This monograph discusses amphotericin B liposomal injection (LAmB); 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 liposomal injection (AmBisome, LAmB) was the last of three lipid amphotericin B preparations approved in the US. LAmB is amphotericin B intercalated into a unilamellar bilayer liposomal membrane that has a diameter of less than 100 nm and consists of hydrogenated soy phosphatidylcholine (HSPC), cholesterol, distearoylphosphatidylglycerol, and alpha tocopherol. Incorporating amphotericin B into a liposomal membrane decreases the toxicity and alters the pharmacokinetic properties of the drug without diminishing its efficacy. In studies involving patients with persistent fever and neutropenia, LAmB showed comparable success rates with fewer adverse events when compared to conventional amphotericin B. Similarly, in studies of AIDS patients with Cryptococcus and Histoplasma capsulatum infections, treatment with LAmB resulted in equivalent success rates and fewer adverse events when compared to conventional amphotericin B. LAmB is approved for empirical therapy in febrile, neutropenic patients with presumed fungal infections; for the treatment of Cryptococcal meningitis in HIV infected patients; for the treatment of patients with Aspergillus, Candida, or Cryptococcus species infections refractory to conventional amphotericin B or in patients where renal impairment or unacceptable toxicity precludes the use of conventional amphotericin B; and for the treatment of visceral leishmaniasis. LAmB was originally FDA approved in August 1997.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Amphotericin B liposomal (LAmB) is not dosed the same as conventional amphotericin B (amphotericin B deoxycholate) or other lipid formulations. 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
-Visually inspect parenteral products for particulate matter and discoloration prior to administration. After reconstitution, liposomal amphotericin B is a yellow, translucent suspension.
Intravenous Administration
Reconstitution
-Add 12 mL of Sterile Water for Injection, USP to each vial to yield a 4 mg/mL suspension. Do not reconstitute with saline, add saline to the reconstituted suspension, or mix with other medications. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause a precipitate to form.
-Immediately after adding the Sterile Water for Injection, shake the vial vigorously for 30 seconds to completely disperse the product. The suspension should be yellow and translucent. Visually inspect vial for particulate matter and continue shaking until completely dispersed.
-Storage: The reconstituted product may be stored for up to 24 hours at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze.
Dilution
-Calculate the amount of reconstituted suspension to be further diluted and withdraw this amount into a sterile syringe.
-Attach the provided 5-micron filter to the syringe; inject the syringe contents through the filter, into the appropriate amount of 5% Dextrose Injection. Use only 1 filter per vial.
-The suspension must be diluted with 5% Dextrose Injection to a final concentration of 1 to 2 mg/mL before administration. For infants and small children, lower concentrations (0.2 to 0.5 mg/mL) may be appropriate to provide sufficient volume for infusion.
--ISMP Recommended Standard Concentration for Neonates: 1 mg/mL
-Storage: Begin injection within 6 hours of dilution.
Intermittent IV infusion
-Flush existing intravenous line with 5% Dextrose Injection before infusion. If this is not feasible, infuse through a separate line.
-An in-line membrane filter may be used provided the mean pore diameter of the filter is not less than 1 micron.
-Administer by intravenous infusion using a controlled infusion device over approximately 120 minutes. May reduce infusion time to approximately 60 minutes in patients who tolerate the infusion. If the patient experiences discomfort during infusion, the duration of infusion may be increased.
