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Amphotericin B (Lipid Complex)

Medically reviewed by Drugs.com. Last updated on Aug 27, 2020.

Pronunciation

(am foe TER i sin bee LIP id KOM pleks)

Index Terms

  • ABLC

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intravenous [preservative free]:

Abelcet: 5 mg/mL (20 mL)

Brand Names: U.S.

  • Abelcet

Pharmacologic Category

  • Antifungal Agent, Parenteral

Pharmacology

Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages.

Distribution

High tissue concentration found in the liver, spleen, and lung; Vd: Increases with higher doses (likely reflects increased uptake by tissues); 131 L/kg with 5 mg/kg/day

Excretion

0.9% of dose excreted in urine over 24 hours; effects of hepatic and renal impairment on drug disposition are unknown

Half-Life Elimination

173 hours following multiple doses

Use: Labeled Indications

Fungal infection (invasive): Treatment of invasive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B (amphotericin B deoxycholate) therapy

Off Label Uses

Candidiasis, empiric therapy

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, amphotericin B lipid complex is an effective and recommended alternative agent for empiric therapy of suspected invasive candidiasis (excluding infection of the urinary tract).

Empiric antifungal therapy (neutropenic fever)

Based on the Infectious Diseases Society of America (IDSA) Practice Guidelines for the Diagnosis and Management of Aspergillosis, amphotericin B lipid complex is an effective and recommended alternative agent for empiric antifungal therapy in high-risk neutropenic patients who remain febrile despite broad-spectrum antibiotic therapy. According to the Aspergillosis guidelines, empiric therapy is not recommended for patients with an anticipated duration of neutropenia <10 days, unless other findings indicate a suspected invasive fungal infection.

Leishmaniasis, visceral

Based on the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) clinical practice guidelines for the diagnosis and treatment of leishmaniasis and the HHS guidelines for prevention and treatment of opportunistic infections in adults and adolescents with HIV, amphotericin B lipid complex is a recommended alternative agent for the management of visceral leishmaniasis in immunocompetent and immunosuppressed patients, including patients with HIV infection.

Contraindications

Hypersensitivity to amphotericin or any component of the formulation

Dosing: Adult

Note: Lipid-based amphotericin formulations (Abelcet) may be confused with conventional formulations (desoxycholate [Amphocin, Fungizone]) or with other lipid-based amphotericin formulations (amphotericin B liposomal [AmBisome]; amphotericin B cholesteryl sulfate complex [Amphotec]). Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.

Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent ± diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

Usual dose: IV: 5 mg/kg once daily

Manufacturer’s labeling: Invasive fungal infections (when patients are intolerant or refractory to conventional amphotericin B): IV: 5 mg/kg/day

Indication-specific dosing:

Aspergillosis, invasive (salvage therapy): IV: 5 mg/kg/day; minimum duration of treatment is 6 to 12 weeks and depends on site of infection, extent of disease, and level/duration of immunosuppression (IDSA [Patterson 2016]). Note: Amphotericin B lipid complex should be reserved as salvage therapy for those intolerant of or refractory to voriconazole, isavuconazole, or liposomal amphotericin B (IDSA [Patterson 2016]).

Blastomycosis, moderately severe to severe, non-CNS disease: IV: 3 to 5 mg/kg/day for 1 to 2 weeks or until improvement, followed by oral itraconazole (Chapman 2008).

Candidiasis:

Candidemia (non-neutropenic patients) (alternative agent): IV: 3 to 5 mg/kg/day; may transition to fluconazole (usually after 5 to 7 days) in clinically stable patients, with fluconazole-susceptible isolates and negative repeat cultures. Total duration of antifungal therapy is at least 2 weeks after the documented clearance of Candida from the bloodstream and resolution of candidemia-associated symptoms in patients without metastatic complications (IDSA [Pappas 2016]).

Candidemia (neutropenic patients) (alternative agent): IV: 3 to 5 mg/kg/day; may transition to fluconazole during persistent neutropenia in clinically stable patients, with fluconazole-susceptible isolates and negative repeat cultures. Total duration of antifungal therapy is at least 2 weeks after the documented clearance of Candida from the bloodstream and resolution of neutropenia and candidemia-associated symptoms in patients without metastatic complications (IDSA [Pappas 2016]).

Chronic disseminated (hepatosplenic): IV: 3 to 5 mg/kg/day for several weeks; transition to oral fluconazole in clinically stable patients unlikely to have a fluconazole-resistant isolate (IDSA [Pappas 2016]).

