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Caspofungin Acetate

Class: Echinocandins
VA Class: AM700
Chemical Name: 1-[(4R,5S)-5-[(2-Aminoethyl)amino]-N2-(10,12-dimethyl-1-oxotetradecyl)-4-hydroxy-l-ornithine]-5-[(3R)-3-hydroxy-l-ornithine]pneumocandin B0 diacetate (salt)
CAS Number: 179463-17-3
Brands: Cancidas

Introduction

Antifungal; echinocandin.1 2 3

Uses for Caspofungin Acetate

Aspergillosis

Treatment of invasive aspergillosis in adults, adolescents, and children ≥3 months of age whose disease is refractory to, or who are intolerant of, other antifungals.1 423 436 Has not been evaluated for initial therapy of invasive aspergillosis.1

IDSA and other clinicians consider IV voriconazole the drug of choice for primary treatment of invasive aspergillosis in adult and pediatric patients, including HIV-infected patients;423 436 440 IV amphotericin B or isavuconazonium (prodrug of isavuconazole) usually recommended as alternatives for primary treatment.423

For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B, an IV echinocandin (caspofungin, micafungin), oral or IV posaconazole, or itraconazole oral suspension.423 IDSA states that echinocandins (either alone or in conjunction with other antifungals) may be effective for salvage therapy of invasive aspergillosis; however, routine use of echinocandin monotherapy not recommended for primary treatment of invasive aspergillosis.423

Consult current IDSA clinical practice guidelines available at 423 and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at 440 441 for additional information on management of aspergillosis.

Candidemia and Other Invasive Candida Infections

Treatment of candidemia and certain other invasive Candida infections (intra-abdominal abscess, peritonitis, pleural space infections) in adults, adolescents, and children ≥3 months of age.1 425 436 A drug of choice.425 436

Has been effective in C. albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis infections, principally in nonneutropenic patients.1

Manufacturer states safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.1

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients in intensive care units (ICUs), IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial therapy;425 IV or oral fluconazole is an acceptable alternative for initial therapy in selected patients, including those who are not critically ill and unlikely to have infections caused by fluconazole-resistant Candida.425 IV amphotericin B recommended if echinocandin- and azole-resistant Candida suspected and is an alternative when echinocandins and fluconazole have been ineffective or cannot be used.425 Consider transition from the echinocandin to fluconazole (usually within 5–7 days) in clinically stable patients if strain susceptible to fluconazole (e.g., C. albicans) and initial treatment resulted in negative repeat blood cultures.425

For treatment of candidemia in neutropenic patients, IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) or, alternatively, IV amphotericin B for initial therapy.425 Fluconazole is an alternative in those who are not critically ill and have had no prior exposure to azole antifungals;425 also can be used for step-down therapy in clinically stable patients who have fluconazole-susceptible isolates and documented bloodstream clearance.425 Voriconazole can be used as an alternative for initial therapy when broader antifungal coverage is required and also can be used as step-down therapy during neutropenia in clinically stable patients who have voriconazole-susceptible isolates and documented bloodstream clearance.425 An echinocandin, amphotericin B, or voriconazole recommended for infections known to be caused by C. krusei.425

For treatment of osteoarticular infections (e.g., osteomyelitis, septic arthritis) caused by Candida, IDSA recommends initial treatment with fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole.425 If septic arthritis involves a prosthetic device that cannot be removed, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended if isolate is susceptible.425

For treatment of endocarditis (native or prosthetic valve) or implantable cardiac device infections caused by Candida, IDSA recommends initial treatment with IV amphotericin B (with or without flucytosine) or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole.425 If isolate is susceptible, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended to prevent recurrence in those with native valve endocarditis who cannot undergo valve replacement and in those with prosthetic valve endocarditis.425

Consult current IDSA clinical practice guidelines available at for additional information on management of candidemia and disseminated candida infections.425

Esophageal Candidiasis

Treatment of esophageal candidiasis in adults, adolescents, and children ≥3 months of age.1 425 436 440 A drug of choice.425 436

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).425 440

IDSA recommends oral fluconazole as the preferred drug of choice for the treatment of esophageal candidiasis;425 if oral therapy not tolerated, IV fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) recommended.425 For fluconazole-refractory infections, IDSA recommends itraconazole oral solution or IV or oral voriconazole;425 alternatives are an IV echinocandin (anidulafungin, caspofungin, micafungin) or IV amphotericin B.425 IDSA states oral posaconazole (oral suspension or delayed-release tablets) is another possible alternative for treatment of fluconazole-refractory esophageal candidiasis.425

For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend IV or oral fluconazole or itraconazole oral solution.440 Alternatives include oral or IV voriconazole, an IV echinocandin (anidulafungin, caspofungin, micafungin), or IV amphotericin B.440 For refractory esophageal candidiasis, including fluconazole-refractory infections, in HIV-infected adults and adolescents, itraconazole oral solution or posaconazole oral suspension is recommended;440 alternatives are IV amphotericin B, an IV echinocandin (anidulafungin, caspofungin, micafungin), or oral or IV voriconazole.440

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for esophageal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of esophageal candidiasis may benefit from secondary prophylaxis with oral fluconazole or posaconazole oral suspension;425 440 441 however, consider potential for development of azole resistance.425 440 441

Consult current IDSA clinical practice guidelines available at 425 and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at 440 441 for additional information on management of esophageal candidiasis.