Anaphylaxis, anaphylactoid reactions, and angioedema have been reported rarely in patients receiving amphotericin B liposomal injection (LAmB). 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 liposomal injection (LAmB) is associated with a lower risk of nephrotoxicity (0-19%) 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, hyposthenuria, nephrolithiasis (specifically nephrocalcinosis), 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 LAmB may attenuate the process. Azotemia can develop after only a few doses. Although renal function can return to baseline in several days if LAmB 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 LAmB-induced nephrotoxicity than those with lower concentrations. Azotemia (7.4-21%), increased serum creatinine (14-47%), hypokalemia (6.7-51.1%), hypomagnesemia (15.3-48.9%), hyponatremia (8.5-11.6%), hypernatremia (4.1%), and hypocalcemia (4.9-18.4%) have been reported in patients receiving LAmB. Other electrolyte disturbances that were reported in 2-10% of patients include hyperchloremia, hyperkalemia, hypermagnesemia, hyperphosphatemia, and hypophosphatemia. Other adverse renal effects reported in patients receiving LAmB include acute renal failure (unspecified) (2-10%), anuria, decreased renal function, dysuria (2-10%), hematuria (14%), toxic nephropathy (2-10%), and urinary incontinence (2-10%). Cases of hemorrhagic cystitis have been observed during the post-marketing period. Additionally, nephrogenic diabetes insipidus has been reported in association with LAmB in a critically ill bone marrow transplant recipient being treated for fungal pneumonia. Patient management should involve laboratory monitoring of renal function and serum electrolytes (particularly potassium and magnesium serum concentrations).
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 26.7-47.9% of patients receiving amphotericin B liposomal injection (LAmB). Other hematologic effects experienced by LAmB recipients include coagulopathy (2-10%), bleeding (e.g., vaginal bleeding) (2-10%), decreased and increased prothrombin times (2-10%), ecchymosis (2-10%), leukopenia (15.1-17%), petechiae (2-10%), and thrombocytopenia (5.8-12.8%). Cases of agranulocytosis were reported during the post-marketing period. Due to the voluntary nature of post-marketing reports, neither a frequency nor a definitive causal relationship can be established.
Intravenous administration of amphotericin B liposomal injection (LAmB) can cause an injection site reaction that includes symptoms such as pain and inflammation at the injection site (2-10%). During clinical trials, phlebitis developed in 9.3-10.6% of LAmB infusion recipients. Cases of erythema, potentially related to infusion, have been observed during the post-marketing period. Due to the voluntary nature of post-marketing reports, neither a frequency nor a definitive causal relationship can be established. Take precautions to avoid extravasation as this may result in local irritation.
Gastrointestinal (GI) adverse reactions, such as abdominal enlargement (2-10%), abdominal pain (7-19.8%), anorexia (9.6-14%), diarrhea (10.5-30.3%), dyspepsia (2-10%), dysphagia (2-10%), constipation (14.9-15.1%), eructation (2-10%), fecal incontinence (2-10%), GI bleeding (9.9%), gingival bleeding (2-10%), hematemesis (2-10%), hemorrhoids (2-10%), flatulence (2-10%), ileus (2-10%), mucositis (2-10%), nausea (16.3-39.7%) and vomiting (10.5-31.8%) (in addition to the nausea/vomiting caused by infusion of amphotericin B liposomal injection, LAmB), stomatitis (2-10%), and xerostomia (2-10%), have occurred in recipients of LAmB during clinical trials.
Infusion-related reactions have been reported with the administration of amphotericin B liposomal injection (LAmB). Infusion-related reactions are toxicities occurring during or shortly after administration of LAmB and include symptoms such as nausea/vomiting (8-14%/4-16%), chills and rigors (6-48.1%), fever (7-23.5%), increased and decreased blood pressure (2.3-8.6% and 3.5%, respectively), tachycardia (2.3-9.9%), shortness of breath (4.7-9.9%), decreased oxygenation (0.3-1.2%), and hyperventilation (1.2%). The severity with which these reactions occur is usually most intense during the first administration and decreases 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 is lower following administration of LAmB than with conventional amphotericin B. In a large, double-blind study of adult and pediatric febrile neutropenic patients, infusion-related reactions occurred less often with the first dose of LAmB (6-18%) than with the first dose of conventional amphotericin B (8-54%). There have been a few reports of patients experiencing flush, pain in the back (with or without chest tightness), and chest pain within a few minutes after initiation of IV infusions of LAmB. These reactions were occasionally severe but disappeared when the infusion was stopped. 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.
