This drug should be used primarily for treatment of patients with progressive and potentially life-threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease such as oral thrush, vaginal candidiasis, and esophageal candidiasis in patients with normal neutrophil counts.
Exercise caution to prevent inadvertent overdose with amphotericin B. Verify the product name and dosage if dose exceeds 1.5 mg/kg.
Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (Abelcet, Amphotec, AmBisome) and conventional amphotericin B for injection; conventional amphotericin B for injection doses should not exceed 1.5 mg/kg/day. Although the manufacturer's labeling suggests a dose escalation approach; most expert recommendations initiate therapy at the target dose (Bradley 2016; Red Book [AAP 2015]).
General dosing, susceptible infections:
IV: 1 mg/kg/dose once daily (Bradley 2016; Red Book [AAP] 2015; Turkova 2011); rapidly progressing or severe disease may require higher doses up to 1.5 mg/kg/day for the short-term. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1 to 1.5 mg/kg/dose Note: Maintaining a sodium intake of >4 mEq/kg/day in premature neonates may reduce amphotericin B-associated nephrotoxicity (Turcu 2009)
Irrigation, bladder: Limited data available: 50 mcg/mL solution, administered as either a continuous irrigation or as an intermittent irrigation 3 times per day with a dwell time of 60 to 90 minutes; dosing based on two case reports in neonates [PNA at treatment: 3 weeks; 3 months (PCA: 42 weeks)] (Ku 2004; Martinez-Pajares 2010)
Intrathecal, intraventricular, or intracisternal (preferably into the lateral ventricles through a cisternal Ommaya reservoir): Limited data available; some dosing based on experience in older pediatric patients: 0.01 to 1 mg; frequency varies widely in the literature; administration has been reported as daily, every other day, and even twice weekly (Chiou 1994; Murphy 2000; IDSA [Pappas 2016]; Red Book [AAP 2015])
Blastomycosis, treatment: IV: 1 mg/kg/dose once daily (IDSA [Chapman 2008])
Candidiasis:
Invasive, treatment: IV: 1 mg/kg/dose once daily; treatment should continue for at least 2 weeks after the first negative blood culture and signs and symptoms have resolved (IDSA [Pappas 2016])
CNS infection: IV: 1 mg/kg/dose once daily; may add flucytosine if there is no clinical response (IDSA [Pappas 2016])
Urinary tract infections, asymptomatic (high-risk patients); treatment: IV: 1 mg/kg/dose once daily (IDSA [Pappas 2016])
Urologic procedures; prophylaxis in patients with candiduria: IV: 0.3 to 0.6 mg/kg/dose once daily for several days before and after procedure (IDSA [Pappas 2016])
Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (Abelcet, Amphotec, AmBisome) and conventional amphotericin B for injection; conventional amphotericin B for injection doses should not exceed 1.5 mg/kg/day
Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.
