Table 4.
Comparison of echinocandins for treatment of invasive candidiasis
| Parameter | Caspofungin | Micafungin | Anidulafungin |
|---|---|---|---|
| Structure99 | C56 H96N10O19 Side chain: fatty acid |
C56H70N9NaO23S Side chain: aromatic (3,5-diphenyl-substituted isoxazole) |
C58H73N7O1 Side chain: lipophilic alkoxytriphenyl (terphenyl) |
| Metabolism106 | Liver metabolism via peptide hydrolysis and N-acetylation |
Liver metabolism via arylsulfatase and COMT | No liver metabolism–slow degradation in plasma Degraded products eliminated into feces by biliary route |
| Protein binding101 | >95% | >99% | >99% |
| Pharmacokinetics100,106,121,157 | Cmax (ug/mL): 12 AUC (ug h/mL): 118 CL (mL/min): 10–12.5 Total half-life (hours) : 8–10 Mean elimination half-life (hours): 8–10 VD (L): 9.67 |
Cmax (ug/mL): 18 AUC (ug h/mL): 101.6 CL (mL/min): 10.5 Total half-life (hours): 13–20 Mean elimination half-life (hours): 12–17 VD (L): 18–19 |
Cmax (ug/mL): 7.7 AUC (ug h/mL): 106 CL (mL/min): 16.67 Total half-life (hours): 40–50 Mean elimination half-life (hours): 24–26 VD (L): 30–50 |
| Pharmacodynamics103–105,158 | AUC/MIC: For C. glabrata: • Wild type: 2.04 • FKS mutation: 2.67 PAFE: For C. albicans: >12 hours at >MIC For C. parapsilosis: 33–>120 hours at MIC For C. glabrata: >120 hours at 2x MIC |
AUC/MIC: For C. glabrata: • Wild type: 6.78 • FKS mutation: 0.90 PAFE: For C. albicans: Shorter than the other two agents (~9.8 hours on average) For C. parapsilosis: 0–8 hours at MIC For C. krusei: >20.1 hours* was observed at 4x MIC concentration |
AUC/MIC: For C. glabrata: • Wild type: 13.2 • FKS mutation: 3.43 PAFE: For C. albicans: >12 hours, at >MIC, PAFE even observed at sub-MIC concentration For C. parapsilosis: 33–>120 hours at MIC, but longer than caspofungin when 2x MIC For C. glabrata: >120 hours at 2x MIC |
| Dose114,137 | 70 mg as a single loading dose on first day, followed by a maintenance dose of 50 mg once daily or 70 mg once daily, when the body weight exceeds 80 kg |
100 mg once daily No loading dose required |
200 mg as a single loading dose on first day, followed by 100 mg dose once daily |
| Dosing in renal patients without replacement therapy106 | No dosing adjustment needed | No dosing adjustment needed | No dose adjustment needed |
| Dosing in renal patients with replacement therapy115,159–164 | Generally no dosing adjustment is needed. However, in critically ill patients on continuous venovenous hemodiafiltration, dose escalation to 100 mg (loading dose) or 200 mg once daily may be required |
No dose adjustment is required for patients undergoing continuous renal replacement therapy However, increase in dose is recommended after 8-hour plasma exchange therapy |
Filter absorption is observed yet clinical significance is unknown No dosing adjustment is needed |
| Drug interactions110,111,121–123,127,129,130,138,165 | • Powerful CYP inducers or inhibitors* (clinically insignificant) • Rifampicin (clinically significant) • Tacrolimus (clinically significant) • Cyclosporine (clinically significant) |
• Cyclosporine (clinically significant) • Sirolimus, nifedipine (clinically insignificant) |
• Cyclosporine (clinically insignificant) |
| Precautions and contraindications106,166–168 | • Relatively safe • Common ADR (>10%): diarrhea, pyrexia, increase in liver enzymes (AST/ALT) and serum alkaline phosphatase |
• Common ADR (>10%): fever, infusion-related reaction, phlebitis, skin rash • Hepatotoxicity (unknown incidence) • Hepatocellular tumors found in vitro in rats when micafungin is given for more than 3 months • Restricted indication, to be used only if other agents are not appropriate |
• Safe • Less frequent ADR (1%–4%): hypokalemia, nausea and vomiting |
Note:
*
For example, phenytoin, carbamazepine, nevirapine, nelfinavir, dexamethasone.
Abbreviations: ADR, adverse drug reaction; ALT, alanine aminotransferase; AST, aspartate transaminase; AUC, area under the curve; CL, clearance; COMT, catechol-O-methyltransferase; MIC, minimum inhibitory concentration; PAFE, post-antifungal effects; VD, volume of distribution.