Aspergillosis, invasive (including disseminated and extrapulmonary) (alternative agent):
Note: Reserve for salvage therapy, typically as part of an appropriate combination regimen. Monotherapy is further reserved for patients who are intolerant of or refractory to azoles and polyenes (Ref); for patients with severe or progressive infection, some experts use as initial therapy in combination with voriconazole (Ref).
IV: 70 mg on day 1, then 50 mg once daily (Ref); if inadequate response, may increase dose to 70 mg once daily (Ref).
Duration: When given as monotherapy, the minimum duration is 6 to 12 weeks depending on degree/duration of immunosuppression, disease site, and response to therapy (Ref); immunosuppressed patients may require more prolonged treatment (Ref). When given as part of a combination regimen, the optimal duration is uncertain. Some experts have given an echinocandin for ~2 weeks in combination with voriconazole before step-down to voriconazole monotherapy (Ref).
Candidiasis:
Candidemia (neutropenic and nonneutropenic patients), including disseminated candidiasis: IV: 70 mg on day 1, then 50 mg once daily. Total duration (including oral step-down therapy) is ≥14 days after first negative blood culture and continues until signs/symptoms of candidemia and neutropenia, if present, have resolved; metastatic complications warrant a longer duration (Ref).
Cardiac device infection (including implantable cardiac defibrillator, pacemaker, ventricular assist device) (off-label use) : IV: 150 mg once daily; step down to azole therapy in clinically stable patients with susceptible isolates and negative repeat cultures; total antifungal duration is ≥4 weeks after device removal for isolated generator pocket infection and ≥6 weeks after device removal for wire infection (Ref).
Chronic disseminated (hepatosplenic) (off-label use): IV: 70 mg on day 1, then 50 mg once daily for several weeks, followed by oral azole step-down therapy until lesion resolution and through periods of immunosuppression (Ref).
Empiric therapy, suspected invasive candidiasis (nonneutropenic ICU patients) (off-label use):
Note: Antifungal therapy is not routinely warranted for initial management of nonneutropenic patients with sepsis. Consider use for critically ill patients with unexplained fever or unexplained hypotension despite broad-spectrum antimicrobial therapy and risk factors for invasive candidiasis (eg, indwelling venous catheter, hemodialysis, trauma or burns, recent surgery, parenteral nutrition) (Ref).
IV: 70 mg on day 1, then 50 mg once daily. For those who improve, continue empiric antifungal therapy for 2 weeks; consider discontinuing after 4 to 5 days in patients with no evidence of invasive candidiasis and no clinical response (Ref).
Endocarditis, native or prosthetic valve (off-label use): IV: 150 mg once daily(Ref); step down to azole therapy in clinically stable patients with susceptible isolates and negative repeat cultures; total antifungal duration is ≥6 weeks after valve replacement surgery, with longer duration for perivalvular abscesses, other complications, or a nonsurgical approach (Ref).
Esophageal, refractory disease (alternative agent):
Note: Reserve for fluconazole-refractory disease in patients who require IV therapy (eg, severe disease) (Ref).
IV: 70 mg on day 1, then 50 mg once daily (Ref); some experts give 50 mg once daily without a loading dose (Ref), and other experts prefer 70 mg once daily (Ref). Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (Ref).
Intra-abdominal infection (eg, peritonitis, abdominal abscess): IV: 70 mg on day 1, then 50 mg once daily. Total duration (including oral step-down therapy) is ≥14 days and continues until source control and clinical resolution (Ref).
Oropharyngeal, refractory disease (alternative therapy) (off-label use):
Note: Reserve for fluconazole-refractory disease in patients who require IV therapy (eg, severe disease) (Ref).
IV: 70 mg on day 1, then 50 mg once daily. Transition to an oral antifungal once patient tolerates oral intake if susceptibility allows; total antifungal duration is 14 to 28 days (Ref).
Osteoarticular infection (osteomyelitis or septic arthritis) (off-label use): IV: 70 mg on day 1, then 50 to 70 mg once daily for ≥2 weeks; total duration of therapy (including oral step-down therapy) is 6 to 12 months for osteomyelitis and ≥6 weeks for septic arthritis (Ref).
