Note: Amphotec has been discontinued in the US for more than 1 year.
Note: Lipid-based amphotericin formulations (Amphotec) may be confused with conventional formulations (desoxycholate [Amphocin, Fungizone]). 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.
Aspergillosis (invasive), treatment: Usual dosage range: 3 to 4 mg/kg/day. Note: 6 mg/kg/day has been used for treatment of life-threatening invasive aspergillosis in immunocompromised patients (Bowden, 2002).
Premedication: For patients who experience chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: A nonsteroidal with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50 to 100 mg with or without a nonsteroidal and diphenhydramine (Paterson, 2008).
Test dose: For patients receiving their first dose in a new treatment course, a small amount (10 mL of the final preparation, containing between 1.6 to 8.3 mg) infused over 15 to 30 minutes is recommended. The patient should then be observed for an additional 30 minutes.
Mild to moderate impairment: No dosage adjustment provided in manufacturer’s labeling. However, no pharmacokinetic changes were noted in patients with mild-to-moderate impairment.
Severe impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied).
No dosage adjustment provided in manufacturer’s labeling (has not been studied).
(For additional information see "Amphotericin B cholesteryl sulfate complex (United States: Not available): Pediatric drug information")
Note: Amphotec has been discontinued in the US for more than 1 year.
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: Premedication for patients who experience fever, chills, hypotension, nausea, or other nonanaphylactic infusion-related immediate reactions may be given 30 to 60 minutes prior to drug administration: NSAIDs (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone may be given (Paterson 2008); if patient experiences rigors during infusion, meperidine may be administered. The manufacturer’s labeling advises a test dose be administered immediately preceding the first dose when a new course of treatment occurs. A small amount of drug (eg, 10 mL of final preparation containing between 1.6 and 8.3 mg of drug) should be infused over 15 to 30 minutes and patient should be carefully observed for the next 30 minutes.
Aspergillosis, treatment:
Invasive: Infants, Children, and Adolescents: IV: Usual dose range: 3 to 4 mg/kg/dose once daily; doses as high as 7.5 mg/kg/dose have been described in open label studies (Sandler 2000)
Endocarditis: Children and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine (AHA [Baltimore 2015])
Candidiasis, treatment: Infants, Children, and Adolescents:
Invasive: IV: 3 to 5 mg/kg/dose once daily (IDSA [Pappas 2016])
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/-infected: Adolescents: IV: 3 to 4 mg/kg/dose once daily for 14 to 21 days (HHS [OI adult 2016])
Coccidiodomycosis, disseminated (non-CNS) or diffuse pulmonary disease: HIV-exposed/-infected:
Infants and Children: IV: 5 mg/kg/dose once daily until clinical improvement; dose may be increased 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 change to fluconazole or itraconazole (HHS [OI adult 2016])
Histoplasmosis, disseminated disease (moderately severe to severe): HIV-exposed/-infected: Adolescents: IV: 3 mg/kg/dose once daily for at least 2 week induction, followed by oral itraconazole (HHS [OI adult 2016])
Mild to moderate impairment: There are no dosage adjustments provided in manufacturer's labeling; however, no pharmacokinetic changes were noted in patients with mild to moderate impairment.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to moderate impairment: There are no dosage adjustments provided in manufacturer's labeling; however, no pharmacokinetic changes were noted in patients with mild to moderate impairment.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
May be product dependent
Amphotec has been discontinued in the US for more than 1 year.
IV: Initially infuse at 1 mg/kg/hour. Rate of infusion may be increased with subsequent doses as patient tolerance allows (minimum infusion time: 2 hours). For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg with or without a nonsteroidal and diphenhydramine (Paterson, 2008). If the patient experiences rigors during the infusion, meperidine may be administered. If severe respiratory distress occurs, the infusion should be immediately discontinued.
Parenteral: IV: Do not filter or use an inline filter for administration. Flush line with D5W prior to and following infusion.
Initially infuse diluted solution at 1 mg/kg/hour. Rate of infusion may be increased with subsequent doses as patient tolerance allows (minimum infusion time: 2 hours). If utilizing test dose as recommended by the manufacturer’s labeling, infuse over 15 to 30 minutes.
Treatment of invasive aspergillosis in patients who have failed amphotericin B deoxycholate treatment, or who have renal impairment or experience unacceptable toxicity which precludes treatment with amphotericin B deoxycholate in effective doses.