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis.425 436 440 Considered an alternative, not a drug of choice.425 440

For mild oropharyngeal candidiasis, IDSA recommends topical treatment with clotrimazole lozenges or miconazole buccal tablets;425 nystatin (oral suspension or tablets) is an alternative.425 For moderate to severe oropharyngeal candidiasis, IDSA recommends oral fluconazole.425 For fluconazole-refractory oropharyngeal candidiasis, IDSA recommends itraconazole oral solution or posaconazole oral suspension;425 oral voriconazole or amphotericin B oral suspension (not commercially available in the US) recommended as alternatives.425 Other alternatives for refractory oropharyngeal candidiasis are IV echinocandins (anidulafungin, caspofungin, micafungin) or IV amphotericin B.425

For treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes;440 if topical therapy used (e.g., mild to moderate episodes), drugs of choice are clotrimazole lozenges or miconazole buccal tablets.440 Alternatives for systemic treatment are itraconazole oral solution or posaconazole oral suspension;440 nystatin oral suspension is an alternative for topical treatment.440 For fluconazole-refractory infections in HIV-infected adults and adolescents, posaconazole oral suspension is preferred;440 itraconazole oral solution is an alternative.440

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for oropharyngeal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of oropharyngeal candidiasis may benefit from secondary prophylaxis with oral fluconazole;425 440 441 however, consider potential for development of azole resistance.425 440 441

Consult current IDSA clinical practice guidelines available at 425 and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at 440 441 for additional information on management of oropharyngeal candidiasis.

Candida auris Infections

Treatment of infections caused by C. auris, an emerging pathogen associated with potentially fatal candidemia or other invasive infections.504 505 506 507 508 509 510

First identified in 2009, C. auris has now been reported as the cause of serious invasive infections (including fatalities) in multiple countries worldwide (e.g., Japan, South Korea, India, Kuwait, South Africa, Pakistan, United Kingdom, Venezuela, Colombia, US).504 505 506 507 509 As of May 2017, a total of 77 clinical cases of C. auris had been reported to CDC from 7 different states.504 May be difficult to identify using standard in vitro methods.507 508 Large percentage of C. auris clinical isolates are resistant to fluconazole;505 507 508 509 multidrug-resistant isolates with reduced susceptibility or resistance to all 3 major classes of antifungal agents (azoles, polyenes, echinocandins) reported.505 507 508 509

CDC issued interim recommendations regarding laboratory diagnosis, treatment, and infection control measures for suspected or known C. auris infections.510 Based on limited data available to date, CDC recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial treatment of invasive C. auris infections (e.g., bloodstream or intra-abdominal infections) in adults.510 CDC states a switch to IV amphotericin B (lipid formulation) could be considered if patient is clinically unresponsive to the echinocandin or if fungemia persists >5 days.510 Consultation with an infectious disease specialist highly recommended.510

CDC recommends that infection control measures be observed for all patients with cultures yielding C. auris, including those with positive cultures only from noninvasive body sites.510

If C. auris infection is suspected, immediately contact state or local public health authorities and the CDC (candidaauris@cdc.gov) for guidance.510 Consult interim recommendations and most recent information from CDC available at for additional information on diagnosis and management of C. auris infections.510

Empiric Therapy in Febrile Neutropenic Patients

Empiric therapy of presumed fungal infections in febrile, neutropenic adults, adolescents, and children ≥3 months of age.1

Caspofungin Acetate Dosage and Administration

Administration

IV Administration

Administer by slow IV infusion.1 Do not administer by rapid IV injection.1

Do not admix or infuse concomitantly with other drugs.1

Must be reconstituted and diluted prior to administration.1 Use strict aseptic technique since the drug contains no preservatives.1

Do not use diluents containing dextrose (e.g., 5% dextrose injection).1

Reconstitution

Prior to reconstitution, allow vial of lyophilized caspofungin to reach room temperature.1

Reconstitute 50- or 70-mg vials by adding 10.8 mL of 0.9% sodium chloride injection, sterile water for injection, bacteriostatic water for injection (with methylparaben and propylparaben or 0.9% benzyl alcohol) to provide solutions containing 5 or 7 mg/mL, respectively.1 Mix gently until drug dissolves completely and a clear solution obtained.1

The 50- and 70-mg reconstituted vials are formulated to provide a slight overfill, yielding 54.6 and 75.6 mg, respectively, of caspofungin.1 3 The vials are for single-use only; discard any unused reconstituted solution.1

