PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Polyene Antifungals

    DEA CLASS

    Rx

    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.

    COMMON BRAND NAMES

    Abelcet

    HOW SUPPLIED

    Abelcet Intravenous Inj Susp: 1mL, 5mg

    DOSAGE & INDICATIONS

    For the treatment of CNS infections, including meningitis, in patients refractory to or intolerant of amphotericin B deoxycholate.
    NOTE: For CNS infections caused by Cryptococcus, see Cryptococcus meningitis.
    For the treatment of CNS infections caused by Aspergillus sp..
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    For the treatment of CNS infections caused by Blastomyces dermatitidis†.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours for 4 to 6 weeks followed by step-down therapy with an oral azole antifungal agent (e.g., fluconazole, itraconazole, or voriconazole) for at least 12 months. Lifelong suppressive therapy may be required when immunosuppression cannot be reversed or in patients who experience relapse. Clinical practice guidelines suggest a lipid formulation amphotericin B as a preferred treatment. Some experts suggest liposomal amphotericin B as the preferred lipid formulation; in animal models, liposomal amphotericin B achieves higher central nervous system concentrations than other lipid formulations.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours for 4 to 6 weeks followed by step-down therapy with oral itraconazole for at least 12 months. Lifelong suppressive therapy may be required when immunosuppression cannot be reversed or in patients who experience relapse. Clinical practice guidelines suggest a lipid formulation amphotericin B as a preferred treatment. Some experts suggest liposomal amphotericin B as the preferred lipid formulation; in animal models, liposomal amphotericin B achieves higher central nervous system concentrations than other lipid formulations.

    For the treatment of candidemia and invasive candidiasis (non-CNS) in patients refractory to or intolerant of amphotericin B deoxycholate.
    For the treatment of chronic disseminated (hepatosplenic candidiasis).
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours for several weeks and followed by oral fluconazole for patients unlikely to have a fluconazole-resistant isolate.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours for several weeks and followed by oral fluconazole for patients unlikely to have a fluconazole-resistant isolate.

    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to 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. Ophthalmological examination is recommended for all patients. Consider intravascular catheter removal.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to 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. Ophthalmological examination is recommended for all patients. Consider intravascular catheter removal.

    Neonates

    3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Ophthalmological examination is recommended for all patients. Consider intravascular catheter removal.

    For the treatment of invasive aspergillosis in patients who are refractory to or intolerant of amphotericin B deoxycholate.
    NOTE: For CNS disease, see meningitis indication.
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    For the treatment of fungal ophthalmic infection, including endophthalmitis, caused by Aspergillus sp. in patients who are refractory to or intolerant of amphotericin B deoxycholate.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Intravitreal amphotericin B deoxycholate or voriconazole is suggested in addition to systemic therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

    For the treatment of cardiovascular system infections, including endocarditis, myocarditis, pericarditis, suppurative thrombophlebitis†, and infected pacemaker†, implantable cardiac defibrillator (ICD)†, or ventricular assist devices (VAD)† in patients who are refractory to or intolerant of other antifungal therapies.
    For the treatment of Candida cardiovascular system infections.
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

    Neonates

    3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

    For the treatment of Aspergillus cardiovascular system infections.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. After surgical replacement of an infected valve, consider lifelong antifungal therapy.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. After surgical replacement of an infected valve, consider lifelong antifungal therapy. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%.

    Neonates

    5 mg/kg/dose IV every 24 hours. Specific neonatal recommendations are not available. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. After surgical replacement of an infected valve, consider lifelong antifungal therapy.

    For the treatment of respiratory infections (i.e., pneumonia, tracheobronchitis, sinusitis) in patients who are refractory to or intolerant of amphotericin B deoxycholate.
    For the treatment of Candida pneumonia.
    Intravenous dosage
    Adults

    Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 3 to 5 mg/kg/dose IV every 24 hours.

    Infants, Children, and Adolescents

    Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 3 to 5 mg/kg/dose IV every 24 hours.

    Neonates

    Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. 3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to amphotericin B deoxycholate or fluconazole for neonatal candidiasis. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement.

    For the treatment of invasive pulmonary, sinus, or tracheobronchial aspergillosis.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. In lung transplant recipients with tracheobronchial aspergillosis (TBA) associated with anastomotic endobronchial ischemia or ischemic reperfusion injury, inhaled amphotericin B is suggested in addition to systemic therapy; treat for at least 3 months or until TBA is resolved, whichever is longer. Surgery alone may be used to treat Aspergillus fungal ball of the paranasal sinus.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. In lung transplant recipients with tracheobronchial aspergillosis (TBA) associated with anastomotic endobronchial ischemia or ischemic reperfusion injury, inhaled amphotericin B is suggested in addition to systemic therapy; treat for at least 3 months or until TBA is resolved, whichever is longer. Surgery alone may be used to treat Aspergillus fungal ball of the paranasal sinus.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. In lung transplant recipients with tracheobronchial aspergillosis (TBA) associated with anastomotic endobronchial ischemia or ischemic reperfusion injury, inhaled amphotericin B is suggested in addition to systemic therapy; treat for at least 3 months or until TBA is resolved, whichever is longer. Surgery alone may be used to treat Aspergillus fungal ball of the paranasal sinus.

