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Mode of action
- inhibit ß-(1,3) glucan synthesis, damaging fungal cell walls
- no drug target in mammalian cells
Spectrum of activity
- rapidly fungicidal against most Candida spp.
- fungistatic against Aspergillus spp.
- active against cyst form of Pneumocystis carinii. Probably only
useful for prophylaxis.
Caspafungin
Pharmacokinetics
- administration: IV
- 96% plasma protein bound
- predominantly hepatic metabolism (hydrolysis and N-acetylation). Hepatic
uptake slow, leading to long terminal half-life of ~10.6 h
- reduce dose to 50% of daily dose in patients with severe hepatic
dysfunction, but give usual loading dose
- also adrenal and splenic metabolism
- plasma concentrations slightly increased in renal failure (unrelated
to renal excretion or plasma protein binding
- cannot be dialysed
- distribution: urinary concentration low, CSF concentration expected to be
low
Clinical use
- as effective and less toxic than amphotericin B in patients with invasive
candidiasis or candidaemia
- insufficient data in patients with endocarditis, persistent infection
with neutropaenia, ophthalmitis, mediastinitis, meningitis or urinary
tract infection
- some suggestion that in C. parapsilosis infection
response may be slower to caspofungin than to amphotericin
- invasive aspergillosis
Adverse effects
- fever (~35% of patients)
- hepatotoxicity
- raised transaminases common in patients receiving caspofungin but may
not be attributable to caspofungin
- hepatic necrosis in animals given large doses (5-8 mg/kg)
- headache in ~15%
- phlebitis in ~20%
- rash infrequent
- haemolysis may occur but clinically significant haemolysis is rare
Drug interactions
- slight increases in clearance with co-adminstration of:
- phenytoin
- carbamazepine
- dexamethasone
- efavirenz, nelfinavir, nevirapine
- rifampicin - concentrations of both drugs increased
- tacrolimus - concentration of tacrolimus decreased by ~20%
- cyclosporin - increased caspofungin plasma concentration
Micafungin
Pharmacokinetics
- administration: IV
- 99.8% plasma protein bound
- predominantly hepatic metabolism (hydrolysis and N-acetylation). Hepatic
uptake slow, leading to long terminal half-life of 11-17 h
- also adrenal and splenic metabolism
- cannot be dialysed
- distribution: urinary concentration low, CSF concentration expected to be
low
Clinical use
Adverse effects
- phlebitis
- abnormal liver function tests
- rash infrequent
- headache in ~3%
- fever uncommon
- clinically significant haemolysis rare
Drug interactions
No interactions reported.
Further reading
Denning DW. Echinocandin antifungal drugs. Lancet, 2003;
362:1142-51
Pappas PG. Guidelines for treatment of candidiasis. Clin
Infect Dis, 2004; 38:161-89
Potential conflict of interest
The Dept of Anaesthesia & Intensive Care of the Chinese
University of Hong Kong received funding for educational activities in 2002 and
2003 from Merck, Sharp & Dohme (HK) Ltd.
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