What are the loading and maintenance doses of caspofungin for an adult with normal hepatic function, and how should the dose be adjusted in hepatic impairment?

Caspofungin Loading and Maintenance Dosing

Standard Adult Dosing (Normal Hepatic Function)

Administer a 70 mg IV loading dose on day 1, followed by 50 mg IV once daily as maintenance therapy for adults with normal hepatic function. 1

• The loading dose is given as a single 70 mg infusion on the first day of treatment 2, 1
• Maintenance dosing begins on day 2 at 50 mg IV once daily 2, 1
• All doses must be administered as a slow IV infusion over approximately 1 hour; never give as an IV bolus 1

Dose Escalation Considerations

• If the 50 mg maintenance dose is well tolerated but does not provide adequate clinical response, increase to 70 mg once daily 2, 1
• Consider empiric escalation to 70 mg daily in patients with body weight >80 kg, as standard dosing may result in subtherapeutic exposure 2
• Consider 70 mg daily in patients with hypoalbuminemia, as lower albumin concentrations significantly reduce caspofungin exposure 2

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Dosing in Hepatic Impairment

Mild Hepatic Impairment (Child-Pugh Score 5–6)

No dose adjustment is required for patients with mild hepatic impairment. 1, 3

• Use the standard regimen: 70 mg loading dose followed by 50 mg daily 1
• Pharmacokinetic studies show only modest increases in exposure (AUC ratio 1.21–1.55) that do not warrant dose reduction 3

Moderate Hepatic Impairment (Child-Pugh Score 7–9)

The FDA label recommends reducing the maintenance dose to 35 mg once daily after a 70 mg loading dose in patients with moderate hepatic impairment. 1

• This recommendation is based on pharmacokinetic data showing increased drug exposure in moderate hepatic impairment 1, 3
• The 70 mg loading dose on day 1 remains appropriate 4, 1

Critical Caveat: Hypoalbuminemia Without True Cirrhosis

In critically ill ICU patients with Child-Pugh B scores driven primarily by hypoalbuminemia (not true cirrhosis), do NOT reduce the dose to 35 mg, as this results in subtherapeutic exposure. 5, 6, 7

• Recent pharmacokinetic studies demonstrate that dose reduction to 35 mg in non-cirrhotic ICU patients with hypoalbuminemia results in significantly lower drug exposure and poor target attainment 5
• Hypoalbuminemia actually increases caspofungin clearance and volume of distribution, leading to lower AUC values 7
• The Child-Pugh score correlates poorly with caspofungin pharmacokinetics in critically ill patients without true cirrhosis 7
• Maintain the full 50 mg (or 70 mg) maintenance dose in ICU patients with trauma- or sepsis-induced liver injury, even if the Child-Pugh score is elevated 6, 7

Severe Hepatic Impairment (Child-Pugh Score >9)

• There is no clinical experience in adults with severe hepatic impairment 1
• Extrapolating from moderate impairment data, a 35 mg maintenance dose after a 70 mg loading dose would be reasonable, though this is not evidence-based 1

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Dosing Algorithm for Hepatic Impairment

Use this approach to determine the appropriate caspofungin dose:

1. Assess for true cirrhosis (imaging, clinical history, portal hypertension) versus acute/critical illness-related liver dysfunction 6, 7

2. If true cirrhosis is present:

   • Child-Pugh A (score 5–6): 70 mg loading, then 50 mg daily 1
   • Child-Pugh B (score 7–9): 70 mg loading, then 35 mg daily 4, 1
   • Child-Pugh C (score >9): Consider 70 mg loading, then 35 mg daily (no data available) 1

3. If critically ill without cirrhosis (sepsis, trauma, hypoalbuminemia):

   • Use standard dosing: 70 mg loading, then 50 mg daily, regardless of Child-Pugh score 5, 6, 7
   • Consider dose escalation to 70 mg daily if body weight >80 kg or severe hypoalbuminemia is present 2, 5

4. Monitor bilirubin specifically:

   • Elevated bilirubin (not albumin) correlates with reduced caspofungin elimination 7
   • If bilirubin is markedly elevated in the context of true cirrhosis, dose reduction is more justified 7

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Special Populations and Adjustments

Renal Impairment and CRRT

• No dose adjustment is required for any degree of renal impairment, including acute kidney injury, hemodialysis, or continuous renal replacement therapy (CRRT) 2, 4
• Caspofungin is eliminated primarily by non-enzymatic degradation; renal clearance is negligible (<1% excreted unchanged in urine) 2

Concomitant Enzyme Inducers

Increase the maintenance dose to 70 mg daily in adults receiving rifampin or other strong CYP enzyme inducers (efavirenz, nevirapine, phenytoin, carbamazepine, dexamethasone). 1

• The 70 mg loading dose remains unchanged 1
• Enzyme inducers reduce caspofungin concentrations, necessitating higher maintenance dosing 2, 1

Drug Interactions

• Caspofungin reduces tacrolimus AUC by approximately 20%; monitor tacrolimus levels closely 2, 4
• Cyclosporine increases caspofungin AUC by approximately 35% and may cause transient hepatic aminotransferase elevations; use with caution 2, 4

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Common Pitfalls to Avoid

• Do not reduce the caspofungin dose in ICU patients based solely on an elevated Child-Pugh score if the patient does not have true cirrhosis 5, 6, 7
• Do not assume that hypoalbuminemia alone warrants dose reduction; it actually increases clearance and may require higher doses 2, 7
• Do not administer caspofungin as an IV bolus; always infuse over approximately 1 hour to avoid histamine-like reactions 1, 8
• Do not forget to increase the dose to 70 mg daily in patients receiving rifampin or other enzyme inducers 1

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