Test dose: Infants, Children, and Adolescents: IV: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 20 to 60 minutes; an alternative method to the 0.1 mg/kg test dose is to initiate therapy with 0.25 mg/kg amphotericin administered over 6 hours; frequent observation of the patient and assessment of vital signs during the first several hours of the infusion is recommended; many clinicians believe a test dose is unnecessary
General dosing, susceptible infections:
IV: Infants, Children, and Adolescents:
Initial: 0.25 to 0.5 mg/kg/dose once daily; gradually increase daily, usually in 0.25 mg/kg increments until the desired daily dose is reached (maximum daily dose: 1.5 mg/kg/day); in critically ill patients, more rapid dosage acceleration may be warranted (eg, ≥0.5 mg/kg daily dose increase); others have initiated at target dose for life-threatening infection (HHS [OI pediatric 2013])
Maintenance dose: 0.25 to 1 mg/kg/dose once daily; rapidly progressing disease may require short-term use of doses up to 1.5 mg/kg/day; once therapy has been established, amphotericin B may be administered on an every-other-day basis at 1 to 1.5 mg/kg/dose in some cases
Intrathecal, intraventricular, or intracisternal (preferably into the lateral ventricles through a cisternal Ommaya reservoir): Limited data available; dose variable: Infants, Children, and Adolescents: 0.01 to 1 mg; frequency varies widely in the literature; administration has been reported as daily, every other day and even twice weekly (Chiou 1994; IDSA [Pappas 2016]; Murphy 2000; Red Book [AAP 2015])
Irrigation, bladder: Infants, Children, and Adolescents: Limited data available: 50 mcg/mL solution, administered as either a continuous irrigation or as an intermittent irrigation 3 times daily with a dwell time of 60 to 90 minutes (Fisher 2011; Gubbins 1999); some experts have also recommended daily administration for 5 days for the treatment of cystitis due to fluconazole-resistant Candida species (C. glabrata, C. krusei) (IDSA [Pappas 2016])
Aspergillosis:
Prophylaxis, immunocompromised: Limited data available: Infants, Children, and Adolescents: Intranasal: 7 mg amphotericin B in 7 mL sterile water was placed in a De Vilbiss atomizer and the aerosolized solution was instilled intranasally to each nostril 4 times daily delivering an average of 5 mg amphotericin/day to reduce the frequency of invasive aspergillosis in neutropenic patients (Jeffery 1991)
Endocarditis: Children and Adolescents: IV: 1 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015])
Blastomycosis (independent of HIV status), moderately severe to severe disease: Infants, Children, and Adolescents: IV: 0.7 to 1 mg/kg/dose once daily as initial therapy for 1 to 2 weeks, followed with oral itraconazole for a total of 12 months (IDSA [Chapman 2008])
Candidiasis; treatment:
Invasive: Infants, Children, and Adolescents: IV: 0.5 to 1 mg/kg/dose once daily; duration of therapy dependent upon severity and site of infection (IDSA [Pappas 2016])
Endocarditis: Children and Adolescents: IV: 1 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015])
Esophageal:
Non-HIV-exposed/-infected: Infants, Children, and Adolescents: IV: 0.3 to 0.7 mg/kg/dose once daily; consider step down to an oral antifungal once patient is able to tolerate oral intake. In fluconazole-refractory disease, continue amphotericin B for 21 days (IDSA [Pappas 2016])
HIV-exposed/-infected:
Infants and Children: IV: 0.3 to 0.7 mg/kg/dose once daily (HHS [OI pediatric 2013])
Adolescents: IV: 0.6 mg/kg/dose once daily for 14 to 21 days (HHS [OI adult 2016])
Oropharyngeal, fluconazole-refractory:
Non-HIV-exposed/-infected: Infants, Children, and Adolescents: IV: 0.3 mg/kg/dose once daily (IDSA [Pappas 2016])
HIV-exposed/-infected:
Infants and Children: IV: 0.3 to 0.5 mg/kg/dose once daily (HHS [OI pediatric 2013])
Adolescent: IV: 0.6 mg/kg/dose once daily for 14 to 21 days (HHS [OI adult 2016])
Urinary tract infections (IDSA [Pappas 2016]):
Prophylaxis, urologic procedures in patients with candiduria: Infants, Children, and Adolescents: IV: 0.3 to 0.6 mg/kg/dose once daily for several days before and after procedure