Thrombophlebitis, suppurative (off-label use): IV: 150 mg once daily; continue antifungal therapy until catheter removed and thrombus resolved, and for ≥2 weeks after candidemia (if present) has cleared (Ref).
Neutropenic fever, empiric antifungal therapy (alternative agent):
Note: Recommended for patients with persistent or recurrent fever after ≥4 days of antimicrobial therapy when the duration of neutropenia is expected to exceed 7 days (Ref). Some experts reserve for patients without suspicion of mold infection (eg, pulmonary nodules) (Ref).
IV: 70 mg on day 1, then 50 mg once daily (Ref).
Prophylaxis against invasive fungal infections (off-label use):
Hematologic malignancy or hematopoietic cell transplant (alternative agent):
Note: Some experts reserve for patients at low risk for mold infection (Ref).
IV: 50 mg once daily. Duration is at least until resolution of neutropenia and varies based on degree and duration of immunosuppression (Ref).
Solid organ transplant (alternative agent): IV: 50 mg once daily; duration varies based on patient risk factors and transplant center protocol (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound): No dosage adjustment necessary (Ref).
CRRT: Poorly dialyzed (Ref): No dosage adjustment necessary (Ref). Note: Significant variability in caspofungin pharmacokinetics has been observed in critically ill patients (Ref) and those on renal replacement therapies (Ref). Results of a Monte Carlo simulation suggest that instead of standard dosing (ie, 70 mg × 1 followed by 50 mg daily), a larger loading dose (ie, 100 mg) and maintenance dose of 50 mg once daily in patients <80 kg or 70 mg once daily in patients >80 kg increases the probability of achieving pharmacodynamic targets (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzed: No dosage adjustment necessary (Ref). Note: Significant variability in caspofungin pharmacokinetics has been observed in critically ill patients (Ref) and those on renal replacement therapies (Ref). Results of a Monte Carlo simulation suggest that instead of standard dosing (ie, 70 mg × 1 followed by 50 mg daily), a larger loading dose (ie, 100 mg) and maintenance dose of 50 mg once daily in patients <80 kg or 70 mg once daily in patients >80 kg increases the probability of achieving pharmacodynamic targets in patients on CRRT (Ref); these results are likely to be applicable to critically ill patients receiving PIRRT therapies as well (Ref).
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): 70 mg on day 1 (where recommended), followed by 35 mg once daily(Ref); however, pharmacokinetic data suggest that this dose reduction may result in suboptimal drug exposure (Ref).
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling. Subsequent pharmacokinetic data suggest that degree of impairment (Child-Pugh class B or C) does not further decrease clearance of caspofungin and patients with severe impairment can be dosed the same as patients with moderate impairment (Ref).
Refer to adult dosing.
(For additional information see "Caspofungin: Pediatric drug information")
Dosage guidance:
Clinical considerations: Caspofungin treatment duration should be based on patient status and clinical response.
Aspergillosis, invasive; treatment: Note: Guidelines recommend caspofungin for salvage therapy or where other antifungals are contraindicated; not recommended for routine use for primary treatment (Ref). Infants ≥3 months, Children, and Adolescents <18 years: IV: Initial 70 mg/m2/dose on day 1, then 50 mg/m2/dose once daily; may increase to 70 mg/m2/dose once daily if clinical response inadequate; maximum dose: 70 mg/dose.
Fungal infections, empiric therapy in neutropenic patients: Infants ≥3 months, Children, and Adolescents <18 years: IV: Initial dose: 70 mg/m2/dose on day 1, then 50 mg/m2/dose once daily; may increase to 70 mg/m2/dose once daily if clinical response inadequate; maximum dose: 70 mg/dose.
Fungal infections, prophylaxis in patients with acute myeloid leukemia: Limited data available: Infants ≥3 months, Children, and Adolescents: IV: Initial 70 mg/m2/dose on day 1 (maximum dose: 70 mg/dose), then 50 mg/m2/dose once daily (maximum dose: 50 mg/dose); begin therapy 24 to 72 hours following completion of each chemotherapy cycle and continue until ANC 100 to 500/µL following nadir or until next chemotherapy cycle, whichever occurs first (Ref).