Empiric therapy, suspected invasive candidiasis (non-neutropenic ICU patients) (alternative agent): IV: 3 to 5 mg/kg/day; treatment should continue for 14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response (IDSA [Pappas 2016]).

Endocarditis (native or prosthetic valve) or infected implantable cardiac devices (eg, pacemaker, ICD, VAD): IV: 3 to 5 mg/kg/day (with or without flucytosine); for native or prosthetic valve endocarditis, therapy should continue for at least 6 weeks after valve replacement surgery (longer durations in patients with abscesses or other complications); for patients with implantable cardiac devices, therapy should continue for 4 to 6 weeks after surgery (4 weeks for infections limited to generator pockets and at least 6 weeks for infections involving the wires). Note: May transition to fluconazole if patient clinically stable with fluconazole-susceptible isolates in whom Candida has cleared from the bloodstream (IDSA [Pappas 2016]).

Esophageal in patients with HIV (alternative agent): IV: 3 to 4 mg/kg/day for 14 to 21 days (HHS [OI adult 2020]).

Intra-abdominal candidiasis (alternative agent): IV: 3 to 5 mg/kg/day; duration of therapy determined by clinical response and source control (IDSA [Pappas 2016]).

Osteomyelitis or septic arthritis (alternative agent): IV: 3 to 5 mg/kg/day for at least 2 weeks, followed by fluconazole (IDSA [Pappas 2016]).

Suppurative thrombophlebitis: IV: 3 to 5 mg/kg/day; continue for at least 2 weeks after candidemia has cleared; consider transition to fluconazole in clinically stable patients with a fluconazole-susceptible isolate who have responded to initial therapy (IDSA [Pappas 2016]).

Coccidioidomycosis, progressive, disseminated (alternative agent): IV: 2 to 5 mg/kg/day (Galgiani 2005)

Coccidioidomycosis in patients with HIV with severe, nonmeningeal infection (ie, diffuse pulmonary or severely ill with extrathoracic disseminated disease): IV: 3 to 5 mg/kg/day until clinical improvement, then switch to fluconazole or itraconazole (HHS [OI adult 2020]).

Cryptococcosis:

Cryptococcal disease (meningitis, disseminated, or severe pulmonary disease) in patients with HIV (alternative agent): Induction therapy: IV: 5 mg/kg/day with flucytosine for at least 2 weeks, followed by fluconazole for consolidation therapy (HHS [OI adult 2020]; IDSA [Perfect 2010]). Note: If flucytosine is not given due to intolerance, duration of amphotericin B lipid complex therapy should be 4 to 6 weeks (IDSA [Perfect 2010]).

Cryptococcal meningoencephalitis in HIV-negative patients and non-transplant patients (alternative agent): Induction therapy: IV: 5 mg/kg/day (with flucytosine) for ≥4 weeks followed by oral fluconazole. Note: If flucytosine is not given or treatment is interrupted, consider prolonging induction therapy for an additional 2 weeks (IDSA [Perfect 2010]).

Cryptococcal meningoencephalitis in transplant recipients: Induction therapy: IV: 5 mg/kg/day (with flucytosine) for at least 2 weeks, followed by oral fluconazole Note: If flucytosine is not given, duration of amphotericin B lipid complex therapy should be 4 to 6 weeks (IDSA [Perfect 2010]).

Nonmeningeal cryptococcosis: Induction therapy: IV: 5 mg/kg/day (with flucytosine) for ≥4 weeks may be used for severe pulmonary cryptococcosis or for cryptococcemia with evidence of high fungal burden, followed by oral fluconazole. Note: If flucytosine is not given or treatment is interrupted, consider prolonging induction therapy for an additional 2 weeks (IDSA [Perfect 2010]).

Empiric antifungal therapy (neutropenic fever) (alternative agent) (off-label use): IV: 5 mg/kg/day once daily (Wingard 2000). Note: Guidelines recommend amphotericin B lipid formulations be considered for invasive aspergillosis only when triazoles, specifically voriconazole, are contraindicated or not tolerated (IDSA [Patterson 2016]).

Histoplasmosis:

Acute pulmonary (moderately severe to severe): IV: 5 mg/kg/day for 1 to 2 weeks, followed by oral itraconazole (IDSA [Wheat 2007]).

Moderately severe to severe disseminated disease in patients with HIV (alternative agent): IV: 5 mg/kg/day for at least 2 weeks, followed by itraconazole maintenance therapy (HHS [OI adult 2020]).

Progressive disseminated, non-CNS disease (alternative agent): IV: 5 mg/kg/day for 1 to 2 weeks, followed by oral itraconazole (IDSA [Wheat 2007]).

