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; lipopeptide synthesized from a fermentation product of Glarea lozoyensis.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 (e.g., amphotericin B [conventional or lipid formulations], itraconazole).1 18 21 Has not been evaluated for initial therapy of invasive aspergillosis.1

IDSA and other clinicians consider voriconazole the drug of choice for the treatment of invasive aspergillosis and amphotericin B (a lipid formulation) the preferred alternative for initial treatment.18 21 For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA and others recommend amphotericin B (a lipid formulation), caspofungin, micafungin, posaconazole, or itraconazole.18 21 For empiric or preemptive therapy, IDSA recommends amphotericin B (a lipid formulation), caspofungin, itraconazole, or voriconazole as drugs of choice.21

For treatment of invasive aspergillosis in HIV-infected adults, adolescents, and children, CDC, National Institutes of Health (NIH), and IDSA recommend voriconazole as the drug of choice;19 20 amphotericin B (conventional or lipid formulation), caspofungin, and posaconazole are recommended as alternatives.19 20

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 17 18 A drug of choice.17 18

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

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in such patients, IDSA recommends fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;17 amphotericin B (conventional or lipid formulation) is the preferred alternative.17 An echinocandin may be preferred for initial treatment in those who have moderately severe to severe candidemia, are allergic to or intolerant of azole antifungals, have recently received an azole, or have or are likely to have infections caused by C. glabrata or C. krusei.17 Fluconazole may be preferred for initial treatment in those who are less critically ill and have not recently received an azole and for infections caused by C. parapsilosis.17 If an echinocandin is used initially, transition to fluconazole is recommended for patients who are clinically stable and have isolates likely to be susceptible to fluconazole (e.g., C. albicans).17

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For treatment of candidemia in neutropenic patients, IDSA recommends an echinocandin (caspofungin, micafungin, anidulafungin) or amphotericin B (a lipid formulation) for initial therapy;17 fluconazole is the preferred alternative in those who are less critically ill or have not recently received an azole;17 voriconazole can be used as an alternative when broader antifungal coverage is required.17 An echinocandin is preferred for C. glabrata infections;17 fluconazole or amphotericin B (a lipid formulation) is preferred for C. parapsilosis infections;17 an echinocandin, amphotericin B (a lipid formulation), or voriconazole is recommended for C. krusei infections.17 For initial empiric treatment of suspected invasive candidiasis in neutropenic patients, amphotericin B (a lipid formulation), caspofungin, or voriconazole is recommended;17 alternatives are fluconazole or itraconazole.17

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

Esophageal Candidiasis

Treatment of esophageal candidiasis in adults, adolescents, and children ≥3 months of age.1 17 18 19 A drug of choice.17 18

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).17 19

IDSA recommends oral fluconazole as the preferred drug of choice for the treatment of esophageal candidiasis;17 if oral therapy is not tolerated, IV fluconazole, IV amphotericin B (conventional formulation), or an IV echinocandin (caspofungin, micafungin, anidulafungin) is recommended.17 For fluconazole-refractory infections, preferred alternatives are itraconazole oral solution, oral posaconazole, or IV or oral voriconazole;17 other alternatives are an IV echinocandin or IV amphotericin B (conventional formulation).17

For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend IV or oral fluconazole as the preferred drug of choice and itraconazole oral solution as a preferred alternative.19 Other alternatives include an IV echinocandin (caspofungin, micafungin, anidulafungin), oral or IV voriconazole, oral posaconazole, or IV amphotericin B (conventional formulation).19 For refractory esophageal candidiasis, including fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;19 alternatives include IV amphotericin B (conventional or a lipid formulation), an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.19

Patients with frequent or severe recurrences of esophageal candidiasis, including HIV-infected patients, may benefit from long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral posaconazole; however, the potential for azole resistance should be considered.17 19 Echinocandins not included in recommendations for secondary prophylaxis of esophageal candidiasis.17 19 Patients with fluconazole-refractory esophageal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.19

