In an adult patient receiving continuous renal replacement therapy (any filter type), does caspofungin require dose adjustment?

Caspofungin Dosing in Patients on CRRT

No dose adjustment of caspofungin is required for patients receiving continuous renal replacement therapy (CRRT), regardless of filter type. Standard dosing of 70 mg loading dose followed by 50 mg daily maintenance should be used.

Evidence-Based Rationale

Elimination Pathway and Renal Independence

• Caspofungin undergoes nonenzymatic degradation as its major route of elimination and does not require dosage adjustment for renal insufficiency or dialysis 1
• The drug is not renally cleared—renal clearance of parent drug is extremely low at approximately 0.15 mL/min, with only ~1.4% of the dose excreted unchanged in urine 2
• Caspofungin is not dialyzable, thus supplementary dosing is not required following hemodialysis 2

CRRT-Specific Pharmacokinetic Data

• Caspofungin clearance by CRRT is negligible 3. In a prospective study of 27 critically ill patients (7 on CVVH, 8 on CVVHD, 13 controls), caspofungin exposure during CRRT was nearly identical to that of patients not requiring CRRT and comparable to healthy volunteers 3
• CRRT clearance of caspofungin was measured at 0.048 ± 0.12 L/h for CVVH and 0.042 ± 0.042 L/h for CVVHDF—both clinically insignificant compared to total body clearance 4
• No dosage adjustment is necessary for patients with renal impairment of any severity, including end-stage renal disease 5, 2

Filter Type Considerations

• The mode of CRRT (hemofiltration vs. hemodialysis vs. hemodiafiltration) does not affect caspofungin pharmacokinetics 4. A population pharmacokinetic study found no significant difference in drug clearance between CVVH and CVVHDF 4
• Patient weight was the only covariate affecting drug clearance and central volume—CRRT modality had no impact 4

Recommended Dosing Strategy

Standard Regimen for CRRT Patients

• Administer 70 mg IV loading dose on day 1, followed by 50 mg IV daily maintenance 5, 3
• This applies to all CRRT modalities including CVVH, CVVHD, and CVVHDF 3, 4

Weight-Based Considerations

• For patients weighing >80 kg on CRRT, consider increasing the maintenance dose to 70 mg daily 4. Monte Carlo simulations demonstrate that standard 50 mg maintenance dosing may result in subtherapeutic exposure in heavier patients 4
• A 100 mg loading dose followed by 50 mg maintenance best achieved pharmacokinetic/pharmacodynamic targets for patients ≤80 kg, while 70 mg maintenance was required for patients >80 kg 4

Critical Pitfalls to Avoid

• Do not reduce caspofungin doses in CRRT patients based on concerns about renal clearance—the drug is not renally eliminated and CRRT removes negligible amounts 1, 3
• Do not confuse caspofungin dosing with colistin dosing—unlike colistin (which requires dose adjustment for CRRT), caspofungin requires no modification 1
• Be aware that critically ill patients may have increasing clearance over the first 3 days of therapy, potentially leading to subtherapeutic concentrations despite standard dosing 6. This time-dependent pharmacokinetic drift is not explained by CRRT or other recorded covariates 6
• Monitor for hypoalbuminemia—lower albumin concentrations significantly reduce caspofungin exposure (the drug is ~97% albumin-bound), though this is independent of CRRT status 5, 2