What is the recommended intravenous dosing and infusion protocol for caspofungin in an adult, including loading dose, maintenance dose, infusion volume and rate, and dose adjustments for hepatic impairment (Child‑Pugh class B and C) and renal impairment?

Caspofungin Intravenous Dosing and Infusion Protocol

Standard Adult Dosing

Administer a 70 mg IV loading dose on day 1, followed by 50 mg IV once daily as maintenance therapy, infused slowly over approximately 1 hour. 1

• Never administer caspofungin as an IV bolus—always infuse over approximately 1 hour to minimize histamine-like reactions. 1, 2
• The loading dose is 70 mg IV on day 1 for all indications except esophageal candidiasis (which requires only 50 mg daily without a loading dose). 1
• Maintenance dose is 50 mg IV once daily starting on day 2. 1

Dose Escalation for Inadequate Response

If the 50 mg daily dose is well tolerated but does not provide adequate clinical response, increase to 70 mg once daily. 1, 2

• Consider dose escalation to 70 mg daily in patients with body weight >80 kg, as standard 50 mg maintenance may result in subtherapeutic exposure. 2
• Consider 70 mg daily in patients with hypoalbuminemia, as lower albumin concentrations significantly reduce caspofungin exposure. 2

Hepatic Impairment Dose Adjustments

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

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

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

The FDA label recommends reducing the maintenance dose to 35 mg once daily (after the standard 70 mg loading dose) for moderate hepatic impairment. 1, 3, 4

However, recent high-quality evidence contradicts this recommendation: Two recent pharmacokinetic studies demonstrate that dose reduction to 35 mg in patients with Child-Pugh B cirrhosis results in suboptimal drug exposure and should be avoided. 5, 6 The 2018 study by Spriet et al. specifically showed that dose reduction to 35 mg in cirrhotic patients resulted in lower drug exposure than the approved dose in non-cirrhotic patients, recommending the full 50 mg dose regardless of cirrhosis severity. 6

Critical distinction: The FDA dose reduction recommendation was based on true cirrhotic patients with hepatocellular dysfunction. 4 In ICU patients with hypoalbuminemia but without true cirrhosis (non-cirrhotic patients with elevated Child-Pugh scores driven by low albumin), do not reduce the dose—these patients actually require standard or higher dosing. 5, 6

Severe Hepatic Impairment (Child-Pugh Score >9)

There is no clinical experience in patients with severe hepatic impairment; use with caution and close monitoring. 1

Practical Approach to Hepatic Impairment

• For true cirrhotic patients with Child-Pugh B: Consider maintaining 50 mg daily rather than reducing to 35 mg, based on recent evidence showing subtherapeutic exposure with dose reduction. 5, 6
• For ICU patients with elevated Child-Pugh scores due to hypoalbuminemia (not true cirrhosis): Use standard 70/50 mg dosing or consider 70/70 mg. 5
• Monitor liver enzymes closely in all patients with hepatic impairment, as Grade IV liver enzyme elevations occurred in 27.7% of liver transplant recipients. 7

Renal Impairment Dose Adjustments

No dose adjustment is required for renal impairment, including acute kidney injury, hemodialysis, or continuous renal replacement therapy (CRRT). 1, 3, 2

• Caspofungin is eliminated primarily by non-enzymatic degradation; renal clearance is negligible (≈0.15 mL/min) with only ~1% excreted unchanged in urine. 2
• CRRT removes only trivial amounts (clearance ≈0.04–0.05 L/h), making standard dosing appropriate. 2

Concomitant Drug Interactions Requiring Dose Adjustment

When caspofungin is co-administered with rifampin or other hepatic enzyme inducers (efavirenz, nevirapine, phenytoin, carbamazepine, dexamethasone), increase the maintenance dose to 70 mg once daily. 1, 7

Important Drug Interactions

• Tacrolimus: Caspofungin reduces tacrolimus AUC by ~20%; monitor tacrolimus levels and adjust accordingly. 3, 7, 2
• Cyclosporine: Increases caspofungin AUC by ~35% and may cause transient hepatic aminotransferase elevations; use together only when benefit outweighs risk. 7, 3, 2

Reconstitution and Preparation

Reconstitute each vial with 10.8 mL of 0.9% Sodium Chloride Injection, Sterile Water for Injection, or Bacteriostatic Water for Injection. 1

• 50 mg vial: Add 10.8 mL diluent → resulting concentration 5 mg/mL 1
• 70 mg vial: Add 10.8 mL diluent → resulting concentration 7 mg/mL 1
• Mix gently until the white to off-white cake dissolves completely. 1
• Visually inspect for particulate matter or discoloration; do not use if cloudy or precipitated. 1

Infusion Volume and Rate

Infuse the reconstituted dose in an appropriate volume of compatible IV solution (typically 100-250 mL of 0.9% Sodium Chloride or other compatible diluent) over approximately 1 hour. 1

• Infusion rates faster than 1 hour are associated with histamine-like reactions. 2
• Slow infusion over approximately 1 hour minimizes infusion-related adverse effects. 1

Common Pitfalls to Avoid

• Do not reduce the dose to 35 mg in ICU patients with hypoalbuminemia who do not have true cirrhosis—this results in subtherapeutic exposure. 5, 6
• Do not administer as an IV bolus—always infuse over 1 hour. 1
• Do not forget to increase the dose to 70 mg daily when co-administering with enzyme inducers like rifampin. 1, 7
• Do not assume dose adjustment is needed for renal impairment or dialysis—it is not. 1, 3, 2