Caspofungin - A review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis

被引:55
作者
Keating, GM [1 ]
Figgitt, DP [1 ]
机构
[1] Adis Int Ltd, Auckland 1311, New Zealand
关键词
caspofungin; invasive aspergillosis; oesophageal candidiasis; invasive candidiasis; pharmacodynamics; pharmacokinetics; therapeutic use;
D O I
10.2165/00003495-200363200-00008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Echinocandins are a new class of antifungal agents with a novel mechanism of action (interference with fungal-cell wall synthesis). Caspofungin (Cancidas(R), Caspofungin MSD(R)) is the first echinocandin to be approved and is administered intravenously. Caspofungin 50 mg/day had similar efficacy to intravenous fluconazole 200 mg/day and was at least as effective as intravenous amphotericin B 0.5 mg/kg/day in patients with oesophageal candidiasis in two randomised, double-blind studies. A favourable combined clinical and endoscopic response occurred in 81% of caspofungin recipients versus 85% of fluconazole recipients and in 74% of caspofungin recipients versus 63% of amphotericin B recipients. A favourable combined response rate of approximate to90% and approximate to60% occurred in the stratum of patients with oesophageal candidiasis who received caspofungin or amphotericin B in a third randomised, double-blind study. Caspofungin (70mg loading dose followed by 50 mg/day) had similar efficacy to intravenous amphotericin B (0.7-1.0 mg/kg/day in patients with neutropenia and 0.6-0.7 mg/kg/day in patients without neutropenia) in patients with invasive candidiasis in a double-blind, randomised trial. A favourable overall response occurred in 73.4% of caspofungin recipients and in 61.7% of amphotericin B recipients. In a noncomparative study, salvage therapy with caspofungin (70mg loading dose followed by 50 mg/day) was effective in patients with invasive aspergillosis who were refractory to or did not tolerate standard antifungal therapy. A favourable response (complete plus partial response) occurred in 37 of 83 patients (45%). Caspofungin was generally well tolerated in clinical trials; it had similar tolerability to intravenous fluconazole and was better tolerated than intravenous amphotericin B. Significantly fewer caspofungin than amphotericin B recipients reported chills, fever, nausea or infusion-related adverse events. In conclusion, caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative trials, caspofungin had similar efficacy to fluconazole and was at least as effective as. amphotericin B in oesophageal candidiasis and had similar efficacy to amphotericin B in invasive candidiasis. In addition, caspofungin had similar tolerability to fluconazole and was better tolerated than amphotericin B in these indications. Caspofungin was also effective in patients with invasive aspergillosis who were refractory to or intolerant of standard antifungal. agents. Thus, caspofungin provides an alternative to triazoles or amphotericin B in oesophageal. candidiasis and an alternative to amphotericin B in invasive candidiasis, as well as being an effective salvage therapy in invasive aspergillosis.
引用
收藏
页码:2235 / 2263
页数:29
相关论文
共 112 条
[31]  
FLATTERY AM, 1998, 38 INT C ANT AG CHEM
[32]  
FLATTERY AM, 2000, 40 INT INT C ANT AG
[33]  
*FUJ PHARM CO LTD, FUJ LAUNCH CAND ANT
[34]  
GEISS HK, 2002, 42 INT C ANT AG CHEM
[35]   Addition of caspofungin to fluconazole does not improve outcome in murine candidiasis [J].
Graybill, JR ;
Bocanegra, R ;
Najvar, LK ;
Hernandez, S ;
Larsen, RA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (07) :2373-2375
[36]   Treatment of murine disseminated candidiasis with L-743,872 [J].
Graybill, JR ;
Najvar, LK ;
Luther, MF ;
Fothergill, AW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (08) :1775-1777
[37]   Treatment of murine Candida krusei or Candida glabrata infection with L-743,872 [J].
Graybill, JR ;
Bocanegra, R ;
Luther, M ;
Fothergill, A ;
Rinaldi, MJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (09) :1937-1939
[38]   Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections [J].
Groll, AH ;
Walsh, TJ .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2001, 10 (08) :1545-1558
[39]   Preliminary animal pharmacokinetics of the parenteral antifungal agent MK-0991 (L-743,872) [J].
Hajdu, R ;
Thompson, R ;
Sundelof, JG ;
Pelak, BA ;
Bouffard, FA ;
Dropinski, JF ;
Kropp, H .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (11) :2339-2344
[40]   Current strategies in the treatment of invasive Aspergillus infections in immunocompromised patients [J].
Harari, S .
DRUGS, 1999, 58 (04) :621-631