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis.17 18 19 Considered an alternative, not a drug of choice.17 19

IDSA recommends topical clotrimazole or topical nystatin for mild oropharyngeal candidiasis;17 oral fluconazole is recommended for moderate to severe disease.17 For refractory oropharyngeal candidiasis, including fluconazole-refractory infections, itraconazole oral solution, oral posaconazole, or oral voriconazole is recommended.17 An IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B (conventional formulation) also are recommended as alternatives for refractory infections.17

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;19 alternatives for initial episodes include topical clotrimazole or topical nystatin.19 For fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;19 alternatives include IV amphotericin B (conventional or lipid formulation), an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.19

Patients with frequent or severe recurrences of oropharyngeal candidiasis, including HIV-infected patients, may benefit from long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or itraconazole oral solution; however, the potential for azole resistance should be considered.17 19 Echinocandins not included in recommendations for secondary prophylaxis of oropharyngeal candidiasis.17 19 Patients with fluconazole-refractory oropharyngeal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.19

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

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 is completely dissolved and a clear solution is 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

Use strict aseptic technique since drug contains no preservative.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

IV infusions are given over approximately 1 hour.1

Dosage

Available as caspofungin acetate; 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 The loading dose (in mg) should be calculated as BSA (m2) x 70 mg/m2 and the maintenance dose (in mg) should be calculated as BSA (m2) x 50 mg/m2.1

Invasive Aspergillosis
IV

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

Optimum duration of antifungal treatment for invasive aspergillosis not established.21 Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response.1

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

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 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 and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.17 18

Esophageal Candidiasis
IV

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

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.17 18 19

Empiric Therapy in Febrile Neutropenic Patients
IV

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 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 both neutropenia and clinical symptoms resolve.1

Adults

Invasive Aspergillosis
IV

A single 70-mg loading dose on day 1, followed by 50 mg once daily.1 18 19 21 Efficacy of dosages >50 mg once daily not evaluated.1

Optimum duration of treatment not established.21 Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response.1

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 17 18

Although a dosage of 150 mg once daily has been used in a clinical study, this high dosage is no more effective than a dosage of 50 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 and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.17 18

Esophageal Candidiasis
IV

50 mg once daily.1 17 18 19

Manufacturer states use of a 70-mg loading dose has not been evaluated for treatment of esophageal candidiasis and efficacy of dosages >50 mg daily has not been evaluated.1

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.17 18 19

Oropharyngeal Candidiasis
IV

IDSA recommends a single 70-mg loading dose on day 1, followed by 50 mg once daily.17 Others recommend 50 mg once daily.18 19

IDSA and others recommend that antifungal treatment be continued for 7–14 days.17 19

Empiric Therapy in Febrile Neutropenic Patients
IV

A single 70-mg loading dose on day 1, followed by 50 mg once daily.1 17 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 and maximum maintenance dose of 70 mg daily.1

Adults

Aspergillosis
IV

Efficacy of maintenance dosages >50 mg daily not evaluated.1

Esophageal Candidiasis
IV

Efficacy of maintenance dosages >50 mg daily not evaluated.1

Empiric Therapy in Febrile Neutropenic Patients
IV

Maximum 70 mg daily.1

Special Populations

Hepatic Impairment

Adults with mild hepatic impairment (Child-Pugh score 5–6): No dosage adjustment 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 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 to caspofungin acetate or any ingredient in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis) reported.1

Possible histamine-mediated symptoms (e.g., rash, facial swelling, pruritus, sensation of warmth, bronchospasm) reported.1

Interactions

Use concomitantly with cyclosporine only when potential benefits outweigh risks.1 Transient elevations in transaminase concentrations reported.1 If abnormal liver function test results occur during concomitant therapy, monitor closely and evaluate the benefits versus risks of continuing such therapy.1 (See Specific Drugs under Interactions.)