Dilution

Aseptically withdraw the appropriate volume of reconstituted solution (mL equivalent to the indicated loading or maintenance dose) and add it to 250 mL of 0.225, 0.45, or 0.9% sodium chloride injection or lactated Ringer’s injection.1 Alternatively, add the appropriate volume of reconstituted solution to a reduced volume of one of these IV solutions, provided the final concentration does not exceed 0.5 mg/mL.1

For pediatric patients 3 months to 17 years of age, withdraw the appropriate volume of reconstituted solution (mL equivalent to the indicated loading or maintenance dose) based on a concentration of 5 mg/mL (if using the 50-mg vial) or 7 mg/mL (if using the 70-mg vial) and add it to 0.225, 0.45, or 0.9% sodium chloride injection or lactated Ringer’s injection.1 Base choice of vial on indicated dose.1 Manufacturer recommends using the 50-mg vial for doses <50 mg and the 70-mg vial for doses >50 mg.1

Rate of Administration

Administer by IV infusion over approximately 1 hour.1

Dosage

Available as caspofungin acetate;1 dosage expressed in terms of the salt.1

Pediatric Patients

Dosage for pediatric patients 3 months to 17 years of age is based on body surface area (BSA) calculated using the Mosteller formula.1

Calculate the loading dose (in mg) as BSA (m2) x 70 mg/m2 and calculate the maintenance dose (in mg) as BSA (m2) x 50 mg/m2.1

Regardless of the patient’s calculated dose, the maximum loading dose and maximum daily maintenance dosage in pediatric patients should not exceed 70 mg.1

Aspergillosis
IV

Pediatric patients 3 months to 17 years of age: A single loading dose of 70 mg/m2 on day 1, followed by 50 mg/m2 once daily.1 If 50 mg/m2 once daily is well tolerated but does not provide an adequate clinical response, dosage may be increased to 70 mg/m2 (up to 70 mg) once daily.1

Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response.1 423 IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks.423

Candidemia and Other Invasive Candida Infections (Intra-abdominal abscess, Peritonitis, Pleural Space Infections)
IV

Pediatric patients 3 months to 17 years of age: A single loading dose of 70 mg/m2 on day 1, followed by 50 mg/m2 once daily.1 If 50 mg/m2 once daily is well tolerated but does not provide adequate clinical response, dosage may be increased to 70 mg/m2 (up to 70 mg) once daily.1

Duration of treatment is based on clinical and microbiological response.1 Manufacturer recommends treatment be continued for at least 14 days after the last positive culture and states that those who remain persistently neutropenic may require a longer course of therapy pending resolution of neutropenia.1 IDSA recommends that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 2 weeks after documented clearance of Candida from the bloodstream, resolution of candidemia symptoms, and resolution of neutropenia.425

Esophageal Candidiasis
IV

Pediatric patients 3 months to 17 years of age: A single loading dose of 70 mg/m2 on day 1, followed by 50 mg/m2 once daily.1 441 If 50 mg/m2 once daily is well tolerated but does not provide adequate clinical response, dosage may be increased to 70 mg/m2 (up to 70 mg) once daily.1

HIV-infected adolescents: 50 mg once daily.440

Manufacturer recommends treatment be continued for 7–14 days after resolution of symptoms.1 IDSA and others recommend that antifungal treatment for esophageal candidiasis be continued for 14–21 days.425 440

Empiric Therapy in Febrile Neutropenic Patients
IV

Pediatric patients 3 months to 17 years of age: A single loading dose of 70 mg/m2 on day 1, followed by 50 mg/m2 once daily.1 If 50 mg/m2 once daily is well tolerated but does not provide adequate clinical response, dosage may be increased to 70 mg/m2 (up to 70 mg) once daily.1

Duration of empiric therapy is based on clinical response;1 continue until neutropenia resolves.1 If fungal infection is identified, continue for at least 14 days total and for at least 7 days after neutropenia and clinical symptoms resolve.1

Adults

Aspergillosis
IV

A single 70-mg loading dose on day 1, followed by 50 mg once daily.1 423 436 440 Efficacy of dosages >50 mg once daily not evaluated.1

Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response.1 423 IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks.423

Candidemia and Other Invasive Candida Infections (Intra-abdominal abscess, Peritonitis, Pleural Space Infections)
IV

A single 70-mg loading dose on day 1, followed by 50 mg once daily.1 425 436

IDSA states consider a transition from the echinocandin to fluconazole (usually within 5–7 days) in patients who are clinically stable, have isolates susceptible to fluconazole (e.g., C. albicans), and have negative repeat blood cultures after initial antifungal treatment.425

Duration of treatment is based on clinical and microbiological response.1 Manufacturer recommends treatment be continued for at least 14 days after the last positive culture and states that those who remain persistently neutropenic may require a longer course of therapy pending resolution of neutropenia.1 IDSA recommends that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 2 weeks after documented clearance of Candida from the bloodstream and resolution of candidemia symptoms and neutropenia.425

