AmBisome

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AmBisome

Classes

Polyene Antifungals

Administration

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.

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.[35434]

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.[35434]
ISMP Recommended Standard Concentration for Neonates: 1 mg/mL
Storage: Begin injection within 6 hours of dilution.[35434]

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.[35434]

Adverse Reactions

Severe

azotemia / Delayed / 7.4-21.0
pleural effusion / Delayed / 12.5-12.5
renal failure (unspecified) / Delayed / 2.0-10.0
hyperkalemia / Delayed / 2.0-10.0
coagulopathy / Delayed / 2.0-10.0
hematemesis / Delayed / 2.0-10.0
ileus / Delayed / 2.0-10.0
pulmonary edema / Early / 2.0-10.0
cardiac arrest / Early / 2.0-10.0
arrhythmia exacerbation / Early / 2.0-10.0
bradycardia / Rapid / 2.0-10.0
atrial fibrillation / Early / 2.0-10.0
veno-occlusive disease (VOD) / Delayed / 2.0-10.0
coma / Early / 2.0-10.0
seizures / Delayed / 2.0-10.0
ocular hemorrhage / Delayed / 2.0-10.0
GI bleeding / Delayed / 9.9-9.9
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
hemorrhagic cystitis / Delayed / Incidence not known
diabetes insipidus / Delayed / Incidence not known
anuria / Delayed / Incidence not known
renal tubular acidosis (RTA) / Delayed / Incidence not known
hyposthenuria / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
cyanosis / Early / Incidence not known
bronchospasm / Rapid / Incidence not known
rhabdomyolysis / Delayed / Incidence not known

Moderate

hypokalemia / Delayed / 6.7-51.1
hypomagnesemia / Delayed / 15.3-48.9
anemia / Delayed / 26.7-47.9
dyspnea / Early / 4.7-23.0
hyperglycemia / Delayed / 8.2-23.0
hypertension / Early / 2.3-19.8
sinus tachycardia / Rapid / 2.3-18.5
hypocalcemia / Delayed / 4.9-18.4
hyperbilirubinemia / Delayed / 8.5-18.1
leukopenia / Delayed / 15.1-17.0
constipation / Delayed / 14.9-15.1
peripheral edema / Delayed / 14.6-14.6
elevated hepatic enzymes / Delayed / 4.3-14.6
hypotension / Rapid / 3.5-14.3
edema / Delayed / 12.3-14.3
hematuria / Delayed / 14.0-14.0
thrombocytopenia / Delayed / 5.8-12.8
hypervolemia / Delayed / 8.2-12.2
chest pain (unspecified) / Early / 8.2-12.0
hyponatremia / Delayed / 8.5-11.6
confusion / Early / 8.6-11.4
phlebitis / Rapid / 9.3-10.6
hyperchloremia / Delayed / 2.0-10.0
dysuria / Early / 2.0-10.0
hypophosphatemia / Delayed / 2.0-10.0
hyperphosphatemia / Delayed / 2.0-10.0
urinary incontinence / Early / 2.0-10.0
hypermagnesemia / Delayed / 2.0-10.0
bleeding / Early / 2.0-10.0
vaginal bleeding / Delayed / 2.0-10.0
stomatitis / Delayed / 2.0-10.0
hemorrhoids / Delayed / 2.0-10.0
fecal incontinence / Early / 2.0-10.0
dysphagia / Delayed / 2.0-10.0
hemoptysis / Delayed / 2.0-10.0
fluid retention / Delayed / 2.0-10.0
peripheral vasodilation / Rapid / 2.0-10.0
orthostatic hypotension / Delayed / 2.0-10.0
hepatomegaly / Delayed / 2.0-10.0
hallucinations / Early / 2.0-10.0
depression / Delayed / 2.0-10.0
skin ulcer / Delayed / 2.0-10.0
bullous rash / Early / 2.0-10.0
bone pain / Delayed / 2.0-10.0
dystonic reaction / Delayed / 2.0-10.0
conjunctivitis / Delayed / 2.0-10.0
metabolic acidosis / Delayed / 2.0-10.0
hypoxia / Early / 0.3-7.6
hypernatremia / Delayed / 4.1-4.1
nephrolithiasis / Delayed / Incidence not known
erythema / Early / Incidence not known
hypoventilation / Rapid / Incidence not known

