Amphotericin B lipid complex (ABLC)
- 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)
$6.30 per mL
*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)
ADULT RENAL DOSING
DOSING IN HEMODIALYSIS
Not removed in dialysis, no supplement needed post HD. Usual dose.
DOSING IN PERITONEAL DIALYSIS
DOSING IN RENAL REPLACEMENT THERAPY
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.
ADVERSE DRUG REACTIONS
- Infusion reactions: fever, chills, phlebitis, pain at the infusion site.
- Infusion-related reactions were higher than liposomal amB but lower than 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 the 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 the fungal cell membrane, resulting in the disruption of the cell membrane. As a result, the cell membrane can no longer function as a selective barrier and leakage of intracellular contents occur. The lipid formulations are designed to reduce the binding of amphotericin to mammalian cell membranes, reducing toxicities.
Not absorbed from the GI tract.
Metabolism and Excretion
Slow renal excretion. Approximately 0.9% of the dose was excreted on the first day.
Cmax, Cmin, and AUC
0.9-2.5 mcg/ml after 5mg/kg IV dose administration.
It attains lower serum concentration but has a greater distribution volume than 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 are 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 are available.
- Abelcet (ABLC) should not be considered interchangeable with other amphotericin products.
- Abelcet has a comparable cost to Amphotec but is generally better tolerated with fewer infusion-related reactions.
- Abelcet has a comparable cost to AmBisome but results in a higher incidence of nephrotoxicity and infusion-related side effects.
- Würthwein G, Groll AH, Hempel G, et al. Population pharmacokinetics of amphotericin B lipid complex in neonates. Antimicrob Agents Chemother. 2005;49(12):5092-8. [PMID:16304177]
Comment: Abelcet dosed at 2.5-5 mg/kg/day is recommended in neonates to treat invasive candidiasis.
- Fleming RV, Kantarjian HM, Husni R, 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. 2001;40(5-6):511-20. [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, White MH, Anaissie E, 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. 2000;31(5):1155-63. [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% of 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. Interestingly, ADR reported with Abelcet in this trial is 2-fold higher than historical rates.
- Walsh TJ, Seibel NL, Arndt C, et al. Amphotericin B lipid complex in pediatric patients with invasive fungal infections. Pediatr Infect Dis J. 1999;18(8):702-8. [PMID:10462340]
Comment: Abelcet at a dosage of 5 mg/kg/day was well tolerated in 111 pediatric patients enrolled in this open-label compassionate use protocol.
- Sharkey PK, Graybill JR, Johnson ES, et al. Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996;22(2):315-21. [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.