Respiratory adverse reactions that have been reported during clinical trials with amphotericin B liposomal injection include asthma (2-10%), atelectasis (2-10%), increased cough (2.1-17.8%), dyspnea (4.7-23%), epistaxis (8.6-14.9%), hemoptysis (2-10%), hiccups (2-10%), hypoxia (0.3-7.6%), nasal dryness (2-10%), pulmonary edema (2-10%), respiratory alkalosis (2-10%), respiratory failure (2-10%), and rhinitis (11.1%). In addition, in patients receiving leukocyte infusions with amphotericin B, pulmonary toxicity has been reported. Cases of pulmonary edema, bronchospasm, and hypoventilation with cyanosis have been reported during the post-marketing period. Due to the voluntary nature of post-marketing reports, neither a frequency nor a definitive causal relationship can be established.
The most common cardiovascular adverse reactions reported during clinical trials with amphotericin B liposomal (LAmB) injection included chest pain (unspecified) (8.2-12%), edema (12.3-14.3%), hypertension (2.3-19.8%), hypotension (3.5-14.3%), hypervolemia (8.2-12.2%), peripheral edema (14.6%), pleural effusion (12.5%), and sinus tachycardia (2.3-18.5%). Other adverse reactions reported by 2-10% of LAmB recipients included arrhythmia exacerbation, atrial fibrillation, bradycardia, cardiac arrest, fluid retention, flushing, cardiomegaly, orthostatic hypotension, peripheral vasodilation, valvular heart disease, and vascular disorder.
Hepatotoxicity has been associated with amphotericin B liposomal injection (LAmB) treatment. During clinical trials, elevated hepatic enzymes and cases of hyperbilirubinemia developed in 4.3-14.6 and 8.5-18.1% of patients, respectively. Other hepatic adverse events experienced by 2-10% of LAmB recipients included hepatocellular damage, hepatomegaly, and hepatic veno-occlusive disease (VOD). Health care providers are advised to monitor the hepatic function of patients receiving LAmB therapy.
The most common neurologic adverse reactions associated with amphotericin B liposomal injection (LAmB) therapy include anxiety (7.4-13.7%), asthenia (6.2-13.1%), confusion (8.6-11.4%), dizziness (7-8.5%), headache (9.4-19.8%), and insomnia (17-22.1%). Other neurologic adverse events experienced by 2-10% of LAmB recipients include abnormal thinking, agitation, coma, depression, dysesthesia, drowsiness, hallucinations, malaise, nervousness, paresthesias, seizures, and tremor.
During amphotericin B liposomal injection (LAmB) clinical trials, the most frequently reported dermatologic adverse events included hyperhidrosis (7%), pruritus (10.8%), and rash (unspecified) (4.7-24.8%). Other dermatologic adverse events experienced by 2-10% of LAmB recipients included alopecia, bullous rash, purpura, maculopapular rash, vesicular rash, skin discoloration, skin ulcer, urticaria, and xerosis.
Generalized pain and back pain were experienced by 14% and 12%, respectively, of amphotericin B liposomal injections (LAmB) recipients during clinical trials. Other musculoskeletal adverse events occurring in 2-10% of patients treated with LAmB included arthralgia, bone pain, dystonic reaction, myalgia, and neck pain. Rhabdomyolysis was reported during the post-marketing period. Due to the voluntary nature of post-marketing reports, neither a frequency nor a definitive causal relationship can be established.
Ophthalmic adverse events experienced by 2-10% of amphotericin B liposomal injection (LAmB) recipients during clinical trials included conjunctivitis, ocular hemorrhage, and xerophthalmia.
Infections developed in 11.1-12.8% of amphotericin B liposomal injection (LAmB) recipients during clinical trials. Specific infection type/sites included cellulitis (2-10%), herpes simplex (2-10%), influenza-like symptoms (2-10%), pharyngitis (2-10%), pneumonia (2-10%), sepsis (12.9-14%), and sinusitis (2-10%). Other immunologic reactions experienced by patients receiving treatment with LAmB included blood product transfusion reactions (10.6-18.4%), cell mediated immunological reactions (2-10%), and graft versus host disease (2-10%).
Metabolic adverse events experienced by recipients of amphotericin B liposomal injection (LAmB) during clinical trials included elevated alkaline phosphatase (7.1-22.2%), elevated lactate dehydrogenase, elevated nonprotein nitrogen (2-10%), elevated amylase (2-10%), hyperglycemia (8.2-23%), hypoproteinemia (2-10%), and metabolic acidosis (2-10%).
