ABCD amphotericin

ABLC = Amphotericin B Lipid Complex ABCD = Amphotericin B Colloidal Dispersion L-AMB = Liposomal Amphotericin B... 

ABCD amphotericin B colloidal dispersion ANCA anti-neutrophil cytoplasmic antibody... 

Amphotericin B Abelcet (ABLC) [injectable 5 mg/ml, Upid complex],Ambisome (L-AMB) [injectable 50 mg/vial,liposomal].Amphocin (injectable 50 mg/vial, nonlipid),Amphotec (ABCD) [injectable 50 mg/vial, 100 mg/vial, colloidal dispersion], Fungizone [injectable 50 mg/vial, nonlipid], generic also available. 

Lipid formulations of amphotericin have individually variable pharmacokinetics. The use of DAMB in 20% Intralipid results in marked changes, with lower antifung-ally active blood concentrations (13). Infusion of ABLC, ABCD, or L-Amb, AmBisome results in plasma amphotericin concentrations specific to the individual formulation. The half-life of amphotericin after lipid formulations is prolonged compared with the deoxycholate formulation (14) 4-10 days for ABCD (15) and about 5 days for ABLC (16). The importance of these differences is unknown, because they do not reflect the biologically active concentration of amphotericin, which also varies with formulation. On a weight for weight basis amphotericin in lipid formulations is less active than in the deoxycholate formulation, because of lower systemic availability (5). One factor that complicates the interpretation of blood concentrations is the sparse data... 

The safety and efficacy of amphotericin colloidal dispersion have been evaluated in 148 immunocompromised patients with candidemia (20). ABCD was given intravenously in a median daily dose of 3.9 (range 0.1-9.1) mg/kg for a median of 12 (range 1-72) days. In the safety analysis (n = 148 patients), nephrotoxicity occurred in 16% of the patients, with either doubling of the baseline serum creatinine concentration or an increase of 88 pmol/l (1.0 mg/dl) or a 50% fall in calculated creatinine clearance. Severe adverse events were believed to be probably or possibly related to ABCD in 36 patients (24%), including chills and fever (9.5%), hypotension and abnormal kidney function (4%), tachycardia, asthma, hypotension (3%), and dyspnea (2%). ABCD was withdrawn in 12%... 

Mucormycosis has an exceedingly high mortality rate in immunocompromised patients. In five phase I and phase II studies of ABCD, 21 patients were given ABCD (mean dose 4.8 mg/kg per infusion for a mean duration of 37 days) on the basis of pre-existing renal insufficiency, nephrotoxicity during amphotericin B therapy, or refractory infections (24). Of 20 evaluable patients, 12 responded to ABCD, and there was no renal or hepatic toxicity. However, a previous randomized, comparative trial showed an at least similar if not increased frequency... 

Amphotericin colloidal dispersion has been compared with amphotericin deoxycholate in a prospective, randomized, double-blind study in the empirical treatment of fever and neutropenia in 213 patients (25). Patients were stratified by age and concomitant use of ciclosporin or tacrolimus and then randomized to receive ABCD (4 mg/kg/day) or amphotericin deoxycholate (0.8 mg/ kg/day) for 14 days. Renal dysfunction was less likely to develop and occurred later with ABCD than with amphotericin deoxycholate. Likewise, the absolute and percentage fall in the serum potassium concentration from baseline to the end of therapy was greater with amphotericin deoxycholate than ABCD. However, probable or possible infusion-related hypoxia and chills were more common with ABCD than amphotericin deoxycholate. There was a therapeutic response in 50% of the patients who received ABCD and 43% of those who received amphotericin deoxycholate. Thus, ABCD was of comparable efficacy and less nephrotoxic than amphotericin deoxycholate, but infusion-related events were more common with ABCD. 

Anorexia, nausea, and vomiting are common effects of parenteral administration of amphotericin. Gastrointestinal complaints are markedly less common with liposomal amphotericin than with ABCD(5). 

