulation is not recommended, but may be considered with patients who develop liposome-induced complement activation-related pseudoallergy (CARPA).
Immunocompromised Adolescents: 2 to 5 mg/kg/dose IV every 24 hours for 10 days or 4 mg/kg/dose IV on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38, for a cumulative total of 20 to 60 mg/kg, as an alternative to liposomal amphotericin B. In general, this formulation is not recommended, but may be considered with patients who develop liposome-induced complement activation-related pseudoallergy (CARPA). Chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is recommended in HIV-infected patients.
Immunocompromised Infants and Children: 3 to 5 mg/kg/dose IV every 24 hours for 10 days as an alternative to liposomal amphotericin B. In general, this formulation is not recommended, but may be considered with patients who develop liposome-induced complement activation-related pseudoallergy (CARPA).
For the treatment of osteoarticular, severe pulmonary, or disseminated sporotrichosis*:
NOTE: For CNS disease, see meningitis indication.
-for the treatment of osteoarticular sporotrichosis*:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours as an alternative to itraconazole. After favorable response, continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy.
-for the treatment of severe pulmonary or disseminated sporotrichosis*:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours until favorable response. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy.
For secondary leishmaniasis prophylaxis* (i.e., long-term suppressive therapy) in HIV-infected patients:
Intravenous dosage:
Adults: 3 mg/kg/dose IV every 21 days until a sustained (at least 3 to 6 months) increase in CD4 count to more than 200 to 350 cells/mm3 in response to antiretroviral therapy; however, indefinite prophylaxis may be used. Prophylaxis is recommended in patients with visceral disease and in some patients with multiple cutaneous relapses.
Adolescents: 3 mg/kg/dose IV every 21 days until a sustained (at least 3 to 6 months) increase in CD4 count to more than 200 to 350 cells/mm3 in response to antiretroviral therapy; however, indefinite prophylaxis may be used. Prophylaxis is recommended in patients with visceral disease and in some patients with multiple cutaneous relapses.
For the treatment of disseminated (nonmeningeal) or pulmonary cryptococcosis in patients refractory to or intolerant of amphotericin B deoxycholate:
NOTE: For the treatment of CNS infections, see cryptococcal meningitis.
-Persons living with HIV:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as an alternative induction therapy. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Adolescents: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as an alternative induction therapy. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants and Children: 5 mg/kg/dose IV every 24 hours with or without flucytosine. Duration of therapy dependent on site and severity of infection and clinical response.
Neonates: 5 mg/kg/dose IV every 24 hours with or without flucytosine. Duration of therapy dependent on site and severity of infection and clinical response.
-Organ transplant recipients:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent for 4 to 6 weeks for patients unable to tolerate flucytosine. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent for 4 to 6 weeks for patients unable to tolerate flucytosine. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B lipid complex in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B lipid complex may be given as a single agent for 4 to 6 weeks for patients unable to tolerate flucytosine. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
-Non-HIV, nontransplant patients:
Intravenous dosage:
Adults: 5 mg/kg/dose IV every 24 hours for at least 4 weeks as an alternative induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours for at least 4 weeks as an alternative induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B lipid complex with flucytosine for at least 4 weeks as an alternative induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
For the treatment of asymptomatic candiduria:
-for the treatment of asymptomatic candiduria in neutropenic persons:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours for 14 days as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours for 14 days as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.
-for the treatment of asymptomatic candiduria in very-low-birth-weight infants (weight less than 1.5 kg):
Intravenous dosage:
Neonates: 3 to 5 mg/kg/dose IV every 24 hours for 14 days as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these infants. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours.
Maximum Dosage Limits:
-Adults
5 mg/kg/day IV.
-Geriatric
5 mg/kg/day IV.
-Adolescents
5 mg/kg/day IV.
-Children
5 mg/kg/day IV.
-Infants
5 mg/kg/day IV.
-Neonates
5 mg/kg/day IV; doses up to 6.5 mg/kg/day have been used rarely.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; dosage interval can be extended. Decisions about dose adjustments should be made only after taking into account the overall clinical condition of the patient.