    For the treatment of intraabdominal infections (i.e., peritonitis, intraabdominal abscess) in patients who are refractory to or intolerant of amphotericin B deoxycholate.
    For the treatment of intraabdominal candidiasis.
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Duration of therapy is dependent on clinical response.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Duration of therapy is dependent on clinical response.

    Neonates

    3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to amphotericin B deoxycholate or fluconazole. 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. Duration of therapy is dependent on clinical response.

    For the treatment of Aspergillus peritonitis.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Remove peritoneal dialysis catheter.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Remove peritoneal dialysis catheter.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Remove peritoneal dialysis catheter.

    For the treatment of bone and joint infections, including osteomyelitis and infectious arthritis, in patients who are refractory to or intolerant of amphotericin B deoxycholate.
    For the treatment of Candida osteomyelitis or infectious arthritis.
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to fluconazole. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative to fluconazole. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.

    Neonates

    3 to 5 mg/kg/dose IV every 24 hours. Amphotericin B lipid complex has been successfully used in neonates with disseminated candidiasis, including in premature neonates, in a dosage range of 3.2 to 6.5 mg/kg/dose (mean 5 mg/kg/dose) IV every 24 hours. Clinical practice guidelines suggest 3 to 5 mg/kg/dose IV every 24 hours as an alternative to amphotericin B deoxycholate or fluconazole for neonatal candidiasis. In general, amphotericin B deoxycholate is preferred in neonates; lipid formulation amphotericin B should be used with caution in neonates, particularly in the presence of urinary tract involvement. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.

    For the treatment of Aspergillus osteomyelitis or infectious arthritis.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 8 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Longer courses (greater than 6 months) are frequently necessary.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. In an analysis of data from pediatric patients (median age, 9 years; 99 patients younger than 2 years; 44 patients younger than 3 months) treated with amphotericin B lipid complex for invasive fungal infections (median dose 4.92 mg/kg/day), the overall response rate (cured plus improved plus stable) was 71.4% for the 255 evaluable patients with documented fungal infections. The response rate for Aspergillus infections was 59.4%. Clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 8 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Longer courses (greater than 6 months) are frequently necessary.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex as salvage therapy. Treat for at least 8 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement. Longer courses (greater than 6 months) are frequently necessary.

    For the treatment of pulmonary and disseminated cryptococcosis, including cryptococcal meningitis, in patients who are refractory to or intolerant of amphotericin B deoxycholate.
    HIV-infected patients.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine for at least 2 weeks as a preferred induction therapy or alternative therapy to liposomal amphotericin B. Amphotericin B lipid complex may also be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Adolescents

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine for at least 2 weeks as a preferred induction therapy or alternative therapy to liposomal amphotericin B. Amphotericin B lipid complex may also be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Infants and Children

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine for 2 weeks as a preferred induction therapy. Amphotericin B lipid complex may also be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine for 2 weeks as a preferred induction therapy. Amphotericin B lipid complex may also be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Organ transplant recipients.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine as a preferred induction therapy. Amphotericin B lipid complex may also be given as a single agent for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine as a preferred induction therapy. Amphotericin B lipid complex may also be given as a single agent for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex in combination with flucytosine as a preferred induction therapy. Amphotericin B lipid complex may also be given as a single agent for patients unable to tolerate flucytosine. If amphotericin B lipid complex is given as a single agent, give induction therapy for 4 to 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Non-HIV-infected, nontransplant patients.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex 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 amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks, and in patients with neurological complications, extend induction therapy for a total of 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B lipid complex 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 amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks, and in patients with neurological complications, extend induction therapy for a total of 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest amphotericin B lipid complex 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 amphotericin B lipid complex is given as a single agent, consider lengthening induction therapy for at least 2 weeks, and in patients with neurological complications, extend induction therapy for a total of 6 weeks. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Induction therapy should be followed with at least 8 weeks of consolidation therapy with fluconazole, and then chronic suppressive therapy.