Fungal infections, prophylaxis in allogeneic hematopoietic stem cell transplantation recipients: Limited data available: Infants ≥8 months, Children, and Adolescents: IV: 50 mg/m2/dose once daily; maximum dose: 50 mg/dose (Ref); some studies used a loading dose (Ref); guidelines recommend administering antifungal prophylaxis from the start of conditioning through engraftment (Ref).
Candida infections, treatment; independent of HIV status:
Infants <3 months: Limited data available: IV: 25 mg/m2/dose once daily; dosing based on a pharmacokinetic study of 18 infants (PNA ≤12 weeks) that showed similar serum concentrations to standard adult doses (50 mg/day). Reported trough concentrations were slightly elevated and not correlated with increased adverse events (Ref).
Infants ≥3 months, Children, and Adolescents <18 years: IV: Initial 70 mg/m2/dose on day 1, then 50 mg/m2/dose once daily; may increase to 70 mg/m2/dose once daily if clinical response inadequate; maximum dose: 70 mg/dose. For esophageal disease, treat 14 to 21 days (Ref). For candidemia, treat until 2 weeks after the last positive blood culture.
Adolescents ≥18 years: IV: Initial 70 mg on day 1, then 50 mg once daily (Ref); for candidemia, treat until 2 weeks after the last positive blood culture and symptom resolution, and longer if neutropenia warrants; for esophageal disease, treat for 14 to 21 days. For esophageal disease, a higher rate of relapse has been reported with echinocandins than with fluconazole (Ref). Transition to fluconazole is recommended in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants ≥3 months, Children, and Adolescents: No adjustment needed
End-stage renal disease (ESRD) requiring dialysis: Poorly dialyzed; no supplemental dose or dosage adjustment necessary in patients on intermittent hemodialysis (IHD). No supplemental dose or dosage adjustment needed in peritoneal dialysis or continuous renal replacement therapy (eg, CVVHD) (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); based on experience in adult patients, dosage reduction may be necessary; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypotension (adults: 3% to 20%; infants, children, and adolescents: 9%), peripheral edema (adults: 6% to 11%), tachycardia (7% to 11%)
Central nervous system: Chills (adults: 9% to 23%; infants, children, and adolescents: 13%), headache (9% to 15%)
Dermatologic: Skin rash (4% to 23%)
Gastrointestinal: Diarrhea (adults: 6% to 27%; infants, children, and adolescents: 7%), vomiting (6% to 17%), nausea (adults: 5% to 15%; infants, children, and adolescents: 4%)
Hematologic & oncologic: Decreased hemoglobin (adults: 18% to 21%), decreased hematocrit (adults: 13% to 18%), decreased white blood cell count (adults: 12%), anemia (adults: 11%)
Hepatic: Increased serum alkaline phosphatase (adults: 9% to 22%), increased serum ALT (adults: 4% to 18%; infants, children, and adolescents: 5%), increased serum AST (adults: 6% to 16%; infants, children, and adolescents: 2%), increased serum bilirubin (adults: 5% to 13%)
Local: Localized phlebitis (adults: 18%)
Renal: Increased serum creatinine (adults: 3% to 11%)
Respiratory: Respiratory failure (adults: 2% to 20%), cough (adults: 6% to 11%), pneumonia (adults: 4% to 11%)
Miscellaneous: Infusion related reaction (20% to 35%), fever (6% to 30%), septic shock (adults: 11% to 14%)
1% to 10%:
Cardiovascular: Hypertension (5% to 9%), atrial fibrillation (<5%), bradycardia (<5%), cardiac arrhythmia (<5%), edema (<5%), flushing (<5%), myocardial infarction (<5%)
Central nervous system: Anxiety (<5%), confusion (<5%), depression (<5%), dizziness (<5%), drowsiness (<5%), fatigue (<5%), insomnia (<5%), seizure (<5%)
Dermatologic: Erythema (5% to 9%), pruritus (infants, children, and adolescents: 6%), skin lesion (<5%), urticaria (<5%), decubitus ulcer (adults: 3% to 5%)
Endocrine & metabolic: Hypomagnesemia (adults: 7%), hyperglycemia (adults: 6%), hypokalemia (5% to 6%), hypercalcemia (<5%), hypervolemia (<5%)