Leishmaniasis (visceral) (off-label use):

Patients with HIV:

Treatment (alternative agent): IV: 2 to 4 mg/kg/dose once daily or an interrupted schedule of 4 mg/kg/dose on days 1 to 5, and on days 10, 17, 24, 31, and 38 to achieve a total dose of 20 to 60 mg/kg (HHS [OI adult 2020]).

Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm3): IV: 3 mg/kg every 21 days (HHS [OI adult 2020]).

Immunocompetent patients: IV: 2 to 3 mg/kg/dose once daily for 5 to 10 days (IDSA/ASTMH [Aronson 2016])

Immunosuppressed patients: IV: 3 to 5 mg/kg/dose once daily for 10 days (IDSA/ASTMH [Aronson 2016]).

Sporotrichosis:

Meningeal: IV: 5 mg/kg/day for 4 to 6 weeks, followed by oral itraconazole (IDSA [Kauffman 2007]).

Pulmonary, osteoarticular, and disseminated: IV: 3 to 5 mg/kg/day, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy (IDSA [Kauffman 2007]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Medication errors, including deaths, have resulted from confusion between lipid-based forms of amphotericin (Abelcet, Amphotec, AmBisome) and conventional amphotericin B for injection. Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.

Note: For patients who experience nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

General dosing, susceptible infections: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily

Aspergillosis, treatment:

Invasive: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily; duration of treatment depends on site of infection, extent of disease, and level of immunosuppression (IDSA [Walsh 2008])

Endocarditis: Children and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015])

Blastomycosis, invasive: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for initial therapy usually for 1 to 2 weeks, if CNS infection 4 to 6 weeks may be needed; follow with oral itraconazole for a total of 12 months (IDSA [Chapman 2008])

Candidiasis, treatment:

Invasive (Independent of HIV status): Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily (IDSA [Pappas 2016]); Note: In HIV-exposed/-positive patients, doses at the higher end of the range may be considered (5 mg/kg/day) (HHS [OI pediatric 2013]).

Endocarditis: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015]; IDSA [Pappas 2016])

Esophageal: HIV-exposed/-positive: Adolescents: IV: 3 to 4 mg/kg/dose once daily for 14 to 21 days (HHS [OI adult 2016])

Coccidioidomycosis, invasive:

Non-HIV-exposed/-infected:

Disseminated infection, nonpulmonary: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily with or without concomitant azole antifungal therapy (IDSA [Galgiani 2005])

Pulmonary infection, diffuse: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily for several weeks, followed by an oral azole antifungal for a total length of therapy ≥12 months (IDSA [Galgiani 2005])

HIV-exposed/-infected: Non-CNS infection, severe (ie, diffuse pulmonary or severely ill with extrathoracic, disseminated disease):

Infants and Children: IV: 5 mg/kg/dose once daily until clinical improvement; dose may be increased to as high as 10 mg/kg/dose once daily for life-threatening infection (HHS [OI pediatric 2013])

Adolescents: IV: 3 to 5 mg/kg/dose once daily until clinical improvement, then switch to fluconazole or itraconazole (HHS [OI adult 2016])

Cryptococcosis:

Disseminated (non-CNS or severe pulmonary disease):

Infants and Children (independent of HIV status): IV: 5 mg/kg/dose once daily; for severe infection in HIV-exposed/-infected patients, may consider the addition of flucytosine (HHS [OI pediatric 2013]; IDSA [Perfect 2010])

Adolescents:

Non-HIV-exposed: IV: 5 mg/kg/dose once daily (with flucytosine) for ≥4 weeks may be used for severe pulmonary cryptococcosis or for cryptococcemia with evidence of high fungal burden, followed by oral fluconazole. Note: If flucytosine is not given or treatment is interrupted, consider prolonging induction therapy for an additional 2 weeks (IDSA [Perfect 2010]).

HIV-exposed/-positive: IV: Induction therapy: 5 mg/kg/dose once daily with flucytosine for at least 2 weeks, followed by oral fluconazole or itraconazole (HHS [OI adult 2016]).