Candida species infections (serious)
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Lipid-based amphotericin formulations (Amphotec) may be confused with conventional formulations (Amphocin, Fungizone)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Amphotericin B colloidal dispersion has an improved therapeutic index compared to conventional amphotericin B, and has been used safely in patients with amphotericin B-related nephrotoxicity; however, continued decline of renal function has occurred in some patients.
>10%:
Cardiovascular: Hypotension, tachycardia
Central nervous system: Chills
Endocrine & metabolic: Hypokalemia
Gastrointestinal: Vomiting
Hepatic: Hyperbilirubinemia
Renal: Increased serum creatinine
Miscellaneous: Fever
5% to 10%:
Cardiovascular: Chest pain, facial edema, hypertension
Central nervous system: Abnormality in thinking, drowsiness, headache, insomnia
Dermatologic: Diaphoresis, pruritus, skin rash
Endocrine & metabolic: Hyperglycemia, hypocalcemia, hypomagnesemia, hypophosphatemia
Gastrointestinal: Abdominal pain, diarrhea, enlargement of abdomen, hematemesis, nausea, stomatitis, xerostomia
Hematologic & oncologic: Anemia, hemorrhage, thrombocytopenia
Hepatic: Abnormal hepatic function tests, increased serum alkaline phosphatase, jaundice
Neuromuscular & skeletal: Back pain, muscle rigidity, tremor
Respiratory: Dyspnea, epistaxis, hypoxia, increased cough, rhinitis
<5%, postmarketing, and/or case reports: Acidosis, atrial arrhythmia, cardiac arrest, cardiac failure, gastrointestinal hemorrhage, hepatic failure, injection site reaction, oliguria, pain at injection site, pleural effusion, renal failure, seizure, syncope, ventricular arrhythmia
Hypersensitivity to amphotericin B or any component of the formulation (unless the benefits outweigh the possible risk to the patient)
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; the patient should not receive further infusions. During the initial dosing, the drug should be administered under close clinical observation.
• Infusion reactions: Acute infusion reactions, sometimes severe, may occur 1-3 hours after starting infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses. Pretreatment with antihistamines/corticosteroids and/or decreasing the rate of infusion can be used to manage reactions. Avoid rapid infusion.
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]).
In a multicenter study of pediatric patients (<16 years of age), amphotericin B cholestyrel sulfate complex (ABCD) use had a significantly lower incidence of renal toxicity (12%; 3/25 patients) than amphotericin B deoxycholate (52%; 11/21 patients).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arsenic Trioxide: Amphotericin B may enhance the hypotensive effect of Arsenic Trioxide. Amphotericin B may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as amphotericin B. Risk D: Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Cardiac Glycosides: Amphotericin B may enhance the adverse/toxic effect of Cardiac Glycosides. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and amphotericin B whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE (Systemic): Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Amphotericin B may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dichlorphenamide: Amphotericin B may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Dronabinol: May increase the serum concentration of Amphotericin B. Specifically, dronabinol may displace amphotericin B from its protein-binding sites, leading to an increased concentration of active, unbound drug. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. Amphotericin B may increase the serum concentration of Flucytosine. Risk C: Monitor therapy
Foscarnet: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methoxyflurane: May enhance the nephrotoxic effect of Amphotericin B. Risk X: Avoid combination
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination
Amphotericin crosses the placenta and enters the fetal circulation. Amphotericin B is recommended for the treatment of serious systemic fungal diseases in pregnant women; refer to current guidelines (IDSA [Pappas 2016]; King 1998; Pilmis 2015).
It is not known if amphotericin is excreted into breast milk. Due to its poor oral absorption, systemic exposure to the nursing infant is expected to be decreased; however, because of the potential for toxicity, breast-feeding is not recommended by the manufacturer (Mactal-Haaf 2001).
Liver function tests, serum electrolytes (especially potassium and magnesium), BUN, serum creatinine, CBC, prothrombin time; temperature, I/O; signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes)
Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
Distribution: Vd: Total volume increases with higher doses, reflects increasing uptake by tissues (with 4 mg/kg/day = 4 L/kg); predominantly distributed in the liver; concentrations in kidneys and other tissues are lower than observed with conventional amphotericin B (Walsh 2008)
Half-life elimination: ~28 hours; prolonged with higher doses
Suspension (reconstituted) (Amphotec Intravenous)
50 mg (1): $93.33
100 mg (1): $160.00
Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.
