What is the recommended dose of Caspofungin (Caspofungin) for adult and pediatric patients with severe fungal infections, such as invasive candidiasis or aspergillosis, considering factors like hepatic impairment and potential drug interactions?

Caspofungin Dosing

For adults with invasive candidiasis or aspergillosis, administer caspofungin 70 mg IV loading dose on day 1, followed by 50 mg IV daily; for pediatric patients ≥2 years, use 70 mg/m² loading dose (day 1) followed by 50 mg/m² daily (maximum 70 mg/day). 1, 2

Adult Dosing

Standard Regimen

• Loading dose: 70 mg IV on day 1 1, 3
• Maintenance dose: 50 mg IV daily 1, 3
• Duration: Continue for at least 14 days after the last positive culture and resolution of symptoms in invasive candidiasis/candidemia 1, 4

Dose Escalation

• For inadequate clinical response: Increase to 70 mg IV daily 1
• Higher doses (up to 150-200 mg daily) have been studied for salvage therapy of invasive aspergillosis and are well-tolerated with linear pharmacokinetics 1, 5
• A multicenter trial demonstrated that 150 mg daily was as safe as standard dosing, with no additional safety concerns 5

Hepatic Impairment

• Moderate hepatic insufficiency (Child-Pugh score 7-9): Reduce maintenance dose to 35 mg daily 6, 4
• Monitor liver enzymes closely in all patients with hepatic impairment, as Grade IV elevations occurred in 27.7% of liver transplant recipients 6
• No adjustment needed for mild hepatic impairment 6

Renal Impairment

• No dose adjustment required for any degree of renal impairment, including acute kidney injury or dialysis 1, 4

Pediatric Dosing

Age-Based Dosing (≥2 years)

Caspofungin is not approved in children <2 years of age 7

• Children 2 to <12 years OR aged 12-14 years weighing <50 kg:

  • Loading dose: 70 mg/m² IV on day 1 (maximum 70 mg) 2
  • Maintenance: 50 mg/m² IV daily (maximum 70 mg/day) 7, 1, 2

• Children ≥15 years OR aged 12-14 years weighing ≥50 kg:

  • Use adult dosing: 70 mg loading dose, then 50 mg daily 7

Pediatric Efficacy Data

• In a prospective multicenter study of 48 pediatric patients (ages 6 months-17 years), success rates were 50% for invasive aspergillosis and 81% for invasive candidiasis 2
• The 50 mg/m²/day dose in children provides exposure comparable to 50 mg/day in adults 1

Drug Interactions

Critical Interactions Requiring Monitoring

Tacrolimus:

• Caspofungin reduces tacrolimus AUC by approximately 20% 1, 6, 4
• Monitor tacrolimus levels and adjust dose accordingly 1, 6

Cyclosporine:

• Cyclosporine increases caspofungin AUC by approximately 35% 1, 6, 4
• Use only when benefit outweighs risk due to transient hepatic aminotransferase elevations 6, 4
• Close monitoring warranted 6

Enzyme Inducers:

• Rifampin, efavirenz, nelfinavir, nevirapine, phenytoin, carbamazepine, and dexamethasone may reduce caspofungin concentrations 1, 6
• Increase maintenance dose to 70 mg daily when co-administered with these agents 6

Special Clinical Considerations

Candida parapsilosis Infections

• Caspofungin has higher MICs against C. parapsilosis compared to other Candida species 4
• Fluconazole or lipid formulation amphotericin B may be preferred as initial therapy 1, 4
• Continuing caspofungin is reasonable if the patient is clinically stable 1, 4

Deep-Seated Infections

• For endocarditis, osteomyelitis, or septic arthritis, doses up to 100 mg daily have been used with dose escalation up to 150 mg 8
• Success rates: osteomyelitis/septic arthritis 100%, peritonitis 77%, abdominal abscess 89%, chronic disseminated candidiasis 88% 8

Invasive Aspergillosis

• Indicated as salvage therapy for refractory or intolerant cases 1, 3
• Consider 70 mg daily for salvage therapy 1

Safety Profile

Common Adverse Effects

• Increased liver aminotransferases, gastrointestinal upset, headaches, fever, and infusion-related reactions 1
• Histamine-like reactions are rare and related to rapid infusion; infuse over approximately 1 hour 1
• In pediatric patients: hypokalemia (12%), elevated bilirubin, and decreased hemoglobin reported 1

Tolerability

• Caspofungin is generally well-tolerated with few discontinuations due to adverse events 1, 2
• Better tolerated than amphotericin B deoxycholate with fewer clinical and laboratory adverse events 1
• No serious drug-related adverse events or discontinuations due to toxicity in pediatric studies 2

Key Clinical Pitfalls

• Do not use standard adult dosing in children <50 kg—weight-based dosing (mg/m²) is essential 7
• Avoid cyclosporine co-administration unless absolutely necessary due to hepatotoxicity risk 6
• Remember to increase dose to 70 mg daily when enzyme inducers are co-administered 6
• Monitor tacrolimus levels closely as dose adjustments will likely be needed 1, 6
• Reduce dose in moderate hepatic impairment to avoid accumulation 6, 4