Caspofungin Dose Modification in Liver Disease
In patients with moderate hepatic impairment (Child-Pugh score 7-9), reduce the maintenance dose of caspofungin to 35 mg daily after the standard 70 mg loading dose, while patients with mild hepatic impairment (Child-Pugh score 5-6) require no dose adjustment. 1, 2
Dosing Algorithm by Hepatic Function
Mild Hepatic Impairment (Child-Pugh Score 5-6)
- No dose adjustment required 1, 2, 3
- Use standard dosing: 70 mg loading dose on Day 1, followed by 50 mg daily 2
- Pharmacokinetic studies show only modest increases in drug exposure (AUC increased by 21-55%) that do not warrant dose reduction 3
Moderate Hepatic Impairment (Child-Pugh Score 7-9)
- Reduce maintenance dose to 35 mg daily after the standard 70 mg loading dose 1, 2, 3
- This recommendation is based on FDA-approved labeling and pharmacokinetic data showing 76% increase in AUC after single dose, but only 7% increase at steady state with reduced maintenance dosing 2, 3
Severe Hepatic Impairment (Child-Pugh Score >9)
- No clinical experience exists in this population 2
- Exercise extreme caution and consider alternative antifungal agents when possible 2
Critical Caveats for Critically Ill Patients
The Child-Pugh score may be misleading in critically ill patients without cirrhosis. Recent evidence challenges routine dose reduction in ICU patients with elevated Child-Pugh scores:
- In critically ill patients with trauma- or sepsis-induced liver injury (not cirrhosis), do not reduce the caspofungin dose despite elevated Child-Pugh scores 4
- A 2018 study in decompensated cirrhosis patients (Child-Pugh B and C) found that dose reduction to 35 mg resulted in subtherapeutic drug exposure compared to standard dosing in non-cirrhotic patients 5
- The Child-Pugh score correlates poorly with caspofungin clearance in critically ill patients; hypoalbuminemia and hyperbilirubinemia have differential effects on pharmacokinetics 4
Specific Laboratory Parameters to Monitor
Hypoalbuminemia (not Child-Pugh score) is the primary driver of altered caspofungin pharmacokinetics:
- Low albumin correlates with decreased drug exposure (lower AUC) and higher clearance 4
- Consider maintaining 50 mg daily dose in hypoalbuminemic patients to ensure adequate exposure 4
Hyperbilirubinemia affects elimination rate but not overall exposure:
- Elevated bilirubin correlates with decreased elimination rate constant but does not significantly impact AUC 4
- This should not drive dose reduction decisions 4
Monitoring Requirements
Monitor liver enzymes closely in all patients with hepatic impairment receiving caspofungin:
- Grade IV liver enzyme elevations occurred in 27.7% of liver transplant recipients in one study 6
- Caspofungin undergoes hepatic metabolism with some spontaneous chemical degradation 1
- Discontinue if significant worsening of hepatic function occurs 1
Special Population: Liver Transplant Recipients
In high-risk liver transplant patients receiving caspofungin prophylaxis:
- Standard dosing is 70 mg loading dose followed by 50 mg daily 6
- Duration studied was 21 days in the pivotal trial 6
- Concomitant use with cyclosporine or tacrolimus is generally safe without additional hepatotoxicity, though close monitoring is warranted 7
Drug Interactions Requiring Dose Adjustment
Increase caspofungin to 70 mg daily when co-administered with hepatic enzyme inducers:
- Rifampin, efavirenz, nevirapine, phenytoin, carbamazepine, or dexamethasone reduce caspofungin concentrations 1, 8, 2
- This applies to both adults and pediatric patients (70 mg/m² in children, not to exceed 70 mg) 2
Avoid cyclosporine co-administration unless benefit outweighs risk:
- Cyclosporine increases caspofungin AUC by approximately 35% 1, 8
- Transient hepatic aminotransferase elevations may occur 8
Renal Function Considerations
No dose adjustment required for renal impairment or dialysis 1, 9, 2