    For the treatment of moderately severe to severe disseminated (nonmeningeal) or invasive pulmonary blastomycosis in patients refractory to or intolerant of amphotericin B deoxycholate.
    NOTE: For CNS disease, see meningitis indication.
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose IV every 24 hours. Treat for 1 to 2 weeks or until improvement is noted. Then, administer itraconazole for 6 to 12 months for pulmonary disease or at least 12 months for disseminated disease or immunosuppressed patients. Lifelong itraconazole suppressive therapy may be required when immunosuppression cannot be reversed or in patients who experience relapse. Clinical practice guidelines suggest a lipid formulation amphotericin B as preferred treatment.

    Infants, Children, and Adolescents

    3 to 5 mg/kg/dose IV every 24 hours. Treat for 1 to 2 weeks or until improvement is noted. Then, administer itraconazole for 6 to 12 months for pulmonary disease or at least 12 months for disseminated disease or immunosuppressed patients. Lifelong itraconazole suppressive therapy may be required when immunosuppression cannot be reversed or in patients who experience relapse. Clinical practice guidelines suggest a lipid formulation amphotericin B as preferred treatment.

    Neonates

    5 mg/kg/dose IV every 24 hours. Alternately, although specific neonatal recommendations are not available, clinical practice guidelines suggest 3 to 5 mg/kg/day IV of a lipid formulation amphotericin B as preferred treatment. Treat for 1 to 2 weeks or until improvement is noted. Then, administer itraconazole for 6 to 12 months for pulmonary disease or at least 12 months for disseminated disease or immunosuppressed patients. Lifelong itraconazole suppressive therapy may be required when immunosuppression cannot be reversed or in patients who experience relapse.

    For the treatment of severe disseminated (nonmeningeal) or diffuse pulmonary coccidioidomycosis in patients refractory to or intolerant of amphotericin B deoxycholate.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. For HIV-infected patients, clinical practice guidelines suggest 3 to 5 mg/kg/day IV until clinical improvement followed by chronic suppressive therapy with either oral fluconazole or itraconazole for at least 12 months and usually much longer. Alternatively, some experts add oral fluconazole or itraconazole to amphotericin B at initiation of therapy, and then continue the triazole once amphotericin B has been stopped.

    Adolescents

    5 mg/kg/dose IV every 24 hours. For HIV-infected patients, clinical practice guidelines suggest 3 to 5 mg/kg/day IV until clinical improvement followed by chronic suppressive therapy with either oral fluconazole or itraconazole for at least 12 months and usually much longer. Alternatively, some experts add oral fluconazole or itraconazole to amphotericin B at initiation of therapy, and then continue the triazole once amphotericin B has been stopped.

    Infants and Children

    5 mg/kg/dose IV every 24 hours. For HIV-infected patients, clinical practice guidelines suggest treatment until clinical improvement followed by chronic suppressive therapy with either oral fluconazole or itraconazole for a total of 12 months. The dose may be increased to 10 mg/kg/dose IV every 24 hours in patients with life-threatening infection. Some experts add oral fluconazole or itraconazole to amphotericin B at initiation of therapy, and then continue the triazole once amphotericin B has been stopped.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, for HIV-infected patients, clinical practice guidelines suggest treatment until clinical improvement followed by chronic suppressive therapy with either oral fluconazole or itraconazole for a total of 12 months. The dose may be increased to 10 mg/kg/dose IV every 24 hours in patients with life-threatening infection. Some experts add oral fluconazole or itraconazole to amphotericin B at initiation of therapy, and then continue the triazole once amphotericin B has been stopped.

    For the treatment of moderately severe to severe disseminated (nonmeningeal) or pulmonary histoplasmosis in patients refractory to or intolerant of amphotericin B deoxycholate.
    For the treatment of pulmonary histoplasmosis.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Alternately, clinical practice guidelines suggest 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for a total of 12 weeks. Clinical practice guidelines suggest a lipid formulation amphotericin B as a preferred treatment.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. Alternately, clinical practice guidelines suggest 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks as alternate therapy for patients unable to tolerate amphotericin B deoxycholate followed by itraconazole for a total of 12 weeks. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred treatment.

    Neonates

    5 mg/kg/dose IV every 24 hours. Alternately, although specific neonatal recommendations are not available, clinical practice guidelines suggest 3 to 5 mg/kg/dose IV every 24 hours for 1 to 2 weeks as alternate therapy for patients unable to tolerate amphotericin B deoxycholate followed by itraconazole for a total of 12 weeks. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred treatment.

    For the treatment of disseminated (nonmeningeal) histoplasmosis.
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. For HIV-infected patients, 3 mg/kg/dose IV every 24 hours for at least 2 weeks or until clinically improved followed by itraconazole for at least 12 months. Longer treatment may be required in patients with persistent immunodeficiency. Clinical practice guidelines suggest amphotericin B lipid complex as an alternate treatment to liposomal amphotericin B.