Amphotericin B liposomal injection (LAmB) is contraindicated in patients with a known hypersensitivity to amphotericin B or any other component in the formulation. Anaphylaxis has been reported with LAmB; thus, administer LAmB only under close observation by medically trained personnel. If a severe anaphylactic reaction occurs during administration of LAmB, 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 LAmB, exercise caution to prevent inadvertent overdose; if an overdose occurs, discontinue therapy and administer supportive measures. In addition, acute pulmonary toxicity has been reported in patients receiving amphotericin B and leukocyte transfusions; concomitant use of leukocyte transfusions and LAmB should be avoided.
Administer amphotericin B liposomal injection (LAmB) with caution to patients with preexisting renal impairment or renal failure. Although LAmB has an improved safety profile when compared to conventional amphotericin B, nephrotoxicity can still develop. In clinical trials the incidence of renal toxicity, defined as a 100% increase in baseline serum creatinine, ranged from 0-19% for doses of LAmB of 1-5 mg/kg/day. The incidence of renal toxicity for conventional amphotericin B in the same studies ranged from 12-64% for doses of 0.6-1 mg/kg/day. According to the manufacturer, LAmB has been successfully administered to patients with preexisting renal disease; no dose adjustment recommendations are given. Renal function should be monitored during LAmB therapy.
Amphotericin B liposomal injection (LAmB) 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 LAmB therapy.
Amphotericin B liposomal injection (LAmB) is known to cause anemia, leukopenia, and thrombocytopenia; administer the drug with caution in patients with preexisting hematological disease including patients with preexisting anemia, leukopenia, and thrombocytopenia. In addition, monitor CBC and platelets during LAmB therapy. A clinical study of LAmB therapy in cryptococcal meningitis patients demonstrated an increased incidence of anemia, leukopenia, and thrombocytopenia as the dose was increased from 3 mg/kg/day to 6 mg/kg/day.
Use caution when administering amphotericin B liposomal injection (LAmB) to patients with an electrolyte imbalance including hypokalemia, hypomagnesemia, hypocalcemia, and hyponatremia. Serum electrolyte abnormalities may occur after administration of LAmB. Monitor serum electrolytes during LAmB treatment.
Administer amphotericin B liposomal injection (LAmB) with caution to patients with preexisting cardiac disease including patients with preexisting tachycardia, hypotension, and hypertension. In clinical studies patients have experienced chest pain, tachycardia, hypotension, and hypertension after LAmB infusions.
The pharmacokinetic properties of amphotericin B liposomal injection (LAmB) 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 LAmB in dosages similar to those used in younger patients. Closely monitor the use of LAmB in elderly patients.
Amphotericin B liposomal injection (LAmB) has been used effectively to treat systemic fungal infections in infants, children, and adolescents 1 month to 16 years. No unusual adverse effects have been reported in pediatric patients who have received LAmB. Safety and efficacy of LAmB in neonates younger than 1 month of age have not been established; however, LAmB has been used for some infections in this population.
There have been no adequate and well-controlled studies of amphotericin B liposomal in human pregnancy. Systemic fungal infections have been successfully treated in pregnant women with amphotericin B deoxycholate; however, the number of reported cases is small. Animal studies in rats and rabbits have concluded that amphotericin B liposomal had no teratogenic potential in these species. Rabbits receiving amphotericin B liposomal doses of 0.5- to 2-times the recommended human dose experienced a higher rate of spontaneous abortions compared to control groups.
It is not known whether amphotericin B liposomal is excreted in human milk. Because of the potential for serious adverse reactions in breast-fed infants, discontinue breast-feeding or discontinue amphotericin B liposomal, taking into account the importance of the drug to the mother. Fluconazole and 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.
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 flavus, Aspergillus fumigatus, Aspergillus sp., Blastomyces dermatitidis, Candida albicans, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida sp., Candida tropicalis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, Leishmania infantum, Paracoccidioides brasiliensis
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.