Gastrointestinal: Abdominal pain (4% to 9%), mucosal inflammation (4% to 6%), abdominal distention (<5%), anorexia (<5%), constipation (<5%), decreased appetite (<5%), dyspepsia (<5%), upper abdominal pain (<5%)
Genitourinary: Urinary tract infection (<5%), nephrotoxicity (adults: 3%; serum creatinine ≥2 x baseline value or ≥1 mg/dL in patients with serum creatinine above ULN range)
Hematologic & oncologic: Blood coagulation disorder (<5%), febrile neutropenia (<5%), neutropenia (<5%), petechia (<5%), thrombocytopenia (<5%)
Hepatic: Decreased serum albumin (adults: 7%), hepatic failure (<5%), hepatomegaly (<5%), hepatotoxicity (<5%), hyperbilirubinemia (<5%), jaundice (<5%)
Infection: Sepsis (adults: 5% to 7%), bacteremia (<5%)
Local: Catheter infection (infants, children, and adolescents: 9%), infusion site reaction (<5%; pain/pruritus/swelling)
Neuromuscular & skeletal: Arthralgia (<5%), back pain (<5%), limb pain (<5%), tremor (<5%), weakness (<5%)
Renal: Hematuria (adults: 10%), increased blood urea nitrogen (adults: 4% to 9%), renal failure (<5%)
Respiratory: Dyspnea (adults: 9%), pleural effusion (adults: 9%), respiratory distress (adults: ≤8%), rales (adults: 7%), epistaxis (<5%), hypoxia (<5%), tachypnea (<5%)
<1%, postmarketing, and/or case reports: Anaphylaxis, erythema multiforme, exfoliation of skin, hepatic necrosis, hepatitis, histamine release (including facial swelling, bronchospasm, sensation of warmth), increased gamma-glutamyl transferase, pancreatitis, renal insufficiency, Stevens-Johnson syndrome, swelling, toxic epidermal necrolysis
Hypersensitivity to caspofungin or any component of the formulation
Concerns related to adverse effects:
• Hepatic effects: Increased transaminases and rare cases of clinically significant hepatic dysfunction (including failure and hepatitis) have been reported in pediatric and adult patients. Monitor liver function tests during therapy; if tests become abnormal or worsen, consider discontinuation.
• Hypersensitivity: Anaphylaxis, other hypersensitivity reactions, histamine-related reactions (eg, angioedema, facial swelling, bronchospasm, rash, sensation of warmth), and cases of Stevens-Johnson syndrome and toxic epidermal necrolysis (some fatal) have been reported. Discontinue if a hypersensitivity reaction occurs. Administer supportive treatment if needed.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage reduction may be necessary in adults with moderate impairment (Child-Pugh class B); safety and efficacy have not been established in children with any degree of hepatic impairment and adults with severe impairment (Child-Pugh class C).
Special populations:
• Obesity: Data with another echinocandin suggest that clearance increases as a function of weight; higher doses may be necessary in patients with obesity (Hall 2011).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous, as acetate [preservative free]:
Cancidas: 50 mg (1 ea); 70 mg (1 ea)
Generic: 50 mg (1 ea); 70 mg (1 ea)
Yes
Solution (reconstituted) (Cancidas Intravenous)
50 mg (per each): $405.25
70 mg (per each): $421.06
Solution (reconstituted) (Caspofungin Acetate Intravenous)
50 mg (per each): $82.80 - $404.40
70 mg (per each): $94.80 - $420.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous, as acetate:
Cancidas: 50 mg (10.5 mL); 70 mg (10.5 mL)
Generic: 50 mg (1 ea); 70 mg (1 ea)
IV: Infuse slowly, over ~1 hour. Do not administer by IV bolus.
Parenteral: IV: Administer by slow IV infusion over 1 hour (manufacturer); higher doses (eg, 150 mg) have been infused over ~2 hours (Ref). Monitor during infusion; isolated cases of possible histamine-related reactions have occurred during clinical trials (rash, flushing, pruritus, facial edema).
Aspergillosis, invasive: Treatment of invasive aspergillosis in patients ≥3 months of age who are refractory to or intolerant of other therapies (eg, amphotericin B, lipid formulations of amphotericin B, itraconazole).