    Adolescents

    5 mg/kg/dose IV every 24 hours. For HIV-infected patients, 3 mg/kg/dose IV every 24 hours for at least 2 weeks or until clinically improved followed by itraconazole for at least 12 months. Longer treatment may be required in patients with persistent immunodeficiency. Clinical practice guidelines suggest amphotericin B lipid complex as an alternate treatment to liposomal amphotericin B.

    Infants and Children

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest liposomal amphotericin B as the preferred treatment in HIV-infected children and amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.

    Neonates

    5 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, clinical practice guidelines suggest liposomal amphotericin B as the preferred treatment in HIV-infected children and amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.

    For the treatment of esophageal candidiasis† in HIV-infected patients.
    Intravenous dosage
    Adults

    3 to 4 mg/kg/dose IV every 24 hours for 14 to 21 days. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative therapy in patients unable to tolerate oral therapy or those who are refractory to fluconazole. The risk of relapse is greater in HIV-infected patients and suppressive antifungal therapy may be considered after a course of treatment.

    Adolescents

    3 to 4 mg/kg/dose IV every 24 hours for 14 to 21 days. Clinical practice guidelines suggest a lipid formulation amphotericin B as an alternative therapy in patients unable to tolerate oral therapy or those who are refractory to fluconazole. The risk of relapse is greater in HIV-infected patients and suppressive antifungal therapy may be considered after a course of treatment.

    For empirical therapy for presumed fungal infection in patients with febrile neutropenia† or non-neutropenic patients at high risk for fungal infection† (e.g., critically ill patients with risk factors for invasive candidiasis and no other known cause of fever).
    Intravenous dosage
    Adults

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines for candidiasis suggest 3 to 5 mg/kg/day IV of a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Aspergillosis clinical practice guidelines suggest empirical therapy for high-risk patients with prolonged neutropenia who remain persistently febrile despite broad-spectrum antibiotic therapy. In neutropenic patients with cancer, empiric antifungal therapy is suggested for patients with persistent or recurrent fever after 4 to 7 days of antibiotics and whose overall duration of neutropenia is expected to be more than 7 days. If already receiving antifungal prophylaxis, consider switching to a different class of mold active agent.

    Infants, Children, and Adolescents

    5 mg/kg/dose IV every 24 hours. Clinical practice guidelines for candidiasis suggest 3 to 5 mg/kg/day IV of a lipid formulation amphotericin B as an alternative to an echinocandin or fluconazole if there is resistance or intolerance. Aspergillosis clinical practice guidelines suggest empirical therapy for high-risk patients with prolonged neutropenia who remain persistently febrile despite broad-spectrum antibiotic therapy. In neutropenic patients with cancer, empiric antifungal therapy is suggested for patients with persistent or recurrent fever after 4 to 7 days of antibiotics and whose overall duration of neutropenia is expected to be more than 7 days. If already receiving antifungal prophylaxis, consider switching to a different class of mold active agent. Caspofungin or liposomal amphotericin B is a preferred agent for empiric antifungal therapy in children with cancer and/or undergoing hematopoietic stem cell transplantation.

    For the treatment of visceral leishmaniasis†, including antimony-resistant, caused by Leishmania infantum.
    For chronic maintenance therapy (secondary prophylaxis)† of visceral leishmaniasis in HIV-infected patients.
    Intravenous dosage
    Adults

    3 mg/kg/dose IV every 21 days. Continue chronic maintenance therapy until CD4 count is more than 200 to 350 cells/mm3 for at least 3 to 6 months after initiation of antiretroviral therapy; however, some experts suggest therapy should be continued indefinitely.

    Adolescents

    3 mg/kg/dose IV every 21 days. Continue chronic maintenance therapy until CD4 count is more than 200 to 350 cells/mm3 for at least 3 to 6 months after initiation of antiretroviral therapy; however, some experts suggest therapy should be continued indefinitely.

    Intravenous dosage
    Adults

    3 mg/kg/dose IV every 24 hours for 5 days. In a randomized, open-label study in 60 Indian patients (5 to 65 years), definitive response rates 6 months after therapy were 84%, 90%, and 100% for patients who received total doses of 5 mg/kg, 10 mg/kg, and 15 mg/kg, respectively. All patients had not responded to or relapsed after treatment for more than 30 days with pentavalent antimony. For HIV-infected patients as an alternative to liposomal amphotericin B, 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 followed by chronic maintenance therapy, to achieve a total dose of 20 to 60 mg/kg. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended.

    Adolescents

    3 mg/kg/dose IV every 24 hours for 5 days. In a randomized, open-label study in 60 Indian patients (5 to 65 years), definitive response rates 6 months after therapy were 84%, 90%, and 100% for patients who received total doses of 5 mg/kg, 10 mg/kg, and 15 mg/kg, respectively. All patients had not responded to or relapsed after treatment for more than 30 days with pentavalent antimony. For HIV-infected patients as an alternative to liposomal amphotericin B, 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 followed by chronic maintenance therapy, to achieve a total dose of 20 to 60 mg/kg. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended.

    Children

    3 mg/kg/dose IV every 24 hours for 5 days. In a randomized, open-label study in 60 Indian patients (5 to 65 years), definitive response rates 6 months after therapy were 84%, 90%, and 100% for patients who received total doses of 5 mg/kg, 10 mg/kg, and 15 mg/kg, respectively. All patients had not responded to or relapsed after treatment for more than 30 days with pentavalent antimony.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    5 mg/kg/day IV.

    Geriatric

    5 mg/kg/day IV.

    Adolescents

    5 mg/kg/day IV.

    Children

    5 mg/kg/day IV.

    Infants

    5 mg/kg/day IV.

    Neonates

    5 mg/kg/day IV; doses up to 6.5 mg/kg/day have been used rarely.

    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.

    ADMINISTRATION

     
    NOTE: Amphotericin B lipid complex (ABLC) is not dosed the same as conventional amphotericin B (amphotericin B deoxycholate) or other lipid formulations (See drug specific monographs for dosing information). Further, amphotericin B lipid formulations may not be substituted for one another. The differences in the chemical composition and lipid component of these products can substantially affect their functional properties.

    Injectable Administration

    •Administer by intravenous infusion.
    •Handle with aseptic technique as amphotericin B lipid complex (ABLC) does not contain any preservatives or bacteriostatic agents.
    •Visually inspect parenteral products for particulate matter and discoloration prior to administration.

    Intravenous Administration

    Filtration and Dilution:
    •Prepare the admixture for infusion by first shaking the vial until there is no evidence of yellow sediment on the bottom of the vial.
    •Transfer the appropriate amount of drug from the required number of vials into one or more sterile syringes using an 18-gauge needle.
    •Attach the provided 5-micron filter needle to the syringe; inject the syringe contents through the filter needle, into the appropriate amount of 5% Dextrose injection. Each filter needle may be used on the contents of no more than four 100 mg vials.
    •The suspension must be diluted with 5% Dextrose injection to a final concentration of 1 mg/mL. For pediatric patients and patients with cardiovascular disease, the final concentration may be 2 mg/mL. DO NOT USE SALINE SOLUTIONS OR MIX WITH OTHER DRUGS OR ELECTROLYTES.
    •The diluted ready-for-use admixture is stable for up to 48 hours at 2—8 degrees C (36—46 degrees F) and an additional 6 hours at room temperature. Do not freeze.
     
    Intravenous infusion:
    •Flush intravenous line with D5W injection prior to infusion. If this cannot be done, then a separate IV line must be used. DO NOT USE AN IN-LINE FILTER.
    •Prior to infusion, shake the bag until the contents are thoroughly mixed.
    •The rate of infusion should not exceed 2.5 mg/kg/hour. If the infusion time exceeds 2 hours, mix the contents by shaking the infusion bag every 2 hours.

    STORAGE

    Abelcet:
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Amphotericin B lipid complex (ABLC) is contraindicated in patients with a known hypersensitivity to amphotericin B or any other component in the formulation. Anaphylaxis has been reported with the use of ABLC; thus, administer ABLC only under close observation by medically trained personnel. If a severe anaphylactic reaction occurs during administration of ABLC, the drug should be immediately discontinued and the patient should not receive further doses of amphotericin B.
     
    Cardiorespiratory arrest has been reported in patients receiving an overdose of amphotericin B. When administering ABLC, exercise caution to prevent inadvertent overdose; if an overdose occurs, discontinue therapy and administer supportive measures.
     
    Acute pulmonary toxicity has been reported in patients receiving amphotericin B and leukocyte transfusions; concomitant use of leukocyte transfusions and amphotericin B lipid complex (ABLC) should be avoided.

    Renal disease, renal failure, renal impairment

    Administer amphotericin B lipid complex (ABLC) with caution to patients with preexisting renal impairment or renal failure. Although ABLC has an improved safety profile when compared to conventional amphotericin B, nephrotoxicity can still develop. In a study of febrile neutropenic patients receiving ABLC, the incidence of renal toxicity, defined as a 100% increase in baseline serum creatinine, was 42%. According to the manufacturer, ABLC has been successfully administered to patients with preexisting renal disease; no dose adjustment recommendations are given. However, renal function should be monitored during ABLC therapy.

    Hepatic disease

    Amphotericin B lipid complex (ABLC) has not been studied in patients with hepatic disease; administer the drug with caution in patients with preexisting hepatic impairment or hepatic failure. Monitor liver function tests during ABLC therapy.