*non-FDA-approved indication
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Aspirin: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Acetazolamide: (Moderate) Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
Acyclovir: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including acyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Albuterol; Budesonide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Aldesleukin, IL-2: (Major) Avoid concomitant use of amphotericin B and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Amikacin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Aminosalicylate sodium, Aminosalicylic acid: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Amiodarone: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including amphotericin B.
Amlodipine; Celecoxib: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as the aprotinin, as the risk of renal impairment may be increased.
Aspirin, ASA: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Dipyridamole: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Omeprazole: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Oxycodone: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Atenolol; Chlorthalidone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Atracurium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Auranofin: (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Azelastine; Fluticasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Azilsartan; Chlorthalidone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Bacillus Calmette-Guerin Vaccine, BCG: (Moderate) Administration of amphotericin B [lipid complex (ABLC), cholesteryl sulfate complex (ABCD), and liposomal (LAmB)] with antineoplastic agents may increase the potential for nephrotoxicity, bronchospasm, and hypotension. Amphotericin B-induced hypokalemia can result in interactions with other drugs.
Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Bacitracin; Hydrocortisone; Neomycin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Bacitracin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Beclomethasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Betamethasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Bismuth Subsalicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Budesonide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Budesonide; Formoterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Bumetanide: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Bupivacaine; Meloxicam: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Cardiac glycosides: (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Celecoxib: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Celecoxib; Tramadol: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Chlorothiazide: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Chlorthalidone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Choline Salicylate; Magnesium Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Ciclesonide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Cidofovir: (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir.
Cisapride: (Major) Amphotericin B- induced electrolyte imbalances can result in significant interactions with other drugs. Hypokalemia or hypomagnesemia can potentiate the cardiac toxicity of cisapride. Electrolytes should be monitored in patients who are taking cisapride prior to and during amphoteracin B treatment. Cisapride is contraindicated for use in patients with known serum electrolyte imbalances; cisapride should be discontinued if such imbalances occur while these medications are taken concurrently.
Cisatracurium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Cisplatin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and amphotericin B is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Clindamycin: (Moderate) Concomitant use of amphotericin B and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Colistimethate, Colistin, Polymyxin E: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Colistin: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Corticosteroids: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Cortisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Cyclophosphamide: (Moderate) Monitor renal function if cyclophosphamide is used concomitantly with amphotericin B as there may be an increased risk of nephrotoxicity.
Cyclosporine: (Moderate) Cyclosporine should be used cautiously with nephrotoxic drugs, such as amphotericin B, as cyclosporine itself can cause structural kidney damage. Additive nephrotoxicity can occur if these drugs are administered together. Monitor renal function and fluid status carefully.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Daunorubicin Liposomal: (Minor) Amphotericin B can reduce cell resistance to daunorubicin, thus enhancing its activity. Amphotericin B can alter cell membranes, which could otherwise impede daunorubicin's entry into the cell. How this may affect liposomal delivery of daunorubicin is not known.
Daunorubicin Liposomal; Cytarabine Liposomal: (Minor) Amphotericin B can reduce cell resistance to daunorubicin, thus enhancing its activity. Amphotericin B can alter cell membranes, which could otherwise impede daunorubicin's entry into the cell. How this may affect liposomal delivery of daunorubicin is not known.
Deflazacort: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Dexamethasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Dichlorphenamide: (Moderate) Use dichlorphenamide and antifungals together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. In addition, both dichlorphenamide and some amphotericin B products (i.e., amphotericin B cholesteryl sulfate complex (ABCD), amphotericin B lipid complex (ABLC), amphotericin B liposomal (LAmB)) can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Diclofenac; Misoprostol: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Diflunisal: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Digoxin: (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Diphenhydramine; Naproxen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Dofetilide: (Major) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs, such as amphotericin B, increasing the potential for dofetilide-induced torsade de pointes. Potassium levels should be within the normal range prior and during administration of dofetilide.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Dronabinol: (Major) Use caution if coadministration of dronabinol with amphotericin B is necessary, and monitor for an increase in amphotericin-related adverse reactions. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as amphotericin B.