Hepatic Effects

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

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

Specific Populations

Pregnancy

Category C.1

Lactation

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

Pediatric Use

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

Although pharmacokinetic data are available for neonates and infants <3 months of age, data are 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; data insufficient 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 (e.g., amphotericin B [conventional or lipid formulations], itraconazole); for treatment of candidemia, certain other invasive Candida infections (intra-abdominal abscesses, peritonitis, pleural space infections), or esophageal candidiasis; or 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

The manufacturer states that the overall safety profile of caspofungin in pediatric patients is comparable to that in adults.1 Adverse effects reported in ≥7% of pediatric patients receiving caspofungin include pyrexia, rash, decreased potassium, increased AST, diarrhea, increased ALT, chills, hypotension, vomiting, tachycardia, mucosal inflammation, hypertension, headache, erythema, central line infection, cough, respiratory distress, hypokalemia, abdominal pain, and pruritus.1

Some experts state data are insufficient to date to recommend use of caspofungin for first-line treatment of invasive candidiasis or for treatment of esophageal or oropharyngeal candidiasis in children (including HIV-infected children).20

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 adjustment not recommended.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 A greater increase in AUC occurs 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 effect on pharmacokinetics. (See Special Populations under Pharmacokinetics.) Dosage adjustment 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 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, synergistic or additive antifungal activity against some Aspergillus, including A. fumigatus, and some Fusarium; 7 8 9 13 in vitro, indifferent or additive antifungal effects 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

Possibility of decreased caspofungin concentrations 1

Consider increasing caspofungin dosage to 70 mg once daily in adults or to 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Corticosteroids (dexamethasone)

Possibility of decreased caspofungin concentrations 1

Consider increasing caspofungin dosage to 70 mg once daily in adults or to 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Efavirenz

Possibility of decreased caspofungin concentrations1

Consider increasing caspofungin dosage to 70 mg once daily in adults or to 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Fluconazole

In vitro, 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 reported;1 possible increased bilirubin concentration1

Mycophenolate: No evidence of pharmacokinetic interactions1

Tacrolimus: Decreased tacrolimus AUC and plasma concentrations;1 no effect on caspofungin concentrations1

Cyclosporine: Use concomitantly only when potential benefits outweigh risks;1 monitor hepatic function;18 if abnormal liver function test results occur, monitor closely and evaluate benefits versus risks of continuing such therapy1

Tacrolimus: Monitor tacrolimus concentrations and adjust dosage as needed1

Itraconazole

Itraconazole: No evidence of pharmacokinetic interactions1

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

Nelfinavir

No effect on caspofungin pharmacokinetics1

Nevirapine

Possibility of decreased caspofungin concentrations1

Consider increasing caspofungin dosage to 70 mg once daily in adults or to 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Phenytoin

Possibility of decreased caspofungin concentrations 1

Consider increasing caspofungin dosage to 70 mg once daily in adults or to 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Posaconazole

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

Rifampin

Decreased trough concentrations of caspofungin1

Increase caspofungin dosage to 70 mg once daily in adults;1 consider increasing caspofungin dosage to 70 mg/m2 once daily (maximum 70 mg daily) in pediatric patients1

Voriconazole

In vitro, additive antifungal effects against C. glabrata;8 in vitro, indifferent, additive, or synergistic antifungal activity 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 Data not available regarding adults with severe hepatic impairment (Child-Pugh score >9).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

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

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 After reconstitution and before dilution, may be stored for up to 1 hour at ≤25°C.1 Following dilution, may be stored for up to 24 hours at ≤25°C or for up to 48 hours at 2–8°C.1

Actions and Spectrum

  • Echinocandins (e.g., caspofungin, anidulafungin, 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

  • 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. A correlation between MICs and clinical outcome has not been established to date.1

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

Advice to Patients

  • 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

  • Advise patients that hypersensitivity reactions can occur (e.g., rash, facial swelling, pruritus, sensation of warmth, bronchospasm).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. (See Cautions.)

Preparations

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

Caspofungin Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

50 mg

Cancidas

Merck

70 mg

Cancidas

Merck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, 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 prescribing information. Whitehouse Station, NJ; 2009 Jul.

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.

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