This drug may also have activity against the following microorganisms: Talaromyces marneffei
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
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: 3 to 5 mg/kg/dose IV every 24 hours. Guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when voriconazole is contraindicated or not tolerated. 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: 3 to 5 mg/kg/dose IV every 24 hours. Guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when voriconazole is contraindicated or not tolerated. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Neonates*: 3 to 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when voriconazole is contraindicated or not tolerated. 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 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 to 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 Candida sp. in patients refractory to or intolerant of amphotericin B deoxycholate:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours. Guidelines suggest 5 mg/kg/dose IV every 24 hours as an alternative to amphotericin B deoxycholate with or without flucytosine. May use fluconazole as step-down therapy after achieving response to initial therapy. Continue treatment until all signs and symptoms and cerebrospinal fluid (CSF) and radiologic abnormalities have resolved. Remove intraventricular devices.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours. Guidelines suggest 5 mg/kg/dose IV every 24 hours as an alternative to amphotericin B deoxycholate with or without flucytosine. May use fluconazole as step-down therapy after achieving response to initial therapy. Continue treatment until all signs and symptoms and cerebrospinal fluid (CSF) and radiologic abnormalities have resolved. Remove intraventricular devices.
Neonates*: 3 to 5 mg/kg/dose IV every 24 hours. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic candidiasis. In general, concurrent flucytosine therapy is not routinely recommended in neonates but may be considered as salvage therapy in patients who do not respond to initial amphotericin therapy. Continue treatment until all signs and symptoms and cerebrospinal fluid (CSF) and radiologic abnormalities have resolved. Remove intraventricular devices.
-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. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic 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 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
-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 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 a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Neonates*: 3 to 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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 and chorioretinitis, in patients refractory to or intolerant of amphotericin B deoxycholate:
-for the treatment of Candida endophthalmitis and chorioretinitis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours with or without flucytosine. Clinical practice guidelines suggest liposomal amphotericin B as alternative therapy for fluconazole- or voriconazole-resistant strains. With macular involvement or vitritis, intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions.
Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours with or without flucytosine. Clinical practice guidelines suggest liposomal amphotericin B as alternative therapy for fluconazole- or voriconazole-resistant strains. With macular involvement or vitritis, intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions.
Neonates*: 3 to 5 mg/kg/dose IV every 24 hours. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic 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. With macular involvement or vitritis, intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions.
-for the treatment of Aspergillus endophthalmitis:
Intravenous dosage:
Adults: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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*: 3 to 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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 refractory to or intolerant of amphotericin B deoxycholate:
-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. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic 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 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: 3 to 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: 3 to 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.
Neonates*: 3 to 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 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. In cases where pneumonia is associated with disseminated infection, 3 to 5 mg/kg/dose IV every 24 hours. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic 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: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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: 3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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*: 3 to 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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 Candida intraabdominal infections:
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. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic 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 bone and joint infections, including osteomyelitis and infectious arthritis, in patients 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 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 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. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic 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: 3 to 5 mg/kg/dose IV every 24 hours as initial and salvage therapy when triazoles are contraindicated or not tolerated. 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: 3 to 5 mg/kg/dose IV every 24 hours as initial and salvage therapy when triazoles are contraindicated or not tolerated. 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*: 3 to 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest a lipid formulation amphotericin B for initial and salvage therapy when triazoles are contraindicated or not tolerated. 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:
Intravenous dosage:
Adults: 3 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: 3 mg/kg/dose IV every 24 hours. In a study of 82 children, liposomal amphotericin B doses were increased to 5 mg/kg/day after 5 days of persistent fever and inadequate clinical response. 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 fungal prophylaxis* (e.g., candidiasis prophylaxis*, aspergillosis prophylaxis*) in high-risk patients:
-in patients undergoing solid organ or hematopoietic stem cell transplantation:
Intravenous dosage:
Infants, Children, and Adolescents: Various regimens may be used depending on local protocols; 1 to 2 mg/kg/dose IV every 24 hours is common. A treatment duration of 5 days has been used for patients immediately after liver transplantation. For hematopoietic stem cell transplant (HSCT) recipients, prophylaxis has been given during the neutropenic phase after HSCT and until neutrophil recovery (median, 14 days). Higher doses (3 mg/kg/day for first 100 days after transplantation) have also been reported in HSCT recipients.