Osteoarticular infections: IDSA recommends 50–70 mg once daily.425 After ≥2 weeks, can switch to fluconazole.425

Endocarditis (native or prosthetic valve) or implantable cardiac device infections: IDSA recommends 150 mg once daily.425 If infection caused by fluconazole-susceptible Candida, can switch to fluconazole after patient stabilized and Candida has been cleared from bloodstream.425

Esophageal Candidiasis
IV

50 mg once daily recommended by manufacturer.1

Although manufacturer states use of a 70-mg loading dose not evaluated for treatment of esophageal candidiasis,1 IDSA recommends a single 70-mg loading dose on day 1, followed by 50 mg once daily.425

HIV-infected adults: 50 mg once daily.440

Manufacturer recommends treatment be continued for 7–14 days after resolution of symptoms.1 IDSA and others recommend that antifungal treatment be continued for 14–21 days.425 440

Oropharyngeal Candidiasis
IV

IDSA recommends a single 70-mg loading dose on day 1, followed by 50 mg once daily for 7–14 days.425

Candida auris Infections
IV

CDC recommends a single 70-mg loading dose on day 1, followed by 50 mg once daily.510

Empiric Therapy in Febrile Neutropenic Patients
IV

A single 70-mg loading dose on day 1, followed by 50 mg once daily.1 425 If 50 mg once daily is well tolerated but does not provide an adequate clinical response, dosage may be increased to 70 mg once daily.1

Duration of empiric therapy is based on clinical response; continue until neutropenia resolves.1 If fungal infection is identified, continue for at least 14 days total and for at least 7 days after both neutropenia and clinical symptoms resolve.1

Prescribing Limits

Pediatric Patients

Maximum loading dose: 70 mg daily.1

Maximum maintenance dose: 70 mg daily.1

Special Populations

Hepatic Impairment

Adults with mild hepatic impairment (Child-Pugh score 5–6): Dosage adjustments not necessary.1

Adults with moderate hepatic impairment (Child-Pugh score 7–9): 35 mg once daily; use an initial 70-mg loading dose (if usually indicated).1

Adults with severe hepatic impairment (Child-Pugh score >9): Data not available.1

Pediatric patients with any degree of hepatic impairment: Data not available.1

Renal Impairment

Adults with renal impairment: Dosage adjustments not necessary.1

Not dialyzable;1 3 supplemental dose not required following hemodialysis.1 3

Geriatric Patients

Adults ≥65 years of age: Dosage adjustments not necessary.1

Cautions for Caspofungin Acetate

Contraindications

  • Known hypersensitivity (e.g., anaphylaxis) to caspofungin or any ingredient in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis) reported.1 If such reactions occur, discontinue the drug and administer appropriate treatment.1

Possible histamine-mediated symptoms (e.g., rash, facial swelling, pruritus, sensation of warmth, bronchospasm) reported;1 may require discontinuance of the drug and/or administration of appropriate treatment.1

Postmarketing reports of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).1 Use with caution in patients with a history of allergic skin reactions.1

Hepatic Effects

Abnormal liver function test results reported when used in healthy volunteers or in adult and pediatric patients.1 Clinically important hepatic dysfunction, hepatitis, and hepatic failure reported in some adult and pediatric patients with serious underlying conditions receiving multiple drugs concomitantly;1 causal relationship not established.1

Transient elevations in liver enzymes reported in patients receiving caspofungin and cyclosporine concomitantly.1 (See Specific Drugs under Interactions.)

If abnormal liver function test results occur, monitor for evidence of worsening hepatic function and evaluate benefits versus risks of continuing caspofungin.1

Specific Populations

Pregnancy

Category C.1

No adequate and well-controlled studies in pregnant women;1 use during pregnancy only if potential benefits justify potential risks to the fetus.1

In animals, embryofetal toxicity (increased resorptions, increased peri-implantation loss, incomplete ossification at multiple fetal sites) reported with caspofungin dosage about 2 times the recommended human dosage (based on body surface area comparisons).1

Lactation

Distributed into milk in rats;1 not known whether distributed into milk in humans.1

Use with caution in nursing women.1

Pediatric Use

Safety and efficacy not established in neonates and infants <3 months of age.1

Although limited pharmacokinetic data are available for neonates and infants <3 months of age, manufacturer states data insufficient to date to establish safe and effective dosage for treatment of neonatal candidiasis.1 Invasive candidiasis in neonates has a higher rate of CNS and multi-organ involvement than in older patients;1 insufficient data to date regarding distribution of caspofungin into CNS or efficacy in the treatment of meningitis and endocarditis.1