Meningitis:

Infants and Children:

Non-HIV-exposed/-positive: IV: 5 mg/kg/dose once daily with or without oral flucytosine for a minimum 2-week induction; combination with flucytosine is the preferred treatment (IDSA [Perfect 2010])

HIV-exposed/-positive: IV: 5 mg/kg/dose once daily plus flucytosine or fluconazole; Note: Minimum 2-week induction, followed by consolidation and chronic suppressive therapy; a longer duration of induction therapy may be necessary if CSF is not negative or lack of clinical improvement (HHS [OI pediatric 2013])

Adolescents:

Non-HIV-exposed/-positive; nontransplant patients: IV: Induction therapy: 5 mg/kg/dose once daily (with flucytosine) for ≥4 weeks followed by oral fluconazole; should be used as an alternative to conventional amphotericin B in patients with renal concerns. Note: If flucytosine is not given or treatment is interrupted, consider prolonging induction therapy for an additional 2 weeks (IDSA [Perfect 2010]).

HIV-exposed/-positive: IV: Induction therapy: 5 mg/kg/dose once daily with flucytosine for at least 2 weeks, followed by fluconazole for consolidation therapy (HHS [OI adult 2016]; IDSA [Perfect 2010]). Note: If flucytosine is not given due to intolerance, duration of amphotericin B lipid complex therapy should be 4 to 6 weeks (IDSA [Perfect 2010]).

Transplant patients: Induction therapy: IV: 5 mg/kg/dose once daily (with flucytosine) for at least 2 weeks followed by oral fluconazole. Note: If flucytosine is not given, duration of therapy should be 4 to 6 weeks (IDSA [Perfect 2010]).

Histoplasmosis:

Non-HIV-exposed/-positive: Disseminated (non-CNS) or pulmonary disease: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 1 to 2 weeks followed by oral itraconazole for a total of 12 weeks; conventional amphotericin B typically preferred (IDSA [Wheat 2007])

HIV-exposed/-positive: Disseminated disease (moderately severe to severe): Adolescents: IV: 3 mg/kg/dose once daily for at least 2-week induction, followed by oral itraconazole (HHS [OI adult 2016])

Leishmaniasis, visceral (HIV-exposed/-positive) (HHS [OI adult 2016]):

Treatment: Adolescents: IV: 2 to 4 mg/kg/dose once daily or an interrupted schedule of 4 mg/kg/dose on days 1 to 5, and on days 10, 17, 24, 31, and 38 to achieve a total dose of 20 to 60 mg/kg

Chronic maintenance: Adolescents: IV: 3 mg/kg/dose every 21 days; Note: Use reserved for patients with visceral infection and CD4 count <200 cells/mm3

Sporotrichosis infection (IDSA [Kauffman 2007]): Adolescents:

Meningeal: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconazole

Pulmonary, osteoarticular, and disseminated: IV: 3 to 5 mg/kg/dose once daily, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy

Reconstitution

Shake the vial gently until there is no evidence of any yellow sediment at the bottom. Withdraw the appropriate dose from the vial using an 18-gauge needle. Remove the 18-gauge needle and attach the provided 5-micron filter needle to filter, and dilute the dose with D5W to a final concentration of 1 mg/mL. Limited data suggests D10W and D15W may also be used for dilution (data on file [Sigma-Tau Pharmaceuticals 2014]). Each filter needle may be used to filter up to four 100 mg vials. A final concentration of 2 mg/mL may be used for patients with cardiovascular disease.

Do not dilute with saline solutions or mix with other drugs or electrolytes - compatibility has not been established

Administration

IV: For patients who experience nonanaphylactic infusion-related reactions, premedicate 30-60 minutes prior to drug administration with a nonsteroidal anti-inflammatory agent ± diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

Administer at an infusion rate of 2.5 mg/kg/hour (eg, over 2 hours for 5 mg/kg). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours. Do not use an in-line filter during administration. Flush line with dextrose; normal saline may cause precipitate.

Pre-infusion administration of 500 to 1,000 mL of NS appears to reduce the risk of nephrotoxicity during amphotericin B treatment (HHS [OI adult 2020]).

Dietary Considerations

If on parenteral nutrition, may need to adjust the amount of lipid infused. The lipid portion of amphotericin B (lipid complex) formulation contains 0.045 kcal per 5 mg (Sacks 1997).

