Johns Hopkins Antibiotic (ABX) GuideBrand Names

Amphotericin B cholesteryl sulfate complex (ABCD)

Paul A. Pham, Pharm.D. BCPS, John G. Bartlett, M.D., Kathryn Dzintars, Pharm.D. BCPS, Alice Jenh Hsu, Pharm.D.

INDICATIONS

FDA

  • Manufacturing currently suspended in U.S.
  • Invasive aspergillosis in patients who are refractory to or intolerant of amphotericin B deoxycholate therapy

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Amphotec

Amphotericin B cholesteryl sulfate complex (ABCD)

Alkopharma

(Ben Venue Laboratories)

IV

vial

50mg

N/A

*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:
  • For obese patients: use ideal body weight (limited data)

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

  • Children: 4 mg/kg/dose IV q24h (max dose 7.5 mg/kg/dose)

PEDIATRIC RENAL DOSING

No renal dosage adjustment in patients with renal insufficiency

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose. Monitor closely for worsening renal function.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose.

DOSING IN HEMODIALYSIS

Not removed in dialysis, no supplement needed post HD. Usual dose.

DOSING IN PERITONEAL DIALYSIS

Usual dose.

DOSING IN HEMOFILTRATION

Standard dose.

ADVERSE DRUG REACTIONS

COMMON

  • Infusion reactions: fever (27%), chills (53%), phlebitis, pain at infusion site.
    • Infusion related reactions were the highest in amphotec treated patients compared to all amphotericin products, including regular amphotericin.
    • Infusion reactions lower with routine premedication (hydrocortisone, NSAID, ASA, meperidine).
  • Creatinine elevation (>2x baseline) observed in up to 25% on ABCD.

OCCASIONAL

  • Anemia
  • Electrolyte wasting: hypokalemia, hypomagnesemia, and hypocalcemia
  • Nausea, vomiting, diarrhea, abdominal pain
  • Metallic taste
  • Headache and insomnia
  • Hypotension
  • Transaminase elevations
  • Increased in bilirubin (>1.5x baseline)

RARE

  • Rash and pruritis

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

MECHANISM

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.

PHARMACOKINETIC PARAMETERS

Absorption

Not absorbed from the GI tract.

Metabolism and Excretion

No data.

Protein Binding

No data.

Cmax, Cmin, and AUC

2-9 mcg/ml after 4mg/kg IV dose administration.

T1/2

25 hrs.

Distribution

Attains lower serum concentration but has greater volume of distribution (vd = 4 L/kg) 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

No data. Usual dose likely in mild/moderate hepatic insufficiency

PREGNANCY RISK

B- There is limited data on the use of Amphotericin B cholesteryl sulfate complex in pregnancy; therefore the use should be limited to patients where the benefit outweighs the risk.

BREAST FEEDING COMPATIBILITY

No data available.

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. Paterson DL 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 62:1392, 2008  [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.

  2. Sandler ES et al: Use of amphotericin B colloidal dispersion in children. J Pediatr Hematol Oncol 22:242, 2000 May-Jun  [PMID:10864055]

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

  3. 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.

  4. Bowden R 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 35:359, 2002  [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.

  5. White MH 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 27:296, 1998  [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.

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Last updated: November 5, 2015