Droperidol: (Moderate) Caution is advised when using droperidol in combination with amphoterecin B, which may cause hypokalemia or hypomagnesemia. Using these drugs together may increase the risk for QT prolongation or cardiac arrhythmias.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Entecavir: (Moderate) Entecavir is primarily eliminated by the kidneys and amphotericin B can affect renal function; concurrent administration may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Ethacrynic Acid: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Etodolac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Fenoprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Fluconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Flucytosine: (Minor) Amphotericin B may increase the toxicity of flucytosine by possibly increasing flucytosine cellular uptake and/or impairing flucytosine renal excretion. However, flucytosine can have synergistic effects when used with amphotericin B, and these two drugs frequently are used together to treat cryptococcal infections. This combination may allow for a reduction in the total daily dose of amphotericin B. However, amphotericin B-induced reductions in renal function can increase bone marrow toxicity from flucytosine.
Fludrocortisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Flunisolide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Flurbiprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Fluticasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Fluticasone; Salmeterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Fluticasone; Vilanterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Formoterol; Mometasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as amphotericin B. Avoid concurrent use, unless the potential benefits outweigh the risks to the patient.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Furosemide: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Ganciclovir: (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Gentamicin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Gold: (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Hydrocodone; Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Hydrocortisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ibuprofen; Famotidine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ibuprofen; Oxycodone: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indapamide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics (indapamide) are coadministered with other drugs with a significant risk of hypokalemia (e.g., amphotericin B).
Indomethacin: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and amphotericin B due to the risk of glomerulonephritis and nephrotoxicity.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Isoproterenol: (Moderate) Both isoproterenol and amphotericin B have the potential to cause potassium-wasting or magnesium-wasting. Use of these drugs together may increase the risk of developing arrhythmias by reducing potassium or magnesium serum concentrations.
Itraconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Ketoconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Ketoprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ketorolac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Levoketoconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Loop diuretics: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Magnesium Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Meclofenamate Sodium: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Mefenamic Acid: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Meloxicam: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Methazolamide: (Moderate) Amphotericin B may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Methenamine; Sodium Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Methotrexate: (Major) Avoid concomitant use of methotrexate with amphotericin B due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Amphotericin B and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with amphotericin B may result in decreased renal function as well as increased methotrexate plasma concentrations.
Methylprednisolone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Metolazone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Mometasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Nabumetone: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Naproxen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Naproxen; Esomeprazole: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Naproxen; Pseudoephedrine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Neomycin: (Minor) Because the systemic absorption of neomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic neomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Neomycin; Polymyxin B; Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Neuromuscular blockers: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Nilotinib: (Moderate) Administration of amphotericin B [lipid complex (ABLC), cholesteryl sulfate complex (ABCD), and liposomal (LAmB)] with antineoplastic agents may increase the potential for nephrotoxicity, bronchospasm, and hypotension. Amphotericin B-induced hypokalemia can result in interactions with other drugs.
Nonsteroidal antiinflammatory drugs: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Olopatadine; Mometasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Oxaprozin: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Pancuronium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Paromomycin: (Minor) Because the systemic absorption of paromomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic paromomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Pentamidine: (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with pentamidine. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Pimozide: (Major) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as amphotericin B. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Piroxicam: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Polymyxin B: (Major) Systemic polymyxin B should not be used concurrently or sequentially with other drugs that have the potential for nephrotoxicity or neurotoxicity such as amphotericin B. Topical products containing polymyxin B, especially when they are applied over a large body surface area, should be used cautiously.
Prednisolone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Prednisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Rocuronium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Salicylates: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Salsalate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Streptomycin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides such as streptomycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Succinylcholine: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Sulindac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Sumatriptan; Naproxen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Tacrolimus: (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tacrolimus. Amphotericin B and/or tacrolimus dosage reduction may be necessary if renal impairment occurs.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as amphotericin B may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Thiazide diuretics: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Tobramycin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Tolmetin: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Torsemide: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Triamcinolone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Valacyclovir: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including valacyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Valganciclovir: (Moderate) Use caution and monitor renal function when valganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Vancomycin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Vecuronium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Voclosporin: (Moderate) Concomitant use of voclosporin and amphotericin B may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Voriconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Zidovudine, ZDV: (Moderate) The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
Amphotericin B, the active ingredient in amphotericin B lipid complex (ABLC), binds to sterols in cell membranes of both fungal and human cells. As a result of this binding, membrane integrity of the cells is impaired, causing loss of intracellular potassium and other cellular contents. Altered permeability of ergosterol-containing membranes, characteristic of fungal cell membranes, occurs at low amphotericin B concentrations; however, beyond a certain concentration threshold amphotericin B induces leakage of cellular contents through human cholesterol-containing membranes. Some adverse reactions to amphotericin B, such as electrolyte loss and nephrotoxicity, are an extension of this pharmacologic action. Amphotericin B is usually fungistatic in vivo but can have fungicidal activity at high concentrations or against extremely susceptible organisms.
