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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.
Pronunciation
(am foe TER i sin bee LIP id KOM pleks)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
Pregnancy Risk Factor
B
Lactation
Enters breast milk/contraindicated
Breast-Feeding Considerations
Due to limited data, consider discontinuing nursing during therapy.
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.
Adverse Reactions
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
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
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 for infusion are stable for 48 hours under refrigeration and 6 hours at room temperature. Protect from light. Following reconstitution, protect from light.
Reconstitution
Shake vial gently to disperse yellow sediment at bottom of container. Dilute with D5W to 1-2 mg/mL.
Compatibility
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.
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
Dosage
Children and Adults: I.V.:
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.
Range: 2.5-5 mg/kg/day as a single infusion
Dosing adjustment in renal impairment: None necessary; effects of renal impairment are not currently known
Hemodialysis: No supplemental dosage necessary
Peritoneal dialysis: No supplemental dosage necessary
Continuous renal replacement therapy (CRRT): No supplemental dosage necessary
Administration: I.V.
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.
Administration: I.V. Detail
Do not use an in-line filter. Flush line with dextrose; normal saline may cause precipitate.
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)
Test Interactions
Increased BUN (S), serum creatinine, alkaline phosphate, bilirubin; decreased magnesium, potassium (S)
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This medication can only be administered by infusion and therapy may last several weeks. Maintain good personal hygiene to reduce spread and recurrence of lesions. Maintain adequate hydration unless instructed to restrict fluid intake. May cause postural hypotension (use caution when changing from lying or sitting position to standing or when climbing stairs); or nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report chest pain or palpitations; CNS disturbances; skin rash; chills or fever; persistent nausea, vomiting, or abdominal pain; sore throat; excessive fatigue; swelling of extremities or unusual weight gain; respiratory difficulty; pain at infusion site; muscle cramping or weakness; or other adverse reactions. Breast-feeding precaution: Do not breast-feed.
Geriatric Considerations
The pharmacokinetics and dosing of amphotericin have not been studied in elderly. It appears that use is similar to young adults; caution should be exercised and renal function and desired effect monitored closely.
Additional Information
As a modification of dimyristoyl phosphatidylcholine:dimyristoyl phosphatidylglycerol 7:3 (DMPC:DMPG) liposome, amphotericin B lipid-complex has a higher drug to lipid ratio and the concentration of amphotericin B is 33 M. ABLC is a ribbon-like structure, not a liposome.
Controlled trials which compare the original formulation of amphotericin B to the newer liposomal formulations (ie, Abelcet®) are lacking. Thus, comparative data discussing differences among the formulations should be interpreted cautiously. Although the risk of nephrotoxicity and infusion-related adverse effects may be less with Abelcet®, the efficacy profiles of Abelcet® and the original amphotericin formulation are comparable. Consequently, Abelcet® should be restricted to those patients who cannot tolerate or fail a standard amphotericin B formulation.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments:
Prevention of infusion-related reactions: Patients may be premedicated with acetaminophen 650 mg and diphenhydramine 25-50 mg 30 minutes prior to infusion. Hydrocortisone can be used if patient has experienced rigors with amphotericin in the past. Meperidine can also be used for the treatment of rigors during the infusion.
This product is significantly more expensive than conventional amphotericin B. The incidence of nephrotoxicity with ABLC appears to be less when compared to conventional amphotericin B. The incidence of infusion-related reactions does not appear to be decreased with ABLC, but tolerance usually develops. Premedication may be considered to prevent/attenuate infusion-related adverse events. To prevent aggregation of the lipid products, it is important to shake the bag before hanging and once every 2 hours. In vitro experiments confirm that liposomal amphotericin B is at least as active as amphotericin B against clinical isolates of Candida, Cryptococcus, Blastomyces, and Aspergillus. Their activities also have appeared to be equal against Fusarium. Abelcet® may be restricted to patients who cannot tolerate or fail a standard amphotericin B formulation.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Sedation is common; may cause delirium
Mental Health: Effects on Psychiatric Treatment
May cause bone marrow suppression; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess culture and sensitivity report and patient's previous exposure to amphotericin B prior to starting therapy. Assess potential for interactions with other medications patient may be taking (eg, other nephrotoxic drugs). See Administration for specific infusion directions and premedication recommendations prior to administering first dose. Patient should be monitored closely for infusion related reactions (eg, anaphylaxis, chills, fever, nausea, vomiting, rigors, hypotension, acute respiratory distress) and cardiopulmonary resuscitation should be available. If acute respiratory distress occurs, infusion should be stopped and prescriber notified. Assess results of laboratory tests, therapeutic effectiveness, and adverse response frequently during therapy. Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
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)
References
De Marie S, “Clinical Use of Liposomal and Lipid-Complexed Amphotericin B,” J Antimicrob Chemother, 1994, 33(5):907-16.
Edwards JE Jr, Bodey GP, Bowden RA, et al, “International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections,” Clin Infect Dis, 1997, 25(1):43-59.
Eggimann P, Francioli P, Bille J, et al, “Fluconazole Prophylaxis Prevents Intra-abdominal Candidiasis in High-Risk Surgical Patients,” Crit Care Med, 1999, 27(6):1066-72.
Fichtenbaum CJ, Zackin R, Rajicic N, et al, “Amphotericin B Oral Suspension for Fluconazole-Refractory Oral Candidiasis in Persons With HIV Infection. Adult AIDS Clinical Trials Group Study Team 295,” AIDS, 2000, 14(7):845-52.
Hiemenz JW and Walsh TJ, “Lipid Formulations of Amphotericin B: Recent Progress and Future Directions,” Clin Infect Dis, 1996, 22(Suppl 2):133-44.
Kline S, Larsen TA, Fieber L, et al, “Limited Toxicity of Prolonged Therapy With High Doses of Amphotericin B Lipid Complex,” Clin Infect Dis, 1995, 21(5):1154-8.
Lyman CA and Walsh TJ, “Systemically Administered Antifungal Agents. A Review of Their Clinical Pharmacology and Therapeutic Applications,” Drugs, 1992, 44(1):9-35.
Mora-Duarte J, Betts R, Rotstein C, et al, “Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis,” N Engl J Med, 2002, 347(25):2020-9.
Patel R, “Antifungal Agents. Part I. Amphotericin B Preparations and Flucytosine,” Mayo Clin Proc, 1998, 73(12):1205-25.
Rapp RP, Gubbins PO, and Evans ME, “Amphotericin B Lipid Complex,” Ann Pharmacother, 1997, 31(10):1174-86.
Rex JH, Bennett JE, and Sugar AM, “A Randomized Trial Comparing Fluconazole With Amphotericin B for the Treatment of Candidemia in Patients Without Neutropenia. Candidemia Study Group and the National Institute,” N Engl J Med, 1994, 331(20):1325-30.
Rex JH, Pappas PG, Karchmer AW, et al, “A Randomized and Blinded Multicenter Trial of High-Dose Fluconazole Plus Placebo Versus Fluconazole Plus Amphotericin B as Therapy for Candidemia and Its Consequences in Nonneutropenic Subjects,” Clin Infect Dis, 2003, 36(10):1221-8.
Rex JH, Walsh TJ, Sobel JD, et al, “Practice Guidelines for the Treatment of Candidiasis. Infectious Diseases Society of America,” Clin Infect Dis, 2000, 30(4):662-78.
Slain D, “Lipid-Based Amphotericin B for the Treatment of Fungal Infections,” Pharmacotherapy, 1999, 19(3):306-23.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
Content last modified July 2009
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