What is the recommended treatment and dosage of Caspofungin for invasive candidiasis?

Caspofungin Treatment for Invasive Candidiasis

For invasive candidiasis, caspofungin should be administered as a 70 mg IV loading dose on day 1, followed by 50 mg IV daily, and continued for at least 14 days after documented clearance of Candida from the bloodstream and resolution of symptoms. 1, 2

Standard Adult Dosing

• Loading dose: 70 mg IV on day 1 1, 3
• Maintenance dose: 50 mg IV daily 1, 3
• Infuse slowly over approximately 1 hour to minimize histamine-like reactions 2, 3

Duration of Therapy

• Continue treatment for at least 14 days after the last positive blood culture AND resolution of clinical symptoms attributable to candidemia 1, 2
• For deep-seated infections (peritonitis, abdominal abscesses, osteomyelitis), longer courses are necessary 1, 4
• Patients with persistent fungemia or metastatic complications require extended therapy beyond the standard 2-week post-clearance period 1

Dose Escalation Considerations

• For inadequate clinical response, escalate to 70 mg IV daily 2
• Higher doses up to 150 mg daily have been studied and are well-tolerated, though the standard 50 mg dose is typically sufficient 2, 5
• For endocarditis, osteomyelitis, or septic arthritis, consider 100 mg daily with potential escalation to 150 mg 4

Pediatric Dosing

• Loading dose: 70 mg/m² IV on day 1 (maximum 70 mg) 1, 6
• Maintenance dose: 50 mg/m² IV daily (maximum 70 mg) 1, 6
• This weight-based approach in children provides comparable drug exposure to adult dosing 2, 6

Species-Specific Considerations

• For C. parapsilosis infections, continuing caspofungin is reasonable if the patient is clinically stable, though fluconazole may be preferred as initial therapy 1, 2
• For C. krusei or C. glabrata, caspofungin is an excellent first-line choice 1
• All echinocandins (caspofungin, micafungin, anidulafungin) are considered equally effective for candidemia 7

Essential Adjunctive Measures

• Remove or replace central venous catheters when feasible—this is strongly recommended and impacts outcomes 1, 7
• Perform dilated funduscopic examination to rule out endophthalmitis in all patients with candidemia 1, 7
• For persistent candidemia, obtain imaging of genitourinary tract, liver, and spleen 1

Dose Adjustments

• No dose adjustment required for renal impairment, including acute kidney injury or dialysis 2, 3
• For moderate hepatic insufficiency (Child-Pugh score 7-9), reduce maintenance dose to 35 mg daily 3, 8
• No adjustment needed based on age, sex, or race 3, 8

Critical Drug Interactions

• Monitor tacrolimus levels closely—caspofungin reduces tacrolimus AUC by approximately 20% 2, 3
• Avoid concomitant cyclosporine unless absolutely necessary, as it increases caspofungin AUC by 35% and may cause transient hepatic transaminase elevations 2, 3
• Enzyme inducers (rifampin, phenytoin, carbamazepine, efavirenz, nevirapine, dexamethasone) may reduce caspofungin concentrations 2

Common Pitfalls to Avoid

• Premature discontinuation before completing 14 days post-clearance leads to relapse 7, 6
• Switching to fluconazole before confirming species identification and susceptibility in critically ill patients is dangerous 7
• Failing to remove central venous catheters significantly compromises treatment success 7
• Overlooking ophthalmologic examination misses endophthalmitis, which requires prolonged therapy 7
• Infusing too rapidly (faster than 1 hour) increases risk of histamine-like reactions 2, 3

Safety Profile

• Caspofungin is generally well-tolerated with significantly fewer infusion-related reactions (20%) compared to amphotericin B (49%) 3
• Most common adverse effects include increased liver transaminases, gastrointestinal upset (nausea, diarrhea), headache, and fever 2, 3
• Significantly lower nephrotoxicity (3%) compared to amphotericin B (12%) in patients with baseline creatinine clearance >30 mL/min 3
• Hypokalemia may occur, particularly in pediatric patients—monitor electrolytes 2, 3
• Serious drug-related adverse events are rare, with discontinuation due to toxicity occurring in <2% of patients 3, 5

Empirical Therapy Context

• Caspofungin is preferred for empirical therapy in critically ill patients, those with recent azole exposure, moderately-to-severely ill patients, or those at high risk for C. glabrata or C. krusei 1
• For non-critically ill patients without recent azole exposure, fluconazole remains an acceptable alternative 1