Safety and efficacy of caspofungin for use in infants and children 3 months to 17 years of age for treatment of invasive aspergillosis in those refractory to or intolerant of other antifungals; for treatment of candidemia or certain other invasive Candida infections (intra-abdominal abscesses, peritonitis, pleural space infections) or esophageal candidiasis; and for empiric treatment of presumed fungal infections in febrile neutropenic patients is based on adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from prospective studies in this age group.1

Data not available regarding efficacy in pediatric patients for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida or for initial therapy of invasive aspergillosis.1

Data not available regarding use in pediatric patients with hepatic impairment.1

Manufacturer states that overall safety profile of caspofungin in pediatric patients is comparable to that in adults.1

Although data limited, some experts state caspofungin can be considered for first-line treatment of invasive candidiasis or for alternative treatment of esophageal candidiasis in HIV-infected children.441

Geriatric Use

Clinical studies did not include a sufficient number of patients ≥65 years of age to determine whether they respond differently than younger individuals.1 No overall differences in efficacy or safety were observed between elderly and younger individuals,1 but possibility of greater sensitivity of some older patients cannot be ruled out.1

Caspofungin plasma concentrations were increased slightly in men and women ≥65 years of age compared to young healthy males.1 Dosage adjustments not necessary.1

Hepatic Impairment

Although AUC is increased slightly in adults with mild hepatic impairment (Child-Pugh score 5–6) compared with healthy adults, dosage adjustment not necessary.1 Increase in AUC is greater in adults with moderate hepatic impairment (Child-Pugh score 7–9), and dosage reduction is recommended in these patients. (See Hepatic Impairment under Dosage and Administration.)

Data not available regarding use in adults with severe hepatic impairment (Child-Pugh score >9)1 or in pediatric patients with any degree of hepatic impairment.1

Renal Impairment

No clinically important effects on pharmacokinetics.1 (See Special Populations under Pharmacokinetics.) Dosage adjustments not necessary in adults with renal impairment.1

Common Adverse Effects

Pyrexia, diarrhea, chills, decreased potassium, increased alkaline phosphatase, decreased hemoglobin, hypotension, respiratory failure, increased ALT, fever, decreased hematocrit, phlebitis, vomiting, rash, increased AST, nausea, headache, increased bilirubin, septic shock, decreased WBC, peripheral edema, cough, pneumonia, increased creatinine, anemia, abdominal pain, dyspnea, increased blood urea, pleural effusion, increased conjugated bilirubin, tachycardia, decreased albumin, decreased magnesium, rales, sepsis.1 7 8 9 10 11 13

Interactions for Caspofungin Acetate

Does not inhibit and is a poor substrate for CYP isoenzymes in vitro.1 Does not induce CYP3A4 isoenzyme.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP isoenzyme inducers: May cause clinically important decreases in caspofungin plasma concentrations;1 specific mechanism involved unclear.1

Drugs Affecting or Affected by P-glycoprotein Transport

Not a substrate of the P-glycoprotein transport system;1 pharmacokinetic interactions unlikely.7

Specific Drugs

Drug

Interaction

Comments

Amphotericin B

No evidence of pharmacokinetic interactions1

In vitro evidence of synergistic or additive antifungal activity against some Aspergillus, including A. fumigatus, and some Fusarium; 7 8 9 13 indifferent or additive antifungal effects in vitro against C. glabrata;8 no in vitro evidence of antagonism against A. fumigatus, C. albicans (including azole-resistant strains), or other Candida1 8 9 10 12

Carbamazepine

Possible decreased caspofungin concentrations 1

Use caspofungin dosage of 70 mg once daily in adults and consider dosage of 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Corticosteroids (dexamethasone)

Possible decreased caspofungin concentrations 1

Use caspofungin dosage of 70 mg once daily in adults and consider dosage of 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Efavirenz

Possible decreased caspofungin concentrations1

Use caspofungin dosage of 70 mg once daily in adults and consider dosage of 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Fluconazole

In vitro evidence of synergistic antifungal activity against C. glabrata;8 no in vitro evidence of antagonism against C. albicans (including azole-resistant strains) or other Candida8

Immunosuppressive agents (cyclosporine, mycophenolate, tacrolimus)

Cyclosporine: Increased AUC of caspofungin;1 no effect on cyclosporine concentrations;1 transient elevations in ALT and AST reported1

Mycophenolate: Pharmacokinetic interactions not reported1

Tacrolimus: Decreased tacrolimus AUC and plasma concentrations;1 no effect on caspofungin pharmacokinetics1

Cyclosporine: Use concomitantly with caution and only when potential benefits outweigh risks;1 monitor hepatic function;436 if abnormal liver function test results occur, monitor closely and evaluate benefits versus risks of continuing concomitant therapy1

Tacrolimus: Monitor tacrolimus concentrations and adjust dosage as needed1

Itraconazole

Itraconazole: No evidence of pharmacokinetic interactions1

In vitro evidence of synergistic or additive antifungal activity against some Aspergillus, including A. fumigatus7 8

