Amphotericin B lipid complex

MEDICATION SAFETY ISSUES
Safety issues:
Lipid-based amphotericin formulations (Abelcet®) 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.

High alert medication: 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.

U.S. BRAND NAMES — Abelcet®

PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral

DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.

Usual dosage: I.V.: 2.5-5 mg/kg/day as a single infusion

DOSING: PEDIATRIC — Refer to adult dosing.

(For additional information see "Amphotericin B lipid complex: Pediatric drug information")

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — The effects of renal impairment on drug pharmacokinetics or pharmacodynamics are currently unknown. The dose of amphotericin B lipid complex may be adjusted or drug administration may have to be interrupted in patients with acute kidney dysfunction to reduce the magnitude of renal impairment.

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Supplemental dose is not necessary.

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

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

Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)

DOSAGE FORMS: CONCISE
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)

GENERIC EQUIVALENT AVAILABLE — No

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 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.

Administer at an infusion rate of 2.5 mg/kg/hour (over 2 hours). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours.

COMPATIBILITY
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.

USE — Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy

USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections

ADVERSE REACTIONS SIGNIFICANT — Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.

>10%:
Central nervous system: Chills, fever
Renal: Serum creatinine increased
Miscellaneous: Multiple organ failure

1% to 10%:
Cardiovascular: Hypotension, cardiac arrest
Central nervous system: Headache, pain
Dermatologic: Rash
Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain
Renal: Renal failure
Respiratory: Respiratory failure, dyspnea, pneumonia

CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation

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 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.

Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.

DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

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

Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification

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

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

CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: 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. Risk C: Monitor therapy

Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination

Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification

PREGNANCY RISK FACTOR — B (show table)

LACTATION — Enters breast milk/contraindicated

BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.

MONITORING PARAMETERS — 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)

CANADIAN BRAND NAMES — Abelcet®; Amphotec®

INTERNATIONAL BRAND NAMES — Abelcet (AR, AT, BE, BR, CZ, DK, FI, FR, GB, GR, HN, IE, NL, NO, NZ, SE); Ambisome (AU, FR, HK, IL, KP); Ampholip (IN)

MECHANISM OF ACTION — 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.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: Increases with higher doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)

Half-life elimination: ~24 hours

Excretion: Clearance: Increases with higher doses (5 mg/kg/day): 400 mL/hour/kg