-in patients with malignancy and not undergoing a hematopoietic stem cell transplantation:
Intravenous dosage:
Infants, Children, and Adolescents: 2.5 mg/kg/dose IV twice weekly.
For the treatment of CNS cryptococcal infections, including cryptococcal meningitis and cerebral cryptococcomas:
NOTE: LAmB has been designated an orphan drug by the FDA for this indication.
-Persons living with HIV:
Intravenous dosage:
Adults: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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 at 4 to 6 mg/kg/dose IV every 24 hours until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 6 mg/kg/dose IV every 24 hours.
Adolescents: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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 at 4 to 6 mg/kg/dose IV every 24 hours until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 6 mg/kg/dose IV every 24 hours.
Infants and Children: 6 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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*: 6 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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 cryptococcal infection, reinstate induction therapy for 4 to 10 weeks; may consider 6 mg/kg/dose IV every 24 hours for persistent or high-burden disease or relapse. 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, liposomal amphotericin B 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 cryptococcal infection, 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 liposomal amphotericin B in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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 cryptococcal infection, 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: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as an alternative induction therapy for patients who are intolerant of amphotericin B deoxycholate. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If liposomal amphotericin B is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, 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 4 weeks as an alternative induction therapy for patients who are intolerant of amphotericin B deoxycholate. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If liposomal amphotericin B is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, 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 liposomal amphotericin B in combination with flucytosine for at least 4 weeks as an alternative induction therapy for patients who are intolerant of amphotericin B deoxycholate. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If liposomal amphotericin B is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, 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 disseminated (nonmeningeal) or pulmonary cryptococcosis:
NOTE: LAmB has been designated an orphan drug by the FDA for this indication.
NOTE: For the treatment of CNS infections, see cryptococcal meningitis.
-Persons living with HIV:
Intravenous dosage:
Adults: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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 at 4 to 6 mg/kg/dose IV every 24 hours until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 3 to 5 mg/kg/dose IV every 24 hours.
Adolescents: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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 at 4 to 6 mg/kg/dose IV every 24 hours until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 3 to 5 mg/kg/dose IV every 24 hours.
Infants and Children: 3 to 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*: 3 to 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: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B may also 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; may consider 6 mg/kg/dose IV every 24 hours for persistent or high-burden disease or relapse. Follow induction therapy with consolidation therapy for at least 8 weeks with fluconazole, and then chronic suppressive therapy. The FDA-approved dosage is 3 to 5 mg/kg/dose IV every 24 hours.
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, liposomal amphotericin B 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. The FDA-approved dosage is 3 to 5 mg/kg/dose IV every 24 hours.
Neonates*: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest liposomal amphotericin B in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, liposomal amphotericin B 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: 3 to 4 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as an alternative induction therapy for patients who are intolerant of amphotericin B deoxycholate. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If liposomal amphotericin B is given as a single agent for patients unable to tolerate flucytosine, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcal infection, 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. The FDA-approved dosage is 3 to 5 mg/kg/dose IV every 24 hours.
Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as an alternative induction therapy for patients who are intolerant of amphotericin B deoxycholate. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If liposomal amphotericin B is given as a single agent for patients unable to tolerate flucytosine, 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. The FDA-approved dosage is 3 to 5 mg/kg/dose IV every 24 hours.
Neonates*: 5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest liposomal amphotericin B in combination with flucytosine for at least 4 weeks as an alternative induction therapy for patients who are intolerant of amphotericin B deoxycholate. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If liposomal amphotericin B is given as a single agent for patients unable to tolerate flucytosine, 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 moderately severe to severe blastomycosis*:
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.
-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.
-for the treatment of blastomycosis* in immunosuppressed patients:
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. Lifelong suppressive therapy may be required.
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.
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*:
NOTE: LAmB has been designated an orphan drug by the FDA for this indication.
NOTE: For CNS infections, see meningitis indication.
-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 liposomal amphotericin B as alternate therapy in patients unable to tolerate amphotericin B deoxycholate.
-for the treatment of disseminated histoplasmosis:
Intravenous dosage:
Adults: 3 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for at least 12 months. 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 liposomal amphotericin B as a preferred treatment.
