- Echinocandin (semisynthetic lipopeptide)
- Anti-fungal derived from Glarea lazoyensis
- Off-white lyophilised powder reconstituted in water for immediate use
- 50 mg and 70 mg vials (with 35.7 mg and 50 mg sucrose respectively)
- Store at 2-8C
- Reconstituted infusion (e.g. 100 mL or 250 mL 09% NaCl or Hartmans) can be safely stored for up to 24 hours at 25C or 48h at 2-8C.
- Do not reconstitute in glucose containing infusions as caspofungin is not stable with glucose.
- 70mg IV loading dose followed by 50mg IV daily (70mg in adults >80kg)
- Slow infusion over 1 hour
- Duration depends on severity of infection and response to treatment
- continue for 14 days after last positive blood culture for invasive candidiasis
- minimum 14 days for most fungal infections, and at least 7 days after neutropenia and clinical symptoms resolve
- continue for 72 hours after resolution of neutropenia in neutropenic sepsis
MECHANISM OF ACTION
- Echinocandins inhibit synthesis of beta(1,3)-D-glucan
- Essential component of cell walls of many yeast and moulds
- Not present in mammalian cells
- Active against Aspergillus spp (fungistatic) and Candida spp (fungicidal), including:
- Those with acquired resistance to amphotericin B, 5-flucytosine, and fluconazole
- Isolates with multiple transport mutations
- biofilms (more so than azoles and polyenes)
- Echinocandin resistance reported for Aspergillus species and non-albicans Candida spp.
- Invasive candidiasis
- Oesophageal candidiasis
- Invasive aspergillosis (intolerant or refractory to other therapies)
- Empiric treatment of neutropenic fever with high risk/ suspected fungal infection
- Metabolic disorders susceptible to sucrose load (e.g. fructose intolerance or sucrase-isomaltase insufficiency)
- Moderate hepatic insufficiency: Child Pugh score 7 to 9
- Reduce daily dose from 50mg to 35mg daily
- No adjustment for renal disease or renal replacement therapy
- A: poor oral availability; given IV
- D: 97% protein binding (albumin); 92% distributed to tissues; peak tissue concentration at 1-2 days
- M: spontaneous degradation to open ring structure, followed by hydrolysis and N-acetylation (including significant liver metabolism). Small amount of irreversible covalent adducts formed between intermediate products and plasma proteins.
- E: Plasma clearance 1-12 mL/min determined by distribution; Polyphasic elimination from plasma: short alpha-half time, beta half time of 9-11 h, and gamma half-time 45 h. Excreted via urine (41%) and feces (34%).
- nausea, diarrhoea
- Hypokalaemia, hypercalcaemia
- Hepatic dysfunction
- Anaemia, leucopenia, neutropenia
- Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
- Peripheral oedema
DRUG-DRUG INTERACTIONS (DDIs)
- Ciclosporin increases casponfungin levels; monitor LFTs
- Tacrolimus and caspofungin may affect each other’s levels; monitor tacrolimus levels and LFTs.
- Rifampicin and other CYP3A4 inducers may cause slight reduction in caspofungin levels.
Other echinocandins can be used as alternatives to caspofungin, neither require dose reduction in hepatic or renal disease:
- Anidulofungin (e.g. 200mg IV loading dose, followed by 100mg IV daily) – spontaneously degrades in plasma
- Micafungin (e.g. 100mg IV daily) – mild CYP3A4 inhibitor, may be associated increased risk of liver tumours
Echinocandins have a more favourable safety profile than other anti-fungals (Mourad and Perfect, 2018)
FOAM and web resources
- Australian Product Information – Caspofungin
Journal articles and textbooks
- Brunton, L., Hilal-Dandan, R., Knollman, B. (2017). Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 13th Edition. United States: McGraw-Hill Education. Ch 61.
- Dockrell, H., Goering, R., Chiodini, P. L., Zuckerman, M. (2018). Mims’ Medical Microbiology and Immunology. United Kingdom: Elsevier. Ch 34.
- Mourad A, Perfect JR. Tolerability profile of the current antifungal armoury. J Antimicrob Chemother. 2018 Jan 1;73(suppl_1):i26-i32. doi: 10.1093/jac/dkx446. PMID: 29304209; PMCID: PMC6636388.