Limitations of use: Has not been studied as initial therapy for invasive aspergillosis.
Candidemia and other Candida infections: Treatment of candidemia and the following Candida infections in patients ≥3 months of age: Intra-abdominal abscesses, peritonitis, and pleural space infections.
Limitations of use: Has not been studied in endocarditis, osteomyelitis, and meningitis due to Candida.
Candidiasis, esophageal: Treatment of esophageal candidiasis in patients ≥3 months of age.
Limitations of use: Not approved for the treatment of oropharyngeal candidiasis.
Neutropenic fever, empiric antifungal therapy: Empiric therapy for presumed fungal infections in febrile, neutropenic patients ≥3 months of age.
Candidiasis, cardiac device infection (including implantable cardiac defibrillator, pacemaker, ventricular assist device); Candidiasis, chronic disseminated (hepatosplenic); Candidiasis, empiric therapy, suspected invasive candidiasis (nonneutropenic ICU patients); Candidiasis, endocarditis, native or prosthetic valve; Candidiasis, oropharyngeal, refractory disease; Candidiasis, osteoarticular infections (osteomyelitis or septic arthritis); Candidiasis, thrombophlebitis, suppurative; Prophylaxis against invasive fungal infections
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
CycloSPORINE (Systemic): May enhance the adverse/toxic effect of Caspofungin. CycloSPORINE (Systemic) may increase the serum concentration of Caspofungin. Caspofungin may increase the serum concentration of CycloSPORINE (Systemic). Management: Weigh potential benefits of caspofungin against a possible elevated risk of hepatotoxicity. Monitor liver function and re-evaluate treatment in patients with abnormal values. Mild transaminase elevations may occur relatively commonly. Risk D: Consider therapy modification
Inducers of Drug Clearance: May decrease the serum concentration of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider therapy modification
RifAMPin: May decrease the serum concentration of Caspofungin. Management: Caspofungin prescribing information recommends using a dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) who are also receiving rifampin. Risk D: Consider therapy modification
Saccharomyces boulardii: Antifungal Agents (Systemic and Oral [Non-Absorbable]) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination
Based on animal data, in utero exposure to caspofungin may cause fetal harm.
When treatment of invasive Aspergillus or Candida infections is needed during pregnancy, other agents are preferred (HHS [OI adult 2020]; IDSA [Pappas 2016]).
It is not known if caspofungin is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Liver function; anaphylaxis, skin rash, or histamine-related reactions (eg, facial swelling, bronchospasm, sensation of warmth)
Inhibits synthesis of β(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi. Highest activity is in regions of active cell growth. Mammalian cells do not require β(1,3)-D-glucan, limiting potential toxicity.
Distribution: CSF concentrations: Nondetectable [<10 ng/mL (n=1)] (Sáez-Llorens 2009)
Protein binding: ~97% to albumin
Metabolism: Slowly, via hydrolysis and N-acetylation as well as by spontaneous degradation, with subsequent metabolism to component amino acids. Overall metabolism is extensive.
Half-life elimination: Beta (distribution): 9 to 11 hours (~8 hours in children <12 years); Terminal: 40 to 50 hours; beta phase half-life is 32% to 43% lower in pediatric patients than in adult patients
Excretion: Urine (41%; primarily as metabolites, ~1% of total dose as unchanged drug); feces (35%; primarily as metabolites)
Altered kidney function: AUC is increased 30% to 49% in patients with CrCl ≤49 mL/minute after administration of a single 70 mg dose. No effect on caspofungin concentrations was seen in patients with mild to end-stage renal impairment after administration of multiple daily doses.
Hepatic function impairment: AUC is increased by ~55% in patients with mild hepatic impairment (Child-Pugh class A) and by 76% in patients with moderate hepatic impairment (Child-Pugh class B).
Older adult: AUC is increased by ~28%.
Sex: AUC in women was ~22% higher than in men after repeat dosing.
Obesity: Data with another echinocandin suggest that clearance increases as a function of weight (Hall 2011). From a small study of patients receiving caspofungin in the surgical ICU, body weight >75 kg was an independent predictor for a lower 24-hour trough concentration (Nguyen 2007).
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