Treatment:
Cystitis: Infants, Children, and Adolescents: IV:
Asymptomatic (high-risk patients): 1 mg/kg/dose once daily
Symptomatic (C. krusei or fluconazole-resistant C. glabrata): 0.3 to 0.6 mg/kg/dose once daily for 1 to 7 days
Pyelonephritis: Infants, Children, and Adolescents: IV: 0.3 to 0.6 mg/kg/dose once daily for 1 to 7 days; depending on organism, consider addition of flucytosine
Coccidioidomycosis:
Non-HIV-exposed/-infected (IDSA [Galgiani 2005]): Infants, Children, and Adolescents:
Disseminated (non-CNS) disease: IV 0.5 to 1.5 mg/kg/dose every day or every other day; with or without concomitant azole antifungal; duration determined by clinical response
CNS disease: Intrathecal: 0.1 to 1.5 mg/dose; frequency ranging from daily to weekly (with or without concomitant azole therapy); initiate at a low dose and increase until intolerance is noted (eg, severe vomiting, exhaustion, or transient dose-related mental status changes); duration determined by clinical response
Pulmonary disease, diffuse: IV 0.5 to 1.5 mg/kg/dose every day or every other day for several weeks, followed by an oral azole antifungal for a total length of therapy ≥12 months
HIV-exposed/-infected: Disseminated (non-CNS) disease, diffuse pulmonary disease; severely ill:
Infants and Children: IV: 0.5 to 1 mg/kg/dose once daily until clinical improvement; minimum of several weeks of therapy (HHS [OI pediatric 2013])
Adolescents: IV: 0.7 to 1 mg/kg/dose once daily until clinical improvement, then initiate triazole therapy (eg, fluconazole or itraconazole) (HHS [OI adult 2016])
Cryptococcal disease:
CNS disease:
Non-HIV-exposed/-infected: Infant, Children, and Adolescents: IV: 0.7 to 1 mg/kg/dose once daily plus flucytosine; Note: Minimum 2- to 4-week induction, followed by consolidation and chronic suppressive therapy; may increase amphotericin dose to 1.5 mg/kg/day if flucytosine is not tolerated (IDSA [Perfect 2010])
HIV-exposed/-infected:
Infants and Children: IV: 1 mg/kg/dose once daily plus flucytosine or fluconazole; Note: Minimum 2-week induction, followed by consolidation and chronic suppressive therapy; a longer duration of induction therapy may be necessary if CSF is not negative or lack of clinical improvement; may increase amphotericin dose to 1.5 mg/kg/day alone or in combination with fluconazole if flucytosine is not tolerated (HHS [OI pediatric 2013])
Adolescents: IV: 0.7 to 1 mg/kg/dose once daily with or without flucytosine or fluconazole; Note: Minimum 2-week induction, followed by consolidation and chronic suppressive therapy (HHS [OI adult 2016])
Disseminated (non-CNS disease) or severe pulmonary disease: Independent of HIV status: Infants, Children, and Adolescents: IV: 0.7 to 1 mg/kg/dose once daily with or without flucytosine; duration of therapy depends on the site and severity of the infection and clinical response (HHS [OI adult 2016]; HHS [OI pediatric 2013]; IDSA [Perfect 2010])
Histoplasmosis:
Non-HIV-exposed/-infected: Severe disseminated (non-CNS) or pulmonary disease: Infants, Children, and Adolescents: IV: 0.7 to 1 mg/kg/dose once daily; Note: Minimum 1- to 2-week induction, followed by consolidation therapy (IDSA [Wheat 2007])
HIV-exposed/-infected: CNS or severe disseminated disease: Infants and Children: IV: 0.7 to 1 mg/kg/dose once daily, followed by consolidation therapy (HHS [OI pediatric 2013])
Duration of induction:
Severe or moderately severe pulmonary disease: 1 to 2 week minimum
Disseminated or clinical improvement delayed: ≥2 weeks
CNS involvement: 4 to 6 weeks
Leishmaniasis, visceral, HIV-exposed/-infected: Adolescents: IV: 0.5 to 1 mg/kg/dose once daily for a total cumulative dose of 1,500 to 2,000 mg (HHS [OI adult 2016])
Peritonitis (CAPD): Limited data available: Note: Amphotericin B has demonstrated poor peritoneal penetration when given systemically and intraperitoneal administration is associated with abdominal pain and peritoneal irritation; other agents may be preferred (ISPD [Warady 2012]).
