Abelcet® is a sterile, pyrogen-free suspension for intravenous infusion. Abelcet® consists of amphotericin B complexed with two phospholipids in a 1:1 drug-to-lipid molar ratio. The two phospholipids, l-α-dimyristoylphosphatidylcholine (DMPC) and l-α-dimyristoylphosphatidylglycerol (DMPG), are present in a 7:3 molar ratio. Abelcet® is yellow and opaque in appearance, with a pH of 5 - 7.
NOTE: Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug’s functional properties relative to those of the unencapsulated or nonlipid-associated drug. In addition, different liposomal or lipid-complexed products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect functional properties of these drug products.
Amphotericin B is a polyene, antifungal antibiotic produced from a strain of Streptomyces nodosus. Amphotericin B is designated chemically as [1R-(1R*, 3S*, 5R*, 6R*, 9R*, 11R*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R*, 35S*, 36R*, 37S*)]-33-[(3-Amino-3, 6-dideoxy- β-D-mannopyranosyl) oxy]-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-carboxylic acid.
It has a molecular weight of 924.09 and a molecular formula of C47H73NO17. The structural formula is:
Abelcet® is provided as a sterile, opaque suspension in 20 mL glass, single-use vials. Each 20 mL vial contains 100 mg of amphotericin B (see DOSAGE AND ADMINISTRATION), and each mL of Abelcet® contains:
Amphotericin B USP 5.0 mg
l-α-dimyristoylphosphatidylcholine (DMPC) 3.4 mg
l-α-dimyristoylphosphatidylglycerol (DMPG) 1.5 mg
Sodium Chloride USP 9.0 mg
Water for Injection USP, q.s. 1 mL
Mechanism of Action
The active component of Abelcet®, amphotericin B, acts by binding to sterols in the cell membrane of susceptible fungi, with a resultant change in the permeability of the membrane. Mammalian cell membranes also contain sterols, and damage to human cells is believed to occur through the same mechanism of action.
Activity in vitro and in vivo
Abelcet® shows in vitro activity against Aspergillus sp. (n=3) and Candida sp. (n=10), with MICs generally <1 μg/mL. Depending upon the species and strain of Aspergillus and Candida tested, significant in vitro differences in susceptibility to amphotericin B have been reported (MICs ranging from 0.1 to >10 mg/mL). However, standardized techniques for susceptibility testing for antifungal agents have not been established, and results of susceptibility studies do not necessarily correlate with clinical outcome.
Abelcet® is active in animal models against Aspergillus fumigatus, Candida albicans, C. guillermondii, C. stellatoideae, and C. tropicalis, Cryptococcus sp., Coccidioidomyces sp., Histoplasma sp., and Blastomyces sp. in which end-points were clearance of microorganisms from target organ(s) and/or prolonged survival of infected animals.
Fungal species with decreased susceptibility to amphotericin B have been isolated after serial passage in culture media containing the drug, and from some patients receiving prolonged therapy. Although the relevance of drug resistance to clinical outcome has not been established, fungal species which are resistant to amphotericin B may also be resistant to Abelcet®.
Anaphylaxis has been reported with amphotericin B desoxycholate and other amphotericin B-containing drugs. Anaphylaxis has been reported with ABELCET® (amphotericin b) with an incidence rate of < 0.1%. If severe respiratory distress occurs, the infusion should be immediately discontinued. The patient should not receive further infusions of ABELCET® (amphotericin b) .
Amphotericin b lipid complex Pregnancy Warnings
Amphotericin B lipid complex has been assigned to pregnancy category B by the FDA. Animal studies failed to reveal evidence of fetal harm. There are no controlled data in human pregnancy. Amphotericin B lipid complex should only be given during pregnancy when benefit outweighs risk.