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Caspofungin

Medically reviewed by Drugs.com. Last updated on Jun 11, 2020.

Pronunciation

(kas poe FUN jin)

Index Terms

  • Caspofungin Acetate

Dosage Forms

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)

Brand Names: U.S.

  • Cancidas

Pharmacologic Category

  • Antifungal Agent, Parenteral
  • Echinocandin

Pharmacology

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)

Metabolism

Slowly, via hydrolysis and N-acetylation as well as by spontaneous degradation, with subsequent metabolism to component amino acids. Overall metabolism is extensive.

Excretion

Urine (41%; primarily as metabolites, ~1% of total dose as unchanged drug); feces (35%; primarily as metabolites)

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

Protein Binding

~97% to albumin

Special Populations: Renal Function Impairment

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.

Special Populations: 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).

Special Populations: Elderly

AUC is increased by ~28%.

Special Populations: Gender

AUC in women was ~22% higher than in men after repeat dosing.

Use: Labeled Indications

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 (OPC).

Fungal infections, empiric therapy (neutropenic patients): Empiric therapy for presumed fungal infections in febrile, neutropenic patients ≥3 months of age.

Off Label Uses

Candida infection, prophylaxis in neutropenic cancer patients at substantial risk

Based on the Infectious Diseases Society of America (IDSA) guidelines for the use of antimicrobial agents in neutropenic patients with cancer, caspofungin is effective and recommended as an alternate agent in the prophylaxis against Candida infection in neutropenic cancer patients with substantial risk (eg, allogeneic transplant or undergoing induction therapy for acute leukemia).

Candidiasis, chronic disseminated (hepatosplenic)

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, caspofungin is an effective and recommended treatment for patients with chronic disseminated (hepatosplenic) candidiasis.

Candidiasis, empiric therapy (non-neutropenic ICU patients)

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, caspofungin is an effective and recommended agent for empiric therapy of suspected invasive candidiasis in non-neutropenic patients in the ICU.

Candidiasis, intravascular infections

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, caspofungin is an effective and recommended treatment for patients with Candida intravascular infections, including patients with endocarditis (native or prosthetic valve), infections of implantable cardiac devices (pacemaker, implantable cardiac defibrillator), and Candida suppurative thrombophlebitis.

Candidiasis, oropharyngeal (refractory disease)

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, caspofungin may be considered as an alternative for patients with oropharyngeal candidiasis refractory to other antifungals.

Candidiasis, osteoarticular infections

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, caspofungin is an effective and recommended treatment for patients with Candida osteoarticular infections, including Candida osteomyelitis and Candida septic arthritis.

Candidiasis, prophylaxis against invasive candidiasis (high-risk ICU patients in units with a high rate of invasive candidiasis)

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, caspofungin may be considered as an alternative agent for prophylaxis against invasive candidiasis in high-risk patients in adult ICUs with a high rate of invasive candidiasis (>5%).

Contraindications

Hypersensitivity to caspofungin or any component of the formulation

Documentation of allergenic cross-reactivity for echinocandin antifungals is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Duration of caspofungin treatment should be determined by patient status and clinical response.

Aspergillosis, invasive (salvage therapy): IV: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg once daily. Duration of therapy should be a minimum of 6 to 12 weeks and depends on site of infection, extent of disease, and level/duration of immunosuppression (IDSA [Patterson 2016]).

Candidemia and other Candida infections: IV: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg once daily; generally continue for at least 14 days after the last positive culture or longer if neutropenia warrants. Higher doses (150 mg once daily infused over ~2 hours) compared to the standard adult dosing regimen (50 mg once daily) have not demonstrated additional benefit or toxicity in patients with invasive candidiasis (Betts 2009). Note: IDSA Candidiasis guidelines recommend transition to fluconazole (usually after 5 to 7 days in non-neutropenic patients) in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures (IDSA [Pappas 2016]).

Candida infection, prophylaxis in neutropenic cancer patients at substantial risk (off-label use): IV: 50 mg once daily (Mattiuzzi 2006).

Candidiasis, chronic disseminated (hepatosplenic) (off-label use): IV: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg daily for several weeks, followed by oral fluconazole therapy (IDSA [Pappas 2016])

Candidiasis, empiric therapy (non-neutropenic ICU patients) (off-label use): IV: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg once daily. Consider discontinuing after 4 to 5 days in patients with no clinical response; continue treatment for 2 weeks in patients who improve on antifungal therapy (IDSA [Pappas 2016]).