Adolescents: 3 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for at least 12 months. 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 liposomal amphotericin B as a preferred treatment.
Infants and Children: 3 to 5 mg/kg/dose IV every 24 hours for at least 2 weeks or longer if clinical improvement is delayed. Continue step-down therapy with itraconazole for 12 months for HIV-infected children. If itraconazole is not tolerated, liposomal amphotericin B may be given alone for 4 to 6 weeks. While liposomal amphotericin B is preferred treatment in HIV-infected children, guidelines suggest amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.
For the treatment of leishmaniasis:
NOTE: LAmB has been designated an orphan drug by the FDA for this indication.
-for the treatment of cutaneous leishmaniasis*:
Intravenous dosage:
Adults: 3 mg/kg/dose IV every 24 hours on days 1 through 5 and on day 10 or on days 1 through 7 for a cumulative total of 18 to 21 mg/kg.
HIV-infected Adults: 2 to 4 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. Chronic maintenance therapy may be indicated in immunocompromised patients with multiple relapses.
Adolescents: 3 mg/kg/dose IV every 24 hours on days 1 through 5 and on day 10 or on days 1 through 7 for a cumulative total of 18 to 21 mg/kg.
HIV-infected Adolescents: 2 to 4 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. Chronic maintenance therapy may be indicated in immunocompromised patients with multiple relapses.
Infants and Children: 3 mg/kg/dose IV every 24 hours on days 1 through 5 and on day 10 or on days 1 through 7 for a cumulative total of 18 to 21 mg/kg.
-for the treatment of mucosal leishmaniasis*:
Intravenous dosage:
Adults: 3 mg/kg/dose IV every 24 hours for a cumulative total of 20 to 60 mg/kg.
Infants, Children, and Adolescents: 3 mg/kg/dose IV every 24 hours for a cumulative total of 20 to 60 mg/kg.
-for the treatment of visceral leishmaniasis:
Intravenous dosage:
Immunocompetent Adults: 3 mg/kg/dose IV on days 1, 2, 3, 4, 5, 14, and 21, for a cumulative total of 21 mg/kg as preferred therapy. For patients who do not achieve parasitic clearance with the recommended dose, repeating the course of therapy may be useful; higher doses or a longer course may be considered. Other regimens with a total dose of 18 to 21 mg/kg have been used effectively. For patients who acquired the infection in East Africa, total doses of 40 mg/kg or more may be needed.
Immunocompromised Adults: 4 mg/kg/dose IV on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38, or 2 to 4 mg/kg/dose IV every 24 hours for 10 days, for a cumulative total of 20 to 60 mg/kg, as preferred therapy. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended; higher doses or a longer course may be considered. Combination therapy with miltefosine may be considered in HIV-infected patients with refractory cases. Chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is recommended in HIV-infected patients.
Immunocompetent Infants, Children, and Adolescents: 3 mg/kg/dose IV on days 1, 2, 3, 4, 5, 14, and 21, for a cumulative total of 21 mg/kg as preferred therapy. For patients who do not achieve parasitic clearance with the recommended dose, repeating the course of therapy may be useful; higher doses or a longer course may be considered. Other regimens with a total dose of 18 to 21 mg/kg have been used effectively. For patients who acquired the infection in East Africa, total doses of 40 mg/kg or more may be needed.
Immunocompromised Adolescents: 4 mg/kg/dose IV on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38, or 2 to 4 mg/kg/dose IV every 24 hours for 10 days, for a cumulative total of 20 to 60 mg/kg, as preferred therapy. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended; higher doses or a longer course may be considered. Combination therapy with miltefosine may be considered in HIV-infected patients with refractory cases. Chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is recommended in HIV-infected patients.
Immunocompromised Infants and Children: 4 mg/kg/dose IV on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38, or 2 to 4 mg/kg/dose IV every 24 hours for 10 days, for a cumulative total of 20 to 60 mg/kg, as preferred therapy. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended; higher doses or a longer course may be considered. Combination therapy with miltefosine may be considered in HIV-infected patients with refractory cases. Chronic maintenance therapy is recommended in HIV-infected patients.