Storage

Intact vials should be stored at 2°C to 8°C (35°F to 46°F); do not freeze. Protect intact vials from exposure to light. Solutions in D5W for infusion are stable for 48 hours under refrigeration and for an additional 6 hours at room temperature.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Consider therapy modification

Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Arsenic Trioxide: Amphotericin B may enhance the hypotensive effect of Arsenic Trioxide. Amphotericin B may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as amphotericin B. Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Cardiac Glycosides: Amphotericin B may enhance the adverse/toxic effect of Cardiac Glycosides. Monitor therapy

Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and amphotericin B whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Consider therapy modification

Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Monitor therapy

CycloSPORINE (Systemic): Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dichlorphenamide: Amphotericin B may enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy

Dronabinol: May increase the serum concentration of Amphotericin B. Specifically, dronabinol may displace amphotericin B from its protein-binding sites, leading to an increased concentration of active, unbound drug. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Fexinidazole [INT]: Amphotericin B may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Amphotericin B. Avoid combination

Ganciclovir-Valganciclovir: May enhance the nephrotoxic effect of Amphotericin B. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Methoxyflurane: May enhance the nephrotoxic effect of Amphotericin B. Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Avoid combination

Sodium Stibogluconate: Amphotericin B may enhance the cardiotoxic effect of Sodium Stibogluconate. Management: Consider separating courses of sodium stibogluconate and amphotericin B by at least 14 days. Correct electrolyte imbalances prior to initiating amphotericin B and closely monitor cardiac status. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.

>10%:

Central nervous system: Chills (18%)

Renal: Increased serum creatinine (11%)

Miscellaneous: Fever (14%), multi-organ failure (11%)

1% to 10%:

Cardiovascular: Hypotension (8%), cardiac arrest (6%), hypertension (5%), chest pain (3%)

Central nervous system: Headache (6%), pain (5%)

Dermatologic: Skin rash (4%)

Endocrine & metabolic: Hypokalemia (5%)

Gastrointestinal: Nausea (9%), vomiting (8%), diarrhea (6%), abdominal pain (4%), gastrointestinal hemorrhage (4%)

Hematologic & oncologic: Thrombocytopenia (5%), anemia (4%), leukopenia (4%)

Hepatic: Hyperbilirubinemia (4%)

Infection: Sepsis (7%), infection (5%)

Renal: Renal failure (5%)

Respiratory: Respiratory failure (8%), dyspnea (6%), respiratory tract disease (4%)

<1%, postmarketing, and/or case reports: Acute hepatic failure, anaphylactoid reaction, anuria, asthma, blood coagulation disorder, brain disease, bronchospasm, cardiac arrhythmia, cardiomyopathy, cerebrovascular accident, cholangitis, cholecystitis, deafness, dysuria, eosinophilia, erythema multiforme, exfoliative dermatitis, extrapyramidal reaction, hearing loss, hematologic disease, hemoptysis, hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease), hepatitis, hepatomegaly, hepatotoxicity, hypercalcemia, hyperkalemia, hypersensitivity reaction, hypocalcemia, hypomagnesemia, increased blood urea nitrogen, increased serum transaminases, injection site reaction, jaundice, leukocytosis, myasthenia, myocardial infarction, oliguria, peripheral neuropathy, pleural effusion, pulmonary edema, pulmonary embolism, renal insufficiency, renal tubular acidosis, seizure, shock, tachycardia, thrombophlebitis, ventricular fibrillation, vertigo (transient), visual impairment

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation.

• Infusion reactions: Acute reactions (including fever and chills) may occur 1-2 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses. Infusion has been rarely associated with hypotension, bronchospasm, arrhythmias, and shock.

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, amphotericin has been determined to be an agent that may cause direct myocardial toxicity (magnitude: moderate/major) (AHA [Page 2016]).

Concurrent drug therapy issues:

• Antineoplastics: Concurrent use with antineoplastic agents may enhance the potential for renal toxicity, bronchospasm or hypotension; use with caution.

• Nephrotoxic drugs: Concurrent use of amphotericin B with other nephrotoxic drugs may enhance the potential for drug-induced renal toxicity.

Other warnings/precautions:

• Leukocyte transfusions: Acute pulmonary toxicity has been reported in patients receiving leukocyte transfusions and amphotericin B; amphotericin B lipid complex and concurrent leukocyte transfusions are not recommended.

Monitoring Parameters

BUN and serum creatinine levels should be determined every other day while therapy is increased and at least weekly thereafter. Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)

Pregnancy Risk Factor

B

Pregnancy Considerations

Amphotericin crosses the placenta and enters the fetal circulation. Amphotericin B is recommended for the treatment of serious, systemic fungal diseases in pregnant women, refer to current guidelines (IDSA [Pappas 2016]; King 1998; Pilmus 2015).

Patient Education

What is this drug used for?

• It is used to treat fungal infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Shortness of breath

• Severe dizziness

• Passing out

• Vision changes

• Abnormal heartbeat

• Chest pain

• Severe headache

• Bruising

• Bleeding

• Infusion reaction like fast breathing, chills, severe dizziness, passing out, severe headache, nausea, or vomiting

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.