- Invasive fungal infections in patients who are refractory to or intolerant of conventional amphotericin B therapy.
NON-FDA APPROVED USES
Amphotericin B lipid complex (ABLC)
Sigma Tau Pharm.
100 mg (5mg/mL 20 mL)
$240 per vial
*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
USUAL ADULT DOSING
- 5mg/kg/day IV
- For obese patients: consider ideal body weight (limited data)
USUAL PEDIATRIC DOSING
- Neonates: 2.5-5 mg/kg/dose IV q24h, duration at least 3 weeks (avoid lipid amphotericin for the treatment of cystitis)
- Pediatrics: 5 mg/kg/dose IV q24h
PEDIATRIC RENAL DOSING
No renal dosage adjustment in patients with renal insufficiency.
OTHER PEDIATRIC INFORMATION
- Lipid amphotericin is not preferred in neonates due to poor urinary concentration. Rather, amphotericin B deoxycholate is the preferred empiric antifungal in neonates.
DOSING FOR GLOMERULAR FILTRATION OF 50-80
DOSING FOR GLOMERULAR FILTRATION OF 10-50
DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN
DOSING IN HEMODIALYSIS
Not removed in dialysis, no supplement needed post HD. Usual dose.
DOSING IN PERITONEAL DIALYSIS
DOSING IN HEMOFILTRATION
ADVERSE DRUG REACTIONS
- Infusion reactions: fever, chills, phlebitis, pain at infusion site.
- Infusion related reactions were higher compared to liposomal amB, but lower compared to standard amphotericin B.
- Infusion reactions lower with premedication (hydrocortisone, NSAID, ASA, APAP, meperidine).
- Creatinine elevation (>2x baseline) observed in up to 8% (with low dose Abelcet)
- Electrolyte wasting: hypokalemia, hypomagnesemia, and hypocalcemia
- Nausea, vomiting, diarrhea, abdominal pain
- Metallic taste
- Headache and insomnia
- Transaminases elevation
- Increased in bilirubin (>1.5x baseline)
- Rash and pruritis
- Digoxin: potential increase in digitalis toxicity secondary to amphotericin-induced potassium depletion. Monitor potassium closely with co-administration.
- Diuretics: may result in additive hypokalemia. Monitor potassium closely with co-administration.
- Nephrotoxic agents (aminoglycosides, cidofovir, foscarnet, pentamidine): may result in additive nephrotoxicity. Avoid co-administration or use with close monitoring.
- Pentamidine: potential for additive hypocalcemia and/or nephrotoxicity. Avoid co-administration or use with close monitoring.
- Skeletal muscle relaxants: may enhance curariform effect of skeletal muscle relaxants (e.g., tubocurarine) due to hypokalemia. Monitor potassium closely with co-administration.
Active against most fungi with the notable exceptions of Candida lusitaniae, Trichosporon beigelii, Aspergillus terreus (some isolates), Pseudallescheria boydii, Scedosporium prolificans, Malassezia furfur and many Fusarium spp.
Amphotericin binds to ergosterol in fungal cell membrane, resulting in the disruption of the cell membrane. As a result the cell membrane is no longer able to function as a selective barrier and leakage of intracellular contents occurs. The lipid formulations are designed to reduce binding of amphotericin to mammalian cell membranes, therefore reducing toxicities.
Not absorbed from the GI tract.
Metabolism and Excretion
Slow renal excretion. Approximately 0.9% of dose excreted in the first day.
Cmax, Cmin, and AUC
0.9-2.5 mcg/ml after 5mg/kg IV dose administration.
Attains lower serum concentration but has greater volume of distribution compared to conventional amphotericin. Increased uptake by the liver and spleen and decreased kidney concentration. Poor fat distribution (animal data).
DOSING FOR DECREASED HEPATIC FUNCTION
B- There is limited data on the use of Amphotericin B lipid complex in pregnancy therefore the use should be limited to patients where the benefit outweighs the risk.
BREAST FEEDING COMPATIBILITY
No data available.
- Abelcet has comparable cost to Amphotec but generally better tolerated with less infusion related reactions.
- Abelcet has comparable cost to AmBisome, but resulted in a higher incidence of nephrotoxicity and infusion related side effects.
- Walsh TJ et al: Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327, 2008 [PMID:18177225]
Comment: The IDSA guidelines recommend Ambisome (3â??5 mg/kg/day IV) or Abelcet (5 mg/ kg/day IV) as alternatives to voriconazole for the treatment of invasive aspergillosis.
- Würthwein G et al: Population pharmacokinetics of amphotericin B lipid complex in neonates. Antimicrob Agents Chemother 49:5092, 2005 [PMID:16304177]
Comment: Abelcet dosed at 2.5-5 mg/kg/day is recommended in neonates for the treatment of invasive candidiasis.
- Fleming RV et al: Comparison of amphotericin B lipid complex (ABLC) vs. ambisome in the treatment of suspected or documented fungal infections in patients with leukemia. Leuk Lymphoma 40:511, 2001 [PMID:11426524]
Comment: This is a prospective, randomized trial comparing the safety and efficacy of Abelcet vs. Ambisome for the treatment of suspected or documented fungal infections in 82 patients with leukemia. The overall response to therapy was 27/43 (63%) for Abelcet and 15/39 (39%) for Ambisome (p=0.03). It is important to note that patients in the Ambisome arm were sicker (i.e more with Fusarium spp .). Patients receiving Abelcet had more infusion related toxicity, whereas patients receiving Ambisome had a higher incidence of bilirubin elevation.
- Wingard JR et al: A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis 31:1155, 2000 [PMID:11073745]
Comment: In this prospective, randomized trial, nephrotoxicity (3x above baseline) was noted in 6.2% and 26.9% of patients receiving Ambisome and Abelcet, respectively (p<0.001). Chills and rigors were reported in 50.5% in the Abelcet arm and 24.3% in the ambisome arm(p<0.001)). Ambisome, at a higher cost, has a lower incidence of nephrotoxicity and infusion related toxicity. It is however interesting to note that ADR reported with Abelcet in this trial is 2-fold higher than historical rates.
- Walsh TJ et al: Amphotericin B lipid complex in pediatric patients with invasive fungal infections. Pediatr Infect Dis J 18:702, 1999 [PMID:10462340]
Comment: Abelcet at a dosage of 5 mg/kg/day was well tolerated in 111 pediatric patients who were enrolled in this open label compassionate use protocol.
- Sharkey PK et al: Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis 22:315, 1996 [PMID:8838189]
Comment: Clinical improvement occurred in 86% of patients treated with Abelcet even though CSF sterilization was achieved in 42% after 2 weeks of therapy. This small study suggests that there may be a role for Abelcet in the treatment of cryptococcal meningitis , however larger trials need to be conducted.
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