    Anemia, hematological disease, leukopenia, thrombocytopenia

    Amphotericin B lipid complex (ABLC) has been shown to cause anemia, leukopenia, and thrombocytopenia in clinical trails. Administer ABLC with caution in patients with preexisting hematological disease including anemia, leukopenia, and thrombocytopenia. In addition, monitor CBC and platelets during ABLC therapy.

    Electrolyte imbalance, hypercalcemia, hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia

    Use caution when administering amphotericin B lipid complex (ABLC) to patients with an electrolyte imbalance including hyperkalemia, hypokalemia, hypomagnesemia, hypercalcemia, and hypocalcemia. Serum electrolyte abnormalities may occur after administration of ABLC. Monitor serum electrolytes during ABLC therapy.

    Cardiac disease, hypertension, hypotension

    Administer amphotericin B lipid complex (ABLC) with caution to patients with preexisting cardiac disease including patients with preexisting hypotension and hypertension. In clinical studies patients have experienced cardiac arrest, chest pain, hypotension, and hypertension after ABLC infusions.

    Geriatric

    The pharmacokinetic properties of amphotericin B lipid complex (ABLC) have not been studied in the geriatric population; however, the drug has been used effectively in this population to treat systemic fungal infections. No serious unexpected adverse effects have been reported in elderly patients who have received ABLC in dosages similar to those used in younger patients. Closely monitor the use of ABLC in elderly patients.

    Children, infants, neonates

    The pharmacokinetic properties of amphotericin B lipid complex (ABLC) have not been studied in neonates, infants, children and adolescents <= 16 years of age; however, the drug has been used effectively in this population to treat systemic fungal infections. No serious unexpected adverse effects have been reported in pediatric patients who have received ABLC in dosages similar to those used in adults. Closely monitor the use of ABLC in pediatric patients.

    Pregnancy

    Amphotericin B lipid complex (ABLC) is classified FDA pregnancy risk category B. No controlled studies have been conducted in pregnant females. Animal studies on rats and rabbits, at doses up to 0.64 times the recommended human dose, have shown no fetal harm. Administer ABLC during pregnancy only when the benefits clearly outweigh the potential risks.

    Breast-feeding

    Data are limited regarding use of amphotericin B lipid complex (ABLC) during breast-feeding and it is not known whether it is excreted into breast milk. According to the manufacturer, because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breast-fed neonates and infants, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Fluconazole and ketoconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to the maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Infusion-related reactions

    Infusion-related reactions have been reported with the administration of amphotericin B lipid complex (ABLC). Acute reactions may include fever, chills, rigors, decreased blood pressure, bronchospasm, arrhythmias, and shock and usually occur during or shortly after (within 1—2 hours) administration of ABLC. The severity with which these reactions occur is usually most intense during the first administration and decreases in strength with subsequent doses. Although several medications frequently are prescribed to suppress these reactions prior to administration of an amphotericin B dose, only hydrocortisone, meperidine, and ibuprofen have been shown to be effective. Slowing the rate of infusion is not helpful. Infusion-related reactions can be more severe if administration occurs shortly after platelet or granulocyte transfusions.

    ADVERSE REACTIONS

    Severe

    cardiac arrest / Early / 6.0-6.0
    renal failure (unspecified) / Delayed / 5.0-5.0
    GI bleeding / Delayed / 4.0-4.0
    anaphylactoid reactions / Rapid / 0-0.1
    bronchospasm / Rapid / Incidence not known
    hyperkalemia / Delayed / Incidence not known
    anuria / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    renal tubular acidosis (RTA) / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    coagulopathy / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    cholecystitis / Delayed / Incidence not known
    veno-occlusive disease (VOD) / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    stroke / Early / Incidence not known
    visual impairment / Early / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known

    Moderate

    hypotension / Rapid / 8.0-8.0
    dyspnea / Early / 7.0-7.0
    hypokalemia / Delayed / 5.0-5.0
    thrombocytopenia / Delayed / 5.0-5.0
    hypertension / Early / 5.0-5.0
    anemia / Delayed / 4.0-4.0
    leukopenia / Delayed / 4.0-4.0
    hyperbilirubinemia / Delayed / 4.0-4.0
    chest pain (unspecified) / Early / 3.0-3.0
    wheezing / Rapid / Incidence not known
    hypophosphatemia / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    dysuria / Early / Incidence not known
    hypercalcemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    tachypnea / Early / Incidence not known
    hemoptysis / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    melena / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    cholangitis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    hyperamylasemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known