Cholestasis has been reported in infants treated with amphotericin for systemic Candida infections (SEDA-14, 230). Most of the above reports were incidental, and amphotericin cannot be regarded as a known cause of liver damage. This does not necessarily also apply to liposomal amphotericin and other lipid formulations. Therapy with L-Amb, AmBisome was associated with a rise in alkaline phosphatase in over a third of children treated with AmBisome (93) and with hepatic dysfunction in a little under 20% of adolescents and adults. In a small retrospective study, ABLC was withdrawn in 27% of patients because of rises in serum bilirubin and alkaline phosphatase, a finding confirmed in a larger prospective study. Cholestasis has also been observed with ABCD, in contrast to reports that L-AmB does not increase transaminases (5). 

Amphotericin B colloidal dispersion During ABCD therapy 8.5% of patients developed nephrotoxicity compared with 21 % in those given amphotericin deoxycholate (5). 

Anaphylaxis after ABCD occurred in a patient who had previously been treated with both amphotericin deoxycholate and ABLC without infusion-related adverse effects (65). During the first infusion of ABCD he developed spontaneously reversible severe back pain and then swelling of his lips, respiratory distress, and left-sided hemipar-esis, which resolved after 24 hours. An MRI scan suggested an ischemic event in the right putamen, lending support to the hypothesis that he had had an anaphylactic reaction to ABCD, hypoperfusion, and a subsequent stroke. 

In another patient, serious adverse events (fever, severe rigors, a fall in blood pressure, worsening mental status, increasing creatinine concentration, and leukocjdosis) occurred after unrecognized substitution of one amphotericin formulation (ABLC) by another (ABCD) (132). After discovery of the switch, ABLC therapy was rein-stituted and tolerated without incident. 

In patients intolerant to amphotericin B or fluconazole, one of the lipid formulations may he used. In a randomized trial, amphotericin B lipid complex (ABLC) was found to he equivalent to 0.6-1 mg/kg per day of amphotericin B, and open-lahel therapy with amphotericin B colloid dispersion (ABCD) has been successful. 

The use of deoxycholate amphotericin B frequently is associated with the development of induced nephrotoxicity. In an attempt to decrease the incidence of nephrotoxicity, three lipid formulations of amphotericin B have been developed and approved for use in humans amphotericin B lipid complex (ABLC, Abelcet Enzon Pharmaceuticals), amphotericin B colloidal dispersion (ABCD, Amphotec Inter-mune Pharmaceuticals), and liposomal amphotericin B (AmBisome Gilead Pharmaceuticals). In these preparations, amphotericin B is incorporated into the phospholipid bilayer membrane rather than in the enclosed aqueous phase. 

Amphotericin B is complexed with deoxycholate (C-AMB) and marketed as a lyophilized powder (fungizone) containing 50 mg of amphotericin B that forms a colloid in water. Three lipid formulations of amphotericin B are marketed in the U.S. Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, amphocil) contains equimolar amounts of amphotericin B and cholesteryl sulfate. AMBISOME is a small, unilamellar vesicle formulation that combines amphotericin B (50 mg) with 350 mg of lipid (phosphatidylcholine, cholesterol, and distearoylphosphatidylglycerol, in molar ratio of 10 5 4) in an -10% molar ratio. Amphotericin B lipid complex (ABLC, abelcet) contains dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7 3 mixture with -35 mol% of amphotericin B. 

Observational studies In clinical trials, in the absence of premedication, the rates of infusion-related reactions have been higher with amphotericin B colloidal dispersion (ABCD) than with other forms of amphotericin B, including amphotericin B deoxy-cholate [7 ]. Data on pre-medication practices and infusion-related reactions in 170 patients (median age 37 years 52% men) who received 1230 infusions of ABCD (mean dose 2.8 mg/kg/day) have been captured in a multicenter, worldwide, observational registry [8 ]. Treatment was according to the site s standard treatment practice. Common pre-medications included glucocorticoids, antihistamines, paracetamol (acetaminophen), and metamizole. The overall rate of infusion-related reactions... 

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