For the treatment of talaromycosis* in HIV-infected patients:
Intravenous dosage:
Adults: 3 to 5 mg/kg/day IV for 2 weeks, then itraconazole for consolidation therapy and chronic suppressive therapy.
Adolescents: 3 to 5 mg/kg/day IV for 2 weeks, then itraconazole for consolidation therapy and chronic suppressive therapy.
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: 4 mg/kg/dose IV every 2 to 4 weeks 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: 4 mg/kg/dose IV every 2 to 4 weeks 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 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. Doses up to 7 mg/kg/dose IV every 24 hours have been successfully used in neonates with systemic candidiasis. 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.
Maximum Dosage Limits:
-Adults
6 mg/kg/day; 15 mg/kg/day IV has been administered with no reported dose-related toxicity in clinical trials.
-Geriatric
6 mg/kg/day; 15 mg/kg/day IV has been administered with no reported dose-related toxicity in clinical trials.
-Adolescents
6 mg/kg/day IV.
-Children
6 mg/kg/day IV.
-Infants
6 mg/kg/day IV.
-Neonates
Safety and efficacy have not been established; however, doses up to 7 mg/kg/day IV have been used off-label.
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
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; 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.
Amphotericin B, the active ingredient in amphotericin B liposomal injection (LAmB), 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 attributed 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.
In vitro activity of LAmB is comparable to conventional amphotericin B for the following organisms: Aspergillus fumigatus, Aspergillus flavus, Blastomyces dermatitidis, Candida albicans, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, and Cryptococcus neoformans. Although standardized susceptibility testing is available for yeast and some filamentous fungi, results do not necessarily correlate with clinical outcome. LAmB is not active against bacteria, Rickettsiae, or viruses.
Amphotericin B liposomal injection (LAmB) is administered intravenously; it cannot be given intramuscularly. Pharmacokinetic parameters for LAmB should not be used to predict the pharmacokinetics of any other amphotericin B formulation. The clinical relevance of pharmacokinetic differences between LAmB 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 LAmB is unknown. Excretion of amphotericin B after administration of LAmB has not been studied. The terminal elimination half-life of amphotericin B is longer after administration of the liposomal formulation (mean 4-6 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 following repeated dosing.
-Route-Specific Pharmacokinetics
Intravenous Route
The pharmacokinetics of amphotericin B liposomal injection (LAmB) after intravenous administration are nonlinear and vary substantially from conventional amphotericin B and from other lipid formulations. In general, plasma amphotericin B concentrations attained following administration of LAmB are higher and the volume of distribution is lower than those reported for similar doses of conventional amphotericin B.
Distribution of amphotericin B is multi-compartmental. Following IV administration of LAmB, the plasma serves as a reservoir with liposome-bound amphotericin B largely remaining in circulation. Amphotericin B is slowly cleared from the plasma via uptake by the reticuloendothelial system and by redistribution into other tissues. This clearance may become saturated as doses increase from 1 to 5 mg/kg/day resulting in greater than proportional increases in plasma concentrations. Tissue concentrations of LAmB, when compared to conventional amphotericin B, are higher in the liver and spleen and lower in the lungs and kidneys. In addition, LAmB has improved tissue penetration into the brain when compared to conventional amphotericin B and other lipid formulations. The relationship of amphotericin B tissue concentration to its biological activity is unknown.
-Special Populations
Renal Impairment
Amphotericin B is poorly hemodialyzable.
Pediatrics
Infants and Children
Very limited pharmacokinetic data in infants and children have revealed some differences in pharmacokinetic properties of liposomal amphotericin B between small children and adults. In a study (n = 14) of once-weekly high-dose liposomal amphotericin B (10 mg/kg/dose) for antifungal prophylaxis in infants and children (4.5 months to 9 years of age), volume of distribution (Vd) and clearance values were approximately 4.2 L/kg and 0.06 to 0.07 L/kg/hr, respectively, which are higher than those reported in adults. Vd and clearance were directly related to body weight. Elimination half-life was also shorter than that reported in adults (43 to 55 hours vs. 152 hours); however, in this study, the pharmacokinetics of the active portion of the drug were measured (non-lipid complexed amphotericin), which makes it difficult to compare with other pharmacokinetic data.