Amphotericin B cholesteryl sulfate complex (ABCD)

INDICATIONS

FORMS

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

• 3-4 mg/kg/day (may be increased up to 7.5 mg/kg)
• Invasive aspergillosis:
  • 6 mg/kg/d IV
  • Note: voriconazole usual first-line therapy
  • If unable to tolerate voriconazole, Ambisome or Abelcet is preferred.
• For obese patients: use ideal body weight (limited data)

PEDIATRIC DOSING

RENAL DOSING

ADVERSE DRUG REACTIONS

DRUG INTERACTIONS

• 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.

SPECTRUM

Aspergillus spp (A. fumigatus, A. flavus), Candida spp (C. albicans, C. krusei, C. parapsilosis, C. tropicalis), Cryptococcus neoformans, and Blastomyces dermatitidis. Active against most fungi with the notable exceptions of Candida lusitaniae, Trichosporon beigelii, Aspergillus terreus (some isolates), Pseudallescheria boydii, Malassezia furfur and Fusarium spp.

PHARMACOLOGY

COMMENTS

• Current shortage due to voluntary suspension of all manufacturing and distribution by Alkopharma.
• Parenteral lipid amphotericin that was the least expensive of all lipid formulations, but also associated with the highest infusion-related side effects compared to standard amphotericin B and other lipid amphotericin formulations.
• Ambisome and Abelcet are generally preferred over Amphotec for most indications.

References

1. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327-60.  [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.
   

2. Paterson DL, David K, Mrsic M, et al. Pre-medication practices and incidence of infusion-related reactions in patients receiving AMPHOTEC: data from the Patient Registry of Amphotericin B Cholesteryl Sulfate Complex for Injection Clinical Tolerability (PRoACT) registry. J Antimicrob Chemother. 2008;62(6):1392-400.  [PMID:18812423]

   Comment: Previous data suggested higher rates of infusion related reactions with ABCD as compared to conventional amphotericin as well as the other lipid formulations. This was largely due to lack of the use of premedications, which have now become routine in clinical practice. This data suggests that the incidence of infusion related reactions is lower than previously thought when corticosteroids are used prior to ABCD administration; acetaminophen and antihistamine use, though, had no effect.
   

3. Bowden R, Chandrasekar P, White MH, et al. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2002;35(4):359-66.  [PMID:12145716]

   Comment: This is a multicenter randomized, double-blind trial of Amphotec (ABCD)6 mg/kg/day vs. Amphotericin B 1.0-1.5 mg/kg/day for treatment of invasive aspergillosis in 174 patients. The results of this trial showed Amphotec and Amphotericin B are comparable in therapeutic efficacy for invasive aspergillosis. The study was under powered to detect a potential difference, nevertheless,overall responses was poor in both groups (17% in the ABCD group vs.23% in the ampho B group).The advantage of ABCD is the reduced rate of nephrotoxicity, but this advantage is offset by a comparable rate of complications requiring discontinuation due to infusion-related adverse reactions.
   

4. White MH, Bowden RA, Sandler ES, et al. Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis. 1998;27(2):296-302.  [PMID:9709879]

   Comment: This trial demonstrated that Amphotec was equivalent to standard amphotericin B for the empiric treatment of febrile neutropenia. The frequency of renal dysfunction was decreased with Amphotec, but more infusion related-reaction was seen. The rate of infusion-related reactions seen in this study is consistent with that seen with historical controls where Amphotec demonstrated the highest incidence of infusion related reaction compared to all other forms of amphotericin including standard Amphotericin B.
   

5. Sandler ES, Mustafa MM, Tkaczewski I, et al. Use of amphotericin B colloidal dispersion in children. J Pediatr Hematol Oncol. 2000;22(3):242-6.  [PMID:10864055]

   Comment: Amphotec (ABCD) dosed at 4 mg/kg/day (up to 7.5mg/kg/day) was well tolerated in children.