Mild

chills / Rapid / 6.0-48.1
nausea / Early / 16.3-39.7
vomiting / Early / 10.5-31.8
diarrhea / Early / 10.5-30.3
rash / Early / 4.7-24.8
fever / Early / 7.0-23.5
insomnia / Early / 17.0-22.1
abdominal pain / Early / 7.0-19.8
headache / Early / 9.4-19.8
cough / Delayed / 2.1-17.8
epistaxis / Delayed / 8.6-14.9
anorexia / Delayed / 9.6-14.0
anxiety / Delayed / 7.4-13.7
asthenia / Delayed / 6.2-13.1
infection / Delayed / 11.1-12.8
back pain / Delayed / 12.0-12.0
rhinitis / Early / 11.1-11.1
pruritus / Rapid / 10.8-10.8
petechiae / Delayed / 2.0-10.0
ecchymosis / Delayed / 2.0-10.0
injection site reaction / Rapid / 2.0-10.0
eructation / Early / 2.0-10.0
flatulence / Early / 2.0-10.0
dyspepsia / Early / 2.0-10.0
xerostomia / Early / 2.0-10.0
nasal dryness / Early / 2.0-10.0
hiccups / Early / 2.0-10.0
flushing / Rapid / 2.0-10.0
paresthesias / Delayed / 2.0-10.0
drowsiness / Early / 2.0-10.0
agitation / Early / 2.0-10.0
malaise / Early / 2.0-10.0
tremor / Early / 2.0-10.0
dysesthesia / Delayed / 2.0-10.0
skin discoloration / Delayed / 2.0-10.0
purpura / Delayed / 2.0-10.0
urticaria / Rapid / 2.0-10.0
maculopapular rash / Early / 2.0-10.0
xerosis / Delayed / 2.0-10.0
vesicular rash / Delayed / 2.0-10.0
alopecia / Delayed / 2.0-10.0
myalgia / Early / 2.0-10.0
arthralgia / Delayed / 2.0-10.0
xerophthalmia / Early / 2.0-10.0
sinusitis / Delayed / 2.0-10.0
influenza / Delayed / 2.0-10.0
pharyngitis / Delayed / 2.0-10.0
dizziness / Early / 7.0-8.5
hyperhidrosis / Delayed / 7.0-7.0
hyperventilation / Early / 1.2-1.2

Common Brand Names

AmBisome

Dea Class

Description

One of 3 lipid-based IV amphotericin B formulations; increases tolerability (e.g., decrease nephrotoxicity); similar spectrum of activity and efficacy as conventional amphotericin B.

Dosage And Indications

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 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

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 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

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.[34215]

Infants, Children, and Adolescents

3 to 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with an oral azole for at least 12 months and until resolution of CSF abnormalities.

For the treatment of CNS infections due to Histoplasma capsulatum†. Intravenous dosage Adults

5 mg/kg/dose IV every 24 hours for 4 to 6 weeks. Continue step-down therapy with itraconazole for at least 12 months and until resolution of abnormal cerebrospinal fluid (CSF) findings.[34362] [44326] Guidelines suggest liposomal amphotericin B as preferred treatment.[34362] [44326]

Adolescents

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.[34361] [44326] Guidelines suggest liposomal amphotericin B as preferred treatment.[34361] [44326]

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.[50784]

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 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 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

Neonates†

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

Infants, Children, and Adolescents

Neonates†

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

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†

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

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

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

Infants, Children, and Adolescents

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

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

Neonates†

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 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

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†

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

Adolescents

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 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.[63762]

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.[34362]

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.[63762]

HIV-infected Adolescents

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.[63762]

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.[35434] [63762] 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.[63762]

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.[34362] [35434] [63762] Combination therapy with miltefosine may be considered in HIV-infected patients with refractory cases.[63762] Chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is recommended in HIV-infected patients.[34362] [35434] [63762]

Immunocompetent Infants, Children, and Adolescents

Immunocompromised Adolescents

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.[35434] [63762] Combination therapy with miltefosine may be considered in HIV-infected patients with refractory cases.[63762] Chronic maintenance therapy is recommended in HIV-infected patients.[35434] [63762]

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

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.

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 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 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.[34215]

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.[34215]

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.[34215]

Infants, Children, and Adolescents

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

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.[44326]

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.[44326]

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.[44326] For HIV-infected patients, continue step-down therapy with itraconazole for at least 12 months.[34362] Longer treatment may be required in patients with persistent immunodeficiency.[44326] Guidelines suggest liposomal amphotericin B as a preferred treatment.[34362] [44326]

Adolescents

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.[34361] 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.[34361] [44326]

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.[50784]

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.[50784]

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.[34362]

Adolescents

†Indicates off-label use

Dosing Considerations

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

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.

Drug Interactions

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.
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.
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.
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.
Atracurium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
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.
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.
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.
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.
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.
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.
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.
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.
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 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 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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Mivacurium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
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.
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.
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.
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.
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.
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.
Valdecoxib: (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.
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.
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.

How Supplied

AmBisome/Amphotericin B Liposomal Intravenous Inj Pwd F/Susp: 50mg

Maximum Dosage

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.

Mechanism Of Action

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.

Pharmacokinetics

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.

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.

Pregnancy And Lactation

Pregnancy

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.[35434]

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.[27500] [35434] [47037]