    Mild

    chills / Rapid / 18.0-18.0
    fever / Early / 14.0-14.0
    nausea / Early / 3.0-9.0
    vomiting / Early / 3.0-8.0
    infection / Delayed / 5.0-7.0
    diarrhea / Early / 6.0-6.0
    headache / Early / 6.0-6.0
    abdominal pain / Early / 4.0-4.0
    rash (unspecified) / Early / 4.0-4.0
    leukocytosis / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    anorexia / Delayed / Incidence not known
    dyspepsia / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    tinnitus / Delayed / Incidence not known
    diplopia / Early / Incidence not known
    vertigo / Early / Incidence not known
    malaise / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    arthralgia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
    Acetazolamide: Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
    Amikacin: 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: 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.
    Aprotinin: 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: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Bacillus Calmette-Guerin Vaccine, BCG: 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: 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: 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; Neomycin; Polymyxin B: 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: 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: 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.
    Capreomycin: 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: 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: 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: 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: 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: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: 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.
    Colistimethate, Colistin, Polymyxin E: 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.
    Conivaptan: Conivaptan has been associated with hypokalemia. Consider the potential for additive hypokalemic effects if conivaptan is coadministered with drugs known to induce hypokalemia, such as amphotericin B.
    Corticosteroids: 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: Use caution if cyclophosphamide is used concomitantly with amphotericin B, as there may be an increased risk of nephrotoxicity.
    Cyclosporine: 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: 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: 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: 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: 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: 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.
    Digitoxin: 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.
    Digoxin: 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: 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: 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: 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.
    Doxacurium: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Doxorubicin Liposomal: Amphotericin B can reduce cell resistance to doxorubicin, thus enhancing its activity. Amphotericin B can affect the integrity of cell membranes that otherwise would impede doxorubicin's entry into the cell. The effect on liposomal release of doxorubicin is not known.
    Dronabinol, THC: 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: 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: 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: 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: 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: 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.
    Esomeprazole; Naproxen: 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.
    Ethacrynic Acid: 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: 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.
    Famotidine; Ibuprofen: 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: 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: Theoretically, azole antifungals could interfere with the action of amphotericin B by depleting polyene binding sites. Whenever possible, azole antifungals should not be coadministered with amphotericin B until more data are available.
    Flucytosine: 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: 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: 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: 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.
    Gallium: Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as amphotericin B, may increase the risk for developing severe renal insufficiency. If use of amphotericin B is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of amphotericin B is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Ganciclovir: 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: 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: 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.
    Halofantrine: Caution is advised when using halofantrine in combination with other agents, such as amphotericin B, that may lead to electrolyte losses, especially hypokalemia or hypomagnesemia. Monitor serum electrolytes closely.
    Hydrocodone; Ibuprofen: 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 lysine: Ibuprofen lysine may inhibit renal prostaglandins; concurrent use with other nephrotoxic agents, such as amphotericin B, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
    Ibuprofen: 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: 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: 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.
    Ifosfamide: Nephrotoxic agents, such as amphotericin B, can increase the nephrotoxicity of ifosfamide. Damaged kidney tubules may be less likely to convert mesna to its active kidney protecting form, which may contribute to the potential for increased ifosfamide toxicity. Clinicians should be alert for an increased risk of ifosfamide toxicity, including neurotoxicity, renal toxicity, and bone marrow suppression.
    Immune Globulin IV, IVIG, IGIV: 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: 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: 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.
    Isoproterenol: 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: Theoretically, azole antifungals could interfere with the action of amphotericin B by depleting polyene binding sites. Whenever possible, azole antifungals should not be coadministered with amphotericin B until more data are available.
    Kanamycin: Kanamycin is a nephrotoxic drug. Additive nephrotoxicity is possible if kanamycin is administered with other nephrotoxic medications such as amphotericin B. The manufacturer of kanamycin indicates that these combinations should be avoided.
    Ketoconazole: Theoretically, azole antifungals could interfere with the action of amphotericin B by depleting polyene binding sites. Whenever possible, azole antifungals should not be coadministered with amphotericin B until more data are available.
    Ketoprofen: 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: Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Lamivudine, 3TC; Zidovudine, ZDV: The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
    Lansoprazole; Naproxen: 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.
    Levomethadyl: Amphotericin B-induced hypokalemia can can potentiate the cardiac toxicity of levomethadyl.
    Loop diuretics: 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: 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: 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: 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: 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.
    Mivacurium: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Nabumetone: 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: 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: 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; Sumatriptan: 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: 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.
    Neuromuscular blockers: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Nilotinib: 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: 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: 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: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Paromomycin: 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: 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.
    Piroxicam: 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: 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.
    Polymyxins: 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.
    Rapacuronium: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Rocuronium: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Rofecoxib: 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.
    Salicylates: Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
    Streptomycin: 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: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Sulindac: 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.
    Sunitinib: 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.
    Tacrolimus: 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: 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.
    Telbivudine: Drugs that alter renal function such as amphotericin B may alter telbivudine plasma concentrations because telbivudine is eliminated primarily by renal excretion. Monitor renal function before and during telbivudine treatment.
    Tenofovir Alafenamide: Tenofovir-containing products should be avoided with concurrent or recent use of 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 drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
    Tenofovir, PMPA: 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: 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: 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: 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: 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.
    Tubocurarine: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Valdecoxib: 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: 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: 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: Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Voriconazole: Theoretically, azole antifungals could interfere with the action of amphotericin B by depleting polyene binding sites. Whenever possible, azole antifungals should not be coadministered with amphotericin B until more data are available to indicate improved outcomes with co-treatment, unless coadministration represents attempts to resolve serious recalcitrant infection.
    Zalcitabine, ddC: Drugs such as amphotericin B may increase the risk of developing peripheral neuropathy or other zalcitabine-associated adverse events by interfering with the renal clearance of zalcitabine and thereby raising systemic drug exposure. Coadministration of these drugs with zalcitabine requires frequent clinical and laboratory monitoring, with dosage adjustment for any significant change in renal function.
    Zidovudine, ZDV: The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.