Nelfinavir

No effect on caspofungin pharmacokinetics1

Nevirapine

Possible decreased caspofungin concentrations1

Use caspofungin dosage of 70 mg once daily in adults and consider dosage of 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Phenytoin

Possible decreased caspofungin concentrations 1

Use caspofungin dosage of 70 mg once daily in adults and consider dosage of 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Posaconazole

In vitro evidence of synergistic antifungal activity against Aspergillus and C. glabrata10 13

Rifampin

Decreased trough concentrations of caspofungin1

Use caspofungin dosage of 70 mg once daily in adults and dosage of 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Voriconazole

In vitro evidence of additive antifungal effects against C. glabrata;8 indifferent, additive, or synergistic antifungal activity in vitro against some Aspergillus, including A. fumigatus;8 13 no in vitro evidence of antagonism against Aspergillus8 12

Caspofungin Acetate Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract; must be administered IV.25

Special Populations

Geriatric adults: Slight increase in plasma concentrations in adults ≥65 years of age compared with younger adults.1

Adults with mild hepatic impairment (Child-Pugh score 5–6): AUC after a single 70-mg IV dose is increased approximately 55% compared with healthy adults.1 After a single 70-mg IV loading dose on day 1 followed by 50 mg once daily, AUC is increased 19–25% on days 7 and 14 compared with healthy adults.1

Adults with moderate hepatic impairment (Child-Pugh score 7–9): AUC after a single 70-mg IV dose is increased 76% compared with healthy adults.1

Adults with severe hepatic impairment (Child-Pugh score >9): Data not available.1

Adults with mild renal impairment (Clcr 50–80 mL/minute): Pharmacokinetics after a single 70-mg IV dose are similar to healthy adults.1

Adults with moderate or severe renal impairment (Clcr 5–49 mL/minute) or with end-stage renal impairment receiving dialysis: AUC after a single IV dose is increased 30–49% compared with healthy adults.1 Mild to end-stage renal impairment had no clinically important effect on caspofungin concentrations following multiple 50-mg doses.1

Distribution

Extent

Distributed into liver, lung, spleen, and GI tract.25

Distribution into CSF probably negligible.25

Crosses placenta in rats and rabbits;1 not known whether crosses placenta in humans.1

Distributed into milk of lactating rats;1 not known whether distributed into human milk.1

Plasma Protein Binding

About 97% bound to albumin.1

Elimination

Metabolism

Slowly metabolized by hydrolysis and N-acetylation1 in the liver.25 Metabolites exhibit no antifungal activity.25 Also undergoes spontaneous chemical degradation to an open-ring peptide.1

Elimination Route

Following a single IV dose, 35 and 41% excreted in feces and urine, respectively, as the parent drug and metabolites;1 <3% of a dose eliminated unchanged in urine.1 24

Not removed by hemodialysis.1

Half-life

A short initial α-phase followed by β-phase with an elimination half-life of 9–11 hours; γ-phase with half-life of 40–50 hours also reported.1

Stability

Storage

Parenteral

Powder for IV Infusion

2–8°C.1

Following reconstitution, may be stored for up to 1 hour at ≤25°C.1

Following further dilution, may be stored in the IV bag or bottle for up to 24 hours at ≤25°C or for up to 48 hours at 2–8°C.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1 HID

Compatible

Dextrose 5%

Ringer’s injection, lactated

Sodium chloride 0.225, 0.45, or 0.9%

Drug CompatibilityHID
Y-Site Compatibility

Compatible

Amikacin sodium

Amiodarone HCl

Azithromycin

Aztreonam

Bumetanide

Carboplatin

Ciprofloxacin

Cisplatin

Cyclosporine

Daptomycin

Daunorubicin HCl

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Dolasetron mesylate

Dopamine HCl

Doripenem

Doxorubicin HCl

Epinephrine HCl

Etoposide phosphate

Famotidine

Fentanyl citrate

Fluconazole

Ganciclovir sodium

Gentamicin sulfate

Hydralazine HCl

Hydrocortisone sodium succinate

Hydromorphone HCl

Ifosfamide

Imipenem-cilastatin sodium

Insulin, regular

Levofloxacin

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Meperidine HCl

Meropenem

Metronidazole

Midazolam HCl

Milrinone lactate

Mitomycin

Morphine sulfate

Mycophenolate mofetil HCl

Norepinephrine bitartrate

Ondansetron HCl

Pantoprazole sodium

Phenylephrine HCl

Posaconazole

Potassium chloride

Quinupristin-dalfopristin

Tacrolimus

Telavancin HCl

Tobramycin sulfate

Vancomycin HCl

Vasopressin

Vincristine sulfate

Voriconazole

Incompatible

Acyclovir sodium

Amphotericin B

Amphotericin B lipid complex

Amphotericin B liposomal

Ampicillin sodium

Cefazolin sodium

Cefepime HCl

Ceftaroline fosamil

Ceftazidime

Ceftriaxone sodium

Clindamycin phosphate

Cytarabine

Ertapenem sodium

Furosemide

Heparin sodium

Methylprednisolone sodium

Nafcillin sodium

Pantoprazole sodium

Piperacillin sodium-tazobactam sodium

Potassium phosphates

TPN

Trimethoprim-sulfamethoxazole

Actions and Spectrum

  • Semisynthetic echinocandin antifungal;1 lipopeptide synthesized from a fermentation product of Glarea lozoyensis.1