Candidiasis, esophageal (alternative agent): IV:

50 mg once daily (HHS [OI adult 2020]; IDSA [Pappas 2016]; Villanueva 2002); some experts favor a loading dose of 70 mg on day 1 (IDSA [Pappas 2016]). May transition to oral fluconazole therapy once oral intake tolerable. In patients with fluconazole-refractory disease, continue caspofungin for 14 to 21 days (HHS [OI adult 2020]; Pappas [IDSA 2016]). Note: Among patients with HIV, a higher relapse rate has been reported with echinocandins than with fluconazole (HHS [OI adult 2020]).

Candidiasis, intravascular infections (native or prosthetic valve endocarditis, infection of implantable cardiac devices, suppurative thrombophlebitis) (off-label use): IV: 150 mg daily. For native or prosthetic valve endocarditis, therapy should continue for at least 6 weeks after valve replacement surgery (longer durations in patients with abscesses or other complications); for patients with implantable cardiac devices, therapy should continue for 4 to 6 weeks after surgery (4 weeks for infections limited to generator pockets and at least 6 weeks for infections involving the wires); for suppurative thrombophlebitis, continue for at least 2 weeks after candidemia has cleared. Note: Step-down to fluconazole therapy is recommended in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures (IDSA [Pappas 2016]).

Candidiasis, osteoarticular infections (osteomyelitis or septic arthritis) (alternative therapy) (off-label use): IV: 50 to 70 mg daily for at least 14 days, followed by fluconazole (IDSA [Pappas 2016])

Candidiasis, prophylaxis against invasive candidiasis (high-risk ICU patients in units with a high rate of invasive candidiasis) (alternative therapy; off-label use): IV: Loading dose: 70 mg on day 1, then 50 mg daily (IDSA [Pappas 2016])

Candidiasis, oropharyngeal (refractory disease) (alternative therapy) (off-label use): IV: Initial dose: 70 mg on day 1; subsequent doses: 50 mg once daily (Pappas [IDSA 2016])

Fungal infections, empiric therapy (neutropenic patients): IV: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg once daily; continue until resolution of neutropenia; if fungal infection confirmed, continue for a minimum of 14 days (continue for at least 7 days after resolution of both neutropenia and clinical symptoms); if clinical response inadequate, may increase up to 70 mg once daily if tolerated

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: 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 (IDSA [Patterson 2016]). 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 (Fisher 2019).

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 (Döring 2012; Iosifidis 2018); some studies used a loading dose (Maximova 2017); guidelines recommend administering antifungal prophylaxis from the start of conditioning through engraftment (Science 2014).

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 (Sáez-Llorens 2009).

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 (HHS [OI pediatric 2019]; IDSA [Pappas 2016]). 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 (IDSA [Pappas 2016]); 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 (HHS [OI adult 2019]). Transition to fluconazole is recommended in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures (IDSA [Pappas 2016]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Bring intact vial to room temperature. Reconstitute vials using 10.8 mL NS for injection, SWFI, or bacteriostatic water for injection, resulting in a concentration of 5 mg/mL for the 50 mg vial, and 7 mg/mL for the 70 mg vial (vials contain overfill). Mix gently to dissolve until clear solution is formed; do not use if cloudy or contains particles. Solution should be further diluted with 0.9%, 0.45%, or 0.225% sodium chloride or LR (do not exceed final concentration of 0.5 mg/mL).

Administration

IV: Infuse slowly, over ~1 hour. Do not administer by IV bolus.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Reconstituted solution may be stored at ≤25°C (≤77°F) for up to 1 hour prior to preparation of infusion solution. Solutions diluted in NS, 1/2NS, 1/4NS, or LR for infusion should be used within 24 hours when stored at ≤25°C (≤77°F) or within 48 hours when stored at 2°C to 8°C (36°F to 46°F).

Drug Interactions

CycloSPORINE (Systemic): May enhance the adverse/toxic effect of Caspofungin. Caspofungin may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Caspofungin. 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. 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. 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. Consider therapy modification

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Avoid combination

Adverse Reactions

>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

Warnings/Precautions

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).

Monitoring Parameters

Liver function; anaphylaxis, skin rash, or histamine-related reactions (eg, facial swelling, bronchospasm, sensation of warmth)

Pregnancy Considerations

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]).

Patient Education

What is this drug used for?

• It is used to treat fungal infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Nausea

• Vomiting

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.

• Low magnesium like mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat.

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.

• Severe headache

• Severe dizziness

• Passing out

• Vision changes

• Fast breathing

• Feeling of warmth

• Flushing

• Fast heartbeat

• Cough

• Severe loss of strength and energy

• Chills

• Injection site pain or irritation

• Shortness of breath

• Swelling of arms or legs

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.