Intraperitoneal, dialysate: Infants, Children, and Adolescents: 1 to 4 mg per liter of dialysate has been used in pediatric patients based on case reports and retrospective reviews (Hogg 1982; Kravitz 1986; Raaijmakers 2007; Warady 2000a); lower doses of 0.5 to 3 mg per liter of dialysate has been reported in adults (with or without concomitant systemic amphotericin B therapy); abdominal pain has been associated with doses ≥2 mg per liter of dialysate (Bastani 1986; Johnson 1985).
IV: Infants, Children, and Adolescents: 1 mg/kg/dose once daily (ISPD [Warady 2000b])
Sporotrichosis, severe infection (IDSA [Kauffman 2007]): Children and Adolescents: 0.7 mg/kg/dose once daily; followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy
Infants, Children, and Adolescents:
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. IV therapy may take several months.
Renal replacement therapy: Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis or CRRT.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Amphotericin B deoxycholate (conventional): Drug information")
Note: Conventional amphotericin formulations (deoxycholate [Amphocin, Fungizone]) may be confused with lipid-based formulations (AmBisome, Abelcet, Amphotec). Lipid-based and conventional formulations are not interchangeable and have different dosage recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.
Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: NSAID and/or diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.
Test dose: IV: 1 mg infused over 20 to 30 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: IV: Adults: 0.3 to 1.5 mg/kg/day; 1 to 1.5 mg/kg over 4 to 6 hours every other day may be given once therapy is established; aspergillosis, rhinocerebral mucormycosis, often require 1 to 1.5 mg/kg/day; do not exceed 1.5 mg/kg/day.
Aspergillosis, disseminated: IV: 0.6 to 0.7 mg/kg/day for 3 to 6 months. Note: IDSA recommends amphotericin B (conventional) be reserved for use in resource limited settings when no alternatives are available; voriconazole is preferred therapy for invasive Aspergillus infections (IDSA [Patterson 2016]).
Aspergillosis (ocular) (off-label use): Ophthalmic:
Intraocular: Inject 5 to 10 mcg in a 0.1 mL volume as a single dose intravitreally or intracamerally to the affected eye; may be repeated in 4 to 7 days as clinically indicated (Kaushik 2001; Patterson 2016). Guidelines recommend concomitant vitrectomy and use in combination with systemic voriconazole (Patterson 2016).
Topical (0.1% to 0.2% solution): Apply to affected eye every 30 to 60 minutes until symptoms resolve (may take weeks) (Kaushik 2001; Ritterband 2002; Tamcelik 2002). Note: Ophthalmic natamycin is the preferred treatment (Patterson 2016).
Blastomycosis: Moderately severe to severe pulmonary disease, disseminated extrapulmonary disease or immunosuppressed patients: IV: 0.7 to 1 mg/kg/day for 1 to 2 weeks or until improvement is noted, followed by oral itraconazole for 6 to 12 months (IDSA [Chapman 2008]).
Candidiasis:
CNS infection (failed to respond to systemic therapy and device removal or when ventricular device cannot be removed) (off-label): Intraventricular: 0.01 to 0.5 mg/2 mL of an extemporaneously prepared solution in D5W administered through the device into the ventricle (IDSA [Pappas 2016]; IDSA [Tunkel 2017]).
Endophthalmitis due to Candida (off-label use): Patients with vitritis or with macular involvement (with or without vitritis): Intravitreal: 5 to 10 mcg/0.1 mL of an extemporaneously prepared solution in sterile water; administer with concomitant systemic antifungal therapy (IDSA [Pappas 2016]).
Esophageal, refractory disease (alternative agent) (off-label use):
Note: Reserve use for patients who have inadequate response to or who are unable to take other agents (Kauffman 2021a).
IV: 0.3 to 0.7 mg/kg/day. Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (HHS [OI adult 2021]; IDSA [Pappas 2016]; Kauffman 2021a).