  • Echinocandins (e.g., anidulafungin, caspofungin, micafungin) differ structurally and pharmacologically from other available antifungals.1 2

  • Inhibits synthesis of β-d-glucan, an integral component of the fungal cell wall that is not present in mammalian cells.1 2

  • May be fungistatic or fungicidal in action.1 7 8 10 12 13 14 Depending on the concentration, may be fungicidal against Candida, but usually fungistatic against Aspergillus.1 7 8 10 12 13 14

  • Active in vitro against Aspergillus fumigatus,1 26 27 A. flavus,1 26 27 A. strictum,27 and A. terreus.1 26 27

  • Active in vitro against Candida, including C. albicans,1 26 27 C. glabrata,1 26 27 C. guilliermondii,1 26 27 C. kefyr,26 C. krusei,1 26 27 C. lusitaniae,26 27 C. metapsilosis,29 C. orthopsilosis,29 C. parapsilosis,1 26 27 28 29 and C. tropicalis.1 26 27 Has been active against some Candida, including C. glabrata and C. krusei, resistant to fluconazole.8 13

  • Clinical isolates of C. auris (often misidentified as C. haemulonii, C. famata, or Rhodotorula glutinis) generally inhibited in vitro by caspofungin concentrations of 0. 06–1 mcg/mL.505 506 508 509

  • Like other echinocandins, not active against Cryptococcus neoformans, Fusarium, Trichosporon, or zygomycetes.8 9 10 12 13 14

  • Strains of Candida,1 including C. albicans,31 C. glabrata,32 C. krusei,30 and C. parapsilosis,28 with reduced susceptibility or resistance to caspofungin have emerged in some patients who received the drug for treatment and, in some cases, were associated with clinical failures.1 Some clinical isolates of C. auris have reduced susceptibility or resistance to caspofungin in vitro (i.e., MICs ≥2 mcg/mL).508 509 510

  • Resistance to caspofungin has been associated with specific mutations in the FKS subunits of the glucan synthase enzyme;1 these mutations associated with higher MICs and breakthrough infection.1 Candida with reduced susceptibility to caspofungin as a result of an increase in chitin content of fungal cell wall also reported; clinical importance unknown.1

  • Some C. albicans with reduced susceptibility to caspofungin also have reduced susceptibility to micafungin.12 22 23

Advice to Patients

  • Inform patients that anaphylactic reactions have been reported in patients receiving caspofungin.1 Advise patients that the drug can cause hypersensitivity reactions (e.g., rash, facial swelling, angioedema, pruritus, sensation of warmth, bronchospasm) and of the importance of contacting clinicians if any of these signs or symptoms occur.1

  • Advise patients about isolated reports of serious hepatic effects (e.g., hepatitis, hepatic failure) associated with caspofungin and the importance of clinicians assessing benefits versus risks of the drug if abnormal liver function tests occur.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Caspofungin Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

50 mg*

Cancidas

Merck

Caspofungin Acetate for Injection

70 mg*

Cancidas

Merck

Caspofungin Acetate for Injection

AHFS DI Essentials. © Copyright 2017, Selected Revisions September 4, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Merck & Co, Inc. Cancidas (caspofungin acetate) for injection for IV use prescribing information. Whitehouse Station, NJ; 2017 Feb.

2. Onishi J, Meinz M, Thompson J et al. Discovery of novel antifungal (1,3)-β-d-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000; 44:368-77.

3. Merck, Whitehouse Station, NJ: Personal communication.

4. Mora-Duarte J, Betts R, Rotstein C et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002; 347:2020-9. [PubMed 12490683]

5. Villanueva A, Gotuzzo E, Arathoon EG et al. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med. 2002; 113:294-9. [PubMed 12361815]

6. Arathoon EG, Gotuzzo E, Noriega LM et al. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother. 2002; 46:451-7. [PubMed 11796357]

7. Stone EA, Fung HB, Kirschenbaum HL. Caspofungin: an echinocandin antifungal agent. Clin Ther. 2002; 24:351-77; discussion 329. [PubMed 11952021]

8. Keating G, Figgitt D. Caspofungin: a review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis. Drugs. 2003; 63:2235-63. [PubMed 14498760]

9. Eschenauer G, Depestel DD, Carver PL. Comparison of echinocandin antifungals. Ther Clin Risk Manag. 2007; 3:71-97. [PubMed 18360617]

