Skip to Content

Amphotericin B (Lipid Complex)

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:

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).

Coccidioidomycosis in HIV-infected patients

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B lipid complex is an effective and recommended agent in the management of severe, nonmeningeal coccidioidomycosis infection (ie, diffuse pulmonary or severely ill with extrathoracic disseminated disease) in adolescent and adult HIV-infected patients.

Cryptococcal meningitis in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B lipid complex in combination with flucytosine is an effective and recommended alternative agent for treatment of cryptococcal meningitis in adolescent and adult HIV-infected patients.

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.

Histoplasmosis in HIV-infected patients (adolescents and adults)

Based on the Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B lipid complex is an effective and recommended alternative agent for the treatment of histoplasmosis in adolescent and adult HIV-infected patients.

Leishmaniasis, visceral in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, amphotericin B lipid complex is an effective and recommended alternative agent for treatment and for chronic maintenance therapy of visceral leishmaniasis in adolescent and adult HIV-infected patients.

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 (off-label dose): IV: 3 to 5 mg/kg/day for 1 to 2 weeks or until improvement, followed by oral itraconazole (Chapman 2008).

Candidiasis (alternative agent) (IDSA [Pappas 2016]): IV:

Candidemia (non-neutropenic patients) (off-label dose): 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. Note: An amphotericin B lipid formation is considered a reasonable alternative agent if there is intolerance, limited availability, or resistance to other antifungals. In patients with suspected azole- and echinocandin-resistant infections, an amphotericin B lipid formulation is recommended.

Candidemia (neutropenic patients) (off-label dose): 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. Note: An amphotericin B lipid formation is considered a potential alternative agent, but less attractive option due to its potential for toxicity. However, for infections due to C. krusei, an amphotericin B lipid formulation is a recommended agent.

Chronic disseminated (hepatosplenic) (off-label dose): 3 to 5 mg/kg/day for several weeks; transition to oral fluconazole in clinically stable patients unlikely to have a fluconazole-resistant isolate.

Empiric therapy (non-neutropenic ICU patients) (off-label use): 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.

Endocarditis (native or prosthetic valve) or infected implantable cardiac devices (eg, pacemaker, ICD, VAD) (off-label dose): 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.

Intra-abdominal candidiasis (off-label dose): 3 to 5 mg/kg/day; duration of therapy determined by clinical response and source control.

Osteomyelitis or septic arthritis (alternative therapy) (off-label dose): 3 to 5 mg/kg/day for at least 2 weeks, followed by fluconazole.

Suppurative thrombophlebitis (off-label dose): 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.

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

Coccidioidomycosis in HIV-infected patients with severe, nonmeningeal infection (ie, diffuse pulmonary or severely ill with extrathoracic disseminated disease) (off-label use): 3 to 5 mg/kg/day until clinical improvement, then switch to fluconazole or itraconazole (HHS [OI adult 2017]).

Cryptococcosis: IV:

Cryptococcal meningitis in HIV-infected patients (alternative agent) (off-label use): Induction therapy: 5 mg/kg/day with flucytosine for at least 2 weeks, followed by fluconazole for consolidation therapy (HHS [OI adult 2017]; 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: 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: 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: 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: IV:

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

Moderate to severe disseminated disease in HIV-infected patients (alternative agent) (off-label use): 3 mg/kg/day for at least 2 weeks, followed by itraconazole maintenance therapy (HHS [OI adult 2017])

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

Leishmaniasis (visceral) in HIV-infected patients (off-label use): IV:

Treatment (alternative agent): 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 2017])

Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm3): 3 mg/kg every 21 days (HHS [OI adult 2017])

Sporotrichosis (off-label dose): IV:

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

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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: Infants, Children, and Adolescents: IV: 5 mg/kg once daily

Indication-specific dosing:

Aspergillosis, treatment:

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

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])

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:

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 2017])

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]).

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) (off-label use):

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 2017])

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 2017]).

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 (off-label use): 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 (off-label use): 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 (off-label use): 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 2017])

Leishmaniasis (visceral), HIV-infected patients (off-label use): Adolescents: IV:

Treatment (alternative agent): 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 2017])

Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm3): 3 mg/kg every 21 days (HHS [OI adult 2017])

Dosing: Renal Impairment

Manufacturer's labeling: No dosage adjustment provided in manufacturer's labeling (has not been studied).

Alternate recommendations (Aronoff 2007):

Intermittent hemodialysis: Not hemodialyzable; no supplemental dosage necessary.

Peritoneal dialysis: No supplemental dosage necessary.

Continuous renal replacement therapy (CRRT): No supplemental dosage necessary.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer's labeling (has not been studied).

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 pediatric patients and patients with cardiovascular disease.

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

Administration

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.

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 amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

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

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

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. Consider therapy modification

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

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

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

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: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. 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. Consider therapy modification

Adverse Reactions

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% (Limited to important or life-threatening): 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

Adverse events were not observed in animal reproduction studies. 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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), shortness of breath, chills, severe dizziness, passing out, abnormal heartbeat, angina, severe headache, bruising, or bleeding (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide