Cancidas (Caspofungin)
caspofungin acetate for injection
Indications for Caspofungin
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Empirical therapy for presumed fungal infection in febrile neutropenia | Adults and pediatrics (≥3 months) | Monotherapy | FDA Approved |
| Candidemia and invasive Candida infections (intra-abdominal abscesses, peritonitis, pleural space infections) | Adults and pediatrics (≥3 months) | Monotherapy | FDA Approved |
| Esophageal candidiasis | Adults and pediatrics (≥3 months) | Monotherapy | FDA Approved |
| Invasive aspergillosis — salvage therapy (refractory to or intolerant of other therapies) | Adults and pediatrics (≥3 months) | Salvage monotherapy | FDA Approved |
Caspofungin was the first echinocandin antifungal to receive FDA approval (2001) and remains a cornerstone agent for invasive candidiasis and empirical antifungal therapy in immunocompromised patients. The IDSA 2016 candidiasis guidelines recommend an echinocandin as first-line therapy for invasive candidiasis in most clinical settings. Caspofungin has not been studied as initial therapy for invasive aspergillosis and is approved only for salvage use in that setting. It has not been approved for oropharyngeal candidiasis, and patients with concomitant OPC had higher relapse rates in clinical trials (FDA PI).
Candida prophylaxis in high-risk neutropenic patients: The IDSA recommends caspofungin as an alternative prophylactic agent in allogeneic stem cell transplant recipients or patients receiving induction chemotherapy for acute leukemia who are at substantial risk for invasive candidiasis. Evidence quality: Moderate
Invasive candidiasis in non-neutropenic ICU patients (empiric): The IDSA 2016 candidiasis guideline recommends an echinocandin for empirical treatment of suspected invasive candidiasis in critically ill, non-neutropenic patients. Evidence quality: Low
Candida endocarditis, osteomyelitis, and CNS infections: The IDSA recommends an echinocandin as step-down therapy after initial treatment with amphotericin B for Candida endocarditis and as an alternative for osteoarticular Candida infections. CNS penetration is limited. Evidence quality: Low
Candida auris infections: The CDC recommends an echinocandin as initial therapy for C. auris infections based on limited data. Evidence quality: Low
Dosing of Caspofungin
Adult Dosing (≥18 years) by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Febrile neutropenia — empirical antifungal therapy | 70 mg IV Day 1 (loading) | 50 mg IV once daily | 70 mg/day | Continue until neutropenia resolves; if fungal infection found, treat ≥14 days after last positive culture + ≥7 days after neutropenia and symptoms resolve Can increase to 70 mg/day if 50 mg tolerated but inadequate response (FDA PI) |
| Candidemia & invasive Candida infections (intra-abdominal, peritonitis, pleural) | 70 mg IV Day 1 (loading) | 50 mg IV once daily | 70 mg/day | Continue ≥14 days after last positive culture; longer if persistently neutropenic IDSA 2016: echinocandin recommended as first-line for invasive candidiasis |
| Esophageal candidiasis | 50 mg IV once daily | 50 mg IV once daily | 50 mg/day | No loading dose for this indication; treat for 7–14 days after symptom resolution Consider suppressive oral azole therapy in HIV patients to prevent relapse |
| Invasive aspergillosis — salvage therapy | 70 mg IV Day 1 (loading) | 50 mg IV once daily | 70 mg/day | Duration based on severity, immunosuppression recovery, and clinical response Not studied as initial therapy for invasive aspergillosis (FDA PI) |
| Moderate hepatic impairment (Child-Pugh 7–9) | 70 mg IV Day 1 (loading, where appropriate) | 35 mg IV once daily | 35 mg/day | No data in severe hepatic impairment (Child-Pugh >9) Mild impairment (Child-Pugh 5–6): no adjustment needed |
| Concomitant CYP inducer therapy (rifampin) | 70 mg IV once daily | 70 mg IV once daily | 70 mg/day | Rifampin reduces caspofungin levels; maintain 70 mg throughout therapy Consider 70 mg/day also with efavirenz, nevirapine, phenytoin, dexamethasone, carbamazepine |
Pediatric Dosing (3 months to 17 years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| All FDA-approved indications | 70 mg/m² IV Day 1 (loading) | 50 mg/m² IV once daily | 70 mg (absolute max) | Dose based on BSA (Mosteller formula); can increase to 70 mg/m²/day if inadequate response Use 50 mg vials (5 mg/mL) for doses <50 mg to ensure accurate dosing |
| With concomitant CYP inducers (rifampin, phenytoin, etc.) | 70 mg/m² IV once daily | 70 mg/m² IV once daily | 70 mg (absolute max) | Same inducers as adult list |
Caspofungin exhibits moderately nonlinear pharmacokinetics with dose-dependent accumulation. The 70 mg loading dose on Day 1 is essential to rapidly achieve therapeutic trough concentrations (≥1 mcg/mL) that would otherwise take several days to reach with 50 mg/day alone. Esophageal candidiasis is the only indication where a loading dose has not been studied and is not recommended.
Reconstitute with 10.8 mL of 0.9% NaCl, Sterile Water for Injection, or Bacteriostatic Water (50 mg vial = 5 mg/mL; 70 mg vial = 7 mg/mL). Dilute into 250 mL of 0.9%, 0.45%, or 0.225% NaCl or Lactated Ringer’s. Do NOT use dextrose-containing solutions (incompatible). Infuse over approximately 1 hour; never administer as IV bolus. Do not mix or co-infuse with other medications (FDA PI).
Pharmacology of Caspofungin
Mechanism of Action
Caspofungin inhibits the synthesis of beta-(1,3)-D-glucan, an essential structural polysaccharide in the fungal cell wall that is absent from mammalian cells. This targeted mechanism accounts for the drug’s favorable safety profile relative to polyene and azole antifungals. By disrupting cell wall integrity, caspofungin exerts fungicidal activity against most Candida species and fungistatic activity against Aspergillus species, targeting actively growing hyphal tips. The selective targeting of a fungal-specific structure explains the lack of significant nephrotoxicity and myelotoxicity that limits other systemic antifungals. Caspofungin retains activity against many azole-resistant Candida species because the glucan synthase target is independent of the ergosterol biosynthesis pathway.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV administration only; oral bioavailability <0.2% | No oral formulation possible; must be given parenterally |
| Distribution | Protein binding ~97% (albumin); 92% tissue distribution within 36–48 hours; distributes to liver, spleen, kidney, lung, gut wall via OATP1B1 transport | Poor CNS and ocular penetration; not recommended for fungal meningitis or endophthalmitis; hypoalbuminemia in ICU patients may alter free drug fraction |
| Metabolism | Hepatic via peptide hydrolysis and N-acetylation; minor CYP involvement; not a CYP substrate, inhibitor, or inducer; not a P-glycoprotein substrate | Low CYP-mediated interaction potential; however, CYP inducers (rifampin, phenytoin) reduce caspofungin levels by ~20–35% through non-CYP clearance pathways |
| Elimination | Beta t½ 9–11 h; terminal t½ 40–50 h; urine 41% (as metabolites, ~1% unchanged); feces 35% (as metabolites); not dialyzable | Long terminal half-life reflects slow tissue redistribution; steady-state by Day 4–5; no supplemental dosing after hemodialysis; no renal dose adjustment required |
Side Effects of Caspofungin
Adverse event data are derived from the overall safety database of 1,951 individuals across 34 clinical studies, and from key comparative trials: the empirical therapy study (caspofungin N=564 vs AmBisome N=547), the invasive candidiasis study (caspofungin N=114 vs amphotericin B N=125), and the esophageal candidiasis study (caspofungin N=83 vs fluconazole N=94). Caspofungin demonstrated a significantly lower incidence of nephrotoxicity and infusion-related reactions compared with amphotericin B formulations (FDA PI).
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Pyrexia | 20% (overall); 27% (empirical therapy) | Includes infusion-related and disease-related fever; differentiate from underlying infection |
| Diarrhea | 14% (overall); 20% (empirical); 27% (esophageal) | Generally self-limiting; rule out C. difficile if persistent; higher rates in esophageal candidiasis study likely reflect HIV-related comorbidity |
| ALT increased | 13% (overall); 18% (empirical) | Usually transient and mild; monitor LFTs; isolated hepatic failure reported rarely |
| AST increased | 12% (overall); 14% (empirical) | Same considerations as ALT elevation |
| Alkaline phosphatase increased | 12% (overall); 15% (empirical); 21% (candidemia) | Cholestatic pattern; may reflect underlying disease; significantly less than amphotericin B |
| Blood potassium decreased | 11% (overall); 15% (empirical); 23% (candidemia) | Less common and milder than with amphotericin B; supplement if clinically significant |
| Chills | 10% (overall); 23% (empirical) | Infusion-related; lower than AmBisome (31% in empirical study) |
| Headache | 10% (overall); 11% (empirical) | Usually mild; rule out CNS infection in relevant populations |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 9% (overall); 11% (empirical) | Usually mild; antiemetics rarely needed |
| Rash | 8% (overall); 16% (empirical) | May be histamine-mediated; discontinue if SJS/TEN suspected |
| Vomiting | 8% (overall); 9% (empirical); 17% (candidemia) | Usually self-limited |
| Tachycardia | 7% (empirical) | Usually infusion-related; less common than with AmBisome (9%) |
| Bilirubin increased | 6% (overall); 10% (empirical); 13% (candidemia) | Part of hepatotoxicity spectrum; monitor trend |
| Hypotension | 6% (overall); 6% (empirical); 10% (candidemia) | May be histamine-mediated; slow infusion rate if occurs |
| Edema peripheral | 6% (overall); 11% (empirical) | Monitor fluid balance |
| Abdominal pain | 6% (overall); 9% (empirical) | Evaluate for GI pathology |
| Pneumonia | 6% (overall) | Likely reflects underlying immunocompromised state rather than drug effect |
| Erythema | 5% (overall) | May be histamine-mediated; usually mild |
| Phlebitis | 5–18% (varies by study) | Infusion site reaction; use larger vein; 18% in esophageal candidiasis study vs 11% fluconazole |
| Creatinine increased | 3% (empirical); 11% (candidemia) | Significantly less nephrotoxicity than amphotericin B (12% vs 3% in empirical study, 28% vs 11% in candidemia study) |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylaxis / severe hypersensitivity | Rare | During or shortly after infusion | Discontinue immediately; treat with epinephrine and supportive care; do not rechallenge |
| Stevens-Johnson syndrome / toxic epidermal necrolysis | Rare (post-marketing; some fatal) | Days to weeks | Discontinue caspofungin at the first sign of mucocutaneous blistering or skin detachment; dermatology consult; supportive care |
| Hepatic dysfunction / hepatitis / hepatic failure | Rare (isolated cases) | Variable; days to weeks | Monitor LFTs; if evidence of worsening hepatic function, evaluate risk-benefit of continuing; causal relationship not established in most cases |
| Hepatic necrosis | Very rare (post-marketing) | Variable | Immediate discontinuation; hepatology consultation; supportive care |
| Clinically significant renal dysfunction | Rare (post-marketing) | Variable | Monitor creatinine; evaluate for other nephrotoxic contributors; dose adjustment not established |
| Pancreatitis | Very rare (post-marketing) | Variable | Evaluate with lipase/amylase and imaging; discontinue if confirmed |
Caspofungin can cause histamine-mediated symptoms including rash, facial swelling, pruritus, sensation of warmth, and bronchospasm. These are distinct from true anaphylaxis and may respond to slowing the infusion rate and administering diphenhydramine. If symptoms are severe or progress to angioedema, dyspnea, or hypotension, discontinue the infusion and treat as anaphylaxis. These reactions do not necessarily recur on rechallenge with slower infusion.
Drug Interactions with Caspofungin
Caspofungin is not metabolized through the cytochrome P450 system and is not a P-glycoprotein substrate, giving it a relatively narrow drug interaction profile compared with azole antifungals. However, it is subject to hepatic clearance mechanisms that can be induced by certain drugs, and it has clinically important pharmacodynamic interactions with cyclosporine and tacrolimus.
Monitoring for Caspofungin
-
Hepatic Function (ALT, AST, Alk Phos, Bilirubin)
Baseline, then 2–3x/week
Routine Transaminase elevations occur in 12–18% of patients. Monitor for evidence of worsening hepatic function. Isolated cases of hepatic dysfunction, hepatitis, and hepatic failure have been reported. Increased vigilance if co-administered with cyclosporine. -
Serum Potassium
Baseline, then 2–3x/week
Routine Hypokalemia occurs in 6–23% of patients depending on population studied. Usually less severe than with amphotericin B. Supplement as clinically indicated. -
Serum Creatinine
Baseline, then weekly
Routine Nephrotoxicity rate is low (3% in empirical study) but renal function should be monitored, particularly in patients receiving concomitant nephrotoxic agents. -
Complete Blood Count
Baseline, then weekly
Routine Anemia (2–11%), neutropenia, and thrombocytopenia can occur, though often attributable to underlying disease. Monitor for hematologic recovery in neutropenic patients. -
Tacrolimus Trough Levels
At initiation and with dose changes
Trigger-based Caspofungin reduces tacrolimus exposure by ~20%. In transplant patients, closely monitor trough levels and adjust tacrolimus dose to prevent rejection. -
Signs of Hypersensitivity
Each infusion
Routine Monitor for rash, pruritus, facial swelling, bronchospasm, and anaphylaxis during and for 1 hour after infusion. SJS/TEN have been reported; discontinue at the first sign of mucocutaneous blistering.
Contraindications & Cautions for Caspofungin
Absolute Contraindications
- Known hypersensitivity (e.g., anaphylaxis) to caspofungin or any component of the formulation (FDA PI)
Relative Contraindications (Specialist Input Recommended)
- Severe hepatic impairment (Child-Pugh >9): No clinical experience; no dosing recommendation available. Avoid unless benefit clearly outweighs risk with close hepatology monitoring.
- Concomitant cyclosporine use: Limit to patients for whom potential benefit outweighs the risk of hepatotoxicity; monitor LFTs closely and evaluate risk/benefit if abnormalities develop.
- Fungal CNS infections or endophthalmitis: Caspofungin has poor CNS and intraocular penetration; not recommended as primary therapy for these sites.
Use with Caution
- Moderate hepatic impairment (Child-Pugh 7–9): Reduce maintenance dose to 35 mg/day (loading dose 70 mg on Day 1 still recommended where appropriate).
- Pregnancy: Animal studies showed embryofetal toxicity (increased resorptions, incomplete ossification) at doses comparable to human dose. Use only if benefit outweighs fetal risk.
- Lactation: Unknown whether caspofungin is excreted in human milk; probably compatible based on high protein binding and molecular weight.
- Pediatrics <3 months: Safety and efficacy not established.
- Elderly (≥65 years): AUC increased ~28%; no dose adjustment recommended, but no overall differences in safety or efficacy observed.
- Concomitant CYP inducers: Dose increase to 70 mg/day may be needed with rifampin, phenytoin, carbamazepine, efavirenz, nevirapine, or dexamethasone.
Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some with fatal outcomes, have been reported with caspofungin use in post-marketing surveillance. Discontinue caspofungin at the first sign or symptom of a progressive skin rash with mucosal involvement and administer appropriate treatment (FDA PI).
Elevated liver enzymes have been observed in patients receiving caspofungin and cyclosporine concomitantly. Only use this combination in patients for whom the potential benefit outweighs the potential risk. Monitor liver function tests and evaluate the risk/benefit of continuing therapy if abnormalities develop (FDA PI).
Patient Counselling for Caspofungin
Purpose of Therapy
Caspofungin is an antifungal medication used to treat serious fungal infections caused by Candida and Aspergillus species, or given as preventive therapy in patients at high risk for fungal infections during periods of very low white blood cell counts. It works by destroying the fungal cell wall and is administered as a daily intravenous infusion in a hospital setting.