Invasive candidiasis (alternative therapy): IV: 0.5 to 0.7 mg/kg/day; dose may be increased to as high as 1 mg/kg/day for infections caused by C. glabrata or C. krusei. Note: Given poor tolerability (eg, nephrotoxicity, infusion-related toxicity), experts preferentially recommend lipid formulations when available (IDSA [Pappas 2016]).
Oropharyngeal, refractory disease (alternative agent) (off-label use):
Note: Reserve use for patients who have inadequate response to or who are unable to take other agents (Kauffman 2021b).
Oral: 500 mg of an extemporaneously compounded 100 mg/mL suspension 3 to 4 times daily for 14 to 28 days; swish in the mouth and retain for as long as possible (several minutes) before swallowing (Fichtenbaum 2000; IDSA [Pappas 2016]; Kauffman 2021b; Talliandier 2000).
Urinary tract candidiasis (off-label use):
Asymptomatic candiduria in patients undergoing urologic procedures: IV: 0.3 to 0.6 mg/kg daily for several days before and after the procedure (IDSA [Pappas 2016]).
Fungus balls: Irrigation via nephrostomy tubes (off-label route): Irrigate with an extemporaneously prepared solution of 25 to 50 mg in 200 to 500 mL sterile water (final concentration range: 0.05 to 0.25 mg/mL) (IDSA [Pappas 2016]).
Pyelonephritis: C. krusei or fluconazole-resistant C. glabrata: IV: 0.3 to 0.6 mg/kg/day for 1 to 7 days (with or without flucytosine for fluconazole-resistant C. glabrata) (IDSA [Pappas 2016]).
Symptomatic cystitis:
C. krusei or fluconazole-resistant C. glabrata: IV: 0.3 to 0.6 mg/kg/day for 1 to 7 days (IDSA [Pappas 2016]).
Fluconazole-resistant species (eg. C. krusei, C. glabrata) Bladder irrigation (off-label route): Irrigate with a 0.05 mg/mL (50 mg/L) sterile water solution instilled for 5 to 7 days or until cultures are clear. Note: Recommended for use in conjunction with other treatment modalities (Fisher 2011).
Vulvovaginal, caused by C. glabrata (alternative agent) (off-label use): Intravaginal: 3% to 4% extemporaneously compounded cream: 1 applicatorful (~5 g) once daily (at bedtime) for 14 days (IDSA [Pappas 2016]; Sivasubramanian 2009; Sobel 2021). Note: Reserve for patients with no other clear cause of symptoms (Sobel 2021). May also be used in combination with intravaginal flucytosine (Challenor 2012; Hettiarachchi 2010; IDSA [Pappas 2016]; White 2001).
Coccidioidomycosis in patients with HIV with severe, non-meningeal infection (ie, diffuse pulmonary or severely ill with extrathoracic disseminated disease): IV: 0.7 to 1 mg/kg/day until clinical improvement, then initiate triazole therapy (eg, fluconazole or itraconazole) (HHS [OI adult 2020]).
Cryptococcal disease (meningitis, disseminated, or severe pulmonary disease), in patients with HIV: IV: Induction: 0.7 to 1 mg/kg/day (with flucytosine [preferred] or fluconazole or without a concomitant agent) for 2 weeks, then change to oral fluconazole for consolidation/maintenance therapy (HHS [OI adult] 2020).
Histoplasmosis (alternative agent): Moderately severe to severe pulmonary or disseminated disease: IV: 0.7 to 1 mg/kg/day for 1 to 2 weeks (at least 2 weeks in patients with HIV), followed by oral itraconazole for 12 weeks (pulmonary disease) or 12 months (disseminated disease) (HHS [OI adult 2021)]; IDSA [Wheat 2007]; Johnson 2002).
Leishmaniasis (alternative agent):
Cutaneous: IV: 0.5 to 1 mg/kg/dose once daily or every other day for a total cumulative dose of ~15 to 30 mg/kg (IDSA/ASTMH [Aronson 2016]).