    PREGNANCY AND LACTATION

    Pregnancy

    Amphotericin B lipid complex (ABLC) is classified FDA pregnancy risk category B. No controlled studies have been conducted in pregnant females. Animal studies on rats and rabbits, at doses up to 0.64 times the recommended human dose, have shown no fetal harm. Administer ABLC during pregnancy only when the benefits clearly outweigh the potential risks.

    Data are limited regarding use of amphotericin B lipid complex (ABLC) during breast-feeding and it is not known whether it is excreted into breast milk. According to the manufacturer, because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breast-fed neonates and infants, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Fluconazole and ketoconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to the maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Amphotericin B, the active ingredient in amphotericin B lipid complex (ABLC), binds to sterols in cell membranes of both fungal and human cells. As a result of this binding, membrane integrity of the cells is impaired, causing loss of intracellular potassium and other cellular contents. Altered permeability of ergosterol-containing membranes, characteristic of fungal cell membranes, occurs at low amphotericin B concentrations; however, beyond a certain concentration threshold amphotericin B induces leakage of cellular contents through human cholesterol-containing membranes. Some adverse reactions to amphotericin B, such as electrolyte loss and nephrotoxicity, are an extension of this pharmacologic action. Amphotericin B is usually fungistatic in vivo but can have fungicidal activity at high concentrations or against extremely susceptible organisms.
     
    ABLC has demonstrated activity in animal models against Aspergillus fumigatus, Blastomyces species, Candida albicans, Candida guilliermondii, Candida stellatoidea, Candida tropicalis, Coccidioidomyces species, Cryptococcus species, and Histoplasma species.
     
    ABLC shows in vitro activity against Aspergillus species and Candida species. Although standardized susceptibility testing is available for yeast and some filamentous fungi, results do not necessarily correlate with clinical outcome. ABLC is not active against bacteria, Rickettsiae, or viruses.

    PHARMACOKINETICS

    Amphotericin B lipid complex (ABLC) is administered intravenously; it cannot be given intramuscularly. Pharmacokinetic parameters for ABLC should not be used to predict the pharmacokinetics of any other amphotericin B formulation. The clinical relevance of pharmacokinetic differences between ABLC and other amphotericin B formulations has not been determined. Further, the interpretation of serum or tissue amphotericin B concentrations is complicated by the fact that many assays to measure amphotericin B concentrations do not distinguish free amphotericin B and amphotericin B that is lipid-complexed, liposome-encapsulated, or protein-bound.
     
    Metabolism of amphotericin B following administration of ABLC is unknown. Amphotericin B is excreted very slowly by the kidneys. The terminal elimination half-life of amphotericin B is longer after administration of the lipid-complexed formulation (mean 7 days) when compared to conventional amphotericin B (mean 4 days). The long terminal half-life reflects slow redistribution from the tissues. Despite being excreted slowly, there is little accumulation in the blood after repeated dosing.

    Intravenous Route

    The pharmacokinetics of amphotericin B lipid complex (ABLC) after intravenous administration are nonlinear and vary substantially from conventional amphotericin B and from other lipid formulations. In general, the volume of distribution following administration of ABLC is greater and serum concentrations are lower compared to conventional amphotericin B. Distribution of amphotericin B is multi-compartmental. Following IV administration, ABLC is rapidly taken up by the reticuloendothelial system concentrating the drug within the liver, spleen, and lungs. This plasma clearance is enhanced as dosage increases from 0.6—5 mg/kg/day resulting in a less than proportional increase in plasma concentrations and in a higher volume of distribution. Tissues function as a reservoir for ABLC, slowly releasing amphotericin B into circulation. Tissue concentrations of ABLC, when compared to conventional amphotericin B, are higher in the liver, spleen, and lungs and lower in the kidneys and brain. The relationship of amphotericin B tissue concentration to its biological activity is unknown.