10. Garnock-Jones KP, Keam SJ. Caspofungin in pediatric patients with fungal infections. Pediatr Drugs. 2009; 11:259-69.

11. 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; 351:1391-402. [PubMed 15459300]

12. Kauffman CA, Carver PL. Update on echinocandin antifungals. Semin Respir Crit Care Med. 2008; 29:211-9. [PubMed 18366002]

13. Kim R, Khachikian D, Reboli AC. A comparative evaluation of properties and clinical efficacy of the echinocandins. Expert Opin Pharmacother. 2007; 8:1479-92. [PubMed 17661730]

14. Morris MI, Villmann M. Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm. 2006; 63:1693-703. [PubMed 16960253]

15. Morris MI, Villmann M. Echinocandins in the management of invasive fungal infections, Part 2. Am J Health Syst Pharm. 2006; 63:1813-20. [PubMed 16990627]

16. Zaoutis TE, Jafri HS, Huang LM et al. A prospective, multicenter study of caspofungin for the treatment of documented Candida or Aspergillus infections in pediatric patients. Pediatrics. 2009; 123:877-84. [PubMed 19255017]

22. Laverdiere M, Lalonde RG, Baril JG et al. Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis. J Antimicrob Chemother. 2006; 57:705-8. [PubMed 16464893]

23. Cappelletty D, Eiselstein-McKitrick K. The echinocandins. Pharmacotherapy. 2007; 27:369-88. [PubMed 17316149]

24. Hoang A. Caspofungin acetate: an antifungal agent. Am J Health Syst Pharm. 2001; 58:1206-14. [PubMed 11449878]

25. Denning DW. Echinocandins: a new class of antifungal. J Antimicrob Chemother. 2002; 49:889-91. [PubMed 12039879]

26. Cuenca-Estrella M, Gomez-Lopez A, Mellado E et al. Head-to-head comparison of the activities of currently available antifungal agents against 3,378 spanish clinical isolates of yeasts and filamentous fungi. Antimicrob Agents Chemother. 2006; 50:917-21.

27. Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol. 1998; 36:2950-6.

28. Moudgal V, Little T, Boikov D et al. Multiechinocandin- and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrob Agents Chemother. 2005; 49:767-9. [PubMed 15673762]

29. Lockhart SR, Messer SA, Pfaller MA et al. Geographic distribution and antifungal susceptibility of the newly described species Candida orthopsilosis and Candida metapsilosis in comparison to the closely related species Candida parapsilosis. J Clin Microbiol. 2008; 46:2659-64. [PubMed 18562582]

30. Hakki M, Staab JF, Marr KA. Emergence of a Candida krusei isolate with reduced susceptibility to caspofungin during therapy. Antimicrob Agents Chemother. 2006; 50:2522-4. [PubMed 16801435]

31. Miller CD, Lomaestro BW, Park S et al. Progressive esophagitis caused by Candida albicans with reduced susceptibility to caspofungin. Pharmacotherapy. 2006; 26:877-80. [PubMed 16716141]

32. Krogh-Madsen M, Arendrup MC, Heslet L et al. Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. Clin Infect Dis. 2006; 42:938-44. [PubMed 16511756]

423. Patterson TF, Thompson GR, 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:e1-e60. Updates may be available at IDSA website at www.idsociety.org. [PubMed 27365388]

425. 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:e1-50. Updates may be available at IDSA website at www.idsociety.org. [PubMed 26679628]

436. . Antifungal drugs. Treat Guidel Med Lett. 2012; 10:61-8; quiz 69-70. [PubMed 22825657]

440. Panel on Opportunistic Infection in HIV-infected Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (September 17, 2015). Updates may be available at HHS AIDS Information (AIDSinfo) website.

441. Panel on Opportunistic Infection in HIV-exposed and HIV-infected children, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics (Nov 6, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

504. Tsay S, Welsh RM, Adams EH et al. Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities - United States, June 2016-May 2017. MMWR Morb Mortal Wkly Rep. 2017; 66:514-515. [PubMed 28520710]

505. Larkin E, Hager C, Chandra J et al. The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation. Antimicrob Agents Chemother. 2017; 61 [PubMed 28223375]

506. Lee WG, Shin JH, Uh Y et al. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011; 49:3139-42. [PubMed 21715586]

507. Vallabhaneni S, Kallen A, Tsay S et al. Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus-United States, May 2013-August 2016. Am J Transplant. 2017; 17:296-299. [PubMed 28029734]

508. Kathuria S, Singh PK, Sharma C et al. Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method. J Clin Microbiol. 2015; 53:1823-30. [PubMed 25809970]

509. Lockhart SR, Etienne KA, Vallabhaneni S et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis. 2017; 64:134-140. [PubMed 27988485]

510. Centers for Disease Control and Prevention. Candida auris interim recommendations for healthcare facilities and laboratories. From CDC website. Accessed 2017 May 30.

HID. ASHP’s interactive handbook on injectable drugs. McEvoy, GK, ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; Updated June 9, 2016. From HID website.

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