Mucosal: IV: 0.5 to 1 mg/kg/dose once daily or every other day for a total cumulative dose of ~20 to 45 mg/kg (IDSA/ASTMH [Aronson 2016]).
Visceral (off label): IV: 1 mg/kg/dose once daily or every other day for a total cumulative dose of 15 to 20 mg/kg (IDSA/ASTMH [Aronson 2016]).
Visceral, patients with HIV (off label): IV: 0.5 to 1 mg/kg/dose once daily for a total cumulative dose of 1,500 to 2,000 mg (HHS [OI adult 2020]).
Sporotrichosis: Pulmonary, meningeal, osteoarticular, or disseminated: IV: 0.7 to 1 mg/kg/day; after the patient has shown a favorable response, can change to oral itraconazole for suppressive therapy for a total duration of therapy of ≥12 months (IDSA [Kauffman 2007).
Talaromycosis (formerly penicilliosis) (alternative agent) (off-label use): IV: 0.7 mg/kg/day for 2 weeks (if liposomal amphotericin B unavailable) followed by oral azole consolidation therapy (HHS [OI adult 2020]).
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. IV therapy may take several months.
Renal replacement therapy: Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis or CRRT.
No dosage adjustment provided in manufacturer’s labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous, as deoxycholate [preservative free]:
Generic: 50 mg (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous, as deoxycholate:
Fungizone IV: 50 mg (1 ea)
IV: Administer by IV infusion over 2 to 6 hours; an in-line filter (>1 micron mean pore diameter) may be used for administration (Kintzel 1992). For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen) ± diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day.
Irrigation solution (bladder): Administer as a continuous irrigation or intermittently with a dwell time of 60 to 90 minutes (Fisher 2011; Gubbins 1999; Ku 2004; Martinez-Pajares 2010).
Intranasal: Administer intranasally via a De Vilbiss atomizer (Jeffrey 1991)
IV: May be infused over 4 to 6 hours. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) ± diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day. Infusion of admixtures more concentrated than 0.25 mg/mL should be limited to patients absolutely requiring volume contraction. Pre-infusion administration of 500 to 1,000 mL of normal saline appears to reduce the risk of nephrotoxicity during amphotericin B treatment (HHS [OI adult 2020]).
Intraventricular (off-label route): Use preservative-free preparations only. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow amphotericin B solution to equilibrate in the CSF (IDSA [Tunkel 2017])
Irrigation (off-label route): A solution for irrigation (final concentration range: 0.05 to 0.25 mg/mL) may be administered via nephrostomy tubes for fungal balls associated with UTI due to candida. A solution for irrigation (final concentration: 0.05 mg/mL solution) may be instilled via bladder irrigation for cystitis (IDSA [Pappas 2016]).
Vaginal (off- label route): Administer intravaginal cream at bedtime, using an appropriately sized intravaginal applicator to deliver the correct dose (Sivasubramanian 2009; White 2001).
Store intact vials under refrigeration. Protect from light. Reconstituted vials are stable, protected from light, for 24 hours at room temperature and 1 week when refrigerated. The manufacturer indicates that solutions diluted for infusion in D5W should be used promptly after preparation and protected from light during administration.
Treatment of progressive, potentially life-threatening susceptible fungal infections (FDA approved in pediatric patients [age not specified] and adults); has also been used for fungal peritonitis, irrigant for bladder fungal infections, used in fungal infection in patients with bone marrow transplantation, and chemoprophylaxis (low-dose IV)
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Amphotericin B may be confused with amphotericin B liposomal
Conventional amphotericin formulations (Amphocin, Fungizone) may be confused with lipid-based formulations (AmBisome, Abelcet, Amphotec).
