ABLC amphotericin

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

ABLC amphotericin B in hpid complex ANDA abbreviated new drug apphcation... 

ABLC amphotericin B in lipid complex ATN acute tubular necrosis... 

Janoff AS, et al. Amphotericin B lipid complex (ABLC ) a molecular rationale for the attenuation of AmB related toxicities. J Liposome Res 1993 3 451. 

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. 

Goldblum et al. studied the ocular penetration of IV amphotericin B and its lipid formulations in a rabbit model and determined L-AMB achieved at least eightfold higher amphotericin B concentrations in the aqueous of inflamed eyes when compared with ABLC or amphotericin B. 

The Collaborative Exchange of Antifungal Research (CLEAR) retrospectively reviewed the efficacy and renal safety in patients with Candida infections treated with hpid-complex amphotericin B (ABLC) and showed comparable response rates compared with conventional amphotericin B and evidence that ABLC may be used safely to treat patients at increased risk for renal impairment (Alexander and Wingard). 

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 ABLC 5 mg/kg/day in patients with neutropenia and intolerance or refractoriness to amphotericin deoxycholate have been reported in two smaller series of 25 treatment courses from the UK. In one, the mean serum creatinine at the start of therapy was 139 pmol/l and at the end of therapy 132 pmol/l there were no infusion-related adverse events (27). There was an increase in alanine transaminase activity in 12 of the 22 analysed treatment courses. In the other, there was an increase in serum creatinine in 5 of 18 courses (28%), and hypokalemia (less than 2.5 mmol/1) in two courses (11%) premedication for infusion-associated reactions was required in three courses (17%) (28). There were modest increases in serum alanine transaminase activities in five patients (30%). 

Liposomal amphotericin and ABLC have been compared in an open randomized study in 75 adults with leukemia and 82 episodes of suspected or documented mycosis (48). The median durations of treatment and dosages were 15 days at 4 mg/kg/day for liposomal amphotericin and 10 days at 3 mg/kg/day for ABLC. Acute but not dose-limiting infusion-related adverse events occurred in 36 versus 70%. Bilirubin increased to over 1.5 times baseline in 59 versus 38%. There was no difference in the effects of either agent on renal function and drug-related withdrawals. The overall response rate to therapy in documented fungal infections (29 and 30% respectively) was not different between the two drugs. 

A life-threatening event has been reported after the use of ABLC in a patient previously treated with amphotericin deoxycholate (81). 

Tachycardia, tachypnea, dyspnea, and severe hjrpoxe-mia occurred 90 minutes after the start of the first dose of ABLC, with radiological evidence of bilateral interstitial infiltrates, and required transient mechanical ventilation. After the event, treatment was continued with amphotericin deoxycholate without undesirable effects. 

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). 

A comparison of ABLC with amphotericin deoxycholate showed significant differences, with a doubling of baseline creatinine in 28% during ABLC compared with 47% during conventional therapy (5). 

There has been a retrospective comparison of the renal effects of ABLC with amphotericin deoxycholate in the treatment of invasive candidiasis and cryptococcosis in dosages of 0.6-5 mg/kg/day most patients received 5 mg/kg/day (115). Changes in serum creatinine were evaluated in three ways doubling of the baseline value, an increase from below 132 pmol/l (1.5 mg/dl) at baseline to over 132 pmol/l, and an increase from below 132 pmol/l at baseline to at least 177 pmol/l (2.0 mg/dl). These endpoints were achieved significantly more often with amphotericin deoxycholate than with ABLC, and the time needed to reach each of the endpoints was significantly shorter with amphotericin deoxycholate. An increased serum creatinine concentration was reported as an adverse event more often in patients receiving amphotericin deoxycholate than in patients receiving ABLC (24 versus 43%). 

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. 

Fleming RV, Kantarjian HM, Husni R, Rolston K, Lim J, Raad I, Pierce S, Cortes J, Estey E. 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. 

Rowles DM, Fraser SL. Amphotericin B lipid complex (ABLC)-associated hypertension case report and review. Clin Infect Dis 1999 29(6) 1564-5. 

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. 

Only ABLC and liposomal amphotericin B have been approved for use in proven candidiasis. Both in vivo and clinical studies indicate that these compounds are less toxic but as effective as amphotericin B when used in appropriate dosages. Nevertheless, their higher cost and the paucity of randomized trials in proven invasive candidiasis limit their front-line use in these infections. ... 

Despite early enthusiasm, more recent studies have yielded more equivocal information. In a randomized, double blind study, Wingard et al [146] have compared the safety of two Upid formulations of amphotericin B in febrile neutropenic patients. Subjects were randomized to receive amphotericin B lipid complex (ABLC) at a dose of 5 mg/kg/d (n=78), liposomal amphotericin B (L-Amph) at a dose of 3 mg/kg/ d (n=85), or L-Amph at a dose of 5 mg/kg/d (n=81). They found that the incidence of nephrotoxicity (doubhng of the base-... 

Wingard J, White M, 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 Comparative Study Group. Clin Infect Dis 2000 31 1155-1163. 

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. 

In a systematic review of the risk of nephrotojddty induced by two different lipid formulations of amphotericin, amphotericin B lipid complex (ABLC) and liposomal amphotericin B (l-AtuB), 11 studies were identified and 8 were included [5 ]. There was a higher probability of nephrotoxicity in patients who received ABLC versus L-AmB (OR=1.75 RR = 1.55), but there was a significant lack of homogeneity across these studies. Restricted analyses, omitting different studies that contributed to the heterogeneity, showed that the risks were more similar between the two formulations. 

Husain S, Capitano B, Corcoran T, Studer SM, Crespo M, Johnson B, Pilewski JM, Shutt K, Pakstis DL, Zhang S, Carey ME, Paterson DL, McCurry KR, Venkataramanan R. Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet ABLC) in lung transplant recipients. Transplantation 2010 90(11) 1215-9. 

Management of adverse reactions Administration of amphotericin B lipid complex (ABLC) may be associated with infusion-related reactions, such as fever, rigors, and chills. Premedication with hydrocortisone may reduce the incidence of these reactions, but there are currently limited confirmatory data from clinical practice [7 ]. In a prospective 18-month study, patients with cancers were given intravenous hydrocortisone 100 mg 15-30 minutes before each infusion of ABLC (275 cycles mean dose per cycle 931 mg) [14. There were 44 infusion-related reactions (16%), most of which followed the first infusion of a cycle (15% subsequent infusions 2.9%). The most common reactions were rigors (15%) and fever (13). There was no significant difference in the rates or types of reactions between ABLC-naive and previously treated patients. The dose of ABLC had no effect on the rate of reactions, but female sex, neutropenia, and being younger were predictive. 

Auron A, Auron-Gomez M, Raina R, Viswanathan S, Mhanna MJ. Effect of amphotericin B hpid complex (ABLC) in very low birth weight infants. Pediatr Nephrol 2009 24 295-9. 

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