Caspofungin Dosing in Adult Sepsis Patients
For an adult sepsis patient with normal renal function and no significant hepatic impairment, administer caspofungin with a loading dose of 70 mg IV on day 1, followed by 50 mg IV daily as maintenance therapy. 1
Standard Dosing Regimen
- Loading dose: 70 mg IV on day 1 1
- Maintenance dose: 50 mg IV daily starting day 2 1
- No renal adjustment needed: Standard doses can be administered regardless of renal function, including patients on continuous renal replacement therapy (CVVH or CVVHD), as caspofungin clearance by dialysis is negligible 2, 3
Clinical Context for Sepsis Patients
The Infectious Diseases Society of America strongly recommends echinocandins (including caspofungin) as first-line empiric therapy for suspected invasive candidiasis in critically ill septic patients, particularly those with risk factors for fungal infection and signs of septic shock. 1
Key advantages in sepsis:
- Superior tolerability compared to amphotericin B with fewer drug-related adverse events 1
- Concentration-dependent killing with efficacy related to AUC/MIC and Cmax/MIC ratios 1
- Minimal drug interactions via CYP450 system, important in polypharmacy-heavy ICU settings 2
Duration of Therapy
- Continue for 14 days after documented bloodstream clearance AND resolution of symptoms attributable to candidemia 1, 2
- Obtain daily or every-other-day blood cultures to establish clearance timepoint 1
- Perform dilated funduscopic examination within first week to rule out endophthalmitis 1
Dose Escalation Considerations
Consider increasing to 70 mg daily in the following scenarios:
- Body weight >80 kg: Standard 50 mg maintenance may result in subtherapeutic exposure 1, 4, 5
- Hypoalbuminemia: Lower albumin concentrations significantly reduce caspofungin exposure, as the drug is 97% protein-bound 1, 6, 5
- Inadequate clinical response after several days at standard dosing 2
- Concomitant enzyme inducers: Rifampin, efavirenz, nevirapine, phenytoin, carbamazepine, or dexamethasone reduce caspofungin concentrations 2, 7
Recent pharmacokinetic modeling demonstrates that patients weighing >70 kg or with hypoalbuminemia achieve significantly lower drug exposure with standard dosing, potentially compromising efficacy. 5
Important Drug Interactions in Sepsis
- Tacrolimus: Caspofungin reduces tacrolimus AUC by ~20%; monitor levels closely 2, 7
- Cyclosporine: Increases caspofungin AUC by ~35% and may cause transient hepatic transaminase elevations; use only when benefit outweighs risk 2, 7
Monitoring Parameters
- Electrolytes: Monitor potassium levels, as hypokalemia can occur (particularly in pediatric patients, though relevant for all) 2, 8
- Liver function tests: Transient elevations in transaminases may occur; monitor in all patients 2, 7
- Clinical response: Assess fever curve, hemodynamic stability, and resolution of sepsis markers 1
Common Pitfalls to Avoid
Do not underdose obese or hypoalbuminemic patients: The standard 50 mg maintenance dose may be inadequate for patients >70-80 kg or with albumin <3 g/dL. 4, 5
Do not delay source control: Remove central venous catheters when feasible and safe, as catheter retention is associated with treatment failure in candidemia. 1
Do not assume adequate peritoneal penetration: Echinocandins achieve limited concentrations in peritoneal fluid due to high protein binding (>95%), which may be relevant in intra-abdominal candidiasis. 1