How Treatment Is Given
The medication is infused through a vein over approximately 1 hour, once daily. The first dose is often higher than subsequent doses. Blood tests are performed regularly to monitor liver function and blood chemistry. Treatment continues until the infection is resolved and the immune system has recovered.
Sources
- CANCIDAS (caspofungin acetate) for injection. Full Prescribing Information. Merck Sharp & Dohme LLC. Revised 05/2022. Merck PI (PDF) Primary source for all FDA-approved dosing, indications, adverse events, PK parameters, and drug interaction data.
- DailyMed. CANCIDAS — caspofungin acetate injection, powder, lyophilized, for solution. U.S. National Library of Medicine. Updated October 2024. DailyMed Continuously updated FDA label database for the most current prescribing information.
- Walsh TJ, Teppler H, Donowitz GR, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351(14):1391–1402. doi:10.1056/NEJMoa040446 Pivotal randomized, double-blind trial (Study 94-0-002 equivalent) establishing non-inferiority of caspofungin to AmBisome for empirical therapy in febrile neutropenia with superior tolerability.
- Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020–2029. doi:10.1056/NEJMoa021585 Landmark RCT demonstrating non-inferiority of caspofungin to amphotericin B deoxycholate for invasive candidiasis with significantly fewer adverse effects.
- Villanueva A, Arathoon EG, Gotuzzo E, et al. A randomized double-blind study of caspofungin versus amphotericin B for the treatment of candidal esophagitis. Clin Infect Dis. 2001;33(9):1529–1535. doi:10.1086/323401 Pivotal trial for esophageal candidiasis indication; established comparable efficacy with better tolerability than amphotericin B.
- Betts RF, Nucci M, Talwar D, et al. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis. 2009;48(12):1676–1684. doi:10.1086/598933 Dose-ranging study showing 150 mg/day did not improve outcomes over standard dosing (70/50 mg), supporting the approved dose.
- Maertens J, Raad I, Petrikkos G, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004;39(11):1563–1571. doi:10.1086/423381 Noncomparative salvage study supporting the invasive aspergillosis indication with 45% favorable response rate.
- Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–e50. doi:10.1093/cid/civ933 IDSA guideline recommending echinocandins as first-line therapy for most forms of invasive candidiasis.
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60. doi:10.1093/cid/ciw326 IDSA guideline positioning echinocandins for salvage therapy of invasive aspergillosis; primary therapy with an echinocandin alone not recommended.
- Letscher-Bru V, Herbrecht R. Caspofungin: the first representative of a new antifungal class. J Antimicrob Chemother. 2003;51(3):513–521. doi:10.1093/jac/dkg117 Review of the echinocandin mechanism of action, spectrum, and the rationale for glucan synthase inhibition as a therapeutic target.
- Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature. Eur J Med Res. 2011;16(4):159–166. doi:10.1186/2047-783X-16-4-159 Comparative review of echinocandin pharmacology, including protein binding, half-life, and metabolism differences across the class.
- Stone JA, Holland SD, Wickersham PJ, et al. Single- and multiple-dose pharmacokinetics of caspofungin in healthy men. Antimicrob Agents Chemother. 2002;46(3):739–745. doi:10.1128/AAC.46.3.739-745.2002 Definitive single- and multiple-dose PK study in healthy volunteers establishing the beta half-life (9–11 h) and loading dose rationale.
- Balani SK, Xu X, Arison BH, et al. Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine. Drug Metab Dispos. 2000;28(11):1274–1278. PubMed Characterization of caspofungin metabolic pathways including peptide hydrolysis and N-acetylation.
- Kurland S, Furebring M, Löwdin E, et al. Pharmacokinetics of caspofungin in critically ill patients in relation to liver dysfunction. Antimicrob Agents Chemother. 2019;63(6):e02466-18. doi:10.1128/AAC.02466-18 ICU population PK study showing differential impact of albumin and bilirubin on caspofungin exposure, relevant to dosing in critically ill patients.
- Dongmo Fotsing LN, Bajaj T. Caspofungin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Feb 28. StatPearls Comprehensive review covering mechanism, pharmacokinetics, dosing, adverse effects, and clinical context for caspofungin use.