ABLC has demonstrated activity in animal models against Aspergillus fumigatus, Blastomyces species, Candida albicans, Candida guilliermondii, Candida stellatoidea, Candida tropicalis, Coccidioidomyces species, Cryptococcus species, and Histoplasma species.
ABLC shows in vitro activity against Aspergillus species and Candida species. Although standardized susceptibility testing is available for yeast and some filamentous fungi, results do not necessarily correlate with clinical outcome. ABLC is not active against bacteria, Rickettsiae, or viruses.
Amphotericin B lipid complex (ABLC) is administered intravenously; it cannot be given intramuscularly. Pharmacokinetic parameters for ABLC should not be used to predict the pharmacokinetics of any other amphotericin B formulation. The clinical relevance of pharmacokinetic differences between ABLC and other amphotericin B formulations has not been determined. Further, the interpretation of serum or tissue amphotericin B concentrations is complicated by the fact that many assays to measure amphotericin B concentrations do not distinguish free amphotericin B and amphotericin B that is lipid-complexed, liposome-encapsulated, or protein-bound.
Metabolism of amphotericin B following administration of ABLC is unknown. Amphotericin B is excreted very slowly by the kidneys. The terminal elimination half-life of amphotericin B is longer after administration of the lipid-complexed formulation (mean 7 days) when compared to conventional amphotericin B (mean 4 days). The long terminal half-life reflects slow redistribution from the tissues. Despite being excreted slowly, there is little accumulation in the blood after repeated dosing.
-Route-Specific Pharmacokinetics
Intravenous Route
The pharmacokinetics of amphotericin B lipid complex (ABLC) after intravenous administration are nonlinear and vary substantially from conventional amphotericin B and from other lipid formulations. In general, the volume of distribution following administration of ABLC is greater and serum concentrations are lower compared to conventional amphotericin B. Distribution of amphotericin B is multi-compartmental. Following IV administration, ABLC is rapidly taken up by the reticuloendothelial system concentrating the drug within the liver, spleen, and lungs. This plasma clearance is enhanced as dosage increases from 0.6-5 mg/kg/day resulting in a less than proportional increase in plasma concentrations and in a higher volume of distribution. Tissues function as a reservoir for ABLC, slowly releasing amphotericin B into circulation. Tissue concentrations of ABLC, when compared to conventional amphotericin B, are higher in the liver, spleen, and lungs and lower in the kidneys and brain. The relationship of amphotericin B tissue concentration to its biological activity is unknown.
-Special Populations
Renal Impairment
Amphotericin B is poorly hemodialyzable.
Pediatrics
Neonates
The pharmacokinetics of amphotericin B lipid complex appear to be similar to those of adults based on limited pharmacokinetic data available in neonates. In a population pharmacokinetic study in 28 neonates (mean gestational age 27 weeks, range 24 to 41 weeks), the final parameter estimates for clearance, volume of distribution, and elimination half-life were 0.399 L/hr/kg, 10.5 L/kg, and 395 hours, respectively. These values were similar to those reported in adults (0.27 to 0.41 L/hr/kg; 12.4 L/kg, and 395 hours, respectively); however, the clearance observed in neonates was approximately twice as high as that observed in children 1 year or older (0.218 L/hr/kg).
Children and Adolescents
There are limited pharmacokinetic data available in children; however, the pharmacokinetics of amphotericin B lipid complex are not expected to be different in children compared with adults. The mean clearance reported from pharmacokinetic data from 3 children was 0.218 L/hr/kg.