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Systemic:
Frequency not defined:
Cardiovascular: Hypotension
Endocrine & metabolic: Hypokalemia, weight loss
Gastrointestinal: Anorexia, diarrhea, dyspepsia, epigastric pain, nausea, stomach cramps, vomiting
Genitourinary: Azotemia
Hematologic & oncologic: Normocytic anemia (normochromic)
Local: Pain at injection site (with or without phlebitis or thrombophlebitis)
Nervous system: Chills, headache, malaise, pain
Neuromuscular & skeletal: Arthralgia, myalgia
Renal: Calcium nephrolithiasis, decreased urine specific gravity (hyposthenuria), renal insufficiency, renal tubular acidosis
Respiratory: Tachypnea
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Cardiac arrhythmia, flushing, heart failure, hypertension, shock, ventricular fibrillation
Dermatologic: Maculopapular rash, pruritus, skin rash
Endocrine & metabolic: Hyperkalemia, hypocalcemia, hypomagnesemia
Gastrointestinal: Hemorrhagic gastroenteritis, melena
Genitourinary: Anuria, oliguria
Hematologic & oncologic: Agranulocytosis, disorder of hemostatic components of blood, eosinophilia, leukocytosis, leukopenia, thrombocytopenia
Hepatic: Acute hepatic failure, hepatitis, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin, jaundice
Hypersensitivity: Hypersensitivity reactions, nonimmune anaphylaxis
Nervous system: Encephalopathy, leukoencephalopathy, peripheral neuropathy, seizure, vertigo (transient)
Ophthalmic: Diplopia, visual disturbance
Otic: Hearing loss, tinnitus
Renal: Acute kidney injury, increased blood urea nitrogen, increased serum creatinine
Respiratory: Bronchospasm, dyspnea, hypersensitivity pneumonitis, pulmonary edema, wheezing
Hypersensitivity to amphotericin or any component of the formulation
Concerns related to adverse effects:
• Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation.
• Infusion reactions: Acute reactions (eg, fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, tachypnea) may occur 1 to 3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses. Avoid rapid infusion to prevent hypotension, hypokalemia, arrhythmias, and shock.
• Leukoencephalopathy: Has been reported following administration of amphotericin. Total body irradiation has been reported to be a possible predisposition.
• Nephrotoxicity: May cause nephrotoxicity; usual risk factors include underlying renal disease, concomitant nephrotoxic medications and daily and/or cumulative dosing of amphotericin. Avoid use with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval. However permanent impairment may occur, especially in patients receiving large cumulative dose (eg, >5 g) and in those also receiving other nephrotoxic drugs. Hydration and sodium repletion prior to administration may reduce the risk of developing nephrotoxicity. Frequent monitoring of renal function is recommended.
Disease-related concerns:
• Fungal infections: [US Boxed Warning]: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections, not noninvasive forms of infection.
• Heart failure: In a scientific statement from the American Heart Association, amphotericin has been determined to be an agent that may cause direct myocardial toxicity (magnitude: moderate/major) (AHA [Page 2016]).
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
Other warnings/precautions:
• Error prevention: [US Boxed warning]: Verify the product name and dosage if dose exceeds 1.5 mg/kg.
• Therapy interruption: If therapy is stopped for >7 days, restart at the lowest dose recommended and increase gradually.
May premedicate patients who experience mild adverse reactions with acetaminophen and diphenhydramine 30 minutes prior to the amphotericin B infusion; meperidine and ibuprofen may help to reduce fevers and chills; hydrocortisone can be added to the infusion solution to reduce febrile and other systemic reactions. If therapy is stopped for >7 days, restart at the lowest dose recommended and increase gradually. Administer by slow IV infusion; rapid infusion has been associated with hypotension, hypokalemia, arrhythmias, and shock. Avoid extravasation; may cause chemical irritation; monitor infusion site; heparin 1 unit/1 mL of infusion solution can be added to reduce phlebitis. Use caution with intraperitoneal administration; use associated with irritation to the peritoneum and abdominal pain; not routinely used unless intolerance to other therapies (ISPD [Warady 2000b]).
