Caspofungin Acetate

Approved Indications:

• Invasive Candidiasis:
• Empiric therapy for suspected invasive Candida infections in febrile, neutropenic patients.
• Treatment of candidemia and other forms of Candida infections including:
• Intra-abdominal abscesses
• Peritonitis
• Pleural space infections
• Esophageal Candidiasis:
• For patients who are refractory to or intolerant of other antifungal therapy.
• Invasive Aspergillosis:
• Salvage therapy in patients who are refractory to or intolerant of other antifungals (e.g., amphotericin B or itraconazole).

Clinically Accepted Off-Label Uses:

• Empirical antifungal treatment in febrile neutropenia.
• Combination therapy for difficult-to-treat fungal infections (e.g., aspergillosis or mucormycosis) in immunocompromised hosts.
• Prophylaxis of fungal infections in patients undergoing hematopoietic stem cell transplantation (limited data, specialist-guided).

General Administration:

• Administer via slow intravenous (IV) infusion over approximately 1 hour.
• Do not administer via IV bolus or IV push.

Adults (≥18 years):

• Empirical Therapy / Invasive Candidiasis / Candidemia:
• Loading dose: 70 mg IV on Day 1
• Maintenance dose: 50 mg IV once daily
• Esophageal Candidiasis:
• 50 mg IV once daily (no loading dose required)
• Invasive Aspergillosis (Salvage Therapy):
• 70 mg IV loading dose on Day 1
• Then 50 mg IV daily

Pediatrics (≥3 months to <18 years):

• All indications:
• 70 mg/m² IV loading dose (max 70 mg), followed by 50 mg/m² IV daily (max 70 mg/day)

Geriatrics:

• No dosage adjustment needed; monitor for hepatic or renal function impairments.

Hepatic Impairment:

• Mild: No adjustment
• Moderate: Reduce daily dose to 35 mg after a 70 mg loading dose
• Severe: Use with caution; insufficient data

Renal Impairment:

• No dose adjustment needed, including in patients on dialysis.

Duration:

• Duration varies based on infection site and clinical response (typically 7–21 days for candidemia).

Caspofungin Acetate is an echinocandin antifungal that inhibits the synthesis of (1,3)-β-D-glucan, an essential component of the fungal cell wall. It acts by non-competitively inhibiting the enzyme β-(1,3)-D-glucan synthase, resulting in structural instability, osmotic lysis, and ultimately fungal cell death. As mammalian cells lack β-D-glucan, caspofungin displays selective toxicity to fungal cells. It is fungicidal against most Candida species and fungistatic against Aspergillus species.

• Absorption: Not orally bioavailable; given intravenously.
• Distribution: Widely distributed; volume of distribution ~9–10 L.
• Protein Binding: ~97%
• Onset of Action: Within 24–48 hours of IV initiation.
• Metabolism: Slowly degraded by hydrolysis and N-acetylation in the liver; does not involve the CYP450 system.
• Half-life: ~9 to 11 hours
• Peak Plasma Concentration: Reached within 1 hour post-infusion
• Excretion: Primarily in urine (41%) and feces (35%) as metabolites
• Steady-State: Achieved by Day 2 with daily dosing

• Pregnancy:
• Category C (FDA): Animal studies have shown adverse effects on the fetus, but no adequate human studies. Use only if potential benefit justifies the risk.
• Lactation:
• Unknown if caspofungin is excreted in human breast milk. Due to potential serious adverse reactions in infants, breastfeeding should be avoided or discontinued while on treatment.
• Recommendation:
• Use caution during pregnancy and lactation. Avoid use unless clearly indicated.

• Primary Class: Echinocandin Antifungal
• Subclass: Glucan synthesis inhibitor
• Route: Parenteral only (IV infusion)

• Known hypersensitivity to caspofungin or any of its components
• Prior anaphylactic reaction to echinocandin-class antifungals
• Severe hepatic dysfunction without specialist supervision
• Co-administration with cyclosporine in hepatic-compromised patients (relative)

• Hepatic Impairment: Requires dose reduction in moderate impairment. Monitor liver enzymes.
• Anaphylaxis and Infusion-related Reactions: Rare, but potentially fatal; includes histamine-mediated symptoms.
• Concurrent Immunosuppressive Therapy: Monitor closely for additive hepatic toxicity, especially with cyclosporine.
• Drug-Induced Hepatotoxicity: Discontinue if significant hepatic injury develops.
• Pregnancy: Use only if absolutely necessary.
• Pediatric Use: Effective, but long-term safety not established.

Common (≥1%):

• Gastrointestinal: Diarrhea, nausea, vomiting
• Hepatic: Elevated liver enzymes (ALT, AST, ALP, bilirubin)
• Infusion-related: Fever, phlebitis at infusion site
• General: Headache, rash, pruritus

Serious (Rare):

• Anaphylaxis, angioedema
• Hepatic dysfunction, hepatotoxicity
• Severe skin reactions (Stevens-Johnson Syndrome, toxic epidermal necrolysis)
• Hypokalemia, thrombocytopenia
• Eosinophilia

Timing & Dose-dependence:

• Most side effects occur within the first few days of treatment.
• Elevated liver enzymes may be dose-dependent.

• Cyclosporine: May increase hepatotoxicity risk—monitor liver function if used together.
• Tacrolimus, Sirolimus: May increase exposure when co-administered.
• Rifampin, Carbamazepine, Dexamethasone, Phenytoin: May reduce caspofungin plasma levels via enzyme induction.
• No significant interaction with CYP450 enzymes.
• Food and Alcohol: No direct food interactions; alcohol should be avoided due to liver risk.

• No major changes in dosage or indications reported in recent years.
• WHO and IDSA continue to recommend caspofungin as first-line for candidemia and salvage for aspergillosis.
• FDA labeling updated to emphasize dose reduction in moderate hepatic impairment and potential infusion-related reactions.
• Ongoing studies evaluating caspofungin combination therapy in refractory fungal infections.

• Powder for Injection:
• Store vials at 20°C to 25°C (68°F to 77°F)
• Protect from excessive heat, moisture, and light
• Do not freeze
• Reconstituted Solution:
• After dilution, store at 2°C to 8°C (36°F to 46°F)
• Use within 24 hours
• Do not freeze or shake vigorously
• Handling Precautions:
• Reconstitute only with sterile water for injection
• Infusion should be prepared with sodium chloride 0.9% or lactated Ringer’s solution