Amphotericin lipid formulations

If a patient is non-neutropenic and has never received prior azole therapy, fluconazole 800 mg/day is an appropriate first-line therapy for invasive candidiasis until identification of the Candida isolate. Amphotericin B deoxycholate 0.7 mg/kg per day or caspofungin 70 mg on day 1, then 50 mg/day, voriconazole, or a lipid amphotericin B formulation are recommended as empiric therapy in patients with neutropenic fever. 

Fusariosis Lipid formulations of amphotericin B OR Voriconazole 6 mg/kg q12hour for 1 day, then 4 mg/kg q12hour OR Posaconazole 200 mg PO qid for 14 days, then 200 mg PO q12hour OR Combination therapy ... 

Response to antifungal therapy in invasive candidiasis is often more rapid than for endemic fungal infections. Resolution of fever and sterilization of blood cultures are indications of response to antifungal therapy. Toxicity associated with antifungal therapy is similar in these patients as described earlier with the caveat that some toxicities maybe more pronounced in crit-ically-ill patients with invasive candidiasis. Nephrotoxicity and electrolyte disturbances, with amphotericin B in particular, are problematic and may not be avoidable even with lipid amphotericin B formulations. Fluconazole and echinocandins are generally safer options, and are generally well tolerated. Decisions to use one class of agents over the other is principally driven by concerns of non-albicans species, patient tolerability, or history of prior fluconazole exposure (risk factor for non-albicans species.). 

For patients unable to tolerate a full course of amphotericin B, consider lipid formulations of amphotericin B or fluconazole >800 mg orally daily. 

Amphotericin B is generally preferred as initial therapy in patients with rapidly progressive disease, whereas azoles are generally preferred in patients with subacute or chronic presentations. Lipid formulations of amphotericin B have not been extensively studied for coccidioidomycosis but can offer a means of giving more drug with less toxicity. Treatments for primary respiratory disease (mainly symptomatic patients) are 3- to 6-month courses of therapy. 

CNS disease Lipid formulation of amphotericin BIV 3-6 mg/kg/day x 6-10 weeks (Note Induction therapy with azoles alone is discouraged.) Amphotericin Brf IV 0.7-1 mg/kg/day + flucytosine 100 mg/kg/ day orally x 2 wk, followed by fluconazole 400 mg orally daily for a minimum of 10 weeks (in patients intolerant to fluconazole, substitute itraconazole 200-400 mg orally daily) or Amphotericin B IV 0.7-1 mg/kg/day + 5-flucytosine 100 mg/kj day orally x 6-10 weeks or Amphotericin Brf IV 0.7-1 mg/kg/day x 10 weeks Refractory disease Intrathecal or intraventricular amphotericin B (continued)... 

In patients with significant renal disease, lipid formulations of amphotericin B can be substituted for deoxycholate amphotericin B... 

Lipid formulation of amphotericin B IV 3-5 m kg/day Chronic disseminated candidiasis Treatment duration Until calcification or resolution of lesions (hepatosplenic candidiasis) stable patients Fluconazole IV/po 6 mg/kg/day... 

Larabi M, et al. New lipid formulation of amphotericin B spectral and microscopic analysis. Biochim Biophys Acta 2004 1664 172. 

Lipid formulations of amphotericin B have been shown to reduce the severe kidney toxicity of amphotericin B and are indicated in patients with renal impairment or when unacceptable toxicity precludes the use of amphotericin B deoxycholate in effective doses. 

Renai function impairment Use amphotericin B desoxycholate with care in patients with reduced renal function frequent monitoring is recommended (see Precautions). Lipid formulations have been reported to overcome most problems of chronic nephrotoxicity, even in patients with impaired renal function following previous treatment with amphotericin B desoxycholate. 

Invasive aspergillosis For the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (ie, amphotericin B, lipid formulations of amphotericin B, itraconazole). Caspofungin has not been studied as initial therapy for invasive aspergillosis. 

Wong-Beringer A, Jacobs RA, and Gugliehno BJ. Lipid formulations of amphotericin B Clinical efficacy and toxicities. CUn Infect Dis 1998 27 603-618. 

Table 48- -1 Properties of Conventional Amphotericin and Some Lipid Formulations.1 ...

Three such formulations are now available and have differing pharmacologic properties as summarized in Table 48-1. Although clinical trials have demonstrated different renal and infusion-related toxicities for these preparations compared with regular amphotericin B, there are no trials comparing the different formulations with each other. Limited studies have suggested at best a moderate improvement in the clinical efficacy of the lipid formulations compared with conventional amphotericin B. Because the lipid preparations are much more expensive, their use is usually restricted to patients intolerant to, or not responding to, conventional amphotericin treatment. 

Conventional formulation (Amphotericin B, Fungizone) 50 mg powder for injection Lipid formulations ... 

Three lipid formulations of Amphotericin B are now either marketed for clinical use or undergoing further study before they can be approved in various countries worldwide (Hiemenz and V felsh,... 

Hiemenz, J. W. and V felsh, T. J. (1996). Lipid formulations of amphotericin B recent progress and future directions.Clin. Infect. Dis., 22 (Suppl. 2), S133-144. 

Lipid formulation of amphotericin BIV 5-6 m kg/dayx 6-10 weeks (Note Induction therapy with azoles alone is discouraged.)... 

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. 

Having a broad-spectrum fungicidal activity, amphotericin remains the mainstay of treatment of most invasive fungal infections. Compared with conventional amphotericin B deoxycholate, other lipid formulations of amphotericin (amphotericin B colloidal dispersion, amphotericin B lipid complex, and liposomal amphotericin B) facilitate treatment in patients with suspected and proven invasive mycoses, who are intolerant of or refractory to conventional amphotericin. 

Because of nephrotoxicity from amphotericin, which is common when amphotericin is given as the deoxycholate, lipid formulations have been developed. The formulations that are currently available are ... 

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