None known.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arsenic Trioxide: Amphotericin B may enhance the hypotensive effect of Arsenic Trioxide. Amphotericin B may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as amphotericin B. Risk D: Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Cardiac Glycosides: Amphotericin B may enhance the adverse/toxic effect of Cardiac Glycosides. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and amphotericin B whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE (Systemic): Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Amphotericin B may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dichlorphenamide: Amphotericin B may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Dronabinol: May increase the serum concentration of Amphotericin B. Specifically, dronabinol may displace amphotericin B from its protein-binding sites, leading to an increased concentration of active, unbound drug. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. Amphotericin B may increase the serum concentration of Flucytosine. Risk C: Monitor therapy
Foscarnet: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methoxyflurane: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination
Sodium Stibogluconate: Amphotericin B Deoxycholate may enhance the cardiotoxic effect of Sodium Stibogluconate. Specifically, arrhythmia and sudden cardiac death risks may be increased. Management: Consider separating courses of sodium stibogluconate and amphotericin B deoxycholate by at least 14 days. Correct electrolyte imbalances prior to initiating amphotericin B deoxycholate and closely monitor cardiac status. Risk D: Consider therapy modification
Amphotericin crosses the placenta and enters the fetal circulation. Amphotericin B is recommended for the treatment of serious systemic fungal diseases in pregnant women. Refer to current guidelines (IDSA [Pappas 2016]; King 1998; Pilmis 2015).
Renal function (monitor frequently during therapy: Every other day during dose increases and at least weekly, thereafter), electrolytes (especially potassium and magnesium), liver function tests, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc); blood pressure, temperature, pulse, respiration, IV site
Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman 1992).
Absorption: Poor oral absorption
Distribution: Minimal amounts enter the aqueous humor, bile, pericardial fluid, pleural fluid, and synovial fluid
CNS penetration:
Preterm neonates (GA: 27.4 ± 5 weeks): High interpatient variability; 40% to 90% of serum concentrations (Baley 1990)
Adults: Poor (inflamed or noninflamed meninges)
Vd: Pediatric patients (0 to 18 years): Highly variable; reported range: 0.38 to 3.99 L/kg (Benson 1989; Koren 1988)
Protein binding, plasma: 90%
Half-life elimination:
Premature neonates (GA: 27.4 ± 5 weeks): 14.8 hours (range: 5 to 82 hours) (Baley 1990)
Infants and Children (4 months to 14 years): 18.1 ± 6.6 hours (range: 11.9 to 40.3 hours) (Benson 1989)
Adults: Biphasic: Initial: 15 to 48 hours; Terminal: 15 days
Time to peak: Within 1 hour following a 4- to 6-hour dose
Excretion: Urine (2% to 5% as biologically active form); ~40% eliminated over a 7-day period and may be detected in urine for at least 7 weeks after discontinued use
Clearance (Benson, 1989):
Infants and Children (8 months to 9 years): 0.57 ± 0.152 mL/minute/kg
Children and Adolescents (10 to 14 years): 0.24 ± 0.02 mL/minute/kg
Intravitreal/intracameral injection: Add 10 mL SWFI to a 50 mg vial; withdraw 1 mL of solution and further dilute with 4 mL SWFI for a concentration of 1 mg/mL. Remove 1 mL of 1 mg/mL solution and further dilute with 9 mL SWFI to achieve a final concentration of 0.1 mg/mL. A volume of 0.1 mL of the 0.1 mg/mL solution will contain 10 mcg of amphotericin. Withdraw dose into a 1 mL syringe for immediate administration (stability data are not available) (Kaushik 2001).
3% to 4% intravaginal cream: Compound with Aquagel or lubricating jelly (Hetticarachchi 2010; IDSA [Pappas 2016]; Sivasubramanian 2009; White 2001).
Solution (reconstituted) (Amphotericin B